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CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
METHODS OF DIAGNOSIS OF LUNG CANCER, COMPOSITIONS AND METHODS
OF SCREENING FOR MODULATORS OF LUNG CANCER
CROSS-REFERENCES TO RELATED APPLICATIONS
This application is related to USSN 60/284,770, filed April 18, 2001; USSN
60/290,492, filed May 10, 2001; USSN 60/334,370, filed November 29, 2001; USSN
60/339,245, filed November 9, 2001; USSN 60/350,666, filed November 13, 2001;
and
USSN 60/xxx,xxx, filed April 12, 2002 (Docket OMNI-002P); each of which is
incorporated
herein by reference in its entirety.
FIELD OF THE INVENTION
The invention relates to the identification of nucleic acid and protein
expression
profiles and nucleic acids, products, and antibodies thereto that are involved
in lung cancer;
and to the use of such expression profiles and compositions in diagnosis and
therapy of lung
cancer. The invention further relates to methods for identifying and using
agents and/or
targets that inhibit lung cancer or related conditions.
~ BACKGROUND OF THE INVENTION
Lung cancer is the second most commonly occurnng cancer in the United States
and
is the leading cause of cancer-related death. It is estimated that there are
over 160,000 new
cases of lung cancer in the United States every year. Of those who are
diagnosed with lung
cancer, 86 percent will die within five years. Lung cancer is the most common
visceral
cancer in men and accounts for nearly one third of all cancer deaths in both
men and women.
In fact, lung cancer accounts for 7% of all deaths, due to any cause, in both
men and women.
Smoking is the primary cause of lung cancer, with more than 80% of lung
cancers
resulting from smoking. About 400 to 500 separate gaseous substances are
present in the
smoke of a non-filter cigarette. The most noteworthy substances include
nitrogen oxides,
hydrogen cyanide, formaldehyde, benzene, and toluene. The particles present in
cigarette
smoke contain at least 3,500 individual compounds such as nicotine, tobacco
alkaloids
(nornicotine, anatabine, anabasine), polycyclic aromatic hydrocarbons (e.g.,
benzo(a)pyrene,
B(a)P), naphthalenes, aromatic amines, phenols, and tobacco-specific
nitrosamines.
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Tobacco-specific nitrosamines are formed during tobacco curing and processing,
and
are suspected of causing lung cancer in humans. In rodent studies, regardless
of the where or
how it is applied, the tobacco-specific nitrosamine known as NNK produces lung
adenomas
and lung adenocarcinomas. The tobacco-specific nitrosamine known as NNAL also
produces -
lung adenocarcinomas in rodents.
Many of the chemicals found in cigarette smoke also affect the nonsmoker
inhaling
"secondhand" or sidestream smoke. Indeed, the smoke inhaled by non-smokers has
a
chemical composition similar to the smoke inhaled by smokers, but,
importantly, the
concentrations of the carcinogenic tobacco-specific nitrosamines are present
in higher
concentrations in second hand smoke. For this and other reasons, "passive
smoking" is an
important cause of lung cancer, causing as many as 3,000 lung cancer deaths in
nonsmokers
each year.
In addition to smoking, other factors thought to be causes of lung cancer
include on-
the job exposure to carcinogens such as asbestos and uranium, exposure to
chemical hazards
such as radon, polycyclic aromatic hydrocarbons, chromium, nickel, and
inorganic arsenic,
genetic factors, and diet.
Histological classification of various lung cancers define the types of cancer
that
begin in the lung. See, e.g., Travis, et al. (1999) Histolo icg al Typing of
Lung and Pleural
Tumours (International Histological Classification of Tumours, No 1. Four
major cell types
make up more than 88% of all primary lung neoplasms. These are: squamous or
epidermoid
carcinoma, small cell (also called oat cell) carcinoma, adenocarcinoma, and
large cell (also
called large cell anaplastic) carcinoma. The remainder include
undifferentiated carcinomas,
carcinoids, bronchial gland tumors, and other rarer types. The various cell
types have
different natural histories and responses to therapy, and, thus, a correct
histologic diagnosis is
the first step of effective treatment.
Small cell lung canccr (SCLC) accounts for 18-25% of all lung cancers, and
occurs
less frequently than non-small cell lung cancers, and generally spread to
distant organs more
rapidly than non-small cell lung cancer. In general, at the time of
presentation small cell lung
cancers have already spread beyond the beyond the bounds where surgery and
curative intent
can be undertaken. Hoever, if identified early enough, these cancers are often
responsive to
chemotherapy and thoracic radiation treatment.
Non-small cell lung cancers (NSCLC) are the more frequently occurring form of
lung
cancer. They comprise squamous cell carcinoma, adenocarcinoma, and large cell
carcinoma
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and account for more than 75% of all lung cancers. Non-small cell tumors that
are localized
at the time of presentation can sometimes be cured with surgery and/or
radiotherapy, but
usually are not identified until significant metastasis has occurred, which
are typically not
very responsive to surgical, chemotherapy, or radiation treatment..
The screening of asymptomatic persons at high risk for lung cancer has often
proven
ineffective. In general, only 5 to 15 percent of lung cancer patients have
their disease
detected while they are asymptomatic. Of course, early detection and treatment
are critical
factors in the fight against lung cancer. The average survival rate is 49% for
those whose
cancer is detected early, before the cancer has spread from the lung. Lung
cancer often
spreads outside of the lung, and it may have spread to the bones or brain by
the time it is
diagnosed. While the prognosis may be better for lung cancers that are
detected early,
because of the lack ofv effective curative treatments, early detection does
not necessarily alter
the total death rate from lung cancer.
Thus, methods for diagnosis and prognosis of lung cancer and effective
treatment of
1 S lung cancer would be desirable. Accordingly, provided herein are methods
that can be used
in diagnosis and prognosis of lung cancer. Further provided are methods that
can be used to
screen candidate therapeutic agents for the ability to modulate, e.g., treat,
lung cancer.
Additionally, provided herein are molecular targets and compositions for
therapeutic
intervention in lung disease and other metastatic cancers.
SUMMARY OF THE INVENTION
The present invention provides nucleotide sequences of genes that are up- and
down-
regulated in lung cancer cells. Such genes are useful for diagnostic purposes,
and also as
targets for screening for therapeutic compounds that modulate lung cancer,
such as
antibodies. The methods of detecting nucleic acids of the invention or their
encoded proteins
can be used for a number of purposes. Examples include early detection of lung
cancers,
monitoring and early detection of relapse following treatment of lung cancers,
monitoring
response to therapy of lung cancers, determining prognosis of lung cancers,
directing therapy
of lung cancers, selecting patients for postoperative chemotherapy or
radiation therapy,
selecting therapy, determining tumor prognosis, treatment, or response to
treatment, and early
detection of precancerous lesions of the lung. Examples of benign or
precancerous lesions
include: atelectasis, emphysema, brochitis, chronic obstructive pulmonary
disease, fibrosis,
hypersensitivity pneumonitis (HP), interstitial pulmonary fibrosis (IPF),
asthma, and
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bronchiectasis. Other aspects of the invention will become apparent to the
skilled artisan by
the following description of the invention.
In one aspect, the present invention provides a method of detecting a lung
cancer-
associated transcript in a cell from a patient, the method comprising
contacting a biological
sample from the patient with a polynucleotide that selectively hybridizes to a
sequence at
least 80% identical to a sequence as shown in Tables 1A-16. Alternatively, the
sample may
be contacted with a specific binding reagent, e.g., antibody.
In one embodiment, the polynucleotide selectively hybridizes to a sequence at
least
95% identical to a sequence as shown in Tables 1A-16. In another embodiment,
the
polynucleotide comprises a sequence as shown in Tables 1A-16.
In one embodiment, the biological sample is a tissue sample, or a body fluid.
In
another embodiment, the biological sample comprises isolated nucleic acids,
e.g., mRNA.
In one embodiment, the polynucleotide is labeled, e.g., with a fluorescent
label. In
one embodiment, the polynucleotide is immobilized on a solid surface. In one
embodiment,
the patient is undergoing a therapeutic regimen to treat lung cancer. In
another embodiment,
the patient is suspected of having lung cancer. In one embodiment, the patient
is a primate,
e.g., a human.
In one embodiment, the method further comprises the step of amplifying nucleic
acids
before the step of contacting the biological sample with the polynucleotide.
In another aspect, the present invention provides a method of monitoring the
efficacy
of a therapeutic treatment of lung cancer, the method comprising the steps of
(i) providing a
biological sample from a patient undergoing the therapeutic treatment; and
(ii) determining
the level of a lung cancer-associated transcript in the biological sample by
contacting the
biological sample with a polynucleotide that selectively hybridizes to a
sequence at least 80%
identical to a sequence as shown in Tables 1A-16, thereby monitoring the
efficacy of the
therapy. Or the sample may be evaluated for protein, e.g., contacting the
sample with an
antibody.
In one embodiment, the method further comprises the step of (iii) comparing
the
level of the lung cancer-associated transcript to a level of the lung cancer-
associated
transcript in a biological sample from the patient prior to, or earlier in,
the therapeutic
treatment. Or the sample may be evalated for comparison of protein.
In another aspect, the present invention provides a method of monitoring the
efficacy
of a therapeutic treatment of lung cancer, the method comprising the steps of:
(i) providing a
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biological sample from a patient undergoing the therapeutic treatment; and
(ii) determining
the level of a lung cancer-associated antibody in the biological sample by
contacting the
biological sample with a polypeptide encoded by a polynucleotide that
selectively hybridizes
to a sequence at least 80% identical to a sequence as shown in Tables .1A-16,
wherein the
polypeptide specifically binds to the lung cancer-associated antibody, thereby
monitoring the
efficacy of the therapy.
In one embodiment, the method further comprises the step of (iii) comparing
the
level of the lung cancer-associated antibody to a level of the lung cancer-
associated antibody
in a biological sample from the patient prior to, or earlier in, the
therapeutic treatment.
In another aspect, the present invention provides a method of monitoring the
efficacy
of a therapeutic treatment of lung cancer, the method comprising the steps of
(i) providing a
biological sample from a patient undergoing the therapeutic treatment; and
(ii) determining
the level of a lung cancer-associated polypeptide in the biological sample by
contacting the
biological sample with an antibody, wherein the antibody specifically binds to
a polypeptide
encoded by a polynucleotide that selectively hybridizes to a sequence at least
80% identical
to a sequence as shown in Tables 1A-16, thereby monitoring the efficacy of the
therapy.
In one embodiment, the method further comprises the step of (iii) comparing
the
level of the lung cancer-associated polypeptide to a level of the ,lung cancer-
associated
polypeptide in a biological sample from the patient prior to, or earlier in,
the therapeutic
treatment. In one aspect, the present invention provides an isolated nucleic
acid molecule
consisting of a polynucleotide sequence as shown in Tables 1A-16. In one
embodiment, an
expression vector or cell comprises the isolated nucleic acid. In one aspect,
the present
invention provides an isolated polypeptide which is encoded by a nucleic acid
molecule
having polynucleotide sequence as shown in Tables 1A-16.
In another aspect, the present invention provides an antibody that
specifically binds to
an isolated polypeptide which is encoded by a nucleic acid molecule having
polynucleotide
sequence as shown in Tables 1A-16. In one embodiment; the antibody is
conjugated to an
effector component, e.g., a fluorescent label, a radioisotope or a cytotoxic
chemical. In one
embodiment, the antibody is an antibody fragment. In another embodiment, the
antibody is
humanized.
In one aspect, the present invention provides a method of detecting lung
cancer in a a
patient, the method comprising contacting a biological sample from the patient
with an
antibody or protein as described herein.
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In another aspect, the present invention provides a method of detecting
antibodies
specific to a lung cancer gene in a patient, the method comprising contacting
a biological
sample from the patient with a polypeptide encoded by a nucleic acid comprises
a sequence
from Tables 1A-16.
In another aspect, the present invention provides a method for identifying a
compound
that modulates a lung cancer-associated polypeptide, the method comprising the
steps of (i)
contacting the compound with a lung cancer-associated polypeptide, the
polypeptide encoded
by a polynucleotide that selectively hybridizes to a sequence at least 80%
identical to a
sequence as shown in Tables 1A-16; and (ii) determining the functional effect
of the
compound upon the polypeptide.
In one embodiment, the functional effect is a physical effect, an enzymatic
effect, or a
chemical effect. In one embodiment, the polypeptide is expressed in a
eukaryotic host cell or
cell membrane. In another embodiment, the polypeptide is recombinant. In one
embodiment, the functional effect is determined by measuring ligand binding to
the
polypeptide.
In another aspect, the present invention provides a method of inhibiting
proliferation
or another critical process of a lung cancer-associated cell to treat lung
cancer in a patient, the
method comprising the step of administering to the subject a therapeutically
effective amount
of a compound identified as described herein. In one embodiment, the compound
is an
antibody.
In another aspect, the present invention provides a drug screening assay
comprising
the steps of (i) administering a test compound to a mammal having lung cancer
or a cell
isolated therefrom; (ii) comparing the level of gene expression of a
polynucleotide that
selectively hybridizes to a sequence at least 80% identical to a sequence as
shown in Tables
1A-16 in a treated cell or mammal with the level of gene expression of the
polynucleotide in
a control cell or mammal, wherein a test compound that modulates the level of
expression of
the polynucleotide is a candidate for the treatment of lung cancer.
In one embodiment, the control is a mammal with lung cancer or a cell
therefrom that
has not been treated with the test compound. In another embodiment, the
control is a normal
cell or mammal, or a non-malignant lung disease.
In another aspect, the present invention provides a method for treating a
mammal
having lung cancer comprising administering a compound identified by the assay
described
herein.
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In another aspect, the present invention provides a pharmaceutical composition
for
treating a mammal having lung cancer, the composition comprising a compound
identified by
the assay described herein and a physiologically acceptable excipient.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the objects outlined above, the present invention provides
novel
methods for diagnosis and treatment of lung disease or cancer, as well as
methods for
screening for compositions which modulate lung cancer. "Treatment, monitoring,
detection
or modulation of lung disease or cancer" includes treatment, monitoring,
detection, or
modulation of lung disease in those patients who have lung disease (whether
malignant or
non-malignant, e.g., emphysema, bronchitis, or fibrosis) as well as patients
with lung cancers
in which gene expression from a gene in Tables 1A-16 is increased or
decreased, indicating
that the subject is more likely to have disease. In particular,while these
targets are identified
primarily from lung cancer samples, these same targets are likely to be
similarly found in
analyses of other medical conditions. These other conditions may result from
similar
pathological processes which affect similar tissues, e.g., lung cancer, small
cell lung
carcinoma (oat cell carcinoma), non-small cell carcinomas (e.g., squamous cell
carcinoma,
adenocarcinoma, large cell lung carcinoma, carcinoid, granulomatous), fibrosis
(idiopathic
pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), interstitial
pneumonitis,
nonspecific idiopathic pneumonitis (NSIP)), chronic obstructive pulmonary
disease (COPD,
e.g., emphysema, chronic bronchitis), asthma, bronchiectasis, and esophageal
cancer. See,
e.g., the NCI webpage and USSN 60/347,349 and USSN 60/xxx,xxx (docket LFBR-001-
1P,
filed March 29, 2002), each of which is incorporated herein by reference. The
treatment may
be of lung cancer or related condition itself, or treatment of metastasis.
In particular, identification of markers selectively expressed on these
cancers allows
for use of that expression in diagnostic, prognostic, or therapeutic methods.
As such, the
invention defines various compositions, e.g., nucleic acids, polypeptides,
antibodies, and
small molecule agonists/antagonists, which will be useful to selectively
identify those
markers. For example, therapeutic methods may take the form of protein
therapeutics which
use the marker expression for selective localization or modulation of function
(for those
markers which have a causative disease effect), for vaccines, identification
of binding
partners, or antagonism, e.g., using antisense or RNAi. The markers may be
useful for
molecular characterization of subsets of lung diseases, which subsets may
actually require
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very different treatments. Moreover, the markers may also be important in
related diseases to
the specific cancers, e.g., which affect similar tissues in non-malignant
diseases, or have
similar mechanisms of induction/maintenance. Metastatic processes'or
characteristics may
also be targeted. Diagnostic and prognostic uses are made available, e.g., to
subset related
but distinct diseases, or to determine treatment strategy. The detection
methods may be based
upon nucleic acid, e.g., PCR or hybridization techniques, or protein, e.g.,
ELISA, imaging,
IHC, etc. The diagnosis may be qualitative or quantitative, and may detect
increases or
decreases in expression levels.
Tables 1A-16 provide unigene cluster identification numbers for the nucleotide
1'0 sequence of genes that exhibit increased or decreased expression in lung
cancer samples. The
tables also provide an exemplar accession number that provides a nucleotide
sequence that is
part of the unigene cluster. In Table 1A, genes marked as "target 1" or
"target 2" are
particularly useful as therapeutic targets. Genes marked as "target 3" are
particularly useful
as diagnostic markers. Genes marked as "chron" are upregulated in chronically
diseased lung
(e.g., emphysema, bronchitis, fibrosis) relative to lung tumors and normal
tissue. In certain
analyses, the ratio for the "chron" category was determined using the 70th
percentile of
chronically diseases lung samples divided by the 90th percentile of normal
lung samples.
The ratio for the targets was determined using the 70th percentile of lung
tumor samples
divided by the 90th percentile of normal lung samples.
Definitions
The term "lung cancer protein" or "lung cancer polynucleotide" or "lung cancer-
associated transcript" refers to nucleic acid and polypeptide polymorphic
variants, alleles,
mutants, and interspecies homologs that: (1) have a nucleotide sequence that
has greater than
about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%,
preferably 91%,
92%, 93%, 94%, 95%, 96%, 97%, 98%, or 99% or greater nucleotide sequence
identity,
preferably over a region of over a region of at least about 25, 50, 100, 200,
500, 1000, or
more nucleotides, to a nucleotide sequence of or associated with a unigene
cluster of Tables
1A-16; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an
immunogen
comprising an amino acid sequence encoded by a nucleotide sequence of or
associated with a
unigene cluster of Tables 1A-16, and conservatively modified variants thereof;
(3)
specifically hybridize under stringent hybridization conditions to a nucleic
acid sequence, or
the complement thereof of Tables 1A-16 and conservatively modified variants
thereof; or (4)
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have an amino acid sequence that has greater than about 60% amino acid
sequence identity,
65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%,
98%,
or 99% or greater amino sequence identity, preferably over a region of over a
region of at
least about 25, 50, 100, 200, 50'0, 1000, or more amino acid, to an amino acid
sequence
encoded by a nucleotide sequence of or associated with a unigene cluster of
Tables 1A-16. A
polynucleotide or polypeptide sequence is typically from a mammal including,
but not
limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig,
horse, sheep, or
other mammal. A "lung cancer polypeptide" and a "lung cancer polynucleotide,"
include
both naturally occurring or recombinant forms.
A "full length" lung cancer protein or nucleic acid refers to a lung cancer
polypeptide
or polynucleotide sequence, or a variant thereof, that contains the elements
normally
contained in one or more naturally occurring, wild type lung cancer
polynucleotide or
polypeptide sequences. The "full length" may be prior to, or after, various
stages of post-
translational processing or splicing, including alternative splicing.
"Biological sample" as used herein is a sample of biological tissue or fluid
that
contains nucleic acids or polypeptides, e.g., of a lung cancer protein,
polynucleotide, or
transcript. Such samples include, but are not limited to, tissue isolated from
primates, e.g.,
humans, or rodents, e.g., mice, and rats. Biological samples may also include
sections of
tissues such as biopsy and autopsy samples, frozen sections taken for
histologic purposes,
archival materials, blood, plasma, serum, sputum, stool, tears, mucus, hair,
skin, etc.
Biological samples also include explants and primary andlor transformed cell
cultures
derived from patient tissues. A biological sample is typically obtained from a
eukaryotic
organism, most preferably a mammal such as a primate, e.g., chimpanzee or
human; cow;
dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or other mammal; or
a bird; reptile;
fish. Livestock and domestic animals are of interest.
"Providing a biological sample" means to obtain a biological sample for use in
methods described in this invention. Most often, this will be done by removing
a sample of
cells from an animal, but can also be accomplished by using previously
isolated cells (e.g.,
isolated by another person, at another time, and/or for another purpose), or
by performing the
methods of the invention in vivo. Archival tissues or materials, having
treatment or outcome
history, will be particularly useful.
The terms "identical" or percent "identity," in the context of two or more
nucleic
acids or polypeptide sequences, refer to two or more sequences or subsequences
that are the
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same or have a specified percentage of amino acid residues or nucleotides that
are the same
(e.g., about 60% identity, preferably 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%,
94%,
95%, 96%, 97%, 98%, 99%, or higher identity over a specified region, when
compared and
aligned for maximum correspondence over a comparison window or designated
region) as
measured using, e.g., a BLAST or BLAST 2.0 sequence comparison algorithms with
default
parameters described below, or by manual alignment and visual inspection (see,
e.g., NCBI
web site http://www.ncbi.nlm.nih.govBLAST/ or the like). Such sequences are
then said to
be "substantially identical." This definition also refers to, or may be
applied to, the
complement of a test sequence. The definition also includes sequences that
have deletions
and/or insertions, substitutions, and naturally occurring, e.g., polymorphic
or allelic variants,
and man-made variants. As described below, the preferred algorithms can
account for gaps
and the like. Preferably, identity exists over a region that is at least about
25 amino acids or
nucleotides in length, or more preferably over a region that is SO-100 amino
acids or
nucleotides in length.
For sequence comparison, typically one sequence acts as a reference sequence,
to
which test sequences are compared. When using a sequence comparison algorithm,
test and
reference sequences are entered into a computer, subsequence coordinates are
designated, if
necessary, and sequence algorithm program parameters are designated.
Preferably, default
program parameters can be used, or alternative parameters can be designated.
The sequence
comparison algorithm then calculates the percent sequence identities for the
test sequences
relative to the reference sequence, based on the program parameters.
A "comparison window", as used herein, includes reference to a segment of
contiguous positions selected from the group consisting typically of from 20
to 600, usually
about 50 to about 200, more usually about 100 to about 150 in which a sequence
may be
compared to a reference sequence of the same number of contiguous positions
after the two
sequences are optimally aligned. Methods of alignment of sequences for
comparison are
well-known in the art. Optimal alignment of sequences for comparison can be
conducted,
e.g., by the local homology algorithm of Smith and Waterman (1981) Adv. Appl.
Math.
2:482, by the homology alignment algorithm of Needleman and Wunsch (1970) J.
Mol. Biol.
48:443, by the search for similarity method of Pearson and Lipman (1988) Proc.
Nat'1. Acad.
Sci. USA 85:2444, by computerized implementations of these algorithms (GAP,
BESTFIT,
FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics
Computer
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Group, 575 Science Dr., Madison, WI), or by manual alignment and visual
inspection (see,
e.g., Ausubel, et al. (eds. 1995 and supplements) Current Protocols in
Molecular Biolo~.v.
Preferred examples of algorithms that are suitable for determining percent
sequence
identity and sequence similarity include the BLAST and BLAST 2.0 algorithms,
which are
described in Altschul, et al. (1977) Nuc. Acids Res. 25:3389-3402 and
Altschul, et al. '(1990)
J. Mol. Biol. 215:403-410. BLAST and BLAST 2.0 are used, with the parameters
described
herein, to determine percent sequence identity for the nucleic acids and
proteins of the
invention. Software for performing BLAST analyses is publicly available
through the
National Center for Biotechnology Information (http://www.ncbi.nlm.nih.gov~.
This
algorithm involves first identifying high scoring sequence pairs (HSPs) by
identifying short
words of length W in the query sequence, which either match or satisfy some
positive-valued
threshold score T when aligned with a word of the same length in a database
sequence. T is
referred to as the neighborhood word score threshold (Altschul, et al.,
supra). These initial
neighborhood word hits act as seeds for initiating searches to find longer
HSPs containing
them. The word hits are extended in both directions along each sequence for as
far as the
cumulative alignment score can be increased. Cumulative scores are calculated
using, e.g.,
for nucleotide sequences, the parameters M (reward score for a pair of
matching residues;
always > 0) and N (penalty score for mismatching residues; always < 0). For
amino acid
sequences, a scoring matrix is used to calculate the cumulative score.
Extension of the word
hits in each direction are halted when: the cumulative alignment score falls
off by the
quantity X from its maximum achieved value; the cumulative score goes to zero
or below,
due to the accumulation of one or more negative-scoring residue alignments; or
the end of
either sequence is reached. The BLAST algorithm parameters W, T, and X
determine the
sensitivity and speed of the alignment. The BLASTN program (for nucleotide
sequences)
uses as defaults a wordlength (W) of 1 l, an expectation (E) of 10, M=5, N=-4
and a
comparison of both strands. For amino acid sequences, the BLASTP program uses
as
defaults a wordlength of 3, and expectation (E) of 10, and the BLOSUM62
scoring matrix
(see Henikoff and Henikoff (1989) Proc. Natl. Acad. Sci. USA 89:10915)
alignments (B) of
50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands.
The BLAST algorithm also performs a statistical analysis of the similarity
between
two sequences (see, e.g., Karlin and Altschul (1993) Proc. Nat'1. Acad. Sci.
USA 90:5873-
5787). One measure of similarity provided by the BLAST algorithm is the
smallest sum
probability (P(I~), which provides an indication of the probability by which a
match between
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two nucleotide or amino acid sequences would occur by chance. For example, a
nucleic acid
is considered similar to a reference sequence if the smallest sum probability
in a comparison
of the test nucleic acid to the reference nucleic acid is less than about 0.2,
more preferably
less than about 0.01, and most preferably less than about 0.001. Log values
may be negative
large numbers, e.g., 5, 10, 20, 30, 40, 40, 70, 90, 110, 150, 170, etc.
An indication that two nucleic acid sequences are substantially identical is
that the
polypeptide encoded by the first nucleic acid is immunologically cross
reactive with the
antibodies raised against the polypeptide encoded by the second nucleic acid.
Thus, a
polypeptide is typically substantially identical to a second polypeptide,
e.g., where the two
peptides differ only by conservative substitutions. Another indication that
two nucleic acid
sequences are substantially identical is that the two molecules or their
complements hybridize
to each other under stringent conditions. Yet another indication that two
nucleic acid
sequences are substantially identical is that the same primers can be used to
amplify the
sequences.
A "host cell" is a naturally occurnng cell or a transformed cell that contains
an
expression vector and supports the replication or expression of the expression
vector. Host
cells may be cultured cells, explants, cells in vivo, and the like. Host cells
may be
prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect,
amphibian, or
mammalian cells such as CHO, HeLa, and the like (see, e.g., the American Type
Culture
Collection catalog or web site, www.atcc.org).
The terms "isolated," "purified," or "biologically pure" refer to material
that is
substantially or essentially free from components that normally accompany it
as found in its
native state. Purity and homogeneity are typically determined using analytical
chemistry
techniques such as polyacrylamide gel electrophoresis or high performance
liquid
chromatography. A protein or nucleic acid that is the predominant species
present in a
preparation is substantially purified. In particular, an isolated nucleic acid
is separated from
some open reading frames that naturally flank the gene and encode proteins
other than protein
encoded by the gene. The term "purified" in some embodiments denotes that a
nucleic acid
or protein gives rise to essentially one band in an electrophoretic gel.
Preferably, it means
that the nucleic acid or protein is at least about 85% pure, more preferably
at least 95% pure,
and most preferably at least 99% pure. "Purify" or "purification" in other
embodiments
means removing at least one contaminant or component from the composition to
be purified.
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In this sense, purification does not require that the purified compound be
homogeneous, e.g.,
100% pure.
The terms "polypeptide," "peptide" and "protein" are used interchangeably
herein to
refer to a polymer of amino acid residues. The terms apply to amino acid
polymers in which
one or more amino acid residue is an artificial chemical mimetic of a
corresponding naturally
occurring amino acid, as well as to naturally occurnng amino acid polymers,
those containing
modified residues, and non-naturally occurring amino acid polymer.
The term "amino acid" refers to naturally occurring and synthetic amino acids,
as well
as amino acid analogs and amino acid mimetics that function similarly to the
naturally
occurring amino acids. Naturally occurring amino acids are those encoded by
the genetic
code, as well as those amino acids that are later modified, e.g.,
hydroxyproline, y-
carboxyglutamate, and O-phosphoserine. Amino acid analogs refer to compounds
that have
the same basic chemical structure as a naturally occurring amino acid, e.g.,
an a carbon that is
bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g.,
homoserine,
norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs
may have
modified R groups (e.g., norleucine) or modified peptide backbones, but retain
some basic
chemical structure as a naturally occurring amino acid. Amino acid mimetics
refer to
chemical compounds that have a structure that is different from the general
chemical
structure of an amino acid, but that function similarly to another amino acid.
Amino acids may be referred to herein by either their commonly known three
letter
symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical
Nomenclature Commission. Nucleotides, likewise, may be referred to by their
commonly
accepted single-letter codes.
"Conservatively modified variants" applies to both amino acid and nucleic acid
sequences. With respect to particular nucleic acid sequences, conservatively
modified
variants refers to those nucleic acids which encode identical or essentially
identical amino
acid sequences, or where the nucleic acid does not encode an amino acid
sequence, to
essentially identical or associated, e.g., naturally contiguous, sequences.
Because of the
degeneracy of the genetic code, a large number of fiznctionally identical
nucleic acids encode
most proteins. For instance, the codons GCA, GCC, GCG, and GCU each encode the
amino
acid alanine. Thus, at each position where an alanine is specified by a codon,
the codon can
be altered to another of the corresponding codons described without altering
the encoded
polypeptide. Such nucleic acid variations are "silent variations," which are
one species of
13
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WO 02/086443 PCT/US02/12476
conservatively modified variations. Every nucleic acid sequence herein which
encodes a
polypeptide also describes silent variations of the nucleic acid. In certain
contexts each
codon in a nucleic acid (except AUG, which is ordinarily the only codon for
methionine, and
TGG, which is ordinarily the only codon for tryptophan) can be modified to
yield a
functionally similar molecule. Accordingly, a silent variation of a nucleic
acid which
encodes a polypeptide is implicit in a described sequence with respect to the
expression
product, but not necessarily with respect to actual probe sequences.
As to amino acid sequences, one of skill will recognize that individual
substitutions,
deletions or additions to a nucleic acid, peptide, polypeptide, or protein
sequence which
alters, adds or deletes a single amino acid or a small percentage of amino
acids in the encoded
sequence is a "conservatively modified variant" where the alteration results
in the substitution
of an amino acid with a chemically similar amino acid. Conservative
substitution tables
providing functionally similar amino acids are well known in the art. Such
conservatively
modified variants are in addition to and do not exclude polymorphic variants,
interspecies
homologs, and alleles of the invention. Typically conservative substitutions
include for one
another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E);
3) Asparagine
(N~, Glutamine (Q); 4) Arginine (R), Lysine (K); S) Isoleucine (I), Leucine
(L), Methionine
(M), Valine (V); 6) Phenylalanine (F), Tyrosine (~, Tryptophan (W); 7) Serine
(S),
Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton,
Proteins (1984)).
Macromolecular structures such as polypeptide structures can be described in
terms of
various levels of organization. For a general discussion of this organization,
see, e.g.,
Alberts, et al. (1994) Molecular Biology of the Cell (3rd ed.) and Cantor and
Schimmel (1980)
Biophysical Chemistry Part I: The Conformation of Biological Macromolecules.
"Primary
structure" refers to the amino acid sequence of a particular peptide.
"Secondary structure"
refers to locally ordered, three dimensional structures within a polypeptide.
These structures
are commonly Down as domains. Domains are portions of a polypeptide that often
form a
compact unit of the polypeptide and are typically 25 to approximately 500
amino acids long.
Typical domains are made up of sections of lesser organization such as
stretches of (3-sheet
and a-helices. "Tertiary structure" refers to the complete three dimensional
structure of a
polypeptide monomer. "Quaternary structure" refers to the three dimensional
structure
formed, usually by the noncovalent association of independent tertiary units.
Anisotropic
terms are also known as energy terms.
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"Nucleic acid" or "oligonucleotide" or "polynucleotide" or grammatical
equivalents
used herein means at least two nucleotides covalently linked together.
Oligonucleotides are
typically from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50 or more
nucleotides in length, up
to about 100 nucleotides in length. Nucleic acids and polynucleotides are a
polymers of any
length, including longer lengths, e.g., 200, 300, 500, 1000, 2000, 3000, 5000,
7000, 10,000,
etc. A nucleic acid of the present invention will generally contain
phosphodiester bonds,
although in some cases, nucleic acid analogs are included that may have at
least one different
linkage, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O-
methylphophoroamidite linkages (see Eckstein (1992) Oli~onucleotides and Analo
u~ es: A
Practical Approach Oxford University Press); and peptide nucleic acid
backbones and
linkages. Other analog nucleic acids include those with positive backbones;
non-ionic
backbones, and non-ribose backbones, including those described in U.S. Patent
Nos.
5,235,033 and 5,034,506, and Chapters 6 and 7, in Sanghui and Cook, eds.
Carbohydrate
Modifications in Antisense Research, ASC Symposium Series 580. Nucleic acids
containing
one or more carbocyclic sugars are also included within one definition of
nucleic acids.
Modifications of the ribose-phosphate backbone may be done for a variety of
reasons, e.g., to
increase the stability and half life of such molecules in physiological
environments or as
probes on a biochip. Mixtures of naturally occurnng nucleic acids and analogs
can be made;
alternatively, mixtures of different nucleic acid analogs, and mixtures of
naturally occurring
nucleic acids and analogs may be made.
Particularly preferred are peptide nucleic acids (PNA) which includes peptide
nucleic
acid analogs. These backbones are substantially non-ionic under neutral
conditions, in
contrast to the highly charged phosphodiester backbone of naturally occurring
nucleic acids.
This results in two advantages. First, the PNA backbone exhibits improved
hybridization
kinetics. PNAs have larger changes in the melting temperature (Tm) for
mismatched versus
perfectly matched basepairs. DNA and RNA typically exhibit a 2-4° C
drop in Tm for an
internal mismatch. With the non-ionic PNA backbone, the drop is closer to 7-
9° C.
Similarly, due to their non-ionic nature, hybridization of the bases attached
to these
backbones is relatively insensitive to salt concentration. In addition, PNAs
are not degraded
by cellular enzymes, and thus can be more stable.
The nucleic acids may be single stranded or double stranded, as specified, or
contain
portions of both double stranded or single stranded sequence. As will be
appreciated by those
in the art, the depiction of a single strand also defines the sequence of the
complementary
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
strand; thus the sequences described herein also provide the complement of the
sequence.
The nucleic acid may be DNA, both genomic and cDNA, RNA, or a hybrid, where
the
nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and
combinations
of bases, including uracil, adenine, thymine, cytosine, guanine, inosine,
xanthine
hypoxanthine, isocytosine, isoguanine, etc. "Transcript" typically refers to a
naturally
occurring RNA, e.g., a pre-mRNA, hnRNA, or mRNA. As used herein, the term
"nucleoside" includes nucleotides and nucleoside and nucleotide analogs, and
modified
nucleosides such as amino modified nucleosides. In addition, "nucleoside"
includes non-
naturally occurnng analog structures. Thus, e.g., the individual units of a
peptide nucleic
acid, each containing a base, are referred to herein as a nucleoside.
A "label" or a "detectable moiety" is a composition detectable by
spectroscopic,
photochemical, biochemical, immunochemical, physiological, chemical, or other
physical
means. For example, useful labels include 3aP, fluorescent dyes, electron-
dense reagents,
enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens
and proteins
or other entities which can be made detectable, e.g., by incorporating a
radiolabel into the
peptide or used to detect antibodies specifically reactive with the peptide.
The labels may be
incorporated into the cancer nucleic acids, proteins, and antibodies. Many
methods known in
the art for conjugating the antibody to the label may be employed, including
those methods
described by Hunter, et al. (1962) Nature 144:945; David, et al. (1974)
Biochemistry
13:1014-1021; Pain, et al. (1981) J. Immunol. Meth., 40:219-230; and Nygren
(1982) J.
Histochem. and Cytochem. 30:407-412.
An "effector" or "effector moiety" or "effector component" is a molecule that
is
bound (or linked, or conjugated), either covalently, through a linker or a
chemical bond, or
noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds,
to an antibody.
The "effector" can be a variety of molecules including, e.g., detection
moieties including
radioactive compounds, fluorescent compounds, an enzyme or substrate, tags
such as epitope
tags, a toxin; activatable moieties, a chemotherapeutic agent; a lipase; an
antibiotic; or a
radioisotope emitting "hard" e.g., beta radiation.
A "labeled nucleic acid probe or oligonucleotide" is one that is bound,'either
covalently, through a linker or a chemical bond, or noncovalently, through
ionic, van der
Waals, electrostatic, or hydrogen bonds to a label such that the presence of
the probe may be
detected by detecting the presence of the label bound to the probe.
Alternatively, method
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WO 02/086443 PCT/US02/12476
using high affinity interactions may achieve the same results where one of a
pair of binding
partners binds to the other, e.g., biotin, streptavidin.
As used herein a "nucleic acid probe or oligonucleotide" is a nucleic acid
capable of
binding to a target nucleic acid of complementary sequence through one or more
types of
chemical bonds, usually through complementary base pairing, e.g., through
hydrogen bond
formation. As used herein, a probe may include natural (i.e., A, G, C, or T)
or modified bases
(7-deazaguanosine, inosine, etc.). In addition, the bases in a probe may be
joined by a
linkage other than a phosphodiester bond, preferably one that does not
functionally interfere
with hybridization. Thus, e.g., probes may be peptide nucleic acids in which
the constituent
bases are joined by peptide bonds rather than phosphodiester linkages. Probes
may bind
target sequences lacking complete complementarity with the probe sequence
depending upon
the stringency of the hybridization conditions. The probes are preferably
directly labeled,
e.g., with isotopes, chromophores, lumiphores, chromogens, or indirectly
labeled, e.g., with
biotin to which a streptavidin complex may later bind. By assaying for the
presence or
absence of the probe, one can detect the presence or absence of the select
sequence or
subsequence. Diagnosis or prognosis may be based at the genomic level, or at
the level of
RNA or protein expression.
The term "recombinant" when used with reference, e.g., to a cell, or nucleic
acid,
protein, or vector, indicates that the cell, nucleic acid, protein or vector,
has been modified by
the introduction of a heterologous nucleic acid or protein or the alteration
of a native nucleic
acid or protein, or that the cell is derived from a cell so modified. Thus,
e.g., recombinant
cells express genes that are not found within the native (non-recombinant)
form of the cell or
express native genes that are otherwise abnormally expressed, under expressed
or not
expressed at all. By the term "recombinant nucleic acid" herein is meant
nucleic acid,
originally formed in vitro, in general, by the manipulation of nucleic acid,
e.g., using
polymerases and endonucleases, in a form not normally found in nature. In this
manner,
operably linkage of different sequences is achieved. Thus an isolated nucleic
acid, in a linear
form, or an expression vector formed in vitro by ligating DNA molecules that
are not
normally joined, are both considered recombinant for the purposes of this
invention. It is
understood that once a recombinant nucleic acid is made and reintroduced into
a host cell or
organism, it will replicate non-recombinantly, i.e., using the in vivo
cellular machinery of the
host cell rather than in vitro manipulations; however, such nucleic acids,
once produced
recombinantly, although subsequently replicated non-recombinantly, are still
considered
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WO 02/086443 PCT/US02/12476
recombinant for the purposes of the invention. Similarly, a "recombinant
protein" is a protein
made using recombinant techniques, i.e., through the expression of a
recombinant nucleic
acid as depicted above.
The term "heterologous" when used with reference to portions of a nucleic acid
indicates that the nucleic acid comprises two or more subsequences that are
not normally
found in the same relationship to each other in nature. For instance, the
nucleic acid is
typically recombinantly produced, having two or more sequences, e.g., from
unrelated genes
arranged to make a new functional nucleic acid, e.g., a promoter from one
source and a
coding region from another source. Similarly, a heterologous protein will
often refer to two
or more subsequences that are not found in the same relationship to each other
in nature (e.g.,
a fusion protein).
A "promoter" is typically an array of nucleic acid control sequences that
direct
transcription of a nucleic acid. As used herein, a promoter includes necessary
nucleic acid
sequences near the start site of transcription, such as, in the case of a
polymerase II type
promoter, a TATA element. A promoter also optionally includes distal enhancer
or repressor
elements, which can be located as much as several thousand base pairs from the
start site of
transcription. A "constitutive" promoter is a promoter that is active under
most
environmental and developmental conditions. An "inducible" promoter is a
promoter that is
active under environmental or developmental regulation. The term "operably
linked" refers
to a functional linkage between a nucleic acid expression control sequence
(such as a
promoter, or array of transcription factor binding sites) and a second nucleic
acid sequence,
e.g., wherein the expression control sequence directs transcription of the
nucleic acid
corresponding to the second sequence.
An "expression vector" is a nucleic acid construct, generated recombinantly or
synthetically, with a series of specified nucleic acid elements that permit
transcription of a
particular nucleic acid in a host cell. The expression vector can be part of a
plasmid, virus, or
nucleic acid fragment. Typically, the expression vector includes a nucleic
acid to be
transcribed in operable linkage to a promoter.
The phrase "selectively (or specifically) hybridizes to" refers to the
binding,
duplexing, or hybridizing of a molecule selectively to a particular nucleotide
sequence under
stringent hybridization conditions when that sequence is present in a complex
mixture (e.g.,
total cellular or library DNA or RNA).
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The phrase "stringent hybridization conditions" refers to conditions under
which a
probe will hybridize to its target subsequence, typically in a complex mixture
of nucleic
acids, but to essentially no other sequences. Stringent conditions are
sequence-dependent and
will be different in different circumstances. Longer sequences hybridize
specifically at
higher temperatures. An extensive guide to the hybridization of nucleic acids
is found in
"Overview of principles of hybridization and the strategy of nucleic acid
assays" in Tijssen
(1993) Techniques in BiochemistrK and Molecular Biology ~-~-Hybridization with
Nucleic
Probes (vol. 24) Elsevier. Generally, stringent conditions are selected to be
about 5-10° C
lower than the thermal melting point (Tm) for the specific sequence at a
defined ionic strength
pH. The Tm is the temperature (under defined ionic strength, pH, and nucleic
concentration)
at which 50% of the probes complementary to the target hybridize to the target
sequence at
equilibrium (as the target sequences are present in excess, at Tm, 50% of the
probes are
occupied at equilibrium). Stringent conditions will be those in which the salt
concentration is
less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion
concentration (or
other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°
C for short probes (e.g.,
10 to 50 nucleotides) and at least about 60° C for long probes (e.g.,
greater than 50
nucleotides). Stringent conditions may also be achieved with the addition of
destabilizing
agents such as formamide. For-selective or specific hybridization, a positive
signal is
typically at least two times background, preferably 10 times background
hybridization.
Exemplary stringent hybridization conditions are often: 50% formamide, 5x SSC,
and 1%
SDS, incubating at 42° C, or, 5x SSC, 1% SDS, incubating at 65°
C, with wash in 0.2x SSC,
and 0.1% SDS at 65° C. For PCR, a temperature of about 36° C is
typical for low stringency
amplification, although annealing temperatures may vary between about
32° C and 48° C
depending on primer length. For high stringency PCR amplification, a
temperature of about
62° C is typical, although high stringency annealing temperatures can
range from about 50° C
to about 65° C, depending on the primer length and specificity. Typical
cycle conditions for
both high and low stringency amplifications include a denaturation phase of
90° C - 95° C for
0.5 - 2 min., an annealing phase lasting 0.5 - 2 min., and an extension phase
of about 72° C
for 1 - 2 min. Protocols and guidelines for low and high stringency
amplification reactions
are provided, e.g., in Innis, et a1.(1990) PCR Protocols. A Guide to Methods
and
Applications.
Nucleic acids that do not hybridize to each other under stringent conditions
are still
substantially identical if the polypeptides which they encode are
substantially identical. This
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occurs, e.g., when a copy of a nucleic acid is created using the maximum codon
degeneracy
permitted by the genetic code. In such cases, the nucleic acids typically
hybridize under
moderately stringent hybridization conditions. Exemplary "moderately stringent
hybridization conditions" include a hybridization in a buffer of 4:0%
formamide, 1 M NaCI,
1% SDS at 37° C, and a wash in 1X SSC at 45° C. A positive
hybridization is at least twice
background. Alternative hybridization and wash conditions can be utilized to
provide
conditions of similar stringency. Additional guidelines for determining
hybridization
parameters are provided in numerous reference, e.g., Ausubel, et al. (ed.)
Current Protocols in
Molecular Biolo~v Lippincott.
The phrase "functional effects" in the context of assays for testing compounds
that
modulate activity of a lung cancer protein includes the determination of a
parameter that is
indirectly or directly under the influence of the lung cancer protein or
nucleic acid, e.g., a
physiological, enzymatic, functional, physical, or chemical effect, such as
the ability to
decrease lung cancer. It includes ligand binding activity; cell viability,
cell growth on soft
agar; anchorage dependence; contact inhibition and density limitation of
growth; cellular
proliferation; cellular transformation; growth factor or serum dependence;
tumor specific
marker levels; invasiveness into Matrigel; tumor growth and metastasis in
vivo; mRNA and
protein expression in cells undergoing metastasis, and other characteristics
of lung cancer
cells. "Functional effects" include ih vitro, in vivo, and ex vivo activities.
By "determining the functional effect" is meant assaying for a compound that
increases or decreases a parameter that is indirectly or directly under the
influence of a lung
cancer protein sequence, e.g., physiological, functional, enzymatic, physical,
or chemical
effects. Such functional effects can be measured by many means known to those
skilled in
the art, e.g., changes in spectroscopic characteristics (e.g., fluorescence,
absorbance,
refractive index), hydrodynamic (e.g., shape), chromatographic, or solubility
properties for
the protein, measuring inducible markers or transcriptional activation of the
lung cancer
protein; measuring binding activity or binding assays, e.g., binding to
antibodies or other
ligands, and measuring cellular proliferation. Determination of the functional
effect of a
compound on lung cancer can also be performed using lung cancer assays known
to those of
skill in the art such as an ifa vitro assays, e.g., cell growth on soft agar;
anchorage
dependence; contact inhibition and density limitation of growth; cellular
proliferation;
cellular transformation; growth factor or serum dependence; tumor specific
marker levels;
invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and
protein
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
expression in cells undergoing metastasis, and other characteristics of lung
cancer cells. The
functional effects can be evaluated by many means known to those skilled in
the art, e.g.,
microscopy for quantitative or qualitative measures of alterations in
morphological features,
measurement of changes in RNA or protein levels for lung cancer-associated
sequences,
measurement of RNA stability, identification of downstream or reporter gene
expression '
(CAT, luciferase, (3-gal, GFP, and the like), e.g., via chemiluminescence,
fluorescence,
colorimetric reactions, antibody binding, inducible markers, and ligand
binding assays.
"Inhibitors", "activators", and "modulators" of lung cancer polynucleotide and
polypeptide sequences are used to refer to activating, inhibitory, or
modulating molecules or
compounds identified using in vitro and in viv~ assays of lung cancer
polynucleotide and
polypeptide sequences. Inhibitors are compounds that, e.g., bind to, partially
or totally block
activity, decrease, prevent, delay activation, inactivate, desensitize, or
down regulate the
activity or expression of lung cancer proteins, e.g., antagonists. Antisense
or inhibitory
nucleic acids may seem to inhibit expression and subsequent function of the
protein.
"Activators" are compounds that increase, open, activate, facilitate, enhance
activation,
sensitize, agonize, or up regulate lung cancer protein activity. Inhibitors,
activators, or'
modulators also include genetically modified versions of lung cancer proteins,
e.g., versions
with altered activity, as well as naturally occurring and synthetic ligands,
antagonists,
agonists, antibodies, small chemical molecules and the like. Such assays for
inhibitors and
activators include, e.g., expressing the lung cancer protein ih vitro, in
cells, or cell
membranes, applying putative modulator compounds, and then determining the
functional
effects on activity, as described above. Activators and inhibitors of lung
cancer can also be
identified by incubating lung cancer cells with the test compound and
determining increases
or decreases in the expression of 1 or more lung cancer proteins, e.g., 1, 2,
3, 4, 5, 10, 15, 20,
25, 30, 40, 50 or more lung cancer proteins, such as lung cancer proteins
encoded by the
sequences set out in Tables 1A-16.
Samples or assays comprising lung cancer proteins that are treated with a
potential
activator, inhibitor, or modulator are compared to control samples without the
inhibitor,
activator, or modulator to examine the extent of inhibition. Control samples
(untreated with
inhibitors) are assigned a relative protein activity value of 100%. Inhibition
of a polypeptide
is achieved when the activity value relative to the control is about 80%,
preferably 50%, more
preferably 25-0%. Activation of a lung cancer polypeptide is achieved when the
activity
value relative to the control (untreated with activators) is 110%, more
preferably 150%, more
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preferably 200-500% (i.e., two to five fold higher relative to the control),
more preferably
1000-3000% higher.
The phrase "changes in cell growth" refers to any change in cell growth and
proliferation characteristics i~ vitro or ira vivo, such as cell viability,
formation of foci,
anchorage independence, semi-solid or soft agar growth, changes in contact
inhibition and
density limitation of growth, loss of growth factor or serum requirements,
changes in cell
morphology, gaining or losing immortalization, gaining or losing tumor
specific markers,
ability to form or suppress tumors when injected into suitable animal hosts,
and/or
immortalization of the cell. See, e.g., Freshney (1994) Culture of Animal
Cells a Manual of
Basic Technique pp. 231-241 (3rd ed.).
"Tumor cell" refers to precancerous, cancerous, and normal cells in a tumor.
"Cancer cells," "transformed" cells, or "transformation" in tissue culture,
refers to
spontaneous or induced phenotypic changes that do not necessarily involve the
uptake of new
genetic material. Although transformation can arise from infection with a
transforming virus
and incorporation of new genomic DNA, or uptake of exogenous DNA, it can also
arise
spontaneously or following exposure to a carcinogen, thereby mutating an
endogenous gene.
Transformation is associated with phenotypic changes, such as immortalization
of cells,
aberrant growth control, nonmorphological changes, and/or malignancy (see,
Freshney
(1994) Culture of Animal Cells a Manual of Basic Technique (3rd ed.)).
"Antibody" refers to a polypeptide comprising a framework region from an
immunoglobulin gene or fragments thereof that specifically binds and
recognizes an antigen.
The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma,
delta,
epsilon, and mu constant region genes, as well as the myriad immunoglobulin
variable region
genes. Light chains are classified as either kappa or lambda. Heavy chains are
classified as
gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin
classes, IgG,
IgM, IgA, IgD, and IgE, respectively. Typically, the antigen-binding region of
an antibody or
its functional equivalent will be most critical in specificity and affinity of
binding. See Paul,
Fundamental Immunolo ~y.
An exemplary immunoglobulin (antibody) structural unit comprises a tetramer.
Each
tetramer is composed of two identical pairs of polypeptide chains, each pair
having one
"light" (about 25 kD) and one "heavy" chain (about 50-70 kD). The N-terminus
of each
chain defines a variable region of about 100 to 110 or more amino acids
primarily responsible
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WO 02/086443 PCT/US02/12476
for antigen recognition. The terms variable light chain (VL) and variable
heavy chain (V~)
refer to these light and heavy chains respectively.
Antibodies exist, e.g., as intact immunoglobulins or as a number of well-
characterized
fragments produced by digestion with various peptidases. Thus, e.g., pepsin
digests an
antibody below the disulfide linkages in the hinge region to produce F(ab)'a,
a dimer of Fab
which itself is a light chain joined to VH-CHl by a disulfide bond. The
F(ab)'2 may be
reduced under mild conditions to break the disulfide linkage in the hinge
region, thereby
converting the F(ab)'2 dimer into an Fab' monomer. The Fab' monomer is
essentially Fab
with part of the hinge region (see Paul (ed. I999) Fundamental Immunolo~y (4th
ed.). While
various antibody fragments are defined in terms of the digestion of an intact
antibody, one of
skill will appreciate that such fragments may be synthesized de raovo either
chemically or by
using recombinant DNA methodology. Thus, the term antibody, as used herein,
also includes
antibody fragments either produced by the modification of whole antibodies, or
those
synthesized de hovo using recombinant DNA methodologies (e.g., single chain
Fv) or those
identified using phage display libraries (see, e.g., McCafferty, et al. (1990)
Nature 348:552-
554).
For preparation of antibodies, e.g., recombinant, monoclonal, or polyclonal
antibodies, many technique known in the art can be used (see, e.g., Kohler and
Milstein
(1975) Nature 256:495-497; Kozbor, et al. (1983) Immunology Today 4:72; Cole,
et al.
(1985), pp. 77-96 in Monoclonal Antibodies and Cancer Therany; Coligan (1991
and
supplements) Current Protocols in Immunolo~y; Harlow and Lane (1988)
Antibodies. A
Laborator~Manual; and Goding (1986) Monoclonal Antibodies: Principles and
Practice (2d
ed.)). Techniques for the production of single chain antibodies (U.S. Patent
4,946,778) can
be adapted to produce antibodies to polypeptides of this invention. Also,
transgenic mice, or
other organisms such as other mammals, may be used to express humanized
antibodies.
Alternatively, phage display technology can be used to identify antibodies and
heteromeric
Fab fragments that specifically bind to selected antigens (see, e.g.,
McCafferty, et al. (1990)
Nature 348:552-554; Marks, et al. (1992) Biotechnolo~y 10:779-783).
A "chimeric antibody" is an antibody molecule in which, e.g, (a) the constant
region,
or a portion thereof, is altered, replaced, or exchanged so that the antigen
binding site
(variable region) is linked to a constant region of a different or altered
class, effector
function, and/or species, or an entirely different molecule which confers new
properties to the
chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.;
or (b) the
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WO 02/086443 PCT/US02/12476
variable region, or a portion thereof, is altered, replaced, or exchanged with
a variable region
having a different or altered antigen specificity.
Identification of lung cancer-associated sequences
In one aspect, the expression levels of genes are determined in different
patient
samples for which diagnosis information is desired, to provide expression
profiles. An
expression profile of a particular sample is essentially a "fingerprint" of
the state of the
sample; while two states may have any particular gene similarly expressed, the
evaluation of
a number of genes simultaneously allows the generation of a gene expression
profile that is
characteristic of the state of the cell. That is, normal tissue may be
distinguished from
cancerous or metastatic cancerous tissue, or metastatic cancerous tissue can
be compared
with tissue from surviving cancer patients. By comparing expression profiles
of tissue in
known different lung cancer states, information regarding which genes are
important
(including both up- and down-regulation of genes) in each of these states is
obtained.
Molecular profiling may distinguish subtypes of a currently collective disease
designation,
e.g., different forms of lung cancer (chronic disease, adenocarcinoma, etc.)
The identification of sequences that are differentially expressed in lung
cancer versus
non-lung cancer tissue allows the use of this information in a number of ways.
For example,
a particular treatment regime may be evaluated: does a chemotherapeutic drug
act to down-
regulate lung cancer, and thus tumor growth or recurrence, in a particular
patient.
Alternatively, a treatment step may induce other markers which may be used as
targets to
destroy tumor cells. Similarly, diagnosis and treatment outcomes may be done
or confirmed
by comparing patient samples with the known expression profiles. Malignant
diseasemay be
compared to non-malignant conditions. Metastatic tissue can also be analyzed
to determine
the stage of lung cancer in the tissue, or origin of primary tumor, e.g.,
metastasis from a
remote primary site. Furthermore, these gene expression profiles (or
individual genes) allow
screening of drug candidates with an eye to mimicking or altering a particular
expression
profile; e.g., screening can be done for drugs that suppress the lung cancer
expression profile.
This may be done by making biochips comprising sets of the important lung
cancer genes,
which can then be used in these screens. PCR methods may be applied with
selected primer
pairs, and analysis may be of RNA or of genomic sequences. These methods can
also be
done on the protein basis; that is, protein expression levels of the lung
cancer proteins can be
evaluated for diagnostic purposes or to screen candidate agents. In addition,
the lung cancer
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WO 02/086443 PCT/US02/12476
nucleic acid sequences can be administered for gene therapy purposes,
including the
administration of antisense nucleic acids, or the lung cancer proteins
(including antibodies
and other modulators thereof) administered as therapeutic drugs or as protein
or DNA
vaccines.
Thus the present invention provides nucleic acid and protein sequences that
are
differentially expressed in lung cancer relative to normal tissues and/or non-
malignant lung
disease, or in different types of lung disease, herein termed "lung cancer
sequences." As
outlined below, lung cancer sequences include those that are up-regulated
(i.e., expressed at a
higher level) in lung cancer, as well as those that are down-regulated (i.e.,
expressed at a
lower level). In a preferred embodiment, the lung cancer sequences are from
humans;
however, as will be appreciated by those in the art, lung cancer sequences
from other
organisms may be useful in animal models of disease and drug evaluation; thus,
other lung
cancer sequences are provided, from vertebrates, including mammals, including
rodents (rats,
mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep,
goats, pigs, cows,
horses, etc.) and pets (dogs, cats, etc.). Lung cancer sequences from other
organisms may be
obtained using the techniques outlined below.
Lung cancer sequences can include both nucleic acid and amino acid sequences.
As
will be appreciated by those in the art and is more fully outlined below, lung
cancer nucleic
acid sequences are useful in a variety of applications, including diagnostic
applications,
which will detect naturally occurring nucleic acids, as well as screening
applications; e.g.,
biochips comprising nucleic acid probes or PCR microtiter plates with selected
probes to the
lung cancer sequences can be generated.
A lung cancer sequence can be initially identified by substantial nucleic acid
and/or
amino acid sequence homology to the lung cancer sequences outlined herein.
Such
homology can be based upon the overall nucleic acid or amino acid sequence,
and is
generally determined as outlined below, e.g., using homology programs or
hybridization
conditions.
For identifying lung cancer-associated sequences, the lung cancer screen
typically
includes comparing genes identified in different tissues, e.g., normal and
cancerous tissues,
cancer and non-malignant conditions, non-malignant conditions and normal
tissues, or tumor
tissue samples from patients who have metastatic disease vs. non metastatic
tissue. Other
suitable tissue comparisons include comparing lung cancer samples with
metastatic cancer
samples from other cancers, such as, breast, other gastrointestinal cancers,
prostate, ovarian,
CA 02444691 2003-10-17
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etc. Samples of, non metastatic disease tissue and tissue undergoing
metastasis are applied to
biochips comprising nucleic acid probes. The samples are first microdissected,
if applicable,
and treated as is known in the art for the preparation of mRNA. Suitable
biochips are
commercially available, e.g., from Affymetrix, Santa Claxa, CA. Gene
expression profiles as
described herein are generated and the data analyzed.
In one embodiment, the genes showing changes in expression as between normal
and
disease states are compared to genes expressed in other normal tissues,
preferably normal
lung, but also including, and not limited to colon, heart, brain, liver,
breast, kidney, muscle,
prostate, small intestine, laxge intestine, spleen, bone, and/or placenta. In
a preferred
embodiment, those genes identified during the lung cancer screen that are
expressed in
significant amounts in other tissues (e.g., essential organs) are removed from
the profile,
although in some embodiments, this is not necessary (e.g., where organs may be
dispensible
at a later stage of life). That is, when screening for drugs, it is usually
preferable that the
target expression be disease specific, to minimize possible side effects on
other organs.
In a preferred embodiment, lung cancer sequences are those that are up-
regulated in
lung cancer; that is, the expression of these genes is higher in cancerous
tissue than in normal
lung or other tissue. "Up-regulation" as used herein means, when the ratio is
presented as a
number greater than one, that the ratio is greater than one, preferably 1.5 or
greater, more
preferably 2.0 or greater. Another embodiment is directed to sequences up-
regulated in non-
malignant conditions relative to normal. Unigene cluster identification
numbers and
accession numbers herein are for the GenBank sequence database and the
sequences of the
accession numbers are hereby expressly incorporated by reference. GenBank is
known in the
art, see, e.g., Benson, DA, et al (1990 Nucleic Acids Research 26:1-7 and
http://www.ncbi.nlm.nih.gov/. Sequences are also available in other databases,
e.g.,
European Molecular Biology Laboratory (EMBL) and DNA Database of Japan (DDBJ).
Another embodiment is directed to sequences up-regulated in non-malignant
conditions
relative to normal. In some situations, the sequences may be derived from
assembly of
available sequences or be predicted from genomic DNA using exon prediction
algorithms,
such as FGENESH (Salamov and Solovyev (2000) Genome Res. 10:516-522). In other
situations, sequences have been derived from cloning and sequencing of
isolated nucleic
acids. '
In another preferred embodiment, lung cancer sequences are those that are down-
regulated in the lung cancer; that is, the expression of these genes is lower
in cancerous tissue
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WO 02/086443 PCT/US02/12476
or normal lung or other tissue. "Down-regulation" as used herein means, when
the ratio is
presented as a number greater than one, that the ratio is greater than one,
preferably 1.5 or
greater, more preferably 2.0 or greater, or, when the ratio is presented as a
number less than
one, that the ratio is less than one, preferably 0.5 or less, more preferably
0.25 or less.
Informatics
The ability to identify genes that are over or under expressed in lung cancer
can
additionally provide high-resolution, high-sensitivity datasets which can be
used in the areas
of diagnostics, therapeutics, drug development, pharmacogenetics, protein
structure,
biosensor development, and other related areas. For example, the expression
profiles can be
used in diagnostic or prognostic evaluation of patients with lung cancer. Or
as another
example, subcellular toxicological information can be generated to better
direct drug structure
and activity correlation (see Anderson (1998) Pharmaceutical Proteomics:
Targets,
Mechanism, and Function, paper presented at the IBC Proteomics conference,
Coronado, CA
(June 11-12, 1998)). Subcellular toxicological information can also be
utilized in a biological
sensor device to predict the likely toxicological effect of chemical exposures
and likely
tolerable exposure thresholds (see U.S. Patent No. 5,811,231). Similar
advantages accrue
from datasets relevant to other biomolecules and bioactive agents (e.g.,
nucleic acids,
saccharides, lipids, drugs, and the like).
Thus, in another embodiment, the present invention provides a database that
includes
at least one set of assay data. The data contained in the database is
acquired, e.g., using array
analysis either singly or in a library format. The database can be in a form
in which data can
be maintained and transmitted, but is preferably an electronic database. The
electronic
database of the invention can be maintained on any electronic device allowing
for the storage
of and access to the database, such as a personal computer, but is preferably
distributed on a
wide area network, such as the World Wide Web.
The focus of the present section on databases that include peptide sequence
data is for
clarity of illustration only. It will be apparent to those of skill in the art
that similar databases
can be assembled for assay data acquired using an assay of the invention.
The compositions and methods for identifying and/or quantitating the relative
and/or
absolute abundance of a variety of molecular and macromolecular species from a
biological
sample representing lung cancer, i.e., the identification of lung cancer-
associated sequences
described herein, provide an abundance of information, which can be correlated
with
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WO 02/086443 PCT/US02/12476
pathological conditions, predisposition to disease, drug testing, therapeutic
monitoring, gene-
disease causal linkages, identification of correlates of immunity and
physiological status,
among others. Although the data generated from the assays of the invention is
suited for
manual review and analysis, in a preferred embodiment, data processing using
high-speed
computers is utilized.
An array of methods for indexing and retrieving biomolecular information is
known
in the art. For example, U.S. Patents 6,023,659 and 5,966,712 disclose a
relational database
system for storing biomolecular sequence information in a manner that allows
sequences to
be catalogued and searched according to one or more protein function
hierarchies. U.S.
Patent 5,953,727 discloses a relational database having sequence records
containing
information in a format that allows a collection of partial-length DNA
sequences to be
catalogued and searched according to association with one or more sequencing
projects for
obtaining full-length sequences from the collection of partial length
sequences. U.S. Patent
5,706,498 discloses a gene database retrieval system for making a retrieval of
a gene
sequence similar to a sequence data item in a gene database based on the
degree of similarity
between a key sequence and a target sequence. U.S. Patent 5,538,897 discloses
a method
using mass spectroscopy fragmentation patterns of peptides to identify amino
acid sequences
in computer databases by comparison of predicted mass spectra with
experimentally-derived
mass spectra using a closeness-of fit measure. U.S. Patent 5,926,818 discloses
a multi-
dimensional database comprising a functionality for mufti-dimensional data
analysis
described as on-line analytical processing (OLAP), which entails the
consolidation of
projected and actual data according to more than one consolidation path or
dimension. U.S.
Patent 5,295,261 reports a hybrid database structure in which the fields of
each database
record are divided into two classes, navigational and informational data, with
navigational
fields stored in a hierarchical topological map which can be viewed as a tree
structure or as
the merger of two or more such tree structures.
See also Mount, et al. (2001) Bioinformatics; Durbin, et al. (eds., 1999)
Biological
Sequence Analysis~ Probabilistic Models of Proteins and Nucleic Acids (;
Baxevanis and
Oeullette (eds., 1998) Bioinformatics~ A Practical Guide to the Analysis of
Genes and
Proteins); Rashidi and Buehler (1999) Bioinformatics: Basic Applications in
Biological
Science and Medicine; Setubal, et al. (eds 1997) Introduction to Computational
Molecular
Biolo ; Misener and Krawetz (eds, 2000) Bioinformatics: Methods and Protocols;
Higgins
and Taylor (eds., 2000) Bioinformatics~ Sequence Structure and Databanks: A
Practical
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Anaroach; Brown (2001) Bioinformatics: A Biologist's Guide to Biocomputin~and
the
Internet; Han and Kamber (2000) Data Minim: Concepts and Techniques (2000);
and
Waterman (1995) Introduction to Computational Biolo~~ Maps, Sequences, and
Genomes.
The present invention provides a computer database comprising a computer and
software for storing in computer-retrievable form assay data records cross-
tabulated, e.g.,
with data specifying the source of the target-containing sample from which
each sequence
specificity record was obtained.
In an exemplary embodiment, at least one of the sources of target-containing
sample
is from a control tissue sample known to be free of pathological disorders. In
a variation, at
least one of the sources is a known pathological tissue specimen, e.g., a
neoplastic lesion or
another tissue specimen to be analyzed for lung cancer. In another variation,
the assay
records cross-tabulate one or more of the following parameters for each target
species in a
sample: (1) a unique identification code, which can include, e.g., a target
molecular structure
and/or characteristic separation coordinate (e.g., electrophoretic
coordinates); (2) sample
source; and (3) absolute andlor relative quantity of the target species
present in the sample.
The invention also provides for the storage and retrieval of a collection of
target data
in a computer data storage apparatus, which can include magnetic disks,
optical disks,
magneto-optical disks, DRAM, SRAM, SGRAM, SDRAM, RDRAM, DDR RAM, magnetic
bubble memory devices, and other data storage devices, including CPU registers
and on-CPU
data storage arrays. Typically, the target data records are stored as a bit
pattern in an array of
magnetic domains on a magnetizable medium or as an array of charge states or
transistor gate
states, such as an array of cells in a DRAM device (e.g., each cell comprised
of a transistor
and a charge storage area, which may be on the transistor). In one embodiment,
the invention
provides such storage devices, and computer systems built therewith,
comprising a bit pattern
encoding a protein expression fingerprint record comprising unique identifiers
for at least 10
target data records cross-tabulated with target source.
When the target is a peptide or nucleic acid, the invention preferably
provides a
method for identifying related peptide or nucleic acid sequences, comprising
performing a
computerized comparison between a peptide or nucleic acid sequence assay
record stored in
or retrieved from a computer storage device or database and at least one other
sequence. The
comparison can include a sequence analysis or comparison algorithm or computer
program
embodiment thereof (e.g., FASTA, TFASTA, GAP, BESTFIT) and/or the comparison
may
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WO 02/086443 PCT/US02/12476
be of the relative amount of a peptide or nucleic acid sequence in a pool of
sequences
determined from a polypeptide or nucleic acid sample of a specimen.
The invention also preferably provides a magnetic disk, such as an IBM-
compatible
(DOS, Windows, Windows95/98/2000, Windows NT, OSl2) or other format (e.g.,
Linux,
SunOS, Solaris, AIX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or
hard (fixed,
Winchester) disk drive, comprising a bit pattern encoding data from an assay
of the invention
in a file format suitable for retrieval and processing in a computerized
sequence analysis,
comparison, or relative quantitation method.
The invention also provides a network, comprising a plurality of computing
devices
linked via a data link, such as an Ethernet cable (coax or lOBaseT), telephone
line, ISDN
line, wireless network, optical fiber, or other suitable signal transmission
medium, whereby at
least one network device (e.g., computer, disk array, etc.) comprises a
pattern of magnetic
domains (e.g., magnetic disk) and/or charge domains (e.g., an array of DRAM
cells)
composing a bit pattern encoding data acquired from an assay of the invention.
The invention also provides a method for transmitting assay data that includes
generating an electronic signal on an electronic communications device, such
as a modem,
ISDN terminal adapter, DSL, cable modem, ATM switch, or the like, wherein the
signal
includes (in native or encrypted format) a bit pattern encoding data from an
assay or a
database comprising a plurality of assay results obtained by the method of the
invention.
In a preferred embodiment, the invention provides a computer system for
comparing a
query target to a database containing an array of data structures, such as an
assay result
obtained by the method of the invention, and ranking database targets based on
the degree of
identity and gap weight to the target data. A central processor is preferably
initialized to load
and execute the computer program for alignment and/or comparison of the assay
results.
Data for a query target is entered into the central processor via an I/O
device. Execution of
the computer program results in the central processor retrieving the assay
data from the data
file, which comprises a binary description of an assay result.
The target data or record and the computer program can be transferred to
secondary
memory, which is typically random access memory (e.g., DRAM, SRAM, SGRAM, or
SDRAM). Targets are ranked according to the degree of correspondence between a
selected
assay characteristic (e.g., binding to a selected affinity moiety) and the
same characteristic of
the query target and results are output via an IJO device. For example, a
central processor
can be a conventional computer (e.g., Intel Pentium, PowerPC, Alpha, PA-8000,
SPARC,
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
MIPS 4400, MIPS 10000, VAX, etc.); a program can be a commercial or public
domain
molecular biology software package (e.g., UWGCG Sequence Analysis Software,
Darwin); a
data file can be an optical or magnetic disk, a data server, a memory device
(e.g., DRAM,
SRAM, SGRAM, SDRAM, EPROM, bubble memory, flash memory, etc.); an I/O device
can
be a terminal comprising a video display and a keyboard, a modem, an ISDN
terminal
adapter, an Ethernet port, a punched card reader, a magnetic strip reader, or
other suitable I/O
device.
The invention also preferably provides the use of a computer system, such as
that
described above, which comprises: (1) a computer; (2) a stored bit pattern
encoding a
collection of peptide sequence specificity records obtained by the methods of
the invention,
which may be stored in the computer; (3) a comparison target, such as a query
target; and (4)
a program for alignment and comparison, typically with rank-ordering of
comparison results
on the basis of computed similarity values.
Characteristics of long cancer-associated proteins
Lung cancer proteins of the present invention may be classified as secreted
proteins,
transmembrane proteins or intracellular proteins. In one embodiment, the lung
cancer protein
is an intracellular protein. Intracellular proteins may be found in the
cytoplasm and/or in the
nucleus. Intracellular proteins are involved in all aspects of cellular
function and replication
(including, e.g., signaling pathways); aberrant expression of such proteins
often results in
unregulated or disregulated cellular processes (see, e.g., Alberts (ed.,1994)
Molecular
Biology of the Cell (3d ed.). For example, many intracellular proteins have
enzymatic
activity such as protein kinase activity, protein phosphatase activity,
protease activity,
nucleotide cyclase activity, polymerase activity and the like. Intracellular
proteins also serve
as docking proteins that are involved in organizing complexes of proteins, or
targeting
proteins to various subcellular localizations, and are involved in maintaining
the structural
integrity of organelles.
An increasingly appreciated concept in characterizing proteins is the presence
in the
proteins of one or more structural motifs for which defined functions have
been attributed. In
addition to the highly conserved sequences found in the enzymatic domain of
proteins, highly
conserved sequences have been identified in proteins that are involved in
protein-protein
interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-
phosphorylated
targets in a sequence dependent manner. PTB domains, which axe distinct from
SH2
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domains, also bind tyrosine phosphorylated targets. SH3 domains bind to
proline-rich
targets. In addition, PH domains, tetratricopeptide repeats and WD domains to
name only a
few, have been shown to mediate protein-protein interactions. Some of these
may also be
involved in binding to phospholipids or other second messengers. As will be
appreciated by
one of ordinary skill in the art, these motifs can be identified on the basis
of amino acid
sequence; thus, an analysis of the sequence of proteins may provide insight
into both the
enzymatic potential of the molecule and/or molecules with which the protein
may associate.
One useful database is Pfam (protein families), which is a Iarge collection of
multiple
sequence alignments and hidden Markov models covering many common protein
domains.
Versions are available via the Internet from Washington University in St.
Louis, the Sanger
Center in England, and the Karolinska Institute in Sweden (see, e.g., Bateman,
et al (2000)
Nuc. Acids Res. 28:263-266; Sonnhammer, et al. (1997) Proteins 28:405-420;
Bateman, et al.
(1999) Nuc. Acids Res. 27:260-262; and Sonnhammer, et al. (1998) Nuc. Acids
Res. 26:320-
322).
In another embodiment, the lung cancer sequences are transmembrane proteins.
Transmembrane proteins are molecules that span a phospholipid bilayer of a
cell. They may
have an intracellular domain, an extracellular domain, or both. The
intracellular domains of
such proteins may have a number of functions including those already described
for
intracellular proteins. For example, the intracellular domain may have
enzymatic activity
and/or may serve as a binding site for additional proteins. Frequently the
intracellular
domain of transmembrane proteins serves both roles. For example certain
receptor tyrosine
kinases have both protein kinase activity and SH2 domains. In addition,
autophosphorylation
of tyrosines on the receptor molecule itself, creates binding sites for
additional SH2 domain
containing proteins.
Transmembrane proteins may contain from one to many transmembrane domains.
For example, receptor tyrosine kinases, certain cytokine receptors, receptor
guanylyl cyclases
and receptor serine/threonine protein kinases contain a single transmembrane
domain.
However, various other proteins including channels, pumps, and adenylyl
cyclases contain
numerous transmembrane domains. Many important cell surface receptors such as
G protein
coupled receptors (GPCRs) are classified as "seven transmembrane domain"
proteins, as they
contain 7 membrane spanning regions. Characteristics of transmembrane domains
include
approximately 17 consecutive hydrophobic amino acids that may be followed by
charged
amino acids. Therefore, upon analysis of the amino acid sequence of a
particular protein, the
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localization and number of transmembrane domains within the protein may be
predicted (see,
e.g., PSORT web site http://psort.nibb.ac jp~.
The extracellular domains of transmembrane proteins are diverse; however,
conserved
motifs are found repeatedly among various extracellular domains. Conserved
structure
and/or functions have been ascribed to different extracellular motifs. Many
extracellular
domains are involved in binding to other molecules. In one aspect,
extracellular domains are
found on receptors. Factors that bind the receptor domain include circulating
ligands, which
may be peptides, proteins, or small molecules such as adenosine and the like.
For example,
growth factors such as EGF, FGF, and PDGF are circulating growth factors that
bind to their
cognate receptors to initiate a variety of cellular responses. Other factors
include cytokines,
mitogenic factors, hormones, neurotrophic factors and the like. Extracellular
domains also
bind to cell-associated molecules. In this respect, they may mediate cell-cell
interactions.
Cell-associated ligands can be tethered to the cell, e.g., via a
glycosylphosphatidylinositol
(GPI) anchor, or may themselves be transmembrane proteins. Extracellular
domains may
also associate with the extracellular matrix and contribute to the maintenance
of the cell
structure.
Lung cancer proteins that are transmembrane are particularly preferred in the
present
invention as they are readily accessible targets for extracellular
immunotherapeutics, as are
described herein. In addition, as outlined below, transmembrane proteins can
be also useful
in imaging modalities. Antibodies may be used to label such readily accessible
proteins ih
situ or in histological analysis. Alternatively, antibodies can also label
intracellular proteins,
in which case analytical samples are typically permeablized to provide access
to intracellular
proteins. In addition, some membrane proteins can be processed to release a
soluble protein,
or to expose a residual fragment. Released soluble proteins may be useful
diagnostic
markers, processed residual protein fragments may be useful lung markers of
disease.
It will also be appreciated by those in the art that a transmembrane protein
can be
made soluble by removing transmembrane sequences, e.g., through recombinant
methods.
Furthermore, transmembrane proteins that have been made soluble can be made to
be
secreted through recombinant means by adding an appropriate signal sequence.
In another embodiment, the lung cancer proteins are secreted proteins; the
secretion of
which can be either constitutive or regulated. These proteins may have a
signal peptide or
signal sequence that targets the molecule to the secretory pathway. Secreted
proteins are
involved in numerous physiological events; e.g., if circulating, they often
serve to transmit
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signals to various other cell types. The secreted protein may function in an
autocrine manner
(acting on the cell that secreted the factor), a paracrine manner (acting on
cells in close
proximity to the cell that secreted the factor), an endocrine manner (acting
on cells at a
distance, e.g., secretion into the blood stream), or exocrine (secretion,
e.g., through a duct or
to adjacent epithelial surface as sweat glands, sebaceous glands, pancreatic
ducts, lacrimal
glands, mammary glands, sax producing glands of the ear, etc.). Thus secreted
molecules
often find use in modulating or altering numerous aspects of physiology. Lung
cancer
proteins that are secreted proteins are particularly preferred in the present
invention as they
serve as good targets for diagnostic markers, e.g., for blood, plasma, serum,
or stool tests.
Those which are enzymes may be antibody or small molecule targets. Others may
be useful
as vaccine targets, e.g., via CTL mechanisms.
Use of dung cancer nucleic acids
As described above, lung cancer sequence is initially identified by
substantial nucleic
acid and/or amino acid sequence homology or linkage to the lung cancer
sequences outlined
herein. Such homology can be based upon the overall nucleic acid or amino acid
sequence,
and is generally determined as outlined below, using either homology programs
or
hybridization conditions. Typically, linked sequences on a mRNA are found on
the same
molecule.
The lung cancer nucleic acid sequences of the invention, e.g., the sequences
in Tables
1A-16, can be fragments of larger genes, i.e., they are nucleic acid segments.
"Genes" in this
context includes coding regions, non-coding regions, and mixtures of coding
and non-coding
regions. Accordingly, as will be appreciated by those in the art, using the
sequences provided
herein, extended sequences, in either direction, of the lung cancer genes can
be obtained,
using techniques well known in the art for cloning either longer sequences or
the full length
sequences; see Ausubel, et al., supra. Much can be done by informatics and
many sequences
can be clustered to include multiple sequences corresponding to a single gene,
e.g., systems
such as UniGene (see, http://www.ncbi.nlm.nih.gov/UniGene~.
Once a lung cancer nucleic acid is identified, it can be cloned and, if
necessary, its
constituent parts recombined to form the entire lung cancer nucleic acid
coding regions or the
entire mRNA sequence. Once isolated from its natural source, e.g., contained
within a
plasmid or other vector or excised therefrom as a linear nucleic acid segment,
the
recombinant lung cancer nucleic acid can be further-used as a probe to
identify and isolate
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other lung cancer nucleic acids, e.g., extended coding regions. It can also be
used as a
"precursor" nucleic acid to make modified or variant lung cancer nucleic acids
and proteins.
The lung cancer nucleic acids of the present invention are used in several
ways. In a
first embodiment, nucleic acid probes to the lung cancer nucleic acids are
made and attached
to biochips to be used in screening and diagnostic methods, as outlined below,
or for
administration, e.g., for gene therapy, RNAi, vaccine, andlor antisense
applications.
Alternatively, the lung cancer nucleic acids that include coding regions of
lung cancer
proteins can be put into expression vectors for the expression of lung cancer
proteins, again
for screening purposes or for administration to a patient.
In a preferred embodiment, nucleic acid probes to lung cancer nucleic acids
(both the
y nucleic acid sequences outlined in the figures and/or the complements
thereof) are made.
The nucleic acid probes attached to the biochip are designed to be
substantially
complementary to the lung cancer nucleic acids, i.e., the target sequence
(either the target
sequence of the sample or to other probe sequences, e.g., in sandwich assays),
such that
hybridization of the target sequence and the probes of the present invention
occurs. As
outlined below, this complementarity need not be perfect; there may be any
number of base
pair mismatches which will interfere with hybridization between the target
sequence and the
single stranded nucleic acids of the present invention. However, if the number
of mutations
is so great that no hybridization can occur under even the least stringent of
hybridization
conditions, the sequence is not a complementary target sequence. Thus, by
"substantially
complementary" herein is meant that the probes are sufficiently complementary
to the target
sequences to hybridize under appropriate reaction conditions, particularly
high stringency
conditions, as outlined herein.
A nucleic acid probe is generally single stranded but can be partially single
and
partially double stranded. The strandedness of the probe is dictated by the
structure,
composition, and properties of the target sequence. In general, the nucleic
acid probes range
from about ~ to about 100 bases long, with from about 10 to about ~0 bases
being preferred,
and from about 30 to about 50 bases being particularly preferred. That is,
generally
complements of ORFs or whole genes are not used. In some embodiments, nucleic
acids of
lengths up to hundreds of bases can be used.
In a preferred embodiment, more than one probe per sequence is used, with
either
overlapping probes or probes to different sections of the target being used.
That is, two,
three, four or more probes, with three being preferred, are used to build in a
redundancy for a
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particular target. The probes can be overlapping (i.e., have some sequence in
common), or
separate. In some cases, PCR primers may be used to amplify signal for higher
sensitivity.
As will be appreciated by those in the art, nucleic acids can be attached or
immobilized to a solid support in a wide variety of ways. By "immobilized" and
grammatical
equivalents herein is meant the association or binding between the nucleic
acid probe and the
solid support is sufficient to be stable under the conditions of binding,
washing, analysis, and
removal as outlined below. The binding can typically be covalent or non-
covalent. By "non-
covalent binding" and grammatical equivalents herein is typically meant one or
more of
electrostatic, hydrophilic, and hydrophobic interactions. Included in non-
covalent binding is
the covalent attachment of a molecule, such as, streptavidin to the support
and the non-
covalent binding of the biotinylated probe to the streptavidin. By "covalent
binding" and
grammatical equivalents herein is meant that the two moieties, the solid
support and the
probe, are attached by at least one bond, including sigma bonds, pi bonds and
coordination
bonds. Covalent bonds can be formed directly between the probe and the solid
support or can
be formed by a cross linker or by inclusion of a specific reactive group on
either the solid
support or the probe or both molecules. Immobilization may also involve a
combination of
covalent and non-covalent interactions.
In general, the probes are attached to a biochip in a wide variety of ways, as
will be
appreciated by those in the art. As described herein, the nucleic acids can
either be
synthesized first, with subsequent attachment to the biochip, or can be
directly synthesized on
the biochip.
The biochip comprises a suitable solid substrate. By "substrate" or "solid
support" or
other grammatical equivalents herein is meant a material that can be modified
for the
attachment or association of the nucleic acid probes and is amenable to at
least one detection
method. Often the substrate may contain discrete individual sites appropriate
for ndivitual
partitioning and identification. As will be appreciated by those in the art,
the number of
possible substrates are very large, and include, but are not limited to, glass
and modified or
functionalized glass, plastics (including acrylics, polystyrene and copolymers
of styrene and
other materials, polypropylene, polyethylene, polybutylene, polyurethanes,
Teflon, etc.),
polysaccharides, nylon or nitrocellulose, resins, silica or silica-based
materials including
silicon and modified silicon, carbon, metals, inorganic glasses, plastics,
etc. In general, the
substrates allow optical detection and do not appreciably fluoresce. A
preferred substrate is
described in US application entitled Reusable Low Fluorescent Plastic Biochip,
U.S.
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WO 02/086443 PCT/US02/12476
Application Serial No. 09/270,214, filed March 15, 1999, herein incorporated
by reference in
its entirety.
Generally the substrate is planar, although as will be appreciated by those in
the art,
other configurations of substrates may be used as well. For example, the
probes may be
placed on the inside surface of a tube, for flow-through sample analysis to
minimize sample
volume. Similarly, the substrate may be flexible, such as a flexible foam,
including closed
cell foams made of particular plastics.
In a preferred embodiment, the surface of the biochip and the probe may be
derivatized with chemical functional groups for subsequent attachment of the
two. Thus, e.g.,
the biochip is derivatized with a chemical functional group including, but not
limited to,
amino groups, carboxy groups, oxo groups and thiol groups, with amino groups
being
particularly preferred. Using these functional groups, the probes can be
attached using
functional groups on the probes. For example, nucleic acids containing amino
groups can be
attached to surfaces comprising amino groups, e.g., using linkers as are known
in the art; e.g.,
homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce
Chemical Company
catalog, technical section on cross-linkers, pages 155-200). In addition, in
some cases,
additional linkers, such as alkyl groups (including substituted and
heteroalkyl groups) may be
used.
In this embodiment, oligonucleotides are synthesized, and then attached to the
surface
of the solid support. Either the 5' or 3' terminus may be attached to the
solid support, or
attachment may be via linkage to an internal nucleoside.
In another embodiment, the immobilization to the solid support may be very
strong,
yet non-covalent. For example, biotinylated oligonucleotides can be made,
which bind to
surfaces covalently coated with streptavidin, resulting in attachment.
Alternatively, the oligonucleotides may be synthesized on the surface, as is
known in
the art. For example, photoactivation techniques utilizing photopolymerization
compounds
and techniques are used. In a preferred embodiment, the nucleic acids can be
synthesized in
situ, using known photolithographic techniques, such as those described in WO
95/25116;
WO 95/35505; U.S. Patent Nos. 5,700,637 and 5,445,934; and references cited
within, all of
which are expressly incorporated by reference; these methods of attachment
form the basis of
the Affymetrix GeneChipTM technology.
Often, amplification-based assays are performed to measure the expression
level of
lung cancer-associated sequences. These assays are typically performed in
conjunction with
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reverse transcription. In such assays, a lung cancer-associated nucleic acid
sequence acts as a
template in an amplification reaction (e.g., Polymerase Chain Reaction, or
PCR). In a
quantitative amplification, the amount of amplification product will be
proportional to the
amount of template in the original sample. Comparison to appropriate controls
provides a
measure of the amount of lung cancer-associated RNA. Methods of quantitative
amplification are well known to those of skill in the art. Detailed protocols
for quantitative
PCR are provided, e.g., in Innis, et al. (1990) PCR Protocols, A Guide to
Methods and
Applications.
In some embodiments, a TaqMan based assay is used to measure expression.
TaqMan based assays use a fluorogenic oligonucleotide probe that contains a 5'
fluorescent
dye and a 3' quenching agent. The probe hybridizes to a PCR product, but
cannot itself be
extended due to a blocking agent at the 3' end. When the PCR product is
amplified in
subsequent cycles, the 5' nuclease activity of the polymerase, e.g., AmpliTaq,
results in the
cleavage of the TaqMan probe. This cleavage separates the 5' fluorescent dye
and the 3'
quenching agent, thereby resulting in an increase in fluorescence as a
function of
amplification (see, e.g., literature provided by Perkin-Elmer, e.g.,
www2.perkin-elmer.com).
Other suitable amplification methods include, but are not limited to, ligase
chain
reaction (LCR) (see Wu and Wallace (1989) Genomics 4:560, Landegren, et al.
(1988)
Science 241:1077, and Barnnger~ et al. (1990) Gene 89:117), transcription
amplification
(Kwoh, et al. (1989) Proc. Natl. Acad. Sci. USA 86:1173), self sustained
sequence
replication (Guatelli, et al. (1990) Proc. Nat. Acad. Sci. USA 87:1874), dot
PCR, and linker
adapter PCR, etc.
Expression of lung cancer proteins from nucleic acids
In a preferred embodiment, lung cancer nucleic acids, e.g., encoding lung
cancer
proteins, are used to make a variety of expression vectors to express lung
cancer proteins
which can then be used in screening assays, as described below. Expression
vectors and
recombinant DNA technology are well known to those of skill in the art (see,
e.g., Ausubel,
supra, and Fernandez and Hoeffler (eds 1999) Gene Expression S.~stems) and are
used to
express proteins. The expression vectors may be either self replicating
extrachromosomal
vectors or vectors which integrate into a host genome. Generally, these
expression vectors
include transcriptional and translational regulatory nucleic acid operably
linked to the nucleic
acid encoding the lung cancer protein. The term "control sequences" refers to
DNA
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sequences used for the expression of an operably linked coding sequence in a
particular host
organism. Control sequences that are suitable for prokaryotes, e.g., include a
promoter,
optionally an operator sequence, and a ribosome binding site. Eukaryotic cells
are known to
utilize promoters, polyadenylation signals, and enhancers.
Nucleic acid is "operably linked" when it is placed into a functional
relationship with
another nucleic acid sequence. For example, DNA for a presequence or secretory
leader is
operably linked to DNA for a polypeptide if it is expressed as a preprotein
that participates in
the secretion of the polypeptide; a promoter or enhancer is operably linked to
a coding
sequence if it affects the transcription of the sequence; or a ribosome
binding site is operably
linked to a coding sequence if it is positioned so as to facilitate
translation. Generally,
"operably linked" means that the DNA sequences being linked are contiguous,
and, in the
case of a secretory leader, contiguous and in reading phase. However,
enhancers do not have
to be contiguous. Linking is typically accomplished by ligation at convenient
restriction
sites. If such sites do not exist, synthetic oligonucleotide adaptors or
linkers are used in
accordance with conventional practice. Transcriptional and translational
regulatory nucleic
acid will generally be appropriate to the host cell used to express the lung
cancer protein.
Numerous types of appropriate expression vectors, and suitable regulatory
sequences are
known in the art for a variety of host cells.
In general, transcriptional and translational regulatory sequences may
include, but are
not limited to, promoter sequences, ribosomal binding sites, transcriptional
start and stop
sequences, translational start and stop sequences, and enhancer or activator
sequences. In a
preferred embodiment, the regulatory sequences include a promoter and
transcriptional start
and stop sequences.
Promoter sequences may be either constitutive or inducible promoters. The
promoters
may be either naturally occurring promoters or hybrid promoters. Hybrid
promoters, which
combine elements of more than one promoter, are also known in the art, and axe
useful in the
present invention.
In addition, an expression vector may comprise additional elements. For
example, the
expression vector may have two replication systems, thus allowing it to be
maintained in two
organisms, e.g., in mammalian or insect cells for expression and in a
prokaryotic host for
cloning and amplification. Furthermore, for integrating expression vectors,
the expression
vector often contains at least one sequence homologous to the host cell
genome, and
preferably two homologous sequences which flank the expression construct. The
integrating
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vector may be directed to a specific locus in the host cell by selecting the
appropriate
homologous sequence for inclusion in the vector. Constructs for integrating
vectors are well
known in the art (e.g., Fernandez and Hoeffler, supra).
In addition, in a preferred embodiment, the expression vector contains a
selectable
marker gene to allow the selection of transformed host cells. Selection genes
are well known
in the art and will vary with the host cell used.
The lung cancer proteins of the present invention are usually produced by
culturing a
host cell transformed with an expression vector containing nucleic acid
encoding a lung
cancer protein, under the appropriate conditions to induce or cause expression
of the lung
cancer protein. Conditions appropriate for lung cancer protein expression will
vary with the
choice of the expression vector and the host cell, and will be easily
ascertained by one skilled
in the art through routine experimentation or optimization. For example, the
use of
constitutive promoters in the expression vector will require optimizing the
growth and
proliferation of the host cell, while the use of an inducible promoter
requires the appropriate
growth conditions for induction. In addition, in some embodiments, the timing
of the harvest
is important. For example, the baculoviral systems used in insect cell
expression are lytic
viruses, and thus harvest time selection can be crucial for product yield.
Appropriate host cells include.yeast, bacteria, archaebacteria, fungi, and
insect and
animal cells, including mammalian cells. Of particular interest are
Saccharomyces cerevisiae
and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, 0129 cells, 293
cells, Neurospora, BHI~,
CHO, COS, HeLa cells, HUVEC (human umbilical vein endothelial cells), THP1
cells (a
macrophage cell line) and various other human cells and cell lines.
In a preferred embodiment, the lung cancer proteins are expressed in mammalian
cells. Mammalian expression systems are also known in the art, and include
retroviral and
adenoviral systems. Of particular use as mammalian promoters are the promoters
from
mammalian viral genes, since the viral genes are often highly expressed and
have a broad
host range. Examples include the SV40 early promoter, mouse mammary tumor
virus LTR
promoter, adenovirus major late promoter, herpes simplex virus promoter, and
the CMV
promoter (see, e.g., Fernandez and Hoeffler, supra). Typically, transcription
termination and
polyadenylation sequences recognized by mammalian cells are regulatory regions
located 3'
to the translation stop codon and thus, together with the promoter elements,
flank the coding
sequence. Examples of transcription terminator and polyadenylation signals
include those
derived form SV40.
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The methods of introducing exogenous nucleic acid into mammalian hosts, as
well as
other hosts, is well known in the art, and will vary with the host cell used.
Techniques
include dextran-mediated transfection, calcium phosphate precipitation,
polybrene mediated
transfection, protoplast fusion, electroporation, viral infection,
encapsulation of the
polynucleotide(s) in liposomes, and direct microinjection of the DNA into
nuclei.
In a preferred embodiment, lung cancer proteins are expressed in bacterial
systems.
Promoters from bacteriophage may also be used and are known in the art. In
addition,
synthetic promoters and hybrid promoters are also useful; e.g., the tac
promoter is a hybrid of
the trp and lac promoter sequences. Furthermore, a bacterial promoter can
include naturally
occurring promoters of non-bacterial origin that have the ability to bind
bacterial RNA
polymerase and initiate transcription. Zn addition to a functioning promoter
sequence, an
efficient ribosome binding site is desirable. The expression vector may also
include a signal
peptide sequence that provides for secretion of the lung cancer protein in
bacteria. The
protein is either secreted into the growth media (gram-positive bacteria) or
into the
periplasmic space, located between the inner and outer membrane of the cell
(gram-negative
bacteria). The bacterial expression vector may also include a selectable
marker gene to allow
for the selection of bacterial strains that have been transformed. Suitable
selection genes
include genes which render the bacteria resistant to drugs such as ampicillin,
chloramphenicol, erythromycin, kanamycin, neomycin and tetracycline.
Selectable markers
?0 also include biosynthetic genes, such as those in the histidine, tryptophan
and leucine
biosynthetic pathways. These components are assembled into expression vectors.
Expression
vectors for bacteria are well known in the art, and include vectors for
Bacillus subtilis, E.
coli, Streptococcus cremoris, and Streptococcus lividans, among others (e.g.,
Fernandez and
Hoeffler, supra). The bacterial expression vectors are transformed into
bacterial host cells
>.5 using techniques well known in the art, such as calcium chloride
treatment, electroporation,
and others.
In one embodiment, lung cancer proteins are produced in insect cells.
Expression
vectors for the transformation of insect cells, and in particular, baculovirus-
based expression
vectors, axe well known in the art.
SO In a preferred embodiment, lung cancer protein is produced in yeast cells.
Yeast
expression systems are well known in the art, and include expression vectors
for
SaccIZaromyces cerevisiae, Candida albicans and C. maltosa, Hartsenula
polymorpha,
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Kluyveromyces fYagilis and K. lactic, Pichia guillerimondii, and P. pasto~is,
Sclzizosaccharomyces pombe, and Yarrowia lipolytica.
The lung cancer protein may also be made as a fusion protein, using techniques
well
known in the art. Thus, e.g., for the creation of monoclonal antibodies, if
the desired epitope
is small, the lung cancer protein may be fused to a carrier protein to form an
immunogen.
Alternatively, the lung cancer protein may be made as a fusion protein to
increase expression
for affinity purification purposes, or for other reasons. For example, when
the lung cancer
protein is a lung cancer peptide, the nucleic acid encoding the peptide may be
linked to other
nucleic acid for expression purposes.
In a preferred embodiment, the lung cancer protein is purified or isolated
after
expression. Lung cancer proteins may be isolated or purified in a variety of
appropriate
ways. Standard purification methods include electrophoretic, molecular,
immunological and
chromatographic techniques, including ion exchange, hydrophobic, affinity, and
reverse-
phase HPLC chromatography, and chromatofocusing. For example, the lung cancer
protein
may be purified using a standard anti-lung cancer protein antibody column.
Ultrafiltration
and diafiltration techniques, in conjunction with protein concentration, are
also useful. For
general guidance in suitable purification techniques, see Scopes (1982)
Protein Purification.
The degree of purification necessary will vary depending on the use of the
lung cancer
protein. In some instances no purification will be necessary.
Once expressed and purified if necessary, the lung cancer proteins and nucleic
acids
are useful in a number of applications. They may be used as immunoselection
reagents, as
vaccine reagents, as screening agents, therapeutic entities, for production of
antibodies, as
transcription or translation inhibitors, etc.
Variants of lung cancer proteins
In one embodiment, the lung cancer proteins are derivative or variant lung
cancer
proteins as compared to the wild-type sequence. That is, as outlined more
ftilly below, the
derivative lung cancer peptide will often contain at least one amino acid
substitution, deletion
or insertion, with amino acid substitutions being particularly preferred. The
amino acid
substitution, insertion or deletion may occur at a particular residue within
the lung cancer
peptide.
Also included within one embodiment of lung cancer proteins of the present
invention
are amino acid sequence variants. These variants typically fall into one or
more of three
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classes: substitutional, insertional or deletional variants. These variants
ordinarily are
prepared by site specific mutagenesis of nucleotides in the DNA encoding the
lung cancer
protein, using cassette or PCR mutagenesis or other techniques, to produce DNA
encoding
the variant, and thereafter expressing the DNA in recombinant cell culture as
outlined above.
S However, variant lung cancer protein fragments having up to about 100-150
residues may be
prepared by in vitro synthesis. Amino acid sequence variants are characterized
by the
predetermined nature of the variation, a feature that sets them apart from
naturally occurring
allelic or interspecies variation of the lung cancer protein amino acid
sequence. The variants
typically exhibit a similar qualitative biological activity as the naturally
occurnng analogue,
although variants can also be selected which have modified characteristics as
will be more
fully outlined below.
While the site or region for introducing an amino acid sequence variation is
often
predetermined, the mutation per se need not be predetermined. For example, in
order to
optimize the performance of a mutation at a given site, random mutagenesis may
be
conducted at the target codon or region and the expressed lung cancer variants
screened for
the optimal combination of desired activity. Techniques exist for making
substitution
mutations at predetermined sites in DNA having a known sequence, e.g., M13
primer
mutagenesis and PCR mutagenesis. Screening of mutants is often done using
assays of lung
cancer protein activities.
Amino acid substitutions are typically of single residues; insertions usually
will be on
the order of from about 1 to 20 amino acids, although considerably larger
insertions may be
occasionally tolerated. Deletions generally range from about 1 to about 20
residues, although
in some cases deletions may be much larger.
Substitutions, deletions, insertions or any combination thereof may be used to
arrive
at a final derivative. Generally these changes are done on a few amino acids
to minimize the
alteration of the molecule. Larger changes may be tolerated in certain
circumstances. When
small alterations in the characteristics of a lung cancer protein are desired,
substitutions are
generally made in accordance with the amino acid substitution chart provided
in the
definition section.
Variants typically exhibit essentially the same qualitative biological
activity and will
elicit the same immune response as a naturally-occurring analog, although
variants also are
selected to modify the characteristics of lung cancer proteins as needed.
Alternatively, the
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variant may be designed or reorganized such that a biological activity of the
lung cancer
protein is altered. For example, glycosylation sites may be added, altered, or
removed.
Covalent modifications of lung cancer polypeptides are included within the
scope of
this invention. One type of covalent modification includes reacting targeted
amino acid
residues of a lung cancer polypeptide with an organic derivatizing agent that
is capable of
reacting with selected side chains or the N-or C-terminal residues of a lung
cancer
polypeptide. Derivatization with bifunctional agents is useful, for instance,
for crosslinking
lung cancer polypeptides to a water-insoluble support matrix or surface for
use in a method
for purifying anti-lung cancer polypeptide antibodies or screening assays, as
is more fully
described below. Commonly used crosslinking agents include, e.g., l,l-
bis(diazoacetyl)-2-
phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, e.g., esters with 4-
azidosalicylic
acid, homobifunctional imidoesters, including disuccinimidyl esters such as
3,3'-
dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-
maleimido-1,8-
octane and agents such as methyl-3-((p-azidophenyl)dithio)propioimidate.
Other modifications include deamidation of glutaminyl and asparaginyl residues
to
the corresponding glutamyl and aspartyl residues, respectively, hydroxylation
of proline and
lysine, phosphorylation of hydroxyl groups of serinyl, threonyl or tyrosyl
residues, '
methylation of the y-amino groups of lysine, arginine, and histidine side
chains (Creighton
(1983) Proteins: Structure and Molecular Properties, pp. 79-86), acetylation
of the N-terminal
amine, and amidation of any C-terminal carboxyl group.
Another type of covalent modification of the lung cancer polypeptide
encompassed by
this invention is an altered native glycosylation pattern of the polypeptide.
"Altering the
native glycosylation pattern" is intended herein to mean adding to or deleting
one or more
carbohydrate moieties of a native sequence lung cancer polypeptide.
Glycosylation patterns
can be altered in many ways. For example the use of different cell types to
express lung
cancer-associated sequences can result in different glycosylation patterns.
Addition of glycosylation sites to lung cancer polypeptides may also be
accomplished
by altering the amino acid sequence thereof. The alteration may be made, e.g.,
by the
addition of, or substitution by, one or more serine or threonine residues to
the native sequence
lung cancer polypeptide (for O-linked glycosylation sites). The lung cancer
amino acid
sequence may optionally be altered through changes at the DNA level,
particularly by
mutating the DNA encoding the lung cancer polypeptide at preselected bases
such that
codons are generated that will translate into the desired amino acids.
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Another means of increasing the number of carbohydrate moieties on the lung
cancer
polypeptide is by chemical or enzymatic coupling of glycosides to the
polypeptide. Such
methods are described in the art, e.g., in WO 87/05330, and in Aplin and
Wriston (1981)
CRC Crit. Rev. Biochem., pp. 259-306.
Removal of carbohydrate moieties present on the lung cancer polypeptide may be
accomplished chemically or enzymatically or by mutational substitution of
codons encoding
for amino acid residues that serve as targets for glycosylation. Chemical
deglycosylation
techniques are known in the art and described, for instance, by Hakimuddin, et
al. (1987)
Arch. Biochem. Biophys., 259:52 and by Edge, et al. (1981) Anal. Biochem.,
118:131.
Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by
the use of a
variety of endo-and exo-glycosidases as described by Thotakura, et al. (1987)
Meth.
Enz~mol., 138:350.
Another type of covalent modification of lung cancer comprises linking the
lung
cancer polypeptide to one of a variety of nonproteinaceous polymers, e.g.,
polyethylene
glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in
U.S. Patent
Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192, or4,179,337.
Lung cancer polypeptides of the present invention may also be modified in a
way to
form chimeric molecules comprising a lung cancer polypeptide fused to another,
heterologous polypeptide or amino acid sequence. In one embodiment, such a
chimeric
molecule comprises a fusion of a lung cancer polypeptide with a tag
polypeptide which
provides an epitope to which an anti-tag antibody can selectively bind. The
epitope tag is
generally placed at the amino-or carboxyl-terminus of the lung cancer
polypeptide. The
presence of such epitope-tagged forms of a lung cancer polypeptide can be
detected using an
antibody against the tag polypeptide. Also, provision of the epitope tag
enables the lung
cancer polypeptide to be readily purified by affinity purification using an
anti-tag antibody or
another type of affinity matrix that binds to the epitope tag. In an
alternative embodiment,
the chimeric molecule may comprise a fusion of a lung cancer polypeptide with
an
irmnunoglobulin or a particular region of an immunoglobulin. For a bivalent
form of the
chimeric molecule, such a fusion could be to the Fc region of an TgG molecule.
Various tag polypeptides and their respective antibodies are well known and
examples
include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly)
tags; HIS6 and metal
chelation tags, the flu HA tag polypeptide and its antibody 12CA5 (Field, et
al. (1988) Mol.
Cell. Biol. 8:2159-2165); the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and
9E10 antibodies
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
thereto (Evan, et a1. (1985) Molecular and Cellular Biolo~v 5:3610-3616); and
the Herpes
Simplex virus glycoprotein D (gD) tag and its antibody (Paborsky, et al.
(1990) Protein
En ig neeri~ 3(6):547-553). Other tag polypeptides include the Flag-peptide
(Hopp, et al.
(1988) BioTechnolo~y 6:1204-1210); the KT3 epitope peptide (Martin, et al.
(1992) Science
255:192-194); tubulin epitope peptide (Skinner, et al. (1991) J. Biol. Chem.
266:15163-
15166); and the T7 gene 10 protein peptide tag (Lutz-Freyennuth, et al. (1990)
Proc. Naf1
Acid. Sci. USA 87:6393-6397).
Also included are other lung cancer proteins of the lung cancer family, and
lung
cancer proteins from other organisms, which are cloned and expressed as
outlined below.
Thus, probe or degenerate polymerise chain reaction (PCR) primer sequences may
be used to
find other related lung cancer proteins from primates or other organisms. As
will be
appreciated by those in the art, particularly useful probe and/or PCR primer
sequences
include unique areas of the lung cancer nucleic acid sequence. As is generally
known in the
art, preferred PCR primers are from about 15 to about 35 nucleotides in
length, with from
about 20 to about 30 being preferred, and may contain inosine as needed. PCR
reaction
conditions are well known in the art (e.g., Innis, PCR Protocols, supra).
Antibodies to lung cancer proteins
In a preferred embodiment, when a lung cancer protein is to be used to
generate
antibodies, e.g., for immunotherapy or immunodiagnosis, the lung cancer
protein should
share at least one epitope or determinant with the full length protein. By
"epitope" or
"determinant" herein is typically meant a portion of a protein which will
generate and/or bind
an antibody or T-cell receptor in the context of MHC. Thus, in most instances,
antibodies
made to a smaller lung cancer protein will be able to bind to the full-length
protein,
particularly linear epitopes. In a preferred embodiment, the epitope is
unique; that is,
antibodies generated to a unique epitope show little or no cross-reactivity.
Methods of preparing polyclonal antibodies are well known (e.g., Coligan,
supra; and
Harlow and Lane, supra). Polyclonal antibodies can be raised in a mammal,
e.g., by one or
more injections of an immunizing agent and, if desired, an adjuvant.
Typically, the
immunizing agent and/or adjuvant will be injected in the mammal by multiple
subcutaneous
or intraperitoneal injections. The immunizing agent may include a protein
encoded by a
nucleic acid of Tables 1A-16 or fragment thereof or a fusion protein thereof.
It may be useful
to conjugate the immunizing agent to a protein known to be immunogenic in the
mammal
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WO 02/086443 PCT/US02/12476
being immunized. Immunogenic proteins include, e.g., keyhole limpet
hemocyanin, serum
albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Adjuvants
include, e.g.,
Freund's complete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A,
synthetic
trehalose dicorynomycolate). The immunization protocol may be selected by one
skilled in
the art.
The antibodies may, alternatively, be monoclonal antibodies. Monoclonal
antibodies
may be prepared using hybridoma methods, such as those described by Kohler and
Milstein
(1975) Nature 256:495. In a hybridoma method, a mouse, hamster, or other
appropriate host
animal, is typically immunized with an immunizing agent to elicit lymphocytes
that produce
or are capable of producing antibodies that will specifically bind to the
immunizing agent.
Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent
will
typically include a polypeptide encoded by a nucleic acid of the tables, or
fragment thereof,
or a fusion protein thereof. Generally, either peripheral blood lymphocytes
("PBLs") are
used if cells of human origin are desired, or spleen cells or lymph node cells
are used if non-
human mammalian sources are desired. The lymphocytes are then fused with an
immortalized cell line using a suitable fusing agent, such as polyethylene
glycol, to form a
hybridoma cell (Goding (1986) Monoclonal Antibodies: Principles and Practice,
pp. 59-103 )
Immortalized cell lines are usually transformed mammalian cells, particularly
myeloma cells
of rodent, bovin, or primate origin. Usually, rat or mouse myeloma cell lines
are employed.
The hybridoma cells may be cultured in a suitable culture medium that
preferably contains
one or more substances that inhibit the growth or survival of the unfused,
immortalized cells.
For example, if the parental cells lack the enzyme hypoxanthine guanine
phosphoribosyl
transferase (HGPRT or HPRT), the culture medium for the hybridomas typically
will include
hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances
prevent the
growth of HGPRT-deficient cells.
In one embodiment, the antibodies are bispecific antibodies. Bispecific
antibodies are
typically monoclonal, preferably human or humanized, antibodies that have
binding
specificities for at least two different antigens or that have binding
specificities for two
epitopes on the same antigen. In one embodiment, one of the binding
specificities is for a
protein encoded by a nucleic acid of the tables or a fragment thereof, the
other one is for any
other antigen, and preferably for a cell-surface protein or receptor or
receptor subunit,
preferably one that is tumor specific. Alternatively, tetramer-type technology
may create
multivalent reagents.
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In a preferred embodiment, the antibodies to lung cancer protein are capable
of
reducing or eliminating a biological function of a lung cancer protein, in a
naked form or
conjugated to an effector moiety. That is, the addition of anti-lung cancer
protein antibodies
(either polyclonal or preferably monoclonal) to lung cancer tissue (or cells
containing lung
cancer) may reduce or eliminate the lung cancer. Generally, at least a 25%
decrease in
activity, growth, size or the like is preferred, with at least about 50% being
particularly
preferred and about a 95-100% decrease being especially preferred.
In a preferred embodiment the antibodies to the lung cancer proteins are
humanized
antibodies (e.g., Xenerex Biosciences, Medarex, Inc., Abgenix, Inc., Protein
Design Labs,
Inc.) Humanized forms of non-human (e.g., marine) antibodies are chimeric
molecules of
immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab,
Fab',
F(ab')2 or other antigen-binding subsequences of antibodies) which contain
minimal
sequence derived from non-human immunoglobulin. Humanized antibodies include
human
immunoglobulins (recipient antibody) in which residues from a complementary
determining
region (CDR) of the recipient are replaced by residues from a CDR of a non-
human species
(donor antibody) such as mouse, rat or rabbit having the desired specificity,
aff pity and
capacity. In some instances, Fv framework residues of a human immunoglobulin
are
replaced by corresponding non-human residues. Humanized antibodies may also
comprise
residues which are found neither in the recipient antibody nor in the imported
CDR or
framework sequences. In general, a humanized antibody will comprise
substantially all of at
least one, and typically two, variable domains, in which all or substantially
all of the CDR
regions correspond to those of a non-human immunoglobulin and all or
substantially all of
the framework (FR) regions are those of a human immunoglobulin consensus
sequence. A
humanized antibody optimally also will typically comprise at least a portion
of an
immunoglobulin constant region (Fc), typically that of a human immunoglobulin
(Jones, et
al. (1986) Nature 321:522-525; Riechmann, et al. (1988) Nature 332:323-329;
and Presta
(1992) Curr. O~. Struct. Biol. 2:593-596). Humanization can be performed
following the
method of Winter and co-workers (Jones, et al. (1986) Nature 321:522-525;
Riechmann, et al.
(1988) Nature 332:323-327; Verhoeyen, et al. (1988) Science 239:1534-1536), by
substituting rodent CDRs or CDR sequences for corresponding sequences of a
human
antibody. Accordingly, such humanized antibodies are chimeric antibodies
(LT.S. Patent No.
4,816,567), wherein substantially less than an intact human variable domain
has been
substituted by corresponding sequence from a non-human species.
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Human-like antibodies can also be produced using various techniques known in
the
art, including phage display libraries (Hoogenboom and Winter (1991) J. Mol.
Biol. 227:381;
Marks, et al. (1991) J. Mol. Biol. 222:581). The techniques of Cole, et al.
and Boerner, et al.
are also available for the preparation of human monoclonal antibodies (Cole,
et al. (1985)
Monoclonal Antibodies and Cancer Therapv, p. 77 and Boerner, et al. (1991) J.
Immunol.
147(1):86-95). Similarly, human antibodies can be made by introducing human
immunoglobulin loci into transgenic animals, e.g., mice in which the
endogenous
immunoglobulin genes have been partially or completely inactivated. Upon
challenge,
human antibody production is observed, which closely resembles that seen in
humans in
nearly all respects, including gene rearrangement, assembly, and antibody
repertoire. This
approach is described, e.g., in U.S. Patent Nos. 5,545,807; 5,545,806;
5,569,825; 5,625,126;
5,633,425; 5,661,016, and in the following scientific publications: Marks, et
al. (1992)
Bio/Technolo~y 10:779-783; Lonberg, et al. (1994) Nature 368:856-859; Morrison
(1994)
Nature 368:812-13; Fishwild, et al. (1996) Nature Biotechnolo~v 14:845-51;
Neuberger
(1996) Nature Biotechnolo~y 14:826; and Lonberg and Huszar (1995) Intern. Rev.
Immunol.
13:65-93.
By immunotherapy is meant treatment of lung cancer with an antibody raised
against
a lung cancer proteins. As used herein, immunotherapy can be passive or
active. Passive
immunotherapy as defined herein is the passive transfer of antibody to a
recipient (patient).
Active immunization is the induction of antibody and/or T-cell responses in a
recipient
(patient). Induction of an immune response is the result of providing the
recipient with an
antigen to which antibodies are raised. The antigen may be provided by
injecting a
polypeptide against which antibodies are desired to be raised into a
recipient, or contacting
the recipient with a nucleic acid capable of expressing the antigen and under
conditions for
expression of the antigen, leading to an immune response.
In a preferred embodiment the lung cancer proteins against which antibodies
are
raised are secreted proteins as described above. Without being bound by
theory, antibodies
used for treatment, may bind and prevent the secreted protein from binding to
its receptor,
thereby inactivating the secreted lung cancer protein.
In another preferred embodiment, the lung cancer protein to which antibodies
are
raised is a transmembrane protein. Without being bound by theory, antibodies
used for
treatment may bind the extracellular domain of the lung cancer protein and
prevent it from
binding to other proteins, such as circulating ligands or cell-associated
molecules. The
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antibody may cause down-regulation of the transmembrane lung cancer protein.
The
antibody may be a competitive, non-competitive or uncompetitive inhibitor of
protein binding
4
to the extracellular domain of the lung cancer protein. The antibody may be an
antagonist of
the lung cancer protein or may prevent activation of a transmembrane lung
cancer protein, or
may induce or suppress a particular cellular pathway. In some embodiments,
when the
antibody prevents the binding of other molecules to the lung cancer protein,
the antibody
prevents growth of the cell. The antibody may also be used to target or
sensitize the cell to
cytotoxic agents, including, but not limited to TNF-a, TNF-(3, IL-1, INF-y,
and IL-2, or
chemotherapeutic agents including SFU, vinblastine, actinomycin D, cisplatin,
methotrexate,
and the like. In some instances the antibody may belong to a sub-type that
activates serum
complement when complexed with the transmembrane protein thereby mediating
cytotoxicity
or antigen-dependent cytotoxicity (ADCC). Thus, lung cancer may be treated by
administering to a patient antibodies directed against the transmembrane lung
cancer protein.
Antibody-labeling may activate a co-toxin, localize a toxin payload, or
otherwise provide
means to locally ablate cells.
In another preferred embodiment, the antibody is conjugated to an effector
moiety.
The effector moiety can be various molecules, including labeling moieties such
as radioactive
labels or fluorescent labels, or can be a therapeutic moiety. In one aspect
the therapeutic
moiety is a small molecule that modulates the activity of a lung cancer
protein. In another
aspect the therapeutic moiety may modulate an activity of molecules associated
with or in
close proximity to a lung cancer protein. The therapeutic moiety may inhibit
enzymatic or
signaling activity such as protease or collagenase activity associated with
lung cancer.
In a preferred embodiment, the therapeutic moiety can also be a cytotoxic
agent. In
this method, targeting the cytotoxic agent to lung cancer tissue or cells
results in a reduction
in the number of afflicted cells, thereby reducing symptoms associated with
lung cancer.
Cytotoxic agents are numerous and varied and include, but are not limited to,
cytotoxic drugs
or toxins or active fragments of such toxins. Suitable toxins and their
corresponding
fragments include diphtheria A chain, exotoxin A chain, ricin A chain, abrin A
chain, curcin,
crotin, phenomycin, enomycin, saporin, auristatin, and the like. Cytotoxic
agents also include
radiochemicals made by conjugating radioisotopes to antibodies raised against
lung cancer
proteins, or binding of a radionuclide to a chelating agent that has been
covalently attached to
the antibody. Targeting the therapeutic moiety to transmembrane lung cancer
proteins not
only serves to increase the local concentration of therapeutic moiety in the
lung cancer
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afflicted area, but also serves to reduce deleterious side effects that may be
associated with
the untargeted therapeutic moiety.
In another preferred embodiment, the lung cancer protein against which the
antibodies
are raised is an intracellular protein. In this case, the antibody may be
conjugated to a protein
S or other entity which facilitates entry into the cell. In one case, the
antibody enters the cell by
endocytosis. In another embodiment, a nucleic acid encoding the antibody is
administered to
the individual or cell. Moreover, wherein the lung cancer protein can be
targeted within a
cell, i.e., the nucleus, an antibody theretomay contain a signal for that
target localization, i.e.,
a nuclear localization signal.
The lung cancer antibodies of the invention specifically bind to Iung cancer
proteins.
By "specifically bind" herein is meant that the antibodies bind to the protein
with a Ka of at
least about 0.1 mM, more usually at least about 1 ~,M, preferably at least
about 0.1 ~M or
better, and most preferably, 0.01 ~.M or better. Selectivity of binding to the
specific target
and not to related other sequences is also important.
Detection of lung cancer sequence for diagnostic and therapeutic applications
In one aspect, the RNA expression levels of genes are determined for different
cellular states in the lung cancer phenotype. Expression levels of genes in
normal tissue (e.g.,
not undergoing lung cancer), in lung cancer tissue (and in some cases, for
varying severities
of lung cancer that relate to prognosis, as outlined below), or in non-
malignant disease are
evaluated to provide expression profiles. A gene expression profile of a
particular cell state
or point of development is essentially a "fingerprint" of the state of the
cell. While two states
may have a particular gene similarly expressed, the evaluation of a number of
genes
simultaneously allows the generation of a gene expression profile that is
reflective of the state
2S of the cell. By comparing expression profiles of cells in different states,
information
regarding which genes are important (including both up- and down-regulation of
genes) in
each of these states is obtained. Then, diagnosis may be performed or
confirmed to
determine whether a tissue sample has the gene expression profile of normal or
cancerous
tissue. This will provide for molecular diagnosis of related conditions.
"Differential expression," or grammatical equivalents as used herein, refers
to
qualitative or quantitative differences in the temporal and/or cellular gene
expression
patterns within and among cells and tissue. Thus, a differentially expressed
gene can
qualitatively have its expression altered, including an activation or
inactivation, in, e.g.,
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normal versus lung cancer tissue. Genes may be turned on or turned off in a
particular state,
relative to another state thus permitting comparison of two or more states. A
qualitatively
regulated gene will exhibit an expression pattern within a state or cell type
which is
detectable by standard techniques. Some genes will be expressed in one state
or cell type, but
not in both. Alternatively, the difference in expression may be quantitative,
e.g., in that
expression is increased or decreased; i.e., gene expression is either
upregulated, resulting in
an increased amount of transcript, or downregulated, resulting in a decreased
amount of
transcript. The degree to which expression differs need only be Iarge enough
to quantify via
standard characterization techniques as outlined below, such as by use of
Affymetrix
GeneChipTM expression arrays, Lockhart (1996) Nature Biotechnolo~y 14:1675-
1680, hereby
expressly incorporated by reference. Other techniques include, but are not
limited to,
quantitative reverse transcriptase PCR, northern analysis and RNase
protection. As outlined
above, preferably the change in expression (i.e., upregulation or
downregulation) is typically
at least about 50%, more preferably at least about 100%, more preferably at
least about
150%, more preferably at least about 200%, with from 300 to at least 1000%
being especially
preferred.
Evaluation may be at the gene transcript or the protein level. The amount of
gene
expression may be monitored using nucleic acid probes to the RNA or DNA
equivalent of the
gene transcript, and the quantification of gene expression levels, or,
alternatively, the final
gene product itself (protein) can be monitored, e.g., with antibodies to the
lung cancer protein
and standard immunoassays (ELISAs, etc.) or other techniques, including mass
spectroscopy
assays, 2D gel electrophoresis assays, etc. Proteins corresponding to lung
cancer genes, e.g.,
those identified as being important in a lung cancer or disease phenotype, can
be evaluated in
a Iung cancer diagnostic test. In a preferred embodiment, gene expression
monitoring is
performed simultaneously on a number of genes.
The lung cancer nucleic acid probes may be attached to biochips as outlined
herein for
the detection and quantification of lung cancer sequences in a particular
cell. The assays are
further described below in the example. PCR techniques can be used to provide
greater
sensitivity. Multiple protein expression monitoring can be performed as well.
Similarly,
these assays may be performed on an individual basis as well.
In a preferred embodiment nucleic acid's encoding the Iung cancer protein are
detected. Although DNA or RNA encoding the lung cancer protein may be
detected, of
particular interest are methods wherein an mRNA encoding a Iung cancer protein
is detected.
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Probes to detect mRNA can be a nucleotide/deoxynucleotide probe that is
complementary to
and hybridizes with the mRNA and includes, but is not limited to,
oligonucleotides, cDNA or
RNA. Probes also should contain a detectable label, as defined herein. In one
method the
mRNA is detected after immobilizing the nucleic acid to be examined on a solid
support such
as nylon membranes and hybridizing the probe with the sample. Following
washing to
remove the non-specifically bound probe, the label is detected. In another
method detection
of the mRNA is performed in situ. In this method permeabilized cells or tissue
samples are
contacted with a detectably labeled nucleic acid probe for sufficient time to
allow the probe
to hybridize with the target mRNA. Following washing to remove the non-
specifically bound
probe, the label is detected. For example a digoxygenin labeled riboprobe (RNA
probe) that
is complementary to the mRNA encoding a lung cancer protein is detected by
binding the
digoxygenin with an anti-digoxygenin secondary antibody and developed with
nitro blue
tetrazolium and 5-bromo-4-chloro-3-indoyl phosphate.
In a preferred embodiment, various proteins from the three classes of proteins
as
described herein (secreted, transmembrane or intracellular proteins) are used
in diagnostic
assays. The lung cancer proteins, antibodies, nucleic acids, modified proteins
and cells
containing lung cancer sequences are used in diagnostic assays. This can be
performed on an
individual gene or corresponding polypeptide level. In a preferred embodiment,
the
expression profiles are used, preferably in conjunction with high throughput
screening
techniques to allow monitoring for expression profile genes and/or
corresponding
polypeptides.
As described and defined herein, lung cancer proteins, including
intracellular,
transmembrane, or secreted proteins, find use as markers of lung cancer, e.g.,
for prognostic
or diagnostic purposes. Detection of these proteins in putative lung cancer
tissue allows for
detection, prognosis, or diagnosis of lung cancer or similar disease, and
perhaps for selection
of therapeutic strategy. In one embodiment, antibodies are used to detect lung
cancer
proteins. A preferred method separates proteins from a sample by
electrophoresis on a gel
(typically a denaturing and reducing protein gel, but may be another type of
gel, including
isoelectric focusing gels and the like). Following separation of proteins, the
lung cancer
protein is detected, e.g., by immunoblotting with antibodies raised against
the lung cancer
protein. Methods of immunoblotting are well known to those of ordinary skill
in the art.
In another preferred method, antibodies to the lung cancer protein find use in
in situ
imaging techniques, e.g., in histology (e.g., Asai (ed. 1993) Methods in Cell
Biolo~y:
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Antibodies in Cell Biolo~y, volume 37. In this method cells are contacted with
from one to
many antibodies to the lung cancer protein(s). Following washing to remove non-
specific
antibody binding, the presence of the antibody or antibodies is detected. In
one embodiment
the antibody is detected by incubating with a secondary antibody that contains
a detectable
label, e.g., multicolor fluorescence or confocal imaging. In another method
the primary
antibody to the lung cancer proteins) contains a detectable label, e.g., an
enzyme marker that
can act on a substrate. In another preferred embodiment each one of multiple
primary
antibodies contains a distinct and detectable label. This method finds
particular use in
simultaneous screening for a plurality of lung cancer proteins. Many other
histological
imaging techniques are also provided by the invention.
In a preferred embodiment the label is detected in a fluorometer which has the
ability
to detect and distinguish emissions of different wavelengths. Tn addition, a
fluorescence
activated cell sorter (FACS) can be used in the method.
In another preferred embodiment, antibodies find use in diagnosing lung cancer
from
blood, serum, plasma, stool, and other samples. Such samples, therefore, are
useful as
samples to be probed or tested for the presence of lung cancer proteins.
Antibodies can be
used to detect a lung cancer protein by previously described immunoassay
techniques
including ELISA, immunoblotting (western blotting), immunoprecipitation,
BIACORE
technology and the like. Conversely, the presence of antibodies may indicate
an immune
response against an endogenous lung cancer protein or vaccine.
In a preferred embodiment, in situ hybridization of labeled lung cancer
nucleic acid
probes to tissue arrays is done. For example, arrays of tissue samples,
including lung cancer
tissue and/or normal tissue, are made. In situ hybridization (see, e.g.,
Ausubel, supra) is then
performed. When comparing the fingerprints between an individual and a
standard, the
skilled artisan can make a diagnosis, a prognosis, or a prediction based on
the findings. It is
further understood that the genes which indicate the diagnosis may differ from
those which
indicate the prognosis and molecular profiling of the condition of the cells
may lead to
distinctions between responsive or refractory conditions or may be predictive
of outcomes.
In a preferred embodiment, the lung cancer proteins, antibodies, nucleic
acids,
modified proteins and cells containing lung cancer sequences are used in
prognosis assays.
As above, gene expression profiles can be generated that correlate to lung
cancer, clinical,
pathological, or other information, in terms of long term prognosis. Again,
this may be done
on either a protein or gene level, with the use of genes being preferred.
Single or multiple
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genes may be useful in various combinations. As above, lung cancer probes may
be attached
to biochips for the detection and quantification of lung cancer sequences in a
tissue or patient.
The assays proceed as outlined above for diagnosis. PCR method may provide
more
sensitive and accurate quantification.
Assays for therapeutic compounds
In a preferred embodiment, the proteins, nucleic acids, and antibodies as
described
herein are used in drug screening assays. The lung cancer proteins,
antibodies, nucleic acids,
modified proteins and cells containing lung cancer sequences are used in drug
screening
assays or by evaluating the effect of drug candidates on a "gene expression
profile" or
expression profile of polypeptides. In a preferred embodiment, the expression
profiles are
used, preferably in conjunction with high throughput screening techniques to
allow
monitoring for expression profile genes after treatment with a candidate agent
(e.g.,
Zlokarnik, et al. (1998) Science 279:84-8; Heid (1996) Genome Res. 6:986-94.
In a preferred embodiment, the lung cancer proteins, antibodies, nucleic
acids,
modified proteins and cells containing the native or modified lung cancer
proteins are used in
screening assays. That is, the present invention provides novel methods for
screening for
compositions which modulate the lung cancer phenotype or an identified
physiological
function of a lung cancer protein. As above, this can be done on an individual
gene level or
by evaluating the effect of drug candidates on a "gene expression profile". In
a preferred
embodiment, the expression profiles are used, preferably in conjunction with
high throughput
screening techniques to allow monitoring for expression profile genes after
treatment with a
candidate agent, see Zlokarnik, supra.
Having identified differentially expressed genes herein, a variety of assays
may be
performed. In a preferred embodiment, assays may be run on an individual gene
or protein
level. That is, having identified a particular gene with altered regulation in
lung cancer, test
compounds can be screened for the ability to modulate gene expression or for
binding to the
lung cancer protein. "Modulation" thus includes an increase or a decrease in
gene
expression. The preferred amount of modulation will depend on the original
change of the
gene expression in normal versus tissue undergoing lung cancer, with changes
of at least
10%, preferably 50%, more preferably 100-300%, and in some embodiments 300-
1000% or
greater. Thus, if a gene exhibits a 4-fold increase in lung cancer tissue
compared to normal
tissue, a decrease of about four-fold is often desired; similarly, a 10-fold
decrease in lung
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cancer tissue compared to normal tissue often provides a target value of a 10-
fold increase in
expression to be induced by the test compound.
The amount of gene expression may be monitored using nucleic acid probes and
the
quantification of gene expression levels, or, alternatively, the gene product
itself can be
monitored, e.g., through the use of antibodies to the lung cancer protein and
standard
immunoassays. Proteomics and separation techniques may also allow
quantification of
expression.
In a preferred embodiment, gene or protein expression monitoring of a number
of
entities, i.e., an expression profile, is monitored simultaneously. Such
profiles will typically
involve a plurality of those entities described herein.
In this embodiment, the lung cancer nucleic acid probes are attached to
biochips as
outlined herein for the detection and quantification of lung cancer sequences
in a particular
cell. Alternatively, PCR may be used. Thus, a series, e.g., of microtiter
plate, may be used
with dispensed primers in desired wells. A PCR reaction can then be performed
and analyzed
for each well.
Expression monitoring can be performed to identify compounds that modify the
expression of one or more lung cancer-associated sequences, e.g., a
polynucleotide sequence
set out in the tables. Generally, in a preferred embodiment, a test compound
is added to the ,
cells prior to analysis. Moreover, screens are also provided to identify
agents that modulate
lung cancer, modulate lung cancer proteins, bind to a lung cancer protein, or
interfere with
the binding of a lung cancer protein and an antibody, substrate, or other
binding partner.
The term "test compound" or "drug candidate" or "modulator" or grammatical
equivalents as used herein describes a molecule, e.g., protein, oligopeptide,
small organic
molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity
to directly or_
indirectly alter the lung cancer phenotype or the expression of a lung cancer
sequence, e.g., a
nucleic acid or protein sequence. In preferred embodiments, modulators alter
expression
profiles of nucleic acids or proteins provided herein. In one embodiment, the
modulator
suppresses a lung cancer phenotype, e.g., to a normal or non-malignant tissue
fingerprint. In
another embodiment, a modulator induces a lung cancer phenotype. Generally, a
plurality of
assay mixtures are run in parallel with different agent concentrations to
obtain a differential
' response to the various concentrations. Typically, one of these
concentrations serves as a
negative control, i.e., at zero concentration or below the level of detection.
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In one aspect, a modulator will neutralize the effect of a lung cancer
protein. By
"neutralize" is meant that activity of a protein and the consequent effect on
the cell is
inhibited or blocked.
In certain embodiments, combinatorial libraries of potential modulators will
be
screened for an ability to bind to a lung cancer polypeptide or to modulate
activity.
Conventionally, new chemical entities with useful properties are generated by
identifying a
chemical compound (called a "lead compound") with some desirable property or
activity,
e.g., inhibiting activity, creating variants of the lead compound, and
evaluating the property
and activity of those variant compounds. Often, high throughput screening
(HTS) methods
are employed for such an analysis.
In one preferred embodiment, high throughput screening methods involve
providing a
library containing a large number of potential therapeutic compounds
(candidate
compounds). Such "combinatorial chemical libraries" are then screened in one
or more
assays to identify those library members (particular chemical species or
subclasses) that
display a desired characteristic activity. The compounds thus identified can
serve as
conventional "lead compounds" or can themselves be used as potential or actual
therapeutics.
A combinatorial chemical library is a collection of diverse chemical compounds
generated by either chemical synthesis or biological synthesis by combining a
number of
chemical "building blocks" such as reagents. For example, a linear
combinatorial chemical
?0 library, such as a polypeptide (e.g., mutein) library, is formed by
combining a set of chemical
building blocks called amino acids in every possible way for a given compound
length (i.e.,
the number of amino acids in a polypeptide compound). Millions of chemical
compounds
can be synthesized through such combinatorial mixing of chemical building
blocks (Gallop,
et al. (1994) J. Med. Chem. 37(9):1233-1251).
?5 Preparation and screening of combinatorial chemical libraries is well known
to those
of skill in the art. Such combinatorial chemical libraries include, but are
not limited to,
peptide libraries (see, e.g., U.S. Patent No. 5,010,175, Furka (1991) Pept.
Prot. Res. 37:487-
493, Houghton, et al. (1991) Nature, 354:84-88), peptoids (PCT Publication No
WO
91/19735), encoded peptides (PCT Publication WO 93/20242), random bio-
oligomers (PCT
s0 Publication WO 92/00091), benzodiazepines (U.5. Pat. No. 5,288,514),
diversomers such as
hydantoins, benzodiazepines and dipeptides (Hobbs, et al. (1993) Proc. Nat.
Acad. Sci. USA
90:6909-6913), vinylogous polypeptides (Hagihara, et al. (1992) J. Amer. Chem.
Soc.
114:6568), nonpeptidal peptidomimetics with a Beta-D-Glucose scaffolding
(Hirschmann, et
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al. (1992) J. Amer. Chem. Soc. 114:9217-9218), analogous organic syntheses of
small
compound libraries (Chen, et al. (1994) J. Amer. Chem. Soc. 116:2661),
oligocarbamates
(Cho, et al. (1993) Science 261:1303), and/or peptidyl phosphonates (Campbell,
et al. (1994)
J. Ors. Chem. 59:658). See, generally, Gordon, et al. (1994) J. Med. Chem.
37:1385, nucleic
acid libraries (see, e.g., Stratagene, Corp.), peptide nucleic acid libraries
(see, e.g., U.S.
Patent 5,539,083), antibody libraries (see, e.g., Vaughn, et al. (1996) Nature
Biotechnolo~y
14(3):309-314, and PCT/US96/10287), carbohydrate libraries (see, e.g., Liang,
et al. (1996)
Science 274:1520-1522, and U.S. Patent No. 5,593,853), and small organic
molecule libraries
(see, e.g., benzodiazepines, Baum (1993) C&EN, Jan 18, page 33; isoprenoids,
U.S. Patent
No. 5,569,588; thiazolidinones and metathiazanones, U.S. Patent No. 5,549,974;
pyrrolidines,
U.S. Patent Nos. 5,525,735 and 5,519,134; morpholino compounds, U.S. Patent
No.
5,506,337; benzodiazepines, U.S. Patent No. 5,288,514; and the like). .
Devices for the preparation of combinatorial libraries are commercially
available (see,
e.g., 357 MPS, 390 MPS, Advanced Chem Tech, Louisville KY, Symphony, Rainin,
Woburn, MA, 433A Applied Biosystems, Foster City, CA, 9050 Plus, Millipore,
Bedford,
MA).
A number of well known robotic systems have also been developed for solution
phase
chemistries. These systems include automated workstations like the automated
synthesis
apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and
many robotic
systems utilizing robotic arms (Zymate II, Zymark Corporation, Hopkinton,
Mass.; Orca,
Hewlett-Packaxd, Palo Alto, Calif.), which mimic the manual synthetic
operations performed
by a chemist. The above devices, with appropriate modification, are suitable
for use with the
present invention. In addition, numerous combinatorial libraries are
themselves
commercially available (see, e.g., ComGenex, Princeton, N.J., Asinex, Moscow,
Ru, Tripos,
Inc., St. Louis, MO, ChemStar, Ltd, Moscow, RU, 3D Pharmaceuticals, Exton, PA,
Martek
Biosciences, Columbia, MD, etc.).
The assays to identify modulators are amenable to high throughput screening.
Preferred assays thus detect modulation of lung cancer gene transcription,
polypeptide
expression, and polypeptide activity.
High throughput assays for evaluating the presence, absence, quantification,
or other
properties of particular nucleic acids or protein products are well known to
those of skill in
the art. Similarly, binding assays and reporter gene assays are similarly well
known. Thus,
e.g., U.S. Patent No. 5,559,410 discloses high throughput screening methods
for proteins,
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U.S. Patent No. 5,55,639 discloses high throughput screening methods for
nucleic acid
binding (i.e., in arrays), while U.S. Patent Nos. 5,576,220 and 5,541,061
disclose high
throughput methods of screening for ligand/antibody binding.
In addition, high throughput screening systems are commercially available
(see, e.g.,
Zymark Corp., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman
Instruments, Inc. Fullerton, CA; Precision Systems, Inc., Natick, MA, etc.).
These systems
typically automate procedures, including sample and reagent pipetting, liquid
dispensing,
timed incubations, and final readings of the microplate in detectors)
appropriate for the
assay. These configurable systems provide high throughput and rapid start up
as well as a
high degree of flexibility and customization. The manufacturers of such
systems provide
detailed protocols for various high throughput systems. Thus, e.g., Zymark
Corp. provides
technical bulletins describing screening systems for detecting the modulation
of gene
transcription, ligand binding, and the like.
In one embodiment, modulators are proteins, often naturally occurring proteins
or
1 S fragments of naturally occurring proteins. Thus, e.g., cellular extracts
containing proteins, or
random or directed digests of proteinaceous cellulax extracts, may be used. In
this way
libraries of proteins may be made for screening in the methods of the
invention. Particularly
preferred in this embodiment are libraries of bacterial, fungal, viral, and
mammalian proteins,
with the latter being preferred, and human proteins being especially
preferred. Particularly
useful test compound will be directed to the class of proteins to which the
target belongs, e.g.,
substrates for enzymes or Iigands and receptors.
In a preferred embodiment, modulators are peptides of from about S to about 30
amino acids, with from about 5 to about 20 amino acids being preferred, and
from about 7 to
about 15 being particularly preferred. The peptides may be digests of
naturally occurring
proteins, random peptides, or "biased" random peptides. By "randomized" or
grammatical
equivalents herein is meant that the nucleic acid or peptide consists of
essentially random
sequences of nucleotides and amino acids, respectively. Since these random
peptides (or
nucleic acids, discussed below) are often chemically synthesized, they may
incorporate a
nucleotide or amino acid at any position. The synthetic process can be
designed to generate
randomized proteins or nucleic acids, to allow the formation of all or most of
the possible
combinations over the length of the sequence, thus forming a library of
randomized candidate
bioactive proteinaceous agents.
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In one embodiment, the library is fully randomized, with no sequence
preferences or
constants at any position. In a preferred embodiment, the library is biased.
That is, some
positions within the sequence are either held constant, or are selected from a
limited number
of possibilities. In a preferred embodiment, the nucleotides or amino acid
residues are
S randomized within a defined class, e.g., of hydrophobic amino acids,
hydrophilic residues,
sterically biased (either small or large) residues, towards the creation of
nucleic acid binding
domains, the creation of cysteines, for cross-linking, prolines for SH-3
domains, serines,
threonines, tyrosines or histidines for phosphorylation sites, etc.
Modulators of lung cancer can also be nucleic acids, as defined above.
As described above generally for proteins, nucleic acid modulating agents may
be
naturally occurring nucleic acids, random nucleic acids, or "biased" random
nucleic acids.
Digests of procaryotic or eucaryotic genomes may be used as is outlined above
for proteins.
In a preferred embodiment, the candidate compounds are organic chemical
moieties, a
wide variety of which are available in the literature.
1 S After a candidate agent has been added and the cells allowed to incubate
for some
period of time, the sample containing a target sequence is analyzed. If
required, the target
sequence is prepared using known techniques. For example, the sample may be
treated to
lyse the cells, using known lysis buffers, electroporation, etc., with
purification and/or
amplification such as PCR performed as appropriate. For example, an in vitro
transcription
with labels covalently attached to the nucleotides is performed. Generally,
the nucleic acids
are labeled with biotin-FITC or PE, or with cy3 or cy5.
In a preferred embodiment, the target sequence is labeled with, e.g., a
fluorescent, a
chemiluminescent, a chemical, or a radioactive signal, to provide a means of
detecting the
target sequence's specific binding to a probe. The label also can be an
enzyme, such as,
alkaline phosphatase or horseradish peroxidase, which when provided with an
appropriate
substrate produces a product that can be detected. Alternatively, the label
can be a labeled
compound or small molecule, such as an enzyme inhibitor, that binds but is not
catalyzed or
altered by the enzyme. The label also can be a moiety or compound, such as, an
epitope tag
or biotin which specifically binds to streptavidin. For the example of biotin,
the streptavidin
is labeled as described above, thereby, providing a detectable signal for the
bound target
sequence. Unbound labeled streptavidin is typically removed prior to analysis.
Nucleic acid assays can be direct hybridization assays or can comprise
"sandwich
assays", which include the use of multiple probes, as is generally outlined in
U.S. Patent Nos.
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5,681,702, 5,597,909, 5,545,730, 5,594,117, 5,591,584, 5,571,670, 5,580,731,
5,571,670,
5,591,584, 5,624,802, 5,635,352, 5,594,118, 5,359,100, 5,124,246 and
5,681,697, all of
which are hereby incorporated by reference. In this embodiment, in general,
the target nucleic
acid is prepared as outlined above, and then added to the biochip comprising a
plurality of
nucleic acid probes, under conditions that allow the formation of a
hybridization complex.
A variety of hybridization conditions may be used in the present invention,
including
high, moderate and low stringency conditions as outlined above. The assays are
generally
run under stringency conditions which allow formation of the label probe
hybridization
complex only in the presence of target. Stringency can be controlled by
altering a step
parameter that is a thermodynamic variable, including, but not limited to,
temperature,
formamide concentration, salt concentration, chaotropic salt concentration,
pH, organic
solvent concentration, etc.
These parameters may also be used to control non-specific binding, as is
generally
outlined in U.S. Patent No. 5,681,697: Thus it may be desirable to perform
certain steps at
higher stringency conditions to reduce non-specific binding.
The reactions outlined herein may be accomplished in a variety of ways.
Components
of the reaction may be added simultaneously, or sequentially, in different
orders, with
preferred embodiments outlined below. In addition, the reaction may include a
variety of
other reagents. These include salts, buffers, neutral proteins, e.g., albumin,
detergents, etc.
which may be used to facilitate optimal hybridization and detection, and/or
reduce non-
specific or background interactions. Reagents that otherwise improve the
efficiency of the
assay, such as protease inhibitors, nuclease inhibitors, anti-microbial
agents, etc., may also be
used as appropriate, depending on the sample preparation methods and purity of
the target.
The assay data are analyzed to determine the expression levels, and changes in
expression levels as between states, of individual genes, forming a gene
expression profile.
Screens are performed to identify modulators of the lung cancer phenotype. In
one
embodiment, screening is performed to identify modulators that can induce or
suppress a
particular expression profile, thus preferably generating the associated
phenotype. In another
embodiment, e.g., for diagnostic applications, having identified
differentially expressed genes
important in a particular state, screens can be performed to identify
modulators that alter
expression of individual genes. In an another embodiment, screening is
performed to identify
modulators that alter a biological function of the expression product of a
differentially
expressed gene. Again, having identified the importance of a gene in a
particular state,
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screens are performed to identify agents that bind and/or modulate the
biological activity of
the gene product, or evaluate genetic polymorphisms.
Genes can be screened for those that are induced in response to a candidate
agent.
After identifying a modulator based upon its ability to suppress a lung cancer
expression
pattern leading to a normal expression pattern, or to modulate a single lung
cancer gene
expression profile so as to mimic the expression of the gene from normal
tissue, a screen as
described above can be performed to identify genes that are specifically
modulated in
response to the agent. Comparing expression profiles between normal tissue and
agent
treated lung cancer tissue reveals genes that are not expressed in normal
tissue or lung cancer
tissue, but are expressed in agent treated tissue. These agent-specific
sequences can be
identified and used by methods described herein for lung cancer genes or
proteins. In
particular these sequences and the proteins they encode find use in marking or
identifying
agent treated cells. In addition, antibodies can be raised against the agent
induced proteins
and used to target novel therapeutics to the treated lung cancer tissue
sample.
Thus, in one embodiment, a test compound is administered to a population of
lung
cancer cells, that have an associated lung cancer expression profile. By
"administration" or
"contacting" herein is meant that the candidate agent is added to the cells in
such a manner as
to allow the agent to act upon the cell, whether by uptake and intracellular
action, or by
action at the cell surface. In some embodiments, nucleic acid encoding a
proteinaceous
candidate agent (i.e., a peptide) may be put into a viral construct such as an
adenoviral or
retroviral construct, and added to the cell, such that expression of the
peptide agent is
accomplished, e.g., PCT US97/01019: Regulatable gene therapy systems can also
be used.
Once a test compound has been administered to the cells, the cells can be
washed if
desired and are allowed to incubate under preferably physiological conditions
for some
period of time. The cells are then harvested and a new gene expression profile
is generated,
as outlined herein.
Thus, e.g., lung cancer or non-malignant tissue may be screened for agents
that
modulate, e.g., induce or suppress a lung cancer phenotype. A change in at
least one gene,
preferably many, of the expression profile indicates that the agent has an
effect on lung
cancer activity. By defining such a signature for the lung cancer phenotype,
screens for new
drugs that alter the phenotype can be devised. With this approach, the drug
target need not be
known and need not be represented in the original expression screening
platform, nor does
the level of transcript for the target protein need to change.
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Measure of lung cancer polypeptide activity, or of lung cancer or the Lung
cancer
phenotype can be performed using a variety of assays. For example, the effects
of the test
compounds upon the function of the metastatic polypeptides can be measured by
examining
parameters described above. A suitable physiological change that affects
activity can be used
to assess the influence of a test compound on the polypeptides of this
invention,. When the
functional consequences are determined using intact cells or animals, one can
also measure a
variety of effects such as, in the case of lung cancer associated with tumors,
tumor growth,
tumor metastasis, neovascularization, hormone release, transcriptional changes
to both known
and uncharacterized genetic markers (e.g., northern blots), changes in cell
metabolism such as
cell growth or pH changes, and changes in intracellular second messengers such
as cGMP. In
the assays of the invention, mammalian lung cancer polypeptide is typically
used, e.g.,
mouse, preferably human.
Assays to identify compounds with modulating activity can be performed in
vitro.
For example, a lung cancer polypeptide is first contacted with a potential
modulator and
1 S incubated for a suitable amount of time, e.g., from 0.5 to 48 hours. In
one embodiment, the
lung cancer polypeptide levels are determined in vitro by measuring the level
of protein or
mRNA. The level of protein is typically measured using immunoassays such as
western
blotting, ELISA and the like with an antibody that selectively binds to the
lung cancer
polypeptide or a fragment thereof. For measurement of mRNA, amplification,
e.g., using
PCR, LCR, or hybridization assays, e.g., northern hybridization, RNAse
protection, dot
blotting, are preferred. The level of protein or mRNA is typically detected
using directly or
indirectly labeled detection agents, e.g., fluorescently or radioactively
labeled nucleic acids,
radioactively or enzymatically labeled antibodies, and the like, as described
herein.
Alternatively, a reporter gene system can be devised using a Lung cancer
protein
promoter operably linked to a reporter gene such as luciferase, green
fluorescent protein,
CAT, or (3-gal. The reporter construct is typically transfected into a cell.
After treatment
with a potential modulator, the amount of reporter gene transcription,
translation, or activity
is measured according to standard techniques known to those of skill in the
art.
In a preferred embodiment, as outlined above, screens may be done on
individual
genes and gene products (proteins). That is, having identified a particular
differentially
expressed gene as important in a particular state, screening of modulators of
the expression of
the gene or the gene product itself can be done. The gene products of
differentially expressed
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genes are sometimes referred to herein as "lung cancer proteins." The lung
cancer protein
may be a fragment, or alternatively, be the full length protein to a fragment
shown herein.
In one embodiment, screening for modulators of expression of specific genes is
performed. Typically, the expression of only one or a few genes are evaluated.
In another
S embodiment, screens are designed to first find compounds that bind to
differentially
expressed proteins. These compounds are then evaluated for the ability to
modulate
differentially expressed activity. Moreover, once initial candidate compounds
are identified,
variants can be further screened to better evaluate structure activity
relationships.
In a preferred embodiment, binding assays are done. In general, purified or
isolated
gene product is used; that is, the gene products of one or more differentially
expressed
nucleic acids are made. For example, antibodies are generated to the protein
gene products,
and standard immunoassays are run to determine the amount of protein present.
Alternatively,
cells comprising the lung cancer proteins can be used in the assays.
Thus, in a preferred embodiment, the methods comprise combining a lung cancer
protein and a candidate compound, and determining the binding of the compound
to the lung
cancer protein. Preferred embodiments utilize the human lung cancer protein,
although other
mammalian proteins may also be used, e.g., for the development of animal
models of human
disease. In some embodiments, as outlined herein, variant or derivative lung
cancer proteins
may be used.
Generally, in a preferred embodiment of the methods herein, the Lung cancer
protein
or the candidate agent is non-diffusably bound to an insoluble support,
preferably having
isolated sample receiving areas (e.g., a microtiter plate, an array, etc.).
The insoluble
supports may be made of a composition to which the compositions can be bound,
is readily
separated from soluble material, and is otherwise compatible with the overall
method of
screening. The surface of such supports may be solid or porous and of a
convenient shape.
Examples of suitable insoluble supports include microtiter plates, arrays,
membranes and
beads. These are typically made of glass, plastic (e.g., polystyrene),
polysaccharides, nylon
or nitrocellulose, teflonTM, etc. Microtiter plates and arrays are especially
convenient because
a large number of assays can be carried out simultaneously, using small
amounts of reagents
and samples. The particular manner of binding of the composition is typically
not crucial so
long as it is compatible with the reagents and overall methods of the
invention, maintains the
activity of the composition, and is nondiffusable. Preferred methods of
binding include the
use of antibodies (which do not sterically block either the ligand binding
site or activation
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sequence when the protein is bound to the support), direct binding to "sticky"
or ionic
supports, chemical crosslinking, the synthesis of the protein or agent on the
surface, etc.
Following binding of the protein or agent, excess unbound material is removed
by washing.
The sample receiving areas may then be blocked through incubation with bovine
serum
albumin (BSA), casein or other innocuous protein or other moiety.
In a preferred embodiment, the lung cancer protein is bound to the support,
and a test
compound is added to the assay. Alternatively, the candidate agent is bound to
the support
and the lung cancer protein is added. Novel binding agents include specific
antibodies, non-
natural binding agents identified in screens of chemical libraries, peptide
analogs, etc.~Of
particular interest are screening assays for agents that have a low toxicity
for human cells. A
wide variety of assays may be used for this purpose, including labeled in
vitro protein-protein
binding assays, electrophoretic mobility shift assays, immunoassays for
protein binding,
functional assays (phosphorylation assays, etc.) and the like.
The determination of the binding of the test modulating compound to the lung
cancer
protein may be done in a number of ways. In a preferred embodiment, the
compound is
labeled, and binding determined directly, e.g., by attaching all or a portion
of the lung cancer
protein to a solid support, adding a labeled candidate agent (e.g., a
fluorescent label), washing
off excess reagent, and determining whether the label is present on the solid
support. Various
blocking and washing steps may be utilized as appropriate.
In some embodiments, only one of the components is labeled, e.g., the proteins
(or
proteinaceous candidate compounds) can be labeled. Alternatively, more than
one
component can be labeled with different labels, e.g., l2sl for the proteins
and a fluorophor for
the compound. Proximity reagents, e.g., quenching or energy transfer reagents
are also
useful.
In one embodiment, the binding of the test compound is determined by
competitive
binding assay. The competitor may be a binding moiety known to bind to the
target molecule
(i.e., a lung cancer protein), such as an antibody, peptide, binding partner,
ligand, etc. Under
certain circumstances, there may be competitive binding between the compound
and the
binding moiety, with the binding moiety displacing the compound. In one
embodiment, the
test compound is labeled. Either the compound, or the competitor, or both, is
added first to
the protein for a time sufficient to allow binding, if present. Incubations
may be performed at
a temperature which facilitates optimal activity, typically between 4 and
40° C. Incubation
periods are typically optimized, e.g., to facilitate rapid high throughput
screening. Typically
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between 0.1 and 1 hour will be sufficient. Excess reagent is generally removed
or washed
away. The second component is then added, and the presence or absence of the
labeled
component is followed, to indicate binding.
In a preferred embodiment, the competitor is added first, followed by a test
compound. Displacement of the competitor is an indication that the test
compound is binding
to the lung cancer protein and thus is capable of binding to, and potentially
modulating, the
activity of the lung cancer protein. In this embodiment, either component can
be labeled.
Thus, e.g., if the competitor is labeled, the presence of label in the wash
solution indicates
displacement by the agent. Alternatively, if the test compound is labeled, the
presence of the
label on the support indicates displacement.
In an alternative embodiment, the test compound is added first, with
incubation and
washing, followed by the competitor. The absence of binding by the competitor
may indicate
that the test compound is bound to the lung cancer protein with a higher
affinity. Thus, if the
test compound is labeled, the presence of the label on the support, coupled
with a lack of d
1 S competitor binding, may indicate that the test compound is capable of
binding to the lung
cancer protein.
In a preferred embodiment, the methods comprise differential screening to
identity
agents that are capable of modulating the activity of the lung cancer
proteins. In one
embodiment, the methods comprise combining a lung cancer protein and a
competitor in a
first sample. A second sample comprises a test compound, a lung cancer
protein, and a
competitor. The binding of the competitor is determined for both samples, and
a change, or
difference in binding between the two samples indicates the presence of an
agent capable of
binding to the lung cancer protein and potentially modulating its activity.
That is, if the
binding of the competitor is different in the second sample relative to the
first sample, the
agent is capable of binding to the lung cancer protein.
Alternatively, differential screening is used to identify drug candidates that
bind to the
native lung cancer protein, but cannot bind to modified lung cancer proteins.
The structure of
the lung cancer protein may be modeled, and used in rational drug design to
synthesize agents
that interact with that site. Drug candidates that affect the activity of a
lung cancer protein
are also identified by screening drugs for the ability to either enhance or
reduce the activity of
the protein.
Positive controls and negative controls may be used in the assays. Preferably
control
and test samples are performed in at least triplicate to obtain statistically
significant results.
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Incubation of all samples is for a time sufficient for the binding of the
agent to the protein.
Following incubation, samples are washed free of non-specifically bound
material and the
amount of bound, generally labeled agent determined. For example, where a
radiolabel is
employed, the samples may be counted in a scintillation counter to determine
the amount of
bound compound.
A variety of other reagents may be included in the screening assays. These
include
reagents like salts, neutral proteins, e.g., albumin, detergents, etc. which
may be used to
facilitate optimal protein-protein binding and/or reduce non-specific or
background
interactions. Also reagents that otherwise improve the efficiency of the
assay, such as
protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be
used. The mixture
of components may be added in an order that provides fox the requisite
binding.
In a preferred embodiment, the invention provides methods for screening for a
compound capable of modulating the activity of a lung cancer protein. The
methods
comprise adding a test compound, as defined above, to a cell comprising lung
cancer
proteins. Preferred cell types include almost any cell. The cells contain a
recombinant
nucleic acid that encodes a lung cancer protein. In a preferred embodiment, a
library of
candidate agents are tested on a plurality of cells.
In one aspect, the assays are evaluated in the presence or absence or previous
or
subsequent exposure of physiological signals, e.g., hormones, antibodies,
peptides, antigens,
cytokines, growth factors, action potentials, pharmacological agents including
chemotherapeutics, radiation, carcinogenics, or other cells (e.g., cell-cell
contacts). In another
example, the determinations are determined at different stages of the cell
cycle process.
In this way, compounds that modulate lung cancer agents axe identified.
Compounds
with pharmacological activity are able to enhance or interfere with the
activity of the lung
cancer protein. Once identified, similar structures are evaluated to identify
critical structural
feature of the compound.
In one embodiment, a method of inhibiting lung cancer cell division is
provided. The
method comprises administration of a lung cancer inhibitor. In another
embodiment, a
method of inhibiting lung cancer is provided. The method may comprise
administration of a
lung cancer inhibitor. In a further embodiment, methods of treating cells or
individuals with
lung cancer are provided, e.g., comprising administration of a lung cancer
inhibitor.
In one embodiment, a lung cancer inhibitor is an antibody as discussed above.
In
another embodiment, the lung cancer inhibitor is an antisense molecule.
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A variety of cell growth, proliferation, viability, and metastasis assays are
known to
those of skill in the art, as described below.
Soft agar gy~owth or coloray forrnation in suspension
Normal cells require a solid substrate to attach and grow. When the cells are
transformed, they lose this phenotype and grow detached from the substrate.
For example,
transformed cells can grow in stirred suspension culture or suspended in semi-
solid media,
such as semi-solid or soft agar. The transformed cells, when transfected with
tumor
suppressor genes, regenerate normal phenotype and require a solid substrate to
attach and
grow. Soft agar growth or colony formation in suspension assays can be used to
identify
modulators of lung cancer sequences, which when expressed in host cells,
inhibit abnormal
cellular proliferation and transformation. A therapeutic compound would reduce
or eliminate
the host cells' ability to grow in stirred suspension culture or suspended in
semi-solid media,
such as semi-solid or soft.
Techniques for soft agar growth or colony formation in suspension assays are
described in Freshney (1994) Culture of Animal CeIIs a Manual of Basic
Techniaue (3rd ed.),
herein incorporated by reference. See also, the methods section of Garkavtsev,
et al. (1996),
supra, herein incorporated by reference.
Contact inhibition and density limitation of growth
Normal cells typically grow in a flat and organized pattern in a petri dish
until they
touch other cells. When the cells touch one another, they are contact
inhibited and stop
growing. When cells are transformed, however, the cells are not contact
inhibited and
continue to grow to high densities in disorganized foci. Thus, the transformed
cells grow to a
higher saturation density than normal cells. This can be detected
morphologically by the
formation of a disoriented monolayer of cells or rounded cells in foci within
the regular
pattern of normal surrounding cells. Alternatively, labeling index with (3H)-
thymidine at
saturation density can be used to measure density limitation of growth. See
Freshney (1994),
supra. The transformed cells, when transfected with tumor suppressor genes,
regenerate a
normal phenotype and become contact inhibited and would grow to a lower
density.
In this assay, labeling index with (3H)-thymidine at saturation density is a
preferred
method of measuring density limitation of growth. Transformed host cells are
transfected
with a lung cancer-associated sequence and are grown for 24 hours at
saturation density in
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non-limiting medium conditions. The percentage of cells labeling with (3H)-
thymidine is
determined autoradiographically. See, Freshney (1994), supra.
Growth factor or serum dependence
Transformed cells typically have a lower serum dependence than their normal
counterparts (see, e.g., Temin (1966) J. Natl. Cancer Insti. 37:167-175;
Eagle, et a1. (1970) J_.
Exu. Med. 131:836-879); Freshney, supra. This is in part due to release of
various growth
factors by the transformed cells. Growth factor or serum dependence of
transformed host
cells can be compared with that of control.
Tumor specific markers levels
Tumor cells release an increased amount of certain factors (hereinafter "tumor
specific markers") than their normal counterparts. For example, plasminogen
activator (PA)
is released from human glioma at a higher level than from normal brain cells
(see, e.g.,
Gullino, "Angiogenesis, tumor vascularization, and potential interference with
tumor growth"
in Mihich (ed. 1985) Biological Responses in Cancer, pp. 178-184). Similarly,
Tumor
angiogenesis factor (TAF) is released at a higher level in tumor cells than
their normal
counterparts. See, e.g., Folkman (1992) "Angiogenesis and Cancer" in Sem
Cancer Biol.).
Various techniques which measure the release of these factors are described in
Freshney (1994), supra. Also, see, Unkeless, et al. (1974) J. Biol. Chem.
249:4295-4305;
Strickland and Beers (I976) J. Biol. Chem. 251:5694-5702; Whur, et al. (I980)
Br. J. Cancer
42:305-312; Gullino, "Angiogenesis, tumor vascularization, and potential
interference with
tumor growth" in Mihich (ed. 1985) Biological Responses in Cancer, pp. 178-
184; Freshney
Anticancer Res. 5:111-130 (1985).
Invasiveness into Matrigel
The degree of invasiveness into Matrigel or some other extracellular matrix
constituent can be used as an assay to identify compounds that modulate lung
cancer-
associated sequences. Tumor cells exhibit a good correlation between
malignancy and
invasiveness of cells into Matrigel or some other extraceIIuIar matrix
constituent. In this
assay, tumorigenic cells are typically used as host cells. Expression of a
tumor suppressor
gene in these host cells would decrease invasiveness of the host cells.
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Techniques described in Freshney (1994), supra, can be used. Briefly, the
level of
invasion of host cells can be measured by using filters coated with Matrigel
or some other
extracellular matrix constituent. Penetration into the gel, or through to the
distal side of the
filter, is rated as invasiveness, and rated histologically by number of cells
and distance
moved, or by prelabeling the cells with lasl and counting the radioactivity on
the distal side of
the filter or bottom of the dish. See, e.g., Freshney (1984), supra.
Tumor growth in vivo
Effects of lung cancer-associated sequences on cell growth can be tested in
transgenic
or immune-suppressed mice. Knock-out transgenic mice can be made, in which the
lung
cancer gene is disrupted or in which a lung cancer gene is inserted. Knock-out
transgenic
mice can be made by insertion of a marker gene or other heterologous gene into
the
endogenous lung cancer gene site in the mouse genome via homologous
recombination.
Such mice can also be made by substituting the endogenous lung cancer gene
with a mutated
version of the lung cancer gene, or by mutating the endogenous lung cancer
gene, e.g., by
exposure to carcinogens.
A DNA construct is introduced into the nuclei of embryonic stem cells. Cells
containing the newly engineered genetic lesion are injected into a host mouse
embryo, which
is re-implanted into a recipient female. Some of these embryos develop into
chimeric mice
that possess germ cells partially derived from the mutant cell line.
Therefore, by breeding the
chimeric mice it is possible to obtain a new line of mice containing the
introduced genetic
lesion (see, e.g., Capecchi, et al. (1989) Science 244:1288). Chimeric
targeted mice can be
derived according to Hogan, et al. (1988) Manipulating the Mouse Embryo: A
Laboratory
Manual, Cold Spring Harbor Laboratory and Robertson (ed. 1987)
Teratocarcinomas and
Embryonic Stem Cells: A Practical Approach, , IRL Press, Washington, D.C.
Alternatively, various immune-suppressed or immune-deficient host animals can
be
used. For example, genetically athymic "nude" mouse (see, e.g., Giovanella, et
al. (1974) J.
Natl. Cancer Inst. 52:921), a SCID mouse, a thymectomized mouse, or an
irradiated mouse
(see, e.g., Bradley, et al. (1978) Br. J. Cancer 38:263; Selby, et al. (1980)
Br. J. Cancer 41:52)
can be used as a host. Transplantable tumor cells (typically about 106 cell)
injected into
isogenic hosts will produce invasive tumors in a high proportions of cases,
while normal cells
of similar origin will not. In hosts which developed invasive tumors, cells
expressing a lung
cancer-associated sequences are injected subcutaneously. After a suitable
length of time,
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preferably 4-8 weeks, tumor growth is measured (e.g., by volume or by its two
largest
dimensions) and compared to the control. Tumors that have statistically
significant reduction
(using, e.g., Student's T test) are said to have inhibited growth.
Polynucleotide modulators of lung cancer
Antisense and RNAi Polynucleotides
In certain embodiments, the activity of a lung cancer-associated protein is
downregulated, or entirely inhibited, by the use of antisense or an inhibitory
polynucleotide,
i.e., a nucleic acid complementary to, and which can preferably hybridize
specifically to, a
coding mRNA nucleic acid sequence, e.g., a lung cancer protein mRNA, or a
subsequence
thereof. Binding of the antisense polynucleotide to the mRNA reduces the
translation and/or
stability of the mRNA.
In the context of this invention, antisense polynucleotides can comprise
naturally-
occurring nucleotides, or synthetic species formed from naturally-occurring
subunits or their
close homologs. Antisense polynucleotides may also have altered sugar moieties
or inter-
sugar linkages. Exemplary among these are the phosphorothioate and other
sulfur containing
species which are known for use in the art. Analogs are comprehended by this
invention so
long as they function effectively to hybridize with the lung cancer protein
mRNA. See, e.g.,
Isis Pharmaceuticals, Carlsbad, CA; Sequitor, Inc., Natick, MA.
Such antisense polynucleotides can readily be synthesized using recombinant
means,
or can be synthesized in vitro. Equipment for such synthesis is sold by
several vendors,
including Applied Biosystems. The preparation of other oligonucleotides such
as
phosphorothioates and alkylated derivatives is also well known to those of
skill in the art.
Antisense molecules as used herein include antisense or sense
oligonucleotides.
Sense oligonucleotides can, e.g., be employed to block transcription by
binding to the anti-
sense strand. The antisense and sense oligonucleotide comprise a single-
stranded nucleic
acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or
DNA
(antisense) sequences for lung cancer molecules. A preferred antisense
molecule is for a lung
cancer sequence in the tables, or for a ligand or activator thereof. Antisense
or sense
oligonucleotides, according to the present invention, comprise a fragment
generally at least
about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability
to derive an
antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a
given protein
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is described in, e.g., Stein and Cohen (1988) Cancer Res. 48:2659 and van der
Krol, et al.
(1988) BioTechnidues 6:958).
RNA interference is a mechanism to suppress gene expression in a sequence
specific
manner. See, e.g., Brumelkamp, et al. (2002) Sciencexpress (2lMarch2002);
Sharp (1999)
Genes Dev. 13:139-141; and Cathew (2001) Curr. Op. Cell Biol. 13:244-248. In
mammalian
cells, short, e.g., 21 nt, double stranded small interfering RNAs (siRNA) have
been shown to
be effective at inducing an RNAi response. See, e.g., Elbashir, et al. (2001)
Nature 411:494-
498. The mechanism may be used to downregulate expression levels of identified
genes, e.g.,
treatment of or validation of relevance to disease.
Ribozymes
In addition to antisense polynucleotides, ribozymes can be used to target and
inhibit
transcription of lung cancer-associated nucleotide sequences. A ribozyme is an
RNA
molecule that catalytically cleaves other RNA molecules. Different kinds of
ribozymes have
been described, including group I ribozymes, hammerhead ribozymes, hairpin
ribozymes,
RNase P, and axhead ribozymes (see, e.g., Castanotto, et al. (1994) Adv. in
Pharmacolo~v
25: 289-317 for a general review of the properties of different ribozymes).
The general features of hairpin ribozymes are described, e.g., in Hampel, et
al. (1990)
Nucl. Acids Res. 18:299-304; European Patent Publication No. 0 360 257; U.S.
Patent No.
5,254,678. Methods of preparing are well known to those of skill in the art
(see, e.g., WO
94/26877; Ojwang, et al. (1993) Proc. Natl. Acad. Sci. USA 90:6340-6344;
Yamada, et al.
(1994) Human Gene Theranv 1:39-45; Leavitt, et al. (1995) Proc. Natl. Acad.
Sci. USA
92:699-703; Leavitt, et al. (19994) Human Gene Therany 5:11 S 1-120; and
Yamada, et al.
(1994) Virolo~y 205: 121-126).
Polynucleotide modulators of lung cancer may be introduced into a cell
containing the
target nucleotide sequence by formation of a conjugate with a ligand binding
molecule, as
described in WO 91/04753. Suitable ligand binding molecules include, but are
not limited to,
cell surface receptors, growth factors, other cytokines, or other ligands that
bind to cell
surface receptors. Preferably, conjugation of the ligand binding molecule does
not
substantially interfere with the ability of the ligand binding molecule to
bind to its
corresponding molecule or receptor, or block entry of the sense or antisense
oligonucleotide
or its conjugated version into the cell. Alternatively, a polynucleotide
modulator of lung
cancer may be introduced into a cell containing the target nucleic acid
sequence, e.g., by
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formation of an polynucleotide-lipid complex, as described in WO 90/10448. It
is
understood that the use of antisense molecules or knock out and knock in
models may also be
used in screening assays as discussed above, in addition to methods of
treatment.
Thus, in one embodiment, methods of modulating lung cancer in cells or
organisms
are provided. In one embodiment, the methods comprise administering to a cell
an anti-lung
cancer antibody that reduces or eliminates the biological activity of an
endogenous lung
cancer protein. Alternatively, the methods comprise administering to a cell or
organism a
recombinant nucleic acid encoding a lung cancer protein. This may be
accomplished in any
number of ways. In a preferred embodiment, e.g., when the lung cancer sequence
is down-
regulated in lung cancer, such state may be reversed by increasing the amount
of lung cancer
gene product in the cell. This can be accomplished, e.g., by overexpressing
the endogenous
lung cancer gene or administering a gene encoding the lung cancer sequence,
using known
gene-therapy techniques. In a preferred embodiment, the gene therapy
techniques include the
incorporation of the exogenous gene using enhanced homologous recombination
(EHR), e.g.,
as described in PCT/US93/03868, hereby incorporated by reference in its
entirety.
Alternatively, e.g., when the lung cancer sequence is up-regulated in lung
cancer, the activity
of the endogenous lung cancer gene is decreased, e.g., by the administration
of a lung cancer
antisense or RNAi nucleic acid.
In one embodiment, the lung cancer proteins of the present invention may be
used to
generate polyclonal and monoclonal antibodies to lung cancer proteins.
Similarly, the lung
cancer proteins can be coupled, using standard technology, to affinity
chromatography
columns. These columns may then be used to purify lung cancer antibodies
useful for
production, diagnostic, or therapeutic purposes. In a preferred embodiment,
the antibodies
are generated to epitopes unique to a lung cancer protein; that is, the
antibodies show little or
no cross-reactivity to other proteins. The lung cancer antibodies may be
coupled to standard
affinity chromatography columns and used to purify lung cancer proteins. The
antibodies
may also be used as blocking polypeptides, as outlined above, since they will
specifically
bind to the lung cancer protein.
Methods of identifying variant lung cancer-associated sequences
Without being bound by theory, expression of various lung cancer sequences is
correlated with lung cancer. Accordingly, disorders based on mutant or variant
lung cancer
genes may be determined. In one embodiment, the invention provides methods for
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identifying cells containing variant lung cancer genes, e.g., determining all
or part of the
sequence of at least one endogenous lung cancer genes in a cell. In a
preferred embodiment,
the invention provides methods of identifying the lung cancer genotype of an
individual, e.g.,
determining all or part of the sequence of at least one lung cancer gene of
the individual.
This is generally done in at least one tissue of the individual, and may
include the evaluation
of a number of tissues or different samples of the same tissue. The method may
include
comparing the sequence of the sequenced lung cancer gene to a known lung
cancer gene, i.e.,
a wild-type gene.
The sequence of all or part of the lung cancer gene can then be compared to
the
sequence of a known lung cancer gene to determine if any differences exist.
This can be
done using known homology programs, such as Bestfit, etc. In a preferred
embodiment, the
presence of a difference in the sequence between the lung cancer gene of the
patient and the
known lung cancer gene correlates with a disease state or a propensity for a
disease state, as
outlined herein.
I S In a preferred embodiment, the lung cancer genes are used as probes to
determine the
number of copies of the lung cancer gene in the genome.
In another preferred embodiment, the lung cancer genes are used as probes to
determine the chromosomal localization of the lung cancer genes. Information
such as
chromosomal localization finds use in providing a diagnosis or prognosis in
particular when
chromosomal abnormalities such as translocations, and the like are identified
in the lung
cancer gene locus.
Administration of pharmaceutical and vaccine compositions
In one embodiment, a therapeutically effective dose of a lung cancer protein
or
modulator thereof, is administered to a patient. By "therapeutically effective
dose" herein is
meant a dose that produces effects for which it is administered. The exact
dose will depend
on the purpose of the treatment, and will be ascertainable by one skilled in
the art using
known techniques (e.g., Ansel, et al. (1992) Pharmaceutical Dosage Forms and
Drug
Delivery; Lieberman, Pharmaceutical Dosage Forms (vols. 1-3), Dekker, ISBN
0824770846,
082476918X, 0824712692, 0824716981; Lloyd (1999) The Art, Science and
Technology
Pharmaceutical Compounding and Pickar (1999) Dosage Calculations). Adjustments
for
lung cancer degradation, systemic versus localized delivery, and rate of new
protease
synthesis, as well as the age, body weight, general health, sex, diet, time of
administration,
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drug interaction and the severity of the condition may be necessary, and will
be ascertainable
with routine experimentation by those skilled in the art.
A "patient" for the purposes of the present invention includes both humans and
other
animals, particularly mammals. Thus the methods are applicable to both human
therapy and
veterinary applications. In the preferred embodiment the patient is a mammal,
preferably a
primate, and in the most preferred embodiment the patient is human.
The administration of the lung cancer proteins and modulators thereof of the
present
invention can be done in a variety of ways, including, but not limited to,
orally,
subcutaneously, intravenously, intranasally, transdermally, intraperitoneally,
intramuscularly,
intrapulmonary, vaginally, rectally, or intraocularly. In some instances,
e.g., in the treatment
of wounds and inflammation, the lung cancer proteins and modulators may be
directly
applied as a solution or spray.
The pharmaceutical compositions of the present invention comprise a lung
cancer
protein in a form suitable for administration to a patient. In the preferred
embodiment, the
pharmaceutical compositions are in a water soluble form, such as being present
as
pharmaceutically acceptable salts, which is meant to include both acid and
base addition
salts. "Pharmaceutically acceptable acid addition salt" refers to those salts
that retain the
biological effectiveness of the free bases and that are not biologically or
otherwise
undesirable, formed with inorganic acids such as hydrochloric acid,
hydrobromic acid,
sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids
such as acetic acid,
propionic acid, glycolic acid, pyruvic acid, oxalic acid, malefic acid,
malonic acid, succinic
acid, fumaric acid, tartaxic acid, citric acid, benzoic acid, cinnamic acid,
mandelic acid,
methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic
acid and the like.
"Pharmaceutically acceptable base addition salts" include those derived from
inorganic bases
such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc,
copper,
manganese, aluminum salts and the like. Particularly preferred are the
ammonium,
potassium, sodium, calcium, and magnesium salts. Salts derived from
pharmaceutically
acceptable organic non-toxic bases include salts of primary, secondary, and
tertiary amines,
substituted amines including naturally occurring substituted amines, cyclic
amines and basic
ion exchange resins, such as isopropylamine, trimethylamine, diethylamine,
triethylamine,
tripropylamine, and ethanolamine.
The pharmaceutical compositions may also include one or more of the following:
carrier proteins such as serum albumin; buffers; fillers such as
microcrystalline cellulose,
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lactose, corn and other starches; binding agents; sweeteners and other
flavoring agents;
coloring agents; and polyethylene glycol.
The pharmaceutical compositions can be administered in a variety of unit
dosage
forms depending upon the method of administration. For example, unit dosage
forms
suitable for oral administration include, but are not limited to, powder,
tablets, pills, capsules
and lozenges. It is recognized that lung cancer protein modulators (e.g.,
antibodies, antisense
constructs, ribozymes, small organic molecules, etc.) when administered
orally, should be
protected from digestion. This is typically accomplished either by complexing
the
molecules) with a composition to render it resistant to acidic and enzymatic
hydrolysis, or by
packaging the molecules) in an appropriately resistant carrier, such as a
liposome or a
protection barner. Means of protecting agents from digestion are well known in
the art.
The compositions for administration will commonly comprise a lung cancer
protein
modulator dissolved in a pharmaceutically acceptable carrier, preferably an
aqueous carrier.
A variety of aqueous carriers can be used, e.g., buffered saline and the like.
These solutions
are sterile and generally free of undesirable matter. These compositions may
be sterilized by
conventional, well known sterilization techniques. The compositions may
contain
pharmaceutically acceptable auxiliary substances as required to approximate
physiological
conditions such as pH adjusting and buffering agents, toxicity adjusting
agents and the like,
e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride,
sodium lactate
and the like. The concentration of active agent in these formulations can vary
widely, and
will be selected primarily based on fluid volumes, viscosities, body weight
and the like in
accordance with the particular mode of administration selected and the
patient's needs (e.g.,
Remington's Pharmaceutical Science (15th ed., 1980) and Hardman, et al. (eds.
1996)
Goodman and Gilman: The Pharmacologial Basis of Therapeutics).
Thus, a typical pharmaceutical composition for intravenous administration
would be
about 0.1 to 10 mg per patient per day. Dosages from 0.1 up to about 100 mg
per patient per
day may be used, particularly when the drug is administered to a secluded site
and not into
the blood stream, such as into a body cavity or into a lumen of an organ.
Substantially higher
dosages are possible in topical administration. Actual methods for preparing
parenterally
administrable compositions will be known or apparent to those skilled in the
art, e.g.,
Remin~ton's Pharmaceutical Science and Goodman and Gilman, The Pharmacologial
Basis
of Therapeutics, supra.
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The compositions containing modulators of lung cancer proteins can be
administered
for therapeutic or prophylactic treatments. In therapeutic applications,
compositions are
administered to a patient suffering from a disease (e.g., a cancer) in an
amount sufficient to
cure or at least partially arrest the disease and its complications. An amount
adequate to
accomplish this is defined as a "therapeutically effective dose." Amounts
effective for this
use will depend upon the severity of the disease and the general state of the
patient's health.
Single or multiple administrations of the compositions may be administered
depending on the
dosage and frequency as required and tolerated by the patient. In any event,
the composition
should provide a sufficient quantity of the agents of this invention to
effectively treat the
patient. An amount of modulator that is capable of preventing or slowing the
development of
cancer in a mammal is referred to as a "prophylactically effective dose." The
particular dose
required for a prophylactic treatment will depend upon the medical condition
and history of
the mammal, the particular cancer being prevented, as well as other factors
such as age,
weight, gender, administration route, efficiency, etc. Such prophylactic
treatments may be
used, e.g., in a mammal who has previously had cancer to prevent a recurrence
of the cancer,
or in a mammal who is suspected of having a significant likelihood of
developing cancer
based, at least in part, upon gene expression profiles. Vaccine strategies may
be used, in
either a DNA vaccine form, or protein vaccine.
It will be appreciated that the present lung cancer protein-modulating
compounds can
be administered alone or in combination with additional lung cancer modulating
compounds
or with other therapeutic agent, e.g., other anti-cancer agents or treatments.
In numerous embodiments, one or more nucleic acids, e.g., polynucleotides
comprising nucleic acid sequences set forth in the tables, such as antisense
or RNAi
polynucleotides or ribozymes, will be introduced into cells, in vitro or ira
vivo. The present
invention provides methods, reagents, vectors, and cells useful for expression
of lung cancer-
associated polypeptides and nucleic acids using ih vitro (cell-free), ex vivo,
or in vivo (cell or
organism-based) recombinant expression systems.
The particular procedure used to introduce the nucleic acids into a host cell
for
expression of a protein or nucleic acid is application specific. Many
procedures for
introducing foreign nucleotide sequences into host cells may be used. These
include the use
of calcium phosphate transfection, spheroplasts, electroporation, liposomes,
microinjection,
plasma vectors, viral vectors and other well known methods for introducing
cloned genomic
DNA, cDNA, synthetic DNA or other foreign genetic material into a host cell
(see, e.g.,
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Berger and Kimmel, Guide to Molecular Cloning Techniques, Methods in Enz
n~ology
volume 152 (Berger), Ausubel, et al. (eds. 1999) Current Protocols
(supplemented through
1999), and Sambrook, et al. (1989) Molecular Cloning,-A Laboratory Manual (2nd
ed., Vol.
1-3).
In a preferred embodiment, lung cancer proteins and modulators are
administered as
therapeutic agents, and can be formulated as outlined above. Similarly, lung
cancer genes
(including both the full-length sequence, partial sequences, or regulatory
sequences of the
lung cancer coding regions) can be administered in a gene therapy application.
These lung
cancer genes can include antisense or inhibitory applications, e.g., as
inhibitory RNA or gene
therapy (e.g., for incorporation into the genome) or as antisense
compositions.
Lung cancer polypeptides and polynucleotides can also be administered as
vaccine
compositions to stimulate HTL, CTL, and antibody responses.. Such vaccine
compositions
can include, e.g., lipidated peptides (see, e.g.,Vitiello, et al. (1995) J.
Clin. Invest. 95:341),
peptide compositions encapsulated in poly(DL-lactide-co-glycolide) ("PLG")
microspheres
(see, e.g., Eldridge, et al. (1991) Molec. Immunol. 28:287-294; Alonso, et al.
(1994) Vaccine
12:299-306; Jones, et al. (1995) Vaccine 13:675-681), peptide compositions
contained in
immune stimulating complexes (ISCOMS) (see, e.g., Takahashi, et al. (1990)
Nature
344:873-875; Hu, et al. (1998) Clin Exp Immunol. 113:235-243), multiple
antigen peptide
systems (MAPs) (see, e.g., Tam (1988) Proc. Natl. Acad. Sci. U.S.A. 85:5409-
5413; Tam
(1996) J. Immunol. Methods 196:17-32), peptides formulated as multivalent
peptides;
peptides for use in ballistic delivery systems, typically crystallized
peptides, viral delivery
vectors (Perkus, et al., p. 379 In: Kaufinann (ed. 1996) Concepts in vaccine
development;
Chakrabarti, et al. (1986) Nature 320:535; Hu, et al. (1986) Nature 320:537;
Kieny, et al.
(1986) AIDS Bio/Technolo~v 4:790; Top, et al. (1971) J. Infect. Dis. 124:148;
Chanda, et al.
(1990) Virolo~v 175:535), particles of viral or synthetic origin (see, e.g.,
Kofler, et al. (1996)
J. Immunol. Methods 192:25; Eldridge, et al. (1993) Sem. Hematol. 30:16; Falo,
et al. (1995)
Nature Med. 7:649), adjuvants (Warren, et al. (1986) Annu. Rev. Immunol.
4:369; Gupta, et
al. (1993) Vaccine 11:293), liposomes (Reddy, et al. (1992) J. Immunol.
148:1585; Rock
(1996) Immunol. Today 17:131), or, naked or particle absorbed cDNA (Ulmer, et
al. (1993)
Science 259:1745; Robinson, et al. (1993) Vaccine 11:957; Shiver, et al., p.
423 In:
Kaufinann (ed. 1996) Concepts in vaccine development; Cease and Berzofsky
(1994) Annu.
Rev. Immunol. 12:923 and Eldridge, et al. (1993) Sem. Hematol. 30:16). Toxin-
targeted
78
CA 02444691 2003-10-17
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delivery technologies, also known as receptor mediated targeting, such as
those of Avant
Immunotherapeutics, Inc. (Needham, Massachusetts) may also be used.
Vaccine compositions often include adjuvants. Many adjuvants contain a
substance
designed to protect the antigen from rapid catabolism, such as aluminum
hydroxide or
mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella
pertussis or
Mycobacterium tuberculosis derived proteins. Certain adjuvants are
commercially available
as, e.g., Freund's Incomplete Adjuvant and Complete Adjuvant (Difco
Laboratories, Detroit,
MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline
Beecham, Philadelphia, PA); aluminum salts such as aluminum hydroxide gel
(alum) or
aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of
acylated
tyrosine; acylated sugars; cationically or anionically derivatized
polysaccharides;
polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil
A.
Cytokines, such as GM-CSF, interleukin-2, -7, -12, and other like growth
factors, may also be
used as adjuvants.
Vaccines can be administered as nucleic acid compositions wherein DNA or RNA
encoding one or more of the polypeptides, or a fragment thereof, is
administered to a patient.
This approach is described, for instance, in Wolff, et. al. (1990) Science
247:1465 as well as
U.S. Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524;
5,679,647; WO
98104720; and in more detail below. Examples of DNA-based delivery
technologies include
"naked DNA", facilitated (bupivicaine, polymers, peptide-mediated) delivery,
cationic lipid
complexes, and particle-mediated ("gene gun") or pressure-mediated delivery
(see, e.g., U.S.
Patent No. 5,922,687).
For therapeutic or prophylactic immunization purposes, the peptides of the
invention
can be expressed by viral or bacterial vectors. Examples of expression vectors
include
attenuated viral hosts, such as vaccinia or fowlpox. This approach involves
the use of
vaccinia virus, e.g., as a vector to express nucleotide sequences that encode
lung cancer
polypeptides or polypeptide fragments. Upon introduction into a host, the
recombinant
vaccinia virus expresses the immunogenic peptide, and thereby elicits an
immune response.
Vaccinia vectors and methods useful in immunization protocols are described
in, e.g., U.S.
Patent No. 4,722,848. Another vector is BCG (Bacille Calmette Guerin). BCG
vectors are
described in Stover, et al. (1991) Nature 351:456-460. A wide variety of other
vectors useful
for therapeutic administration or immunization e.g., adeno and adeno-
associated virus
vectors, retroviral vectors, Salmonella typhi vectors, detoxified anthrax
toxin vectors, and the
79
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
like, will be apparent to those skilled in the art from the description herein
(see, e.g., Shata, et
al. (2000) Mol Med Today 6:66-71; Shedlock, et al. (2000) J. Leukoc. Biol.
68:793-806;
Hipp, et al. (2000) In Vivo 14:571-85).
Methods for the use of genes as DNA vaccines are well known, and include
placing a
lung cancer gene or portion of a lung cancer gene under the control of a
regulatable promoter
or a tissue-specific promoter for expression in a lung cancer patient. The
lung cancer gene
used for DNA vaccines can encode full-length lung cancer proteins, but more
preferably
encodes portions of the lung cancer proteins including peptides derived from
the lung cancer
protein. In one embodiment, a patient is immunized with a DNA vaccine
comprising a
plurality of nucleotide sequences derived from a lung cancer gene. For
example, lung cancer-
associated genes or sequence encoding subfragments of a lung cancer protein
are introduced
into expression vectors and tested for their immunogenicity in the context of
Class I MHC
and an ability to generate cytotoxic T cell responses. This procedure provides
for production
of cytotoxic T cell responses against cells which present antigen, including
intracellular
epitopes.
In a preferred embodiment, DNA vaccines include a gene encoding an adjuvant
molecule with the DNA vaccine. Such adjuvant molecules include cytokines that
increase
the immunogenic response to the lung cancer polypeptide encoded by the DNA
vaccine.
Additional or alternative adjuvants are available.
In another preferred embodiment lung cancer genes find use in generating
animal
models of lung cancer. When the lung cancer gene identified is repressed or
diminished in
metastatic tissue, gene therapy technology, e.g., wherein antisense or
inhibitory RNA directed
to the lung cancer gene will also diminish or repress expression of the gene.
Animal models
of lung cancer find use in screening for modulators of a lung cancer-
associated sequence or
modulators of lung cancer. Similarly, transgenic animal technology including
gene knockout
technology, e.g., as a result of homologous recombination with an appropriate
gene targeting
vector, will result in the absence or increased expression of the lung cancer
protein. When
desired, tissue-specific expression or knockout of the lung cancer protein may
be necessary.
It is also possible that the lung cancer protein is overexpressed in lung
cancer. As
such, transgenic animals can be generated that overexpress the lung cancer
protein.
Depending on the desired expression level, promoters of various strengths can
be employed
to express the transgene. Also, the number of copies of the integrated
transgene can be
determined and compared for a determination of the expression level of the
transgene.
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Animals generated by such methods will find use as animal models of lung
cancer and are
additionally useful in screening for modulators to treat lung cancer.
Kits fox Use in Diagnostic and/or Prognostic Applications
For use in diagnostic, research, and therapeutic applications suggested above,
kits are
also provided by the invention. In diagnostic and research applications such
kits may include
at least one of the following: assay reagents, buffers, lung cancer-specific
nucleic acids or
antibodies, hybridization probes andlor primers, antisense polynucleotides,
ribozymes, RNAi,
dominant negative lung cancer polypeptides or polynucleotides, small molecule
inhibitors of
lung cancer-associated sequences, etc. A therapeutic product may include
sterile saline or
another pharmaceutically acceptable emulsion and suspension base.
In addition, the kits may include instructional materials containing
instructions (e.g.,
protocols) for the practice of the methods of this invention. While the
instructional materials
typically comprise written or printed materials they are not limited to such.
A medium
capable of storing such instructions and communicating them to an end user is
contemplated
by this invention. Such media include, but are not limited to electronic
storage media (e.g.,
magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and
the like. Such
media may include addresses to Internet sites that provide such instructional
materials.
The present invention also provides for kits for screening for modulators of
lung
cancer-associated sequences. Such kits can be prepared from readily available
materials and
reagents. For example, such kits can comprise one or more of the following
materials: a lung
cancer-associated polypeptide or polynucleotide, reaction tubes, and
instructions for testing
lung cancer-associated activity. Optionally, the kit contains biologically
active lung cancer
protein. A wide variety of kits and components can be prepared according to
the present
invention, depending upon the intended user of the kit and the particular
needs of the user.
Diagnosis would typically involve evaluation of a plurality of genes or
products. The genes
typically will be selected based on correlations with important parameters in
disease which
may be identified in historical or outcome data.
81
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EXAMPLES
Example 1: Gene Chip Analysis
Molecular profiles of various normal and cancerous tissues were determined and
analyzed using gene chips. RNA was isolated and gene chip analysis was
performed as
described (Glynne, et al. (2000) Nature 403:672-676; Zhao, et al. (2000) Genes
Dev. 14:981=
993).
82
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Tables 1A and 1 B were previously filed on April 18, 2001 in USSN 601284,770
(18501-001500US) and on November 29, 2001 in USSN 601334,370
(18501-001520US)
J Table
1A
Pkey ExAccnUnigenelDUnigene Title 70% chron190%70% SQADI90%
NL NL
100134D13264Hs.49macrophage scavengerreceptorl1.61 0.74
100780HG3731-HT4001 """Immunoglobulin 2.68 3.28
Heavy Chain, Vdjrc
Reg
100971J02874Hs.83213fatty acid binding 1.96 0.14
protein 4; adipocyte
1 101088L05568Hs.553solute carrier family0.79 0.07
~ 6 (neurolransmitte
101102L07594Hs.79059transforming growth 2.55 1
factor; beta recepto
101168L15388Hs.211569G protein-coupled 0.88 0.27
receptor kinase
5
101277L38486Hs.118223microfibrillar-associated0.89 0.26
protein 4
101330L43821Hs.80261enhanceroffilamentation0.59 0.29
1 (cas-like do
I 101336L49169Hs.75678FBJ murine osteosarcoma1.15 0.41
S viral oncogene h
101345L76380Hs.152175calcitonin receptor-like0.81 0.31
101678M62505Hs.2161complement component1.31 0.77
5 receptor 1 (C5a
I
101764M80563Hs.81256S100 calcium-binding1.44 0.82
protein A4 (calcium
101771M81750Hs.153837myeloid cell nuclear0.96 0.45
differentiation
ant
101842M93221Hs.75182mannose receptor, 1.27 0.37
C type f
102283U31384Hs.83381guanine nucleotide 1.04 0.3
binding protein
11
102363U39447Hs.198241amine oxidase; copper0.96 0.26
containing 3 (vase
102507U52154Hs.193044potassium inwardly-rectifying2.81 3.45
channel; s
102698U75272Hs.1867progastricsin (pepsinogen0.95 0.23
C)
103025X54131Hs.123641proteintyrosine phosphatase;receptort1.62 0.21
103280X79981Hs.76206cadherin 5; VE-cadhedn0.9 0.41
(vascular epithe
103496Y09267Hs.132821flavin containing 1.27 0.49
monooxygenase 2
103541211697Hs.79197CD83 antigen (activated1.86 1
, ~ B lymphocytes; 1
103554218951Hs.74034caveolin 1; caveolae1.27 0.47
protein; 22kD
3 104212AB002298Hs.173035KIAA030D protein 1.17 0.16
~
104691AA011176Hs.37744ESTs 1.08 0.35
104825AA035613Hs.141883ESTs 0.75 0.27
104857AA043219Hs.19058ESTs 2.6 3.3
104865AA045136Hs.22575ESTs 1.23 0.49
35104989AA102098Hs.118615ESTs 0.63 0.32
105729AA292694Hs.3807ESTs; Weakly similar0.86 0.34
to PHOSPHOLEMMAN
PR
105847AA398606Hs.32241ESTs 1.32 0.4
105894AA400979Hs.25691calcitonin receptor-like0.78 0.28
receptor activi
106490AA451861Hs.115537ESTs; Weakly similar1.2 0.47
to dipeptidase prec
106536AA453997Hs.23804ESTs 0.82 0.15
106605AA457718Hs.21103Homo sapiens mRNA; 0.99 0.07
cDNA DKFZp564B076
(fr
106667AA461086Hs.16578ESTs 1.17 0.4
106773AA478109Hs.188833ESTs 1.46 0.43
106797AA478962Hs.169943ESTs 1.18 0.32
45106844AA485055Hs.158213sperm associated 0.98 0.51
antigen 6
106870AA487576Hs.26530serum deprivation 1.05 0.14
response (phosphatidyl
106954AAd96980Hs.204038ESTs 1.25 0.33
107054AA600150Hs.14366ESTs 1.11 0.4
107292T30407Hs.4789ESTs; Weakly similar1.07 2.58
to oxidative.stress
107994AA036811Hs.165030ESTs 0.7 0.21
107997AA037388Hs.82223Human DNA sequence 1.02 0.48
from clone 141 H5
on c
108041AA041552Hs.61957ESTs 1.44 0.51
108087AA045709Hs.40545ESTs 1.98 1
f AA074885Hs.67726macrophage receptor 1.52 0.72
06382 with collagenous
str
55108435AA078787Hs.194101ESTs 2.53 1.53
108480AA081093Hs.68055ESTs 1.56 0.48
109252AA194830Hs.85944ESTs , 2.69 3.18
109550F01534Hs.26981ESTs 1.19 0.65
109613F03031Hs.27519ESTs 1.01 0.29
60109837H00656Hs.29792ESTs 0.81 0.15
109893H04768Hs.30484ESTs 1.44 0.32
109984H09594Hs.10299ESTs 0.62 0.14
110099H16568Hs.23748ESTs 1.01 0.28
110837N30796Hs.17424ESTs; Weakly similar1.1 0.22
to semaphorin F
[H.
65111247N69825Hs.16762Homo sapiens mRNA; 1.26 0.26
cDNA DKFZp564B2062
(f
111341N80935Hs.22483ESTs 1.57 0.52
111510807856Hs.16355ESTs 3.96 1
111737825410Hs.9218ESTs 0.97 0.24
1f3f95T57112 """yc20g11.s1Stratagenelung(#937210)1.22 0.35
.
113238T62979Hs.189813ESTs 2.27 0.45
113540T90496Hs.16757ESTs 1.06 0.22
113552T90889Hs.16026ESTs 1.16 0.42
113606T93093Hs.17125ESTs 1.48 0.7
113695T96965Hs.17948ESTs 1.54 0.28
75113946W84753Hs.37896ESTs 1.79 0.72
114251239898Hs.21948ESTs 1.95 0.25
114359241589Hs.153483ESTs; Moderately 1.42 0.13
similar to H1 chloride
115230AA278300Hs.182980ESTs 2.62 0.42
115279AA279760Hs.63671ESTs 1.79 0.91
8~115566AA398083Hs.43977ESTs 0.86 0.2
115965AA446661Hs.173233ESTs 0.79 0.04
116166AA461556Hs.202949KIAA1102 protein 2.29 0.68
116279AA486073Hs.57362ESTs 2.27 0.78
117023H88157Hs.411D5ESTs 1.36 0.16
83
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
117209H99959 Hs.42768ESTs 1.46 0.48
118901N90719 Hs.94445ESTs 1.51 1
118981' N93839Hs.39288ESTs 1.34 0.48
119073832894 Hs.45514vets avian erythroblastosis1.14 0.27
virus E26 0
119221898105 """yr30g11.s1 Soares1.32 0.53
fetal liver spleen
119824W74536 Hs.184advanced glycosylation1 0.19
end product-speci
119861W80715 ESTs; Moderately 1.83 0.45
similar to !!!!
ALU SUB
120041W92775 Hs.59368ESTs 1.23 0.55
120132238839 Hs.125019ESTs; Highly similar0.91 0.37
to KIAA0886 protein
1 120467AA251579Hs.187628ESTs 1.87 1.91
~
121314AA402799Hs.182538ESTs 1.3 0.31
121643AA417078Hs.193767ESTs 2.31 0.68
121690AA418074Hs.iESTs 1.47 0.51
10286
122633AA454080Hs.34853inhibitor of DNA 1.31 0.63
binding 4; dominant
neg
1 123978C20653 Hs.170278ESTs 1.52 0.32
124214H58608 Hs.151323ESTs 0.93 0.35
124357N22401 """yw37g07.s1 Morton1.29 1
Fetal Cochlea Homo
124438N40188 Hs.102550ESTs 1.36 0.7
125167W45560 Hs.102541ESTs 1.46 0.69
125174W51835 Hs.231082EST 3.07 3.76
125422AA903229Hs.153717ESTs 1.34 0.3
125561AI417667Hs.22978ESTs 1.89 0.63
125831D60988 """HUM145t309B Clontech0.94 0.36
human fetal brain
127002835380 Hs.24979ESTs 3.02 4.06
127307AA369367Hs.126712ESTs; Weakly similar1.01 0.69
to pIL2 hypothetica
127609AA622559Hs.150318ESTs 1.21 0.32
127959AI302471Hs.124292ESTs 2.5 1
128458D52193 Hs.56340ESTs 1.13 0.33
128624AA479209Hs.i02647ESTs 1.45 0.58
128789AA486567Hs.105695ESTs 1.1 0.34
128798AF014958Hs.105938chemokine (GC motif)1.16 0.55
receptor-like 2
128952851076 Hs.f0736fESTs; Highly similar2.04 2.4
to Rapt interaoting
129057X62466 Hs.214742CDW52 antigen (CAMPATH-11.77 0.73
antigen)
129210AA401654Hs.202949KIAA1102 protein 1.11 0.36
35129240W24360 Hs.237868interleukin 7 receptor0.91 0.41
129402T63781 """yc2lgOt.s1 Stratagenelung(#937210)1.36 0.93
129565X77777 Hs.198726vasoactive intestinal0.67 0.08
peptide receptor
1
129593AA487015Hs.983i4Homo Sapiens mRNA; 1.3 O.d2
cDNA DKFZp586L0120
(f
129626AA447410Hs.11712ESTs; Weakly similar1.28 0.46
to !!!! ALU SUBFAMI
4~129699AA458578Hs.12017KIAA0439 protein; 1.58 1
homolog of yeast
ubiqu
129898N48595 Hs.13256ESTs 1.13 0.53
129958L20591 Hs.1378annexin A3 0.81 0.31
130273059914 Hs.153863MAD (mothers against0.59 0.22
decapentaplegic;
Dr
130655N92934 Hs.17409cysteine-rich protein1.44 0.76
1 (intestinal)
45130657T94452 Hs.201591ESTs 0.96 0.42
131061N64328 Hs.22567ESTs; Moderately 1.51 0.45
similar to HYPOTHETICAL
131066F09006 Hs.22588ESTs 0.97 0.37
131263838334 Hs.24950regulator of G-protein2.34 2.82
signalling 5
131569052100 Hs.29191epithelial membrane 1.2 0.62
protein 2
131686AA157428Hs.30687Grb2-associated binder0.95 0.38
2
131751H18335 Hs.31562ESTs 1.47 0.52
132430T23630 Hs.258675EST 1.86 2.09
132476N67192 Hs.49476Homo Sapiens clone 1.73 0.58
TUAB Cri-du-chat
regi
132836F09557 Hs.57929slit (Drosophila) 0.91 0.29
homolog 3
5 133120X64559 Hs.65424tetranectin (plasminogen-binding0.82 0.2
S protein
133488D45370 Hs.74120adipose specific 1.29 0.48
2
133565N57056 Hs.204831ESTs 2.25 0.57
133651097105 Hs.173381dihydropyrimidinase-like1.65 0.62
2
133835AA059489Hs.76640ESTs; Highly similar1.16 0.34
to RGG32 [R.norveg
133978W73859 Hs.78061transcription factor0.79 0.27
21
133985L34657 Hs.78146plateletlendothelial0.99 0.28
cell adhesion moiec
134299AA487558Hs.8135ESTs 1.02 0.46
134300081984 Hs.166082endothelial PAS domain0.86 0.42
protein 1,
134323AA028976Hs.8175Homo Sapiens mRNA; 1.19 0.27
cDNA DKFZp564M0763
(f
65134343D50683 Hs.82028transforming growth 1.21 0.67
factor; beta recepto
134417D87969 Hs.82921solute carrier family1.26 1
35 (CMP-static act
134561076421 Hs.85302adenosine deaminase;2.12 0.55
RNA-specific; B1
(h
134624W67147 Hs.8700deleted in liver 2.35 2.74
cancer 1
134696H88354 Hs.8861ESTs 1.35 0.33
7O134749L10955 Hs.B9485carbonic anhydrase 0.89 0.2
IV
134786L06139 Hs.89640TEK tyrosine kinase;0.48 0.21
endothelial (venous
134869T35288 Hs.90421ESTs; Moderately 2.14 2.64
similar to !!!!
ALU SUB
135346M21056 Hs.992phospholipaseA2; 0.63 O.i3
group IB (pancreas)
100113D00591 Hs.84746Chromosome condensation1 2.15
1
75100147D13666 Hs.136348Homo Sapiens mRNA 0.5 2
for osteoblast specifi
100280D42085 Hs.155314KIAA0095 gene product1.02 1.39
100335063391 Hs.6793platelef-activating 1 5.58
factor acetylhydrola
100360D78335 Hs.75939Uridine monophosphate0.91 2.04
kinase
100372D79997 Hs.184339KIAA0175 gene product0.75 2.03
8~100486HG1112-HT1112 TIGR: ras-like protein1.09 1.93
TC4
100559HG2197-HT2267 "collagen, type VII,0.97 3.6
alpha 1"
100576HG2290-HT2386 "calcitoninlalpha-CGRP,1 1
alt, transcript
100668HG2981-HT3938 'TIGR: CD44 (epican,0.85 1.9
alt. transcript
12
100906HG4716-HT5158 Guanosine 5'-Monophosphate1.18 2.29
Synthase
g 100930HG721-HT4827 'TIGR: placental 1 1.45
5 protein 14, endometrial
84
CA 02444691 2003-10-17
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02/086443
100960J00124Hs.117729keratin 14 (epidermolysis0.84 2.6
bullosa simple
101031J05070Hs.151738"Matrix metalloproteinase0.77 1.52
9 (gelatinase
101111L08424Hs.1619Achaete-scute complex1 1
(Drosophila) homol
101124L10343Hs.112341"Protease inhibitor0.62 2.67
3, skin-derived
(SKA
101175L18920Hs.36980"Melanoma antigen, 1 1
family A, 2"
101204L24203Hs.82237Ataxia-telangiectasia0.74 4.1
group D-associated
101431M19888Hs.1076Small proline-rich 0.85 2.51
protein 1B (cornifln)
101448M21389Hs.195850keratin 5 (epidermolysis0.61 8.83
bullosa simplex
101511M27826Hs.267319Endogenousretroviralprotease1.03 1.13
1 101526M29540Hs.220529Carcinoembryonic 1.07 4.61
~ antigen-related
cell ad
101548M31328Hs.71642"Guanine nucleotide0.97 1.13
binding protein
(G p
101625M57293 "Human parathyroid 1 1
hormone-related
pepti
101649M60047Hs.1690Heparin-binding 1 2.7
growth factor binding
pr
101724M69225Hs.620bullous pemphigoid 1 8.98
antigen 1 (2301240k0)
I 101748M76482Hs.1925Desmoglein 3 (pemphigus1 2.78
S vulgaris antigen
101759M80244Hs.184601"Solute carrier 1.07 2.45
family 7 (cationic
amino
101804M86699Hs.169840TTK protein kinase 1 1
101806M86757Hs.112408S100 calcium-binding0.74 1.76
protein A7 (psorias
101809M86849 "Homo sapiens connexin1 7
26 (GJ82) mRNA,
c
20101845M93426Hs.78867"Protein tyrosine 1 1
phosphatase, receptor-
101851M94250Hs.82045Midkine (neurite 1.13 2.6
growth-promoting
factor
102083010323Hs.75117"Interleukin enhancer1.03 1.61
binding factor
2,
102154017760Hs.75517"Laminin, beta 3 0.94 3.62
(nicein (125k0),
kalini
102193020758Hs.313secreted phosphoprotein0.34 4.59
1 (osteopontin;
25102305033286Hs.90073chromosome segregation1.45 2.97
1 (yeast homology
102348037519Hs.87539Aldehyde dehydrogenase0.52 2.25
8
102581061145Hs.77256Enhancerofzeste 0.91 2.46
(Drosophila)homolog
2
102610065011Hs.30743Preferentially expressed1 3.88
antigen in mela
102623066083Hs.37110"Melanoma antigen, 1 1
family A, 9 IMAGE-9)"
3 102669071207Hs.29279Eyes absent (Drosophila)1 1
0 homolog 2
102696074612Hs.239Forkhead box M1 1.06 2.77
102829091618Hs.80962Neurotensin 1 , 1
102888X04741Hs.76118Ubiquitin carboxyl-terminal1.13 2.59
esterase L1
102913X07696Hs.80342keratin 15 0.7 4.72
3 102915X07820Hs.2258Matrix Metalloproteinase1.15 3.35
10 (Slromolysin
102963X15943Hs.37058"Calcitoninicalcitonin-related1 1
polypepti
103021X53587Hs.85266"Integrin,beta 4" 1.38 2.34
103036X54925Hs.83169Matrix metalloprotease1 14.93
1 (interstitial
c
103058X57348Hs.184510Stratifin 1.25 4.17
103060X57766Hs.155324matrix matalloproteinase1 1.72
11 (stromelys!n
103119X63629Hs.2877"Cadherin 3, P-cadherin1.16 7.38
(placental)"
103206X72755Hs.77367monokine induced 0.71 1.48
by gamma interferon
103242X76342Hs.389"Alcohol dehydrogenase1 1
7 (class IV), mu
103312X82693Hs.3185"Lymphocyte antigen0.92 1.28
6 complex, locus
D;
45103478Y07755Hs.38991S100 calcium-binding1.05 5.81
protein A2
103558219574Hs.2785keratin 17 0.65 6.68
103576226317Hs.2631Desmoglein 2 0.79 1.73
103587229083Hs.821285T4 Oncofetal antigen1 3.93
,
103594231560Hs.816"SRY (sex determining0.71 7.23
region Y)-box 2,
p
103768AA089997 "ESTs, Highly similar0.99 1.8
to integral membra
104158AA454908Hs.8127KIAA0144 gene product0.96 1.29
104558856678Hs.88959Human DNA sequence 1.23 7.23
from clone 967N21
on
104689AA010665 ESTs 0.96 2.11
104733AA019498Hs.23071ESTs 1.18 1.88
55104906AA055809Hs.26802Profein kinase domains1.11 3.15
contain!ng protei
104978AA088458Hs.19322ESTs; Weakly similar1.64 2.89
to !!!! ALU SUBFAMI
105012AA116036Hs.9329"Homo sapiens mRNA 1.19 3.91
for fls353, complete
105175AA186804Hs.25740ESTs; Weakly similar0.9 4.63
to unknown [S.cerev
105263AA227926Hs.6682ESTs 0.95 2.87
105298AA233459Hs.26369ESTs 1 1.13
105312AA233854Hs.23348S-phase kinase-associated1.32 3.01
protein 2 (p45
105719AA291644Hs.36793Hypothetical protein1.28 2.31
FLJ23188
105743AA293300Hs.9598ESTs 1 1
106012AA411621Hs.8895ESTs; same as BFH6?0.94 2.04
.
65106231AA429571Hs.38002KIAA1355 protein 1.04 1.5
106540AA454607Hs.38114Hypothetical protein1.26 2.26
FLJ11100
106575AA456039Hs.105421ESTs 1 2
106632AA459897Hs.11950GPI-anchored metastasis-associated0.87 1.32
prote
106727AA465342Hs.34045Hypotheticalprotein0.87 1.59
FLJ20764
70106906AA490237Hs.222024Transcription factor0.61 1.6
BMAL2 (cycle-like
f
107059AAfi08545Hs.23044RAD51 (S. cerevisiae)0.48 2.67
homolog (E coli
Re
107104AA609786Hs.15243Nucleolar protein 1.01 1.44
1 (120k0)
107151AA621169Hs.8687ESTs; procollagen 0.97 2.89
I-N prote!nase
107284S74039Hs.291904Accessory proteins 1.15 3.65
BAP31IBAP29
75107901AA026418Hs.91539ESTs 0.72 3.44
107922AA028028Hs.61460Ig superfamily receptor1 2.46
LNIR precursor
107932AA029317Hs.18878Hypothetical protein1 1
FLJ21620
108695AA121315Hs.70823KIAA1077 protein 0.91 3.53
108657AA133250Hs.62180ESTs 1 1
8~108860AA133334Hs.129911ESTs 0.73 7.3
108990AA152296Hs.72045ESTs 1 1
109166AA179845Hs.73625"8A86 interacting, 1 4.55
kinesin-like (rabkine
109424AA227919Hs.85962Hyaluronan synlhase1 1.28
3
109665F05012Hs.27027Hypothetical protein1.42 2
DKFZp762H1311
85109970H09281Hs.13234ESTs 1.13 2.16
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
110015H10998Hs.7164A disintegrin and 0.84 1.95
metalloproteinase
doma
110156H18957Hs.4213ESTs 0.94 1.41
110561H59617Hs.5199HSPC150 protein similar0.91 3.18
to ubiquitin-con
111223N68921Hs.34806ESTs; Weakly similar0.91 3.13
to neogenin [H.sapi
111345N89820Hs.14559Hypothetical protein1 1.25
FLJ10540
111876838239Hs.293246"ESTs, Weakly similar0.83 1.27
to putative p150
[
111902839191Hs.109445KIAA1020 protein 0.91 0.91
112244851309Hs.70823KIAA1077 protein 0.77 3.01
112973T17271 "cDNA FLJ13308 fis, 1 1
clone OVARC1001436,
1 112989T23482Hs.89981"Diacylglycerol kinase,0.55 1.03
~ zeta (104kD)"
113047T25867Hs.7549ESTs 0.87 2
113095T40920Hs.126733ESTs 1 1
113531T90345Hs.16740Hypotheticalprotein 0.42 1.44
FLJ11036
113970W86748Hs.8109ESTs 1.17 1.73
I 114346241450Hs.130489"ATPase, aminophospholipid0.86 0.82
S transporter-I
114407AA010188Hs.103305ESTs 0.8 1.88
114471AA028074Hs.104613RP42 homolog 1.06 1.34
114509AA043551Hs.101799KIAA1350 protein 1.82 2.32
115060AA253214Hs.198249"Gap junction protein,0.79 1.49
beta 5 (connexin
115091AA255900Hs.184523KIAA0965 protein 0.72 1.92
115123AA256642Hs.236894"ESTs, High sim to 0.59 1.97
LRP1 hu low density
I
115291AA279943Hs.122579ESTs 1 1.25
115506AA292537Hs.45207Hypothetical protein1.15 1.48
KIAA1335
115522AA331393Hs.47378ESTs 0.5 3.29
115536AA347193Hs.62180ESTs 1 1
115697AA411502Hs.63325Homo sapiens type 1 6.53
II membrane serine
pro
115909AA436666Hs.59761ESTs 1 6.98
115978AA447522Hs.69517Differentially expressed1 2.31
in Fanconi anem
116028AA452112Hs.42644thioredoxin-like 0.99 1.68
116107AA456968Hs.92030ESTs 1.14 1.8
116134AA460246Hs.50441CGI-04 protein - 1.11 1.86
116157AA461063Hs.d4298Hypothetical protein0.99 1.9
116158AA461187Hs.61762Hypoxia-inducible 0.44 0.86
protein 2
116335AA495830Hs.87013"Homo Sapiens cDNA 0.62 3.89
FLJ10238 fis, clone
H
3 116483C14092Hs.76118Ubiquitin carboxyl-terminal1.04 2.36
S esterase L1
117320N23239Hs.211092LUNX protein; PLUNC(palate0.51 0.64
lung & nasal
117557N33920Hs.44532Diubiquitin 1.11 2.63 -
117693N40939Hs.112110PTD007 protein 0.98 1.79
117881N50073Hs.260622Butyrate-induced 1 1.43
transcript 1
118368N64339Hs.48956ESTs 0.67 2.86
118566N68558Hs.42824Hypothetical protein1.21 0.83
FLJ10718
118695N71781Hs.50081KIAA1199 see CVA7.doc0.8B 1.63
119780W72967Hs.191381ESTs; Weakly similar1 1
to hypothetical
pro
119845W79920Hs.58561G protein-coupled 1 1
receptor 87
45120102W95428Hs.132927"ESTs, Moderately 1 1
similar to p53 regulat
120104W95477Hs.180479ESTs 0.69 3.07
120486AA253400Hs.137569Tumor protein 63 1.08 12.05
kDa with strong
homolog
120859AA350158Hs.1619Achaete-scute complex1 1
(Drosophila) homol
120880AA360240Hs.97019EST f 1
120948AA397822Hs.104650Hypothetical protein1.04 2.15
FLJ10292
120983AA398209Hs.97587EST 1 1
121362AA405500Hs.97932Chondromodulin I 1 1
precursor
121369AA405657Hs.128791CGI-09 protein 1 1.8
121791AA423978Hs.293317"ESTs, Weakly similar1 1
to JM27 [H.sapiens
55123005AA479726Hs.105577ESTs 1 1
123044AA481549Hs.130881B-cell CLLOymphoma 0.95 1.88
11A (zinc finger
pro
123160AA488687Hs.284235ESTs 1.59 4.98
123479AA599469Hs.135056clone RP5-850E9 on 1.19 1.64
chromosome 20
123571AA608956Hs.112619"ESTs, Weakly similar1.03 1.14
to P00109 Purkinje
123829AA620697Hs.112208XAGE-1 protein 1.39 2.2
124006D60302Hs.108977ESTs 1 4.85
124059F13673Hs.99769ESTs 1.49 8.62
124960T15386Hs.194766Seizure related gene0.76 0.77
6 (mouse)-like
125218W73561Hs.110024NADH:ubiquinone oxidoreductase1.33 1.77
MLRQ subu
65125453806041Hs.18048"Melanoma antigen, 0.8 1.42
family A,10"
125759AA425587Hs.82226Glycoprotein (lransmembrane)1.52 2.26
nmb
125972AA434562Hs.35406"ESTs, Highly similar1.05 2.48 .
io unnamed protein
125994H55782Hs.270799EST 1 1.95
126395N70.192Hs.278956Hypothetical protein1 1.35
FLJ12929 .
126645AI167942Hs.61635STEAP1 (Homo Sapiens1 2.23
BAC clone RG041D11
127221AI354332Hs.72365ESTs 0.73 3.27
127479AA513722Hs.179729collagen; type X; 0.51 1.94
alpha 1 (Schmid
metaph
128192AI204246 KIAA1085 protein 1.8 3.16
128610L38608Hs.10247activated leucocyte 0.89 0.97
cell adhesion molecu
75128777U46006Hs.10526Cysteine and glycine-rich1 1
protein 2
128924AA234962Hs.26557Plakophilin 3 1.3 2.97
129041H58873Hs.169902"Solute carrier family0.84 2.04
2 (facilitated g7
129099H50398Hs.108660"ATP-binding cassette,0.87 1.04
sub-family C (CFT
129404AA172056Hs.111128ESTs 1 f
8~129466L42583 "Genbank Homo Sapiens0.72 12.67
keratin 6 isoform
129605572493Hs.115947Keratin 16 (focal 0.92 1.5
non-epidermolytic
palm
129628U26727Hs.1174"Cyclin-dependent 0.85 1.93
kinase inhibitor
2A (m
130023X13461Hs.239600Calmodulin-like 3 0.84 1.22
130080X14850Hs.147097"H2A histone family,0.96 1.96
member X"
85130385AA126474Hs.155223stanniocalcin 2 1 1
86
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
130410V01514Hs.15542fAlpha-fetoprotetn 0.63 0.63
130441035835Hs.301387"Human DNA-PK mRNA,1.15 3.65
partial cds"
130482L32866Hs.1578Baculoviral IAP 1 1.88
repeat-containing
5 (sur
130553AA430032Hs.252587Pituitary tumor-transforming0.92 1.96
1
130577M35410Hs.162Insulin-like growth1.17 4.7
factor binding
prote
130627L23B08Hs.1695Matrix metalloproteinase0.69 4.05
12 (macrophage
130800AA223386Hs.19574ESTs; Weakly similar1.13 2.41
to katanin p80
subu
130939AA598689Hs.21400ESTs 0.8 0.89
131046X02530Hs.2248INTERFERON-GAMMA 1.15
INDUCED PROTEIN
PRECURS 0.8
1 131244D38076Hs.24763RAN binding protein1.13 1.85
~ t
131877J0408BHs.156346Topoisomerase (DNA)1 1
II alpha (170kD)
131927AA461549Hs.34780"Doublecortex; lissencephaly,0.81 0.62
X-linked (
131965W90146Hs.35962ESTs 0.74 3.27
131978DB0008Hs.36232KIAA0186 gene product1 1
15132354L05187Hs.211913Small proline-rich 0.69 1.43
protein 1A
132543AA417152Hs.5101ESTs; Highly similar0.79 4.27
to protein regulati
132632N59764Hs.5398guanine-monophosphate1 1.08
synthetase
132653031201Hs.54451"laminin gamma2 1 1
chain gene (LAMC2),
exon
132659275190Hs.54481"Low density lipoprotein0.89 0.89
receptor-relate
132710W93726Hs.55279"Serine (or cysteine)0.64 4.41
proteinase inhibit
132758W52432Hs.56105"ESTs, Weakly similar1.55 2.08
to WDNM RAT WDNM1
132767L05188Hs.231622Small proline-rich 0.83 1.66
protein 2B
132816M74542Hs.575Aldehyde dehydrogenase0.55 0.55
3
132990AA458761Hs.18387transcription factor1 3.53
AP-2 alpha (activat
133070069611Hs.64311"A disintegrin and 1.16 2
metalloproletnase
dom
133282052960Hs.286145"SRBl (suppressor 1 2.7
of RNA polymerase
8, y
133317AA215299Hs.70830U6 snRNA-associated0.95 1.42
Sm-like protein
LSm7
133370AA156897Hs.72157Homo Sapiens mRNA; 1.12 2.55
cDNA DKFZp56411922
133391X57579Hs.727H.sapiens activin 1.65 1.76
beta-A subunit
(exon 2
133832H03387Ns.241305estrogen-responsive1.02 1.39
B box protein (EBBP)
134032281326Hs.78589"Serine (or cysteine)1 1
proteinase inhibit
134168AA398908Hs.181634"Homo Sapiens cDNA:0.95 1.53
FLJ23602 fis, clone
134218AA227480Hs.80205Pim-2 oncogene 1.36 2.48
134405867275Hs.82772"""collagen, type 0.76 2.86
Xl, alpha 1"""
3 134453X70683Hs.83484SRY (sex determining1.89 3.78
region Y)-box 4
134470X54942Hs.83758CDC28 protein kinase1.82 4.11
2
134645087459Hs.167379"Canceritestls antigen0.82 0.83
(NY-ESO-1, CTAG1,
134781Mi7183Hs.89626Parathyroid hormone-like1 1
hormone
135002019147Hs.272484Gantigen6 1 1
40100040M97935 AFFXcontroI:STAT1 0.92 1.25
101201L22524Hs.2256matrix metalloproteinase2.92 8.5
7 (matrilysin;
101664M60752Hs.121017H2A histone family;1 1
member A
102025003911Hs.78934mutS (E. coli) homolog0.8 1.61
2 (colon cancer;
102031004898Hs.2156RAR-related orphan 1 1
receptor A
45102221024576 LIM domain only 1 1
4
102270030255Hs.75888phosphogluconate 1.08 1.43
dehydrogenase
102339037022Hs.95577cyclin-dependentkinase0.88 1.32
4
102391041668Hs.77494deoxyguanosine kinase1.07 1.58
103000X51956Hs.146580enolase 2; (gamma; 0.91 1.49
neuronal)
So103395X94754Hs.119503methionine-IRNAsynthetase0.89 1.32
105638AA281599Hs.20418Homo Sapiens mRNA 0.91 1.25
for for histone
H2B; c
105726AA292328Hs.9754activating transcription0.94 1.48
factor 5
114841AA234722Hs.55408ESTs; Moderately 0.78 1.56
similar to CALCIUM-DEPE
115206AA262491Hs.186572ESTs 1 1
55115906AA436616Hs.82302ESTs 0.74 2.52
119132849046Hs.107911ATP-binding cassette;1.1 1.51
sub-family B (MDRI
124163H30539Hs.189838ESTs 1 1
126487AA482505Hs.184601solute carrier family1.01 1.46
7 (cationic amino
127141AA307960Hs.75478KIAA0956 protein 0.85 1.4
128034AA905754Hs.75103tyrosine 3-monooxygenaseltryptophan1 1.18
5-mo
128609AA234365Hs.102456survival of motor 1 1.5
neuron protein
interac
128895837753Hs.106985ESTs 1.7 2
130199248579Hs.172028a disinlegrin and 1 1
metalloprotease
domain
130524089995Hs.159234forkhead box E1 1 1
65133000024152Hs.62402p211Cdc421Rac1-activated1 1
kinase 1 (yeast
133658M25756Hs.75426secretogranin II 1 1
(chromogranin C)
135047AA460466Hs.93597ESTs 1 1
100053M27830 AFFX control: 28S 0.88 1.53
ribosomal RNA
100114D00596Hs.82962ihymidylate synthetase0.6B 1.86
100128D11094Hs.61153proteasome (prosome;1.29 2.03
macropain) 26S
subu
100154D14657Hs.81892KIAA0101 gene product0.71 4.26
100161Di4694Hs.77329phosphatidylserine 1.02 1.56
synthase 1
100168D14874Hs.394adrenomedullin 0.46 1.17
100187D17793Hs.78183aldo-keto reductase1 1
family 1; member
C3
75100188D21063Hs.57101minichromosome maintenance0.97 1.4
deficient (S.
100217D26600Hs.89545proteasome (prosome;1.13 1.9
macropain) subunit;
100220D28364 """Human mRNA for 1.11 1.53
annexin II, 5'0T8
(seq
1002137D43950Hs.1600chaperonin containing1.13 2.09
TCP1; subunit 5
(e
100297D49489Hs.182429protein disulfide 0.92 1.78
isomerase-related
prat
100330D55716Hs.77152minichromosome maintenance1.07 1.61
deficient (S.
100355D78129 """Homo Sapiens 0.96 1.87
mRNA for squalene
epoxid
100364D78586Hs.154868carbamoyl-phosphate1.49 2.46
synthetase 2; aspart
100368D79987Hs.153479extra spindle poles;0.59 1.32
S. cerevisiae;
homo
100398D84557Hs.155462minichromosome maintenance1.08 1.9
deficient (m1
g5100438D87448Hs.91417topoisomerase (DNA)1 2.15
II binding protein
g7
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
100455D87953Hs.75789N-myc downsUeam regulated0.91 1.48
100491HG1153-HT1153 Nucleoside Diphosphate0.99 1.41
Kinase Nm23-H2s
100518HG174-HT174 Desmoplakin I 1.28 3.17
100528HG1828-HT1857 """Nexin, Glia-Derived"""0.68 1.9
100661HG2874-HT3018 Ribosomal Protein 1.1 5.44
L39 Homolog
100667HG2981-HT3127 """Epican, Alt. Splice0.8 1.97
11"""
100830HG4074-HT4344 Rad2 1.01 2.12
101061K03515Hs.944glucose phosphate 0.91 1.79
isomerase
101131L10838Hs.167460splicing factor; 1.23 1.87
argininelserine-rich
3
1 101162L14595Hs.174203solute carrier family1.35 2.73
~ 1 (glutamatelneuU
101181L19686Hs.73798macrophage migraUon 1.03 1.78
inhibifory factor
(
101183L19779Hs.795H2A histone family; 0.57 1.3
member 0
101216L25876Hs.84113cyclin-dependent 0.7 2.2
kinase inhibitor
3 (CDK
101228L27706Hs.82916chaperonin containing0.99 1.99
TCP1; subunit 6A
(
15101233L29008Hs.878sorbitol dehydrogenase0.82 2.11
101247L33801Hs.78802,glycogen synthase 1.2 1.91
kinase 3 beta
101332L47276 """Homo sapiens (cell0.69 2.78
line HL-6) alpha
t
101342L76191Hs.182018interleukin-1 receptor-associated1.04 1.84
kinase
101396M15796Hs.78996proliferating cell 0.95 3.55
nuclear antigen
101423M18391Hs.89839EphA1 1 1.5
101445M21259Hs.1066small nuclear dbonucleoprotein1.21 1.96
polypept
101505M27396Hs.75692asparagine synthetase0.93 1.6
101525M29536Hs.12163eukaryotic translation1.19 1.93
initiation factor
101535M30448Hs.251669casein kinase 2; 0.96 1.42
beta polypeptide
25101607M38690Hs.1244CD9 antigen (p24) 1.11 1.25
10162dM55998 """Human alpha-1 1.17 1.98
collagen type I
gene, 3
101758M77836Hs.79217pyrroline-5-carboxylate1.77 3.45
reductase 1
101839M93036Hs.692membrane component; 0.71 1.45
chromosomal 4; surfs
101853M94362Hs.76084lamin 82 0.84 1.19
101977583364 """putative RabS-interacting0.89 1.9
protein (c1
101992001038Hs.77597polo (Drosophia)-like0.66 1.46
kinase
102009002680Hs.82643protein tyrosine 1.23 3.35
kinase 9
102012003057Hs.118400singed (Drosophila)-like0.85 1.88
(sea urchin fas
102039005861Hs.201967aido-keto reductase 0.93 2.32
family 1; member
C1
3 102123014518Hs.1594centromere protein 1 4.28
A (17kD)
102130015009Hs.1575small nuclear ribonucleoprotein0.89 1.42
D3 polyp
102148016954Hs.75823ALL1-fused gene from0.8 2.95
chromosome 1q
102210023028Hs.2437eukaryctic translation1.01 1.34
initiation factor
102220024389Hs.65436lysyl oxidase-like 1.15 2.34
1
102260028386Hs.159557karyopherin alpha 1.14 2.69
2 (RAG cohort 1;
impor
102330035451Hs.77254chromobox homolog 1.05 1.7
1 (Drosophila HP1
beta
102423044754Hs.179312small nuclear RNA 1.14 2.99
activating complex;
po
102455048705Hs.75562discoidin domain 1.05 2.01
receptor family;
member
102499051478Hs.76941ATPase; Na+IK+transporting;1.27 1.92
beta 3 poly
45102522053347Hs.183556solute carrier family0.84 1.31
1 (neutral amino
a
102590062136 """Homo sapiens enterocyte1.11 1.6
differentiati
102676072514Hs.i2045putative protein 1.04 2.17
102687073379Hs.93002ubiquitin carrier 0.86 2.28
protein E2-C
102704076638Hs.54089BRCA1 associated 1.12 1.63
RING domain 1
102781083843 """Human HIV-1 Nef 0.9 1.39
interacting protein
(
102784085658Hs.61796transcription factor0.96 2.16
AP-2 gamma (activat
102827091327Hs.6456chaperonin containing0.96 1.62
TCP1; subunit 2
(b
102935X13482Hs.80506small nuclear ribonucleoprotein1.21 4.2
polypept
102972X16662Hs.87268annexin A8 1.25 2.32
55102983X17620Hs.118638non-metastatic cells1.03 1.83
1; protein (NM23A)
103023X53793Hs.117950multifunctional polypeptide1.58 5.44
similar to S
103038X54941Hs.77550CDC28 protein kinase1.32 3.79
1
103075X59543Hs.2934ribonucleotide reductase1.11 2.56
Mt polypeptide
103168X68314Hs.2704glutathione peroxidase0.75 3.05
2 (gastrcintestin
60103185X69910Hs.74368transmembrane protein1.01 1.97
(63kD); endoplasmi
103212X73874Hs.2393phosphorylase kinase;0.95 1.72
alpha 1 (muscle)
103223X74801Hs.1708chaperonin containing0.97 1.77
TCP1; subunit 3
(g
103260X78416Hs.3155casein; alpha 1 1
103262X78565Hs.204133hexabrachicn (lenascin1.23 3.09
C; cytotactin)
65103330X85373Hs.77496small nuclear ribonucleoprotein1.12 2.25
polypept
103364X90872Hs.75854SULT1C sulfotransferase' 2.854.62
103375X91868Hs.54416sine oculis homeobox1 2.48
(Drosophila) homolo
103391X94453Hs.114366pyrroline-5-carboxytate1 1.53
synthetase (glut
103404X95586Hs.78596proteasome (prosome;0.92 1.53
macropain) subunit;
,
103437X98260Hs.82254M-phase phosphoprotein0.92 1.54
11
103448X99133Hs.204238lipocalin 2 (oncogene0.55 0.96
24p3)
103605235402Hs.194657cadhedn 1; E-cadherin1.32 2.51
(epithelial)
103646268228Hs.2340junction plakoglobin0.88 1.28
103658274615Hs.172928collagen; type I; 1.06 2.98
alpha 1
75103774AA092898Hs.92918ESTs; Weakly similar1.88 4.66
to R07G3.8 [C.elega
104261AF008442Hs.5409RNA polymerase I 0.87 2.17
subunit
104276C02193Hs.85222ESTs; Weakly similart.4 2.49
to 827090_2 [H.sapi
104289C16281Hs.75478KIAA0956 protein 1.15 1.68
104434L02870Hs.1640collagen; type VII; 1.04 1.49
alpha 1 (epidermolys
104453M19169Hs.123114cystatin SN 0.38 0.76
104611898280Hs.125845ribulose-5-phosphate-3-epimerase1.08 2.25
104758AA024661Hs.7010ESTs; Weakly similar1.14 1.65
1o ACYL-COA DEHYDRO
105114AA156532Hs.11801adenosine A2b receptor0.91 1.38
pseudogene
105132AA159501Hs.247280HBV associated factor1.08 1.7
g5105174AA186613Hs.34744ESTs 0.95 2.05
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
105280AA232215Hs.14600ESTs 1 1.4
105344AA235303Hs.8645ESTs 0.72 2.02
105516AA257971Hs.21214ESTs 1.35 3.56
105621AA280865Hs.6375Homc sapiens mRNA; 1.23 1.82
cDNA DKFZp564K0222
(f
105698AA287393Hs.15202ESTs; Weakly similar0.98 1.28
to oligodendrocyte-
105705AA290767Hs.101282Homo sapiens mRNA; 0.92 1.32
cDNA DKFZp434B102
(fr
105724AA292098Hs.22934ESTs; Weakly similar0.99 1.41
to ZINC FINGER PROT
105782AA350215Hs.21580ESTs 1 1
105799AA372018Hs.24743ESTs 1.08 1.78
10105807AA393803Hs.16869ESTs; Moderately 0.95 1.34
similar to COLLAGEN
ALP
105891AA400768Hs.26662ESTs; Weakly similar0.87 2.25
to tumor necrosis
f
105936AA404338 ESTs 1.14 1.46
106069AA417741Hs.29899ESTs; Weakly similar1 1
to ZINC FINGER PROT
106103AA421104Hs.12094ESTs 1.04 1.44
1 106140AA424524Hs.14912KIAA0286 protein 1.23 2.11
106149AA424881Hs.256301ESTs 0.83 1.48
106154AA425304Hs.6994ESTs 0.77 2.05
106182AA426609Hs.10862ESTs 0.74 2.23
106220AA428582Hs.32196ESTs; Moderately 0.97 1.99
similar to metargidin
p
106228AA429290Hs.17719ESTs 0.99 1.54
106318AA436570Hs.9605pre-mRNA cleavage 0.95 2.09
factor Im (25kD)
106341AA441798Hs.5243ESTs; Moderately 0.98 2.66
similar to pIL2
hypothe
106432AA448850Hs.17138ESTs 0.95 1.93
106474AA450212Hs.42484Homo sapiens mRNA; 1 1
cDNA DKFZp564C053
(fr
25106483AA451676Hs.30299IGF-II mRNA-binding 1.4 2.29
protein 2
106599AA457235Hs.12842ESTs; Moderately 1 1.82
similar to non-function
106611AA458904Hs.26267ESTs; Weakly similar1.49 2.78
to torsinA [H.sapie
106654AA460449Hs.3784ESTs; Nighty similar1 1.4
to phosphoserine
am
107076AA609145Hs.21143ESTs; Weakly similar1.11 1.49
to fos39554-1 [H.sa
107115AA610108Hs.27693ESTs; Highly similar1 1.03
to CGI-124 protein
107129AA620553Hs.4756flap structure-specific1.13 3.63
endonuclease 1
107159AA621340Hs.10600ESTs; Weakly similar1.05 2.09
to ORF YKR081c [S.c
107444W28391Hs.5181proliferation-associated1.18 1.9
2G4; 38kD
107481W58247Hs.27437Homo sapiens kinesin0.99 2.74
superfamily molar
K
3 107516X56597Hs.99853fibrillarin 0.94 1.77
S
107529Y12065Hs.5092nucleolar protein 1.05 2.29
(KKEID repeat)
107531Y13936Hs.17883protein phosphatase 1.06 1.62
1G (formerly 2C);
ma
107801AA019433Hs.173100ESTs 1.03 1.4
107957AA031948Hs.57548ESTs 0.95 1.46
108565AA085342Hs.1526ATPase; Caa+iransporting;0.59 1.35
cardiac muscl
108780AA128561Hs.117938collagen; type XVIi;1 7.63
alpha 1
108828AA131584Hs.71435DKFZP56400463 protein1.33 2.56
109060AA160879Hs.241551chloride channel; 0.67 1.42
calcium activated;
Tam
109112AA169379Hs.72865ESTs 1.03 2.31
45109344AA213696Hs.86559poly(A)-binding protein-like0.97 1.55
1
109412AA227145Hs.209473ESTs; Weakly similar0.76 1.87
to REGULATOR OF
MIT
t N23174Hs.22891solute carrier family0.9 0.95
10780 7 (cationic amino
110958N50550Hs.24587signal transduclion 1.17 2.26
protein (SH3 contain
1 N54067Hs.3628mitogen-activated 1.21 1.85
1 protein kinase kinase
1018
111337N79612Hs.16607ESTs; Highly similar1 1.45
to Myosin heavy
cha
112305854822Hs.26244ESTs 1 1
112401861279Hs.237536ESTs; Weakly similar1.24 1.64
to F25B5.3 [C.elega
112853T02843Hs.4351EST 1.56 1.96
112869T03313Hs.4747dyskeratosis congenita1.03 1.57
1; dyskerin
55112992T2351371s.7147ESTs 1 1
113048T25895Hs.184008ESTs; Weakly similar1.37 2.26
to RNA-binding prot
113063T32438Hs.5027ESTs 1 1
113179T55182Hs.152571ESTs; Highly similar1.33 2.7
to IGF-II mRNA-bind
113573T91166Hs.15990ESTs 0.76 1.47
113811W44928Hs.4878ESTs 0.79 1.51
114086236266Hs.12770Homo sapiens PAC 0.9 1.34
clone DJ0777023
from 7p
114587AA070827Hs.180320ESTs; Weakly similar1.02 1.76
to GOLGI 4-TRANSMEM
114846AA234929Hs.44343ESTs 1.32 2.36
114964AA243873Hs.82184ring finger protein 1.1 1.84
3
65115047AA252627Hs.22554homeo box B5 1.01 2.36
115166AA258409Hs.198907myelin protein zero-like1.05 2.31
1
115167AA258421Hs.43728hypotheticalprotein 1.52 2.52
115239AA278650Hs.73291ESTs; Weakly similar0.7 2.57
to similar to the
b
115278AA279757Hs.67466ESTs; Weakly similar1.14 2.12
to BACN32G11.d [D.m
115652AA405098Hs.38178ESTs 0.82 4.67
115875AA433943Hs.43946ESTs; Weakly similar1.2 1.96
to Weak similarity
116004AA449122Hs.76086ESTs; Highly similar0.96 1.31
to small zinc Tinge
116121AA459254Hs.48855ESTs 0.97 1.55
116129AA459956Hs.d9163ESTs; Highly similar1.08 2.73
to putative ribonuc
75116190AA464963Hs.67776ESTs 0.8 1.57
116312AA490494Hs.65403ESTs 1.37 2.65
116732F13779Hs.165909ESTs 0.92 1.8
117602N35020Hs.44685ESTs; Weakly similar1.15 1.84
to GOLIATH PROTEIN
117950N51394Hs.75478KIAA0956 protein 1.04 2.36
8~117992N52000Hs.172089Homo sapiens mRNA; 0.62 1.29
cDNA DKFZp586B0222
(f
118785N75386Hs.111867GLI-Kruppel family 1 1
member GLI2
119717W69134Hs.57987ESTs 1 1.4
119814W74069Hs.58350ESTs 0.78 1.77
120128238499Hs.91448MKP-1 like protein 0.86 1.46
tyrosine phosphatase
85120242298443Hs.86366ESTs 0.83 2.01
89
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
120483AA252994Hs.1578apoptosis inhibitor 0.74 1.64
4 (survivin)
121054AA398604Hs.97387ESTs 1.05 1.93
121326AA404246Hs.97031ESTs; Weakly similar0.98 1.3
to Similar to phyto
121376AA405699Hs.166232ESTs;ModeratelysimilartoSODIUM-AND0.91 1.83
121457AA411448Hs.208985ESTs 0.91 1.59
121780AA422086Hs.124660ESTs 0.46 0.55
121781AA422150Hs.98370cytochrome P540 family1.07 1.54
member predicted
121844AA425732Hs.98485gapjunction prolein;beta0.94 1.4
2;26kD (coon
122059AA431737Ns.98749ES7 1.93 2,33
1 122338AA443311Hs.98998ESTs 1 1
0
122354AA443772Hs.t86692ESTs 0.88 1.39
122591AA453265Hs.99311ESTs; Weakly similar2.28 2.93
to MRJ [H.sapiens]
122790AA460156Hs.99556ESTs 0.88 1.3
123398AA521265Hs.105514ESTs 1 1.93
1 123518AA608531Hs.170313ESTs 1 1
123673AA609471Hs.112712ESTs 1 1.15
124000D57317Hs.74861activated RNA polymerase0.74 1.12
II transcriptio
124367N24006Hs.99348distal-less homeo 0.67 1.1
box 5
124447N48000Hs.140945Homo sapiens mRNA; 1.19 1.7
cDNA DKFZp586L141
(fr
125756W25498Hs.81634ATP synthase; H+transporting;0.93 1.59
mitochond
125769AI382972Hs.821285T4 oncofetal lrophoblast1.65 6.76
glycoprotein
125652H09290Hs.76550Homo sapiens mRNA; 0.72 2.26
cDNA DKFZp564B1264
(f
12592dAA526849Hs.82109syndecan 1 1.22 2.25
126037M85772Hs.6066KIAA1112 protein 1.36 1.63
126214N29455Hs.74316desmoplakin (DPI; 1.93 3.55
DPII)
126414N78770Hs.223439ESTs 1.21 1.66
126737AA488132Hs.62741ESTs 1 1
126743AA179253Hs.172182poly(A)-binding protein;1.3 2.16
cyloplasmic 1
126926AA179546Hs.832ESTs;HighlysimilartolNTEGRINBETA-82.53 2.8
30 127432AA501734Hs.170311heterogeneous nuclear1.57 2.12
ribonucleoprotein
128218H02682Hs.99189ESTs; Moderately 1.24 2.09
similar to recombinatio
128527M31523Hs.101047transcription factor1.08 1.78
3 (E2A immunoglobul
128568X60673Hs.247568adenylate ktnase 1.23 3.48
3
128584M11433Hs.101850retinol-binding protein0.87 2.42
1; cellular
35 128628C14037Hs.251978EST 1.22 1.9
128691W27939Hs.103834ESTs 1.1 1.73
128714V00599Hs.179661Homo sapiens clone 0.92 1.17
24703 beta-tubulin
mR
128733AA328993Hs.104558ESTs 1.34 1.94
128781X85372Hs.105465small nuclear ribonuoleoprotein0.9 1.34
polypept
40 129052AA496297Hs.182740ribosomal protein 2.59 3.19
811
129095L12350Hs.108623thrombospondin 2 1.04 3.2
129241AA435665Hs.109706ESTs; Moderately 0.95 1.61
similar to HNt [M.muscu
129665M88458Hs.118778KDEL (Lys-Asp-Glu-Leu)1.28 2.63
endoplasmic relic
129703AA401348Hs.179999ESTs 0.97 1.63
45 129720AA476582Hs.12152ESTs; Moderately 1.09 1.79
similar to SIGNAL
RECOG
129850N20593Hs.56845GDP dissociation 0.74 1.68
inhibitor 2
129896AA043021Hs.13225UDP-Gal:betaGIcNAo 1.43 4.19
beta 1;4-galactosylt
130069AA055896Hs.146428collagen; type V; 1.17 1.98
alpha 1
130405H88359Hs.155396nuclear factor (erythroid-derived1.26 1.79
2)-lik
50 130541X05608Hs.211584neurofilament; light1 1
polypeptide (68kD)
130599M91670Hs.174070ubiquitin carrier 1.07 1.66
protein
130867J04093Hs.2056UDP glycosyltransferase1 4.8
1
131009AA063596Hs.22142ESTs; Weakly similar0.93 1.05
to NADH-CYTOCHROME
131028020240Hs.2227CCAATIenhancer binding1 1.23
protein (CIEBP);
55 131083066661Hs.22785gamma-amtnobutyric 1.1 1.8
acid (GABA) A recepto
131091T35341Hs.22880ESTs; Highly similar1.28 1.98
to dipeptidyl pepti
' 131144C14412Hs.23528ESTs; Highly similar1.43 2.06
to HSPC038 protein
131148C00038Hs.23579ESTs 0.88 3.38
131164Y00503Hs.182265keratin 19 1.19 2.77
60 131185M25753Hs.23960cyclin B1 0.86 3.84
131219C00476Hs.24395small inducible cytokine0.66 2.96
subfamily B (Cy
131454AA455896Hs.2699glypican 1 0.99 1.54
131687L11066Hs.3069heat shock 70kD protein1 1.18
9B (mortalin-2)
131689AA599653Hs.30696transcription factor-like1 1.95
5 (basic helix
65 131692D50914Hs.30736KIAA0124 protein 1.55 2.39
131786AA135554Hs.32125ESTs 1 1.33
131843AA195893Hs.184062ESTs; Moderately 0.83 1.63
similar to putative
Rab
131860002082Hs.334Oncogene TIM 1.08 2.2
131884H90124Hs.3463ribosomal protein 1.23 1.24
523
70 131903AAd81723Hs.3436deleted in oral cancer0.91 1.18
(mouse; homology
131945M87339Hs.35120replication factor 1 2.8
C (activator 1)
4 (37
131958AA093998Hs.3566ESTs; Highly similar0.87 1.36
to phosphorylation
131964W42508Hs.3593ESTs 1 1.25
132001J00277Hs.37003v-Ha-ras Harvey rat 1.12 1.43
sarcoma viral oncoge
75 132040AA146843Hs.172894BH3 interacting domain1 1.55
death agonist
132065D82226Hs.211594proteasome (prosome;0.89 1.27
macropain) 26S subu
132109AA599801Hs.40098ESTs 1 1.05
132112AA150661Hs.40154jumonji (mouse) homolog0.99 1.44
132123AA447123Hs.250705ESTs 1.06 2.46 -
g0 132162H89551Hs.41241ESTs 1.08 2.46
132180AA405569Hs.418fibroblast activation1.02 4.56
protein; alpha;
se
132309AA460917Hs.2780jun D proto-oncogene1.16 1.8
132371AA235448Hs.46677ESTs 0.8 1.26
132618AA253330Hs.5344adaptor-related protein0.5 1.49
complex 1; gamma
g 132736068019Hs.211578MAD (mothers against1.21 1.81
5 decapentaplegic;
Dr
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
132771AA488432Hs.56407phosphoserine phosphatase1 1.3
132833078525Hs.57783eukaryotic translation0.91 1,43
initiation factor
132922T23641Hs.6066KIAA1112 protein 1.16 1.53
132959AA028103Hs.61472ESTs; Weakly similar1.02 1.88
to unknown [S.cerev
132994AA505133Hs.7594solute carrier family0.72 2.97
2 (facilitated
glu
133005C21400Hs.103329KIAA0970 protein 0.88 1.34
133065X62535Hs.172690diacylglyceroi kinase;0.93 1.23
alpha (80kD)
133083N70633Hs.6456chaperonin containing1.14 1.76
TCP1; subunit 2
(b
133086L17131Hs.139800high-mobility group0.97 1.43
(nonhistone chromoso
10133134T89703Hs.65648RNA binding motif 1.1 1.8
protein 8
133195AA350744Hs.181409KIAA1007 protein 2.29 2.69
133313AA249427Hs.70704ESTs 1.07 1.68
133331T62039Hs.158675ribosomal protein 0.85 1.18
L14
133438D13370Hs.73722APEX nuclease (multifunctional0,91 1.45
DNA repai
15133445T99303Hs.73797guanine nucleotide 0.94 1.68
binding protein
(G pr
133483X52426Hs.74070keratin 13 0.85 1.14
133492L40397Hs.74137transmembrane trafficking1.1 1.69
protein
133504W95070Hs.74316desmoplakin (DPI; 0.7 6.21
DPII)
133517X52947Hs.74471gap junction protein;0.95 1.3
alpha 1; 43kD (con
133540D78151Hs.74619proteasome (prosome;0.91 1.25
macropain) 26S
subu
133594L07758Hs.172589nuclearphosphoprotein0.84 1.29
similarto S.cer
133627009587Hs.75280glycyl-tRNA synthetase1.09 1.99
133671T25747Hs.75471zinc finger protein1.02 1.5
146
133859086782Hs.17876126S proteasome-associated1.11 3.33
padl homolog
133865F09315Hs.170290discs; large (Drosophila)1.84 6.7
homolog 5
133913W84712Hs.7753calumenin 1.15 1.86
133963L34587Hs.184693transcription elongation1.3 1.91
factor B (SIII)
133982047621Hs,207251nucleolar autoantigen1.3 1.99
(55kD) similar
to
134100L07540Hs.171075replication factor 0.72 1.fi5
C (activator 1)
5 (36
134110041060Hs.79136LIV-1 protein; estrogen1.04 1.62
regulated
134158015174Hs.79428BCL2ladenovirus 1 1.55
E1B l9kD-interacting
pro
134161097188Hs,79440IGF-II mRNA-binding0.82 1.95
protein 3
134193F09570Hs.7980ESTs 0.98 1.46
134367X54199Hs.82285phosphoribosylglycinamide1 2.8
formyltransfer
35134402025165Hs.82712fragile X mental 1.26 2
retardation; autosomal
134457D86963Hs.174044dishevelled 3 (homologous1 1.47
to Drosophila
134469X17567Hs.83753small nuclear ribonucleoprotein0.94 1.57
polypept
134498M63180Hs.84131threonyl-tRNA synthetase1.2 2.64
134501W84870Hs.211568eukaryotic translation0.84 1.36
initiation factor
134507M63488Hs.84318replication protein1.7 2.93
A1 (70kD)
134548041515Hs.85215Deleted in split-handlsplit-foot1.46 2.73
1 regio
134599X99226Hs.86297Fanconi anemia; 1.36 2.22
complementation
group A
134692873567Hs.8850a disintegrin and 0.77 1.64
metalloproteinase
doma
134693N70361Hs.8854ESTs 1.09 1.82
45134806249099Hs.89718spermine synthase 0.98 1.35
134821234974Hs.198382plakophilin 1 (ectodermal0.99 1.4
dysplasialskin
134864Y08999Hs.90370actin related protein0.95 1.42
213 complex; subun
134914029615Ns.91093chitlnase 1 (chitotriosidase)1.16 1.29
134953L10678Hs.91747profilin 2 0.95 1.76
134993AA282343Hs.9242purine-rich element0.98 1.73
binding protein
B
135051C15324Hs,93668ESTs 1.35 2.11
135158051711 Human desmocollin-20,86 1.16
mRNA; 3' UTR
Table 1 B shows the accession numbers for those pkeys in Table 1A lacking
unigenelD's. For each probeset we have listed the gene cluster number from
which the
55 oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based
onsequence
similarity using Clustering and Alignment Tools (DoubleTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
Accession column.
Pkey: Unique Eos probeset identifier number
60 CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT Accessions
65 100661 23182_1 BE623001 L05096 AA383604 AW9fi6416 N53295 AA460213 AW571519
AA603655
100667 26401_3 L05424 X56794 S66400 X55150 W60071 AW351820 X55938 M83326
BE005289 BE070059 M83324 BE005248 BE069717 BE181648 BE069700
AW606203 BE069721 AW382138 AW803776 BE463954 BE005334 8E005274 T27386 AA932714
AA972695 AW377728 AI632506 T29066
AI783934 AW377727 BE163715 AL047291 AA279047 AA523003 BE008048 BE440141 W23614
BE090519 BE092193 N29181 N20358 N44153
BE546944 T69231 AW377441 AA907406 H50799 AW051416 A1420712 BE620922 A1279161
AA992549 Wd7198 BE005241 AI342696 H50700
AI969974 AI863855 AA374490 AW130676'AI950633 AA146fi87 H99482 X55150 BE005414
BE005339 N28294 AI673068 AI887890 AW804171
AI675961 AW804172 AA778841 AL048050 AI127757 A1095568 AW204965 AW468978 W31898
A1052595 AI278771 BE464018 A1081503 AI824196
AA513211 AA411062 AW084376 N48752 AA703209 N35580 AW059918 AA054563 AI280942
T27619 BE621435 N66010 AW589527 AI160414
AA283090 AA962536 H82726 W52115 W45432 W60433 AA577548 AA146714 BE150994
AA054615 AW796025 AW382768 BE565671 C00444
AA054555
75 100668 26401_3 L05424 X56794 S66400 X55150 W60071 AW351820 X55938 M83326
BE005289 BE070059 M83324 BE005248 BE069717 BE181648 BE069700
AW606203 BE069721 AW382138 AW803776 BE463954 BE005334 BE005274 T27386 AA932714
AA972695 AW377728 AI632506 T29066
AI783934 AW377727 BE163715 AL047291 AA279047 AA523003 BE008048 BE440141 W23614
BE090519 BE092193 N29181 N20358 N44153
BE546944 T69231 AW377441 AA907406 H50799 AW051416 AI420712 BE620922 AI279161
AA992549 W47198 BE005241 AI342696 H50700
AI969974 AI863855 AA374490 AW130675 AI950633 AA146687 H99482 X55150 BE005414
BE005339 N28294 A1673068 AI887890 AW804171
AI675961 AW804172 AA778841 AL048050 AI127757 A1095568 AW204965 AW468978 W31898
A1052595 AI278771 BE464018 A1081503 AI824196
AA513211 AA411062 AW08437fi N48752 AA703209 N35580 AW059918 AA054563 AI280942
T27619 BE621435 N66010 AW589527 AI160414
AA283090 AA962536 H82726 W52115 W45432 W60433 AA577548 AA146714 BE150994
AA054615 AW796025 AW382768 BE565671 C00444
AA054555
101332 25130_1 J04088 NM_001067 AF071747 AJ011741 N85424 AL042407 AA218572
BE29fi748 BE08398i AL040877 AW499918 AW675045 H17813
BE081283 AA670403 AW504327 BE094229 AA104024 AI471482 AI970337 AA737616
AI827444 AW003286 AI742333 AI344044 AI765634
91
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
AI948838 AW235336 AW172827 AA095289 BE046383 AI734240 W16699 AI660329 AI289433
AA933778 AW469242 AA468838 AA8069B3
AA625873 W78031 BE206307 AA550803 AI743147 AI990075 AA948274 AA129533 AI635399
AA605313 AI624669 AW594319 AI221834 AI337434
AA307706 BE550282 AI760467 AI630636 AI221521 AW674314 AW078889 AI933732
AI686969 AI186928 AW074595 A1127486 AL079644
AI910815 H17814 AA31 D903 AW137854 T19279 AA026682 AA306035 AW383390 AW383389
AW383422 AW383427 AW383395 H09977
AA306247 AA352501 AW403639 F05421 AA224473 AA305321 H93904 AA089612 AW391543
AW402915 AW1733B2 AW402701 AW403113
894438 N73126 H93466 AA090928 AA095051 T29025 AW951071 L47277 L47276 AI375913
BE384156 W24652 AA746288 AA568223 BE090591
H93033 N57027 AA504348 AA327653 AW959913 N53767 AA843715 AI453437 AW263710
A1076594 AA583483 AW873194 AW575166 AI128799
AI803319 AL042776 AW074313 AI8B7722 A1032284 AA447521 AI123885 N29334 AI354911
AW090687 AA236763 AA435535 AA236910
AA047124 AA236734 AW514610 H93467 AA962007 AI446783 AA127259 AI613495 AI686720
AI587374 AA936731 AA702453 AI859757
AA216786 AI251819 AI469227 AA80fi022 A1092324 N71868 AA9fi8782 AA23fi919
AA809450 AA227220 AA765284 AI192007 AA768810
AA805794 AA729280 AA806238 AW768817 N71879 A1050686 AA505B22 AA668974 AI688160
BE045915 AW466315 AA731314 AA649568
AA834316 AW591901 AW063876 AW294770 AI300266 AI336094 AI560380 AA721755 H09978
D20305 D29155 AW821790 BE150864 F01675
AI457474 AW466316 AA550969 AA630788
100780 458_127 BE561958 BE561728 8E397612 BE514391 BE269037 BE514207 BE562381
BE514256 BE514403 BE514250 BE397832 BE269598 BE559865
BE396881 BE560031 BE514199 BE560037 BE560454
100830 4002_1 AC004770 W05005 AA356068 AA094281 H29358 T56781 AW875313 L37374
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AI392926 AF139065 AW370813 AW370827 AW798417 AW798780
AW798883 AW798569 833557 AA149190 C03029 AW177783 AA088866
AW370829 AA247685 BE002273 AI760816 AI439101 AW879451
AI700963 AA451923 AI340326 AI590975 T48793 AI568096
AI142882 AA039975
AI470146 AA946936 BE067737 BE067786 W19287 AA644381
AA702424 AI417612 AI306554 AI686869 AI568892 AW190555
AI571075 AI220573
AA056527 AI471874 AI304772 AW517828 AI915596 AI627383
AI270345 AW021347 AW1668D7 AW105614 AI346078 AA552300
W95070
AI494069 AI911702 AA149191 AA026864 AI830049 AI887258
AW780435 AI910434 AI819984 AI858282 A1078449 A1025932
AI860584 AI635878
AA026047 AA703232 D12062 AW192085 AA658154 AW514597
AW591892 T87181 AA782066 AW243815 AW 150038 AW268383
AW004633
1 o AI927207 AA782109 AW473233 AI804485 AW169216 AI572669
AA602182 AW015480 AW771865 AI270027 AA961816 AA283207
A1076962
AI498487 AI348053 AI783914 H44405 AW799118 AA128330
AA515500 AA918281 W02156 AI905927 AA022701 W38382 820795
T77861
AW860878
100528 45979_1BE386801 AU077299 AA143755 BE302747 AA853375 030162
BE274163 BE277479 BE408180 BE274874 C15000AA047476
N27099 AI359165
A1638794 A1151283 A1863925 AW444977 A1207392 AA931263
AA443112 840138 AW068538 AA351008 AA676972 862503 AA916492
AW001865
I S H42334 H38280 AA121497 AA114137 AI750938 M17783 AA383786
BE274462 AI753182 C05975 AA347404 AW069298 AI754351
AI754044
AA188808 AA186879 AA565243 AL040655 AA456177 AI750722
AA045756 AA213580 C16936 AW578747 AW753731 H41632 N44761858560
861260 AA039902 N59721 AW992543 868380 AA149686 T29017
H03739 BE383822 BE387105 BE408251 BE410425 H41560 AA247591
BE389677 AI752233 AI566195 AA868004 AI424523 AW753720
AA852159 BE386803
100559 2260-iNM_000094 L02870 D13694 S51236 M96984 AW946290 M65158
AI285422 D29523 AL119886 AW630655 L06862 AI884355 AWi
68737 T29085
AW797005 AW801340 AI355504 AW079048 AW801337 AI690455
AI972063 AW268565 W68588 AA587326 AA883498 A1033523
AW510356
AW591998 H98463 AL043852 AI150055 AI566239 AI624803
AA844717 H40670 AA922334 AI864424 AW615094 AW451233
AI302203 F31221
AI872170 W68589 AA904478 AI917631 AW014208 AW450759
AA847625 AI284033 AA848176 AA598501
100576 9986_1X00356 NM_001741 M26095 X03662 M12667 X02330 X02330
AA716058 AW296074 X04861 AI695720 AA719597
124357 genbankN22401 N22401
25 101624
enhez-M55998M55998
101625 entrez
M57293M57293
135158 57963-iAL037551 A1804716 AW439811 A1569470 AA075299 AI738572
AI270388 AI816783 AW263026 Ai633951 AI655285 AI990572
AI950425
AW241533 AA916883 AA576693 AA160156 AA613783 AW078884
AI888282 AI275241 AI133467 AA164921
94
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Tables
2A-8C
were
previously
filed
on
November
9,
2001
in
USSN
601339,245
(18501-004100US)
Tableshows 504 genes down-regulated in lung tumors relafive
2A to normal lung and chronically diseased lung. Chronically
diseased lung samples represent chronic non-
malignant
lung
diseases
such
as
fibrosis,
emphysema,
and
bronchifis.
These
genes
were
selected
from
59680
probesets
on
the
EosIAffymetrix
Hu03
Genechip
array.
Gene
expression
data
for
each
probeset
obtained
from
this
analysis
was
expressed
as
average
intensity
(AI),
a
normalized
value
reflecfing
the
relafive
level
of
mRNA
expression.
Pkey:Unique Eos probeset identifier number
ExAccn:ExempIarAccession number, Genbank accession number
UnigenelD:
Unigene
number
1 Unigene
~ Title:
Unigene
gene
fide
R1: 90th percentile of AI for normal lung samples divided by
the 80th percentile of AI far adenocarcinoma and squamous
cell carcinoma lung tumor
samples.
R2: median of AI for normal lung samples divided by 90th percenfile
of AI for adenocarcinoma and squamous cell carcinoma lung
tumor samples.
R3: median of AI for normal lung samples minus the 15th percenUle
of AI for all normal lung, chronically diseased lung and
tumor samples divided by
I the 90th percentile of AI for adenocarcinoma and squamous
S cell carcinoma lung tumor samples minus the 15th percentile
of AI for all normal
lung, chronically diseased lung and tumor samples.
R4: average of AI for normal lung samples divided by average
AI for squamous cell carcinoma and adenocarcinoma lung
tumors.
R5: median of AI for normal lung samples divided by the 90th
percentile of AI for adenocarcinomas.
R6: median of AI for normal lung samples minus the 15th percentile
of AI for all normal lung, chronically diseased lung and
tumor samples divided by the 90th
percentile of AI for adenocarcinomas minus the 15th percentile
of AI for all normal lung, chronically diseased lung and
tumor samples.
R7: average of AI for normal lung samples divided by the 90th
percentile of AI for squamous cell carcinomas.
R8: median of AI for normal lung samples minus the 15th percentile
of AI for all normal lung, chronically diseased lung and
tumor samples divided by the 90th
percentile of AI for squamous cell carcinomas minus the
15th percentile of AI for all normal lung, chronically
diseased lung and tumor samples.
25 Pkey ExAccn UnigenelD UnigeneTitle R1 R2 R3 R4 R5 R6 R7 R8
100095297171 Hs.78454 myocilin; trabecular meshwork inducible
40.20
100115NM 002084 Hs.336920 glutathione peroxidase 3 (plasma) 3.46
100138083508 Hs.2463 angiopoietin 1 2.30
100299D49493 Hs.2171 growth differentiation factor 10 11.00
100306086749 Hs.80598 transcription elongafion factor A (S11);
3.06
100447NM 014767 Hs.74583 KIAA0275 gene product 3.16
100458S74019 Hs.247979 Vpre-B 42.40
100862AA005247 Hs.285754 Hepatocyte Growth Factor Receptor 4.13
35 100959AA359129 Hs.118127 actin; alpha; cardiac muscle 125.60
101032BE206854 Hs.46039 phosphoglycerate mutase 2(muscle) 36.40
101081AF047347 Hs.4880 amyloid beta (A4) precursor protein-bind
34.60
101088X70697 Hs.553 solute carrier family 6 (neurotransmide 193.20
101125AJ250562 Hs.82749 transmembrane 4 superfamily member 2
3.10
101180011874 Hs.846 interleukin 8 receptor; beta 54.86
101308L41390 "Homo sapiens core 2 beta-1,6-N-acetylgl 33.20
101330L43821 Hs.80261 enhanceroffilamentafion 1 (cas-like do
36.40
101345NM 005795 Hs.152175 Calcitonin receptor-like 2.29
101346AI738616 Hs.77348 hydroxyprostaglandin dehydrogenase 15-(N
70.55
45 101397M26380 Hs.180878 lipoprotein lipase 3.54
101414NM 000066 Hs.38069 complement component 8; beta polypeptide
3.81
101435NM_001100 Hs.1288 actin; alpha 1; skeletal muscle 34.60
101507X16896 Hs.82112 interleukin 1 receptor; type I 37.60
101530M29874 Hs.1360 cytochrome P450; subfamily IIB (phenobar
4.25
101537AI469059 Hs.184915 zinc finger protein; Y-linked 2.54
101542NM_000102 Hs.1363 cytochrome P450; subfamily XVII (steroid
5.50
101545BE246154 Hs.154210 EDG1; endothelial differenfiation, sphin
39.40
101554BE207611 Hs.123078 thyroid stimulafing hormone receptor
13.00
101560AW958272 Hs.83733 Intercellular adhesion molecule 2, axon
3.38
55 101574M34182 Hs.158029 protein kinase; cAMP-dependent; catalyti
4.37
101605M37984 Hs.118845 troponin C; slow 3.80
101621BE391804 Hs.62661 guanytale binding protein 1; interferon-
30.20
101680AA299330 Hs.1042 5jogren syndrome antigen A1 (52kD; ribon
2.75
101829AW452398 Hs.129763 solute carrier family 8 (sodiumicalcium
3.37
101842M93221 Hs.75182 mannose receptor; C type 1 38.20
101961AW004056 Hs.168357 "Hs-TBX2=T-box gene {T-box region} [huma
2.32
101994T92248 Hs.2240 uteroglobin 6.85
102020AU077315 Hs.154970 transcription factor CP2 2.45
102091BE280901 Hs.83155 aldehyde dehydrogenase 7 6.75
65 102112AW025430 Hs.155591 forkhead box F1 54.60
102190AA723157 Hs.73769 folate receptor 1 (adult) 3.98
102202NM 000507 Hs.574 fructose-bisphosphatase 1 3.62
102241NM_007351 Hs.268107 MulUmerin 2.32
102310033839 Accession not listed in Genbank 7.00
102397041898 "Human sodium cotransporter RKST1 mRNA, 29.40
102571060115 Hs.239069 "Homo sapiens skeletal muscle LIM-protei
3.75
102620AA976427 Hs.121513 Human clone W2-6 mRNA from chromosome
X 3.07
102636067092 "Human ataxia-telangiectasia locus prote 2.40
102667070867 Hs.83974 solute carderfamily 21 (prostaglandin 3.15
75 102675072512 Hs.7771 "Human B-cell receptor associated protei
3.56
102698M18667 Hs.1867 progastricsin (pepsinogen C) 4.51
102727079251 Hs.99902 opioid-binding protein/cell adhesion mot
12.00
102852V00571 Hs.75294 corticolropin releasing hormone 37.40
103026X54162 Hs.79386 thyroid and eye muscle autoantigen D1 (6
13.00
g0 103028X54380 Hs.74094 pregnancy-zone protein 28.80
103098M86361 Human mRNA for T cell receptor; clone IG 10.00
103117X63578 Hs.295449 parvalbumin 6.00
103241X76223 H.sapiens MAL gene axon 4 2.d1
103280084722 Hs.76206 Cadherin 5, VE-cadherin (vascular epithe
2.69
103360Y1fi791 Hs.73082 keratin; hair; acidic; 5 2.16
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103496Y09267Hs.132821flavin containing 5.97
monooxygenase 2
103508Y10141 "H.sapiens DAT1 3.27
gene, partial,
VNTR"
103561NM Hs.143434contactin 1 2.40
001843
103569NM Hs.151641glycoprotein A repetitions2.99
005512 predominant
103575226256 "H.sapiens isoform 4.18
1 gene for L-type
cal
103627248513 H.sapiens XG mRNA 3.44
(clone PEP6)
103767BE244667Hs.296155CGI-100 protein 2.25
103850AA187101Hs.213194Hypothetical protein46.55
MGC10895; sim 1o
SR
104078AA402801Hs.303276ESTs 3.05
1~104326AW732858Hs.f43067ESTs 3~
104352BE219898Hs.173135dual-specificity 3.16
tyrosine-(Y)-phosphoryl
104398AI423930Hs.36790ESTs; Weakly similar64.80
to putative p150
[H
104473AI904823Hs.31297ESTs 3.38
104493AW960427Hs.79059ESTs; Moderately 2.47
similar to TGF-BETA
REC
1 104495AW975687Hs.292979ESTs 28.60
S
104595A1799603Hs.271568ESTs 3.42
104597A1364504Hs.93967ESTs; Weakly similar6.00
to Slit-1 protein
[
104659AW969769Hs.105201ESTs 34.00
104686AA010539Hs.18912ESTs 11.00
104691029690Hs.37744ESTs; Beta-1-adrenergicreceptor56.80
104764A1039243Hs.278585ESTs 60.40
104776AA026349 ESTs 34.20
104825AA035613Hs.141883ESTs 3.03
104865T79340Hs.22575Homo Sapiens cDNA: 41.20
FLJ21042 fis, clone
C
25104942NM Hs.10235ESTs 3.27
016348
104989865998Hs.285243ESTs 40.00
105062AW954355Hs.36529ESTs 3.20
105101H63202Hs.38163ESTs 34.20
105173054617Hs.8364ESTs 4.17
105194806780Hs.19800ESTs 16.00
105226858958Hs.26608ESTs 2.34
105256AA430650Hs.16529transmembrane 4 2.72
superfamily member
(tetr
105394BE245812Hs.8941ESTs 2.61
105647Y09306Hs.30148homeodomain-interacflng33.60
protein kinase
3
3 105789AF106941Hs.18142arrestin; beta 2 3.59
105817AA397825 synaptopodin 4.46
105847AW964490Hs.32241ESTs 35.40
105894A1904740Hs.25691calcitonin receptor-like3.43
receptor activi
105999BE268786Hs.21543ESTs 7.00
106075AA045290Hs.25930ESTs 42.60
106178AL049935Hs.301763KIAA0554 protein 34.80
~
106381AB040916Hs.24106ESTs 12.00
106467AA450040Hs.154162ADP-ribosylation 3.69
factor-like 2
106536AA329648Hs.2380dESTs 96.40
45106569820909Hs.300741sorcin 47.20
106605AW772298Hs.21103Homo Sapiens mRNA; 220.40
cDNA DKFZp564B076
(fr
106842AF124251Hs.26054novel SH2-containing2.55
protein 3
106844AA485055Hs.158213sperm associated 39.20
antigen 6
106870A1983730Hs.26530serum deprivation 2.28
response (phosphatidyl
106943AW88B222Hs.9973ESTs 4.28
106954AF128847Hs.204038ESTs 4.32
107106AA862496Hs.28482ESTs 10.45
107163AF233588Hs.27018ESTs 2.57
107201D20378Hs.30731EST 3.84
55107238D59362Hs.330777EST 8.00
107376090545Hs.327179solute carrier family10.67
17 (sodium phospha
107530Y13622Hs.85087latenttransforming 2.32
growlhfactorbeta
b
107688AW082221Hs.60536ESTs 34.60
107706AA015579Hs.29276ESTs 28.40
60107723AA015967 EST 3.29
107727AA149707Hs.173091DKFZP434K151 protein80.80
107750AA017291Hs.60781ESTs 51.40
107751AA017301Hs.235390ESTs 3.14
107873AK000520Hs.143811ESTs 9.00
65107899BE019261Hs.83869ESTs; Weakly similar3.65
to 1111 ALU SUBFAMI
107994AA036B11Hs.48469ESTs 44.60
107997AL049176Hs.82223Human DNA sequence 32.00
from clone 141
H5 on c
108041AW204712Hs.61957ESTs 30.80
108048A1797341Hs.165195ESTs 4.75
108338AA070773 "zm53g11.s1 Stratagene2.33
fibroblast (#9372
108434AA078899 "zm94bt.s1 Stratagene2.92
colon HT29 (#93722
108447AA079126 "zm92a11.s1 Siratagene3.06
ovarian cancer
(#
108480AL133092Hs.68055ESTs 34.00
108499AA083103 "zn1b12.s1 Stratagene3.36
hNT neuron (#93723
75108535813949Hs.226440Homo Sapiens clone 19.00
24881 mRNA sequence
108550AA084867 "zn11f6.s1 Stratagene12.00
hNT neuron(#93723
108604AA934589Hs.49696ESTs 2.33
108625AW972330Hs.283022ESTs 5.82
108629AA102425 "zn24c6.s1 Stratagene3.42
neuroepithelium
NT
g0108655AA099960 "zm65c6.s1 Stratagenefibroblast(#937217.00
108756AA127221Hs.117037Homo Sapiens mRNA; 6.05
cDNA DKFZp564N1164
(f
108864AI733852Hs.199957ESTs 28.80
108895AL138272Hs.62713ESTs 32.80
108921A1568801Hs.71721ESTs 57.80
85108967AA142989Hs.71730ESTs 28.80
96
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109001A1056548Hs.72116ESTs, Moderately 2.57
similar to hedgehog-int
109003AA147497Hs.71825ESTs 2.11
109004AA156235Hs.139077EST 5.60
109065AA161125Hs.252739EST 10.00
109250H83784Hs.62113ESTs; Weakly similar3.44
to PHOSPHATIDYLETHA
109490AA233416Hs.139202ESTs 2.92
109510A1798863Hs.87191ESTs 2.40
109578F02208Hs.27214ESTs 10.00
109601F02695Hs.311662EST 40.80
10109613H47315Hs.27519ESTs 54.40
109650831770Hs.23540ESTs 31.20
109682H18017Hs.22869ESTs 8.40
109724D59899Hs.127842ESTs 29.40
109782AB020644Hs.14945long fatty acyl-CoA8.00
synthetase 2 gene
15109833879864Hs.29889ESTs 10.00
109837H00656Hs.29792ESTs 6.49
109977T64183Hs.2B2982ESTs 2.75
109984A1796320Hs.10299ESTs 107.00
110146H41324Hs.31581ESTs; Moderately 2.22
similar to SYNTAXIN
1B
110271H28985Hs.31330ESTs 3.48
110280AW874263Hs.32468ESTs 44.20
110420893141Hs.184261ESTs 32.00
110578T62507Hs.11038ESTs 28.40
110634898905Hs.35992ESTs 20,00
25110726AW961818Hs.24379potassium voltage-gated4.15
channel; shaker-
110837H03109Hs.108920ESTs; Weakly similar56.80
to semaphorin F
[H.
110875N35070Hs.26401tumor necrosis factor3.13
(ligand) superfami
110894892356Hs.668B1ESTs; Moderately 5.33
similar to cytoplasmic
110971AI760098Hs.21411ESTs 44.60
3 1 AV655386Hs.7645ESTs 32.40
0 i
1023
111057T79639Hs.14629ESTs 17.14
111247AW058350Hs.16762Homo sapiens mRNA; 4.58
cDNA DKFZp564B2062
(f
111330BE247767Hs.18166KIAA0870 protein 3.42
111374BE250726Hs.283724ESTs; Moderately 3.91
similar to HYA22
[H.sap
3 111442AW449573Hs.181003ESTs 33.20
111737H04607Hs.9218ESTs 53.00
111747AI741471Hs.23666ESTs 46.20
111807833508Hs.18827ESTs 16.00
111862837472Hs.21559EST 3.91
112045A1372588Hs.8022TU3A protein 2.74
112057843713Hs.22945EST 4.92
112214AW148652Hs.167398ESTs 13.00
112263852393Hs.25917ESTs 2.43
112314AW206093Hs.748ESTs 9.00
45112324855965Hs.26479limbic system-associated14.00
' membrane protei
112362AW300887Hs.26638ESTs; Weakly similar2.49
to CD20 receptor
[H
112380H63010Hs.5740ESTs 2.34
112425AA324998Hs.321677ESTs; Weakly similar8.00
to !!!! ALU SUBFAMI
112473865993Hs.279798pregnancy specific 4.53
beta-1-glycoprotein
9
112492N51620Hs.28694ESTs 29.80
112541AF038392Hs.116674ESTs 3.62
112620880552Hs.29040ESTs 2.37
112623AW373104Hs.25094ESTs 2.26
112867T03254Hs.167393ESTs 12.00
55112894T08188Hs.3770ESTs 6.50
112954AA928953Hs.6655ESTs 7.00
113029AW081710Hs.7369ESTs; Weakly similar4.39
to !!!1 ALU SUBFAMI
113086AA346839Hs.209100DKFZP4340171 protein4.47
113140T50405Hs.175967ESTs 10.00
113252NM Hs.11392c-fosinduced growthfactor(vascularen14.00
004469
113257A1821378Hs.159367ESTs 3.72
113394T81473Hs.177894ESTs 3.60
113437T85349Hs.15923EST 35.00
113454A1022166Hs.16188ESTs 6.00
65f T8913Q ESTs 39.60
f
3502
113552AI654223Hs.16026ESTs 3.88
113645T95358Hs.333181ESTs 2.58
113691T96935Hs.17932EST 38.20
113706AA004693Hs.269192ESTs 3.09
113883U89281Hs.11958oxidative 3 alpha 2.31
hydroxysteroid
dehydro
113924BE178285Hs.170056Homo sapiens mRNA; 30.40
cDNA DKFZp586B0220
(f
114035W92798Ns.269181ESTs 13.00
114058AK002016Hs.114727ESTs 5.00
114084AA708035Hs.12248ESTs 40.60
75114121H05785Hs.25425ESTs 2.31
114124W57554Hs.125019Human lymphoid nuclear7.00
protein (LAF-4)
114275AW515443Hs.306117interleukin 13 receptor;6.00
alpha 1
114297AA149707Hs.173091DKFZP434K151 protein48.80
114427AA017176Hs.33532ESTs; Highly similar3.45
to Miz-1 protein
[H
114449AA020736 "ze63b11.s1 Soares 10.00
retina N2b4HR Homo
so
114452AI369275Hs.243010ESTs, Moderately 14.00
similar to RTCD-HUMAN
G
114609AA079505 "zm97a5.s1 Stratagene3.13
colon HT29 (#93722
114648AA101056 "zn25b3.s1 Sfratagene35.40
neuroepithelium
NT
114731BE094291Hs.155651Homo sapiens HNF-3beta3.42
mRNA for hepatocy
g5114762AA146979Hs.28B464ESTs 33.00
97
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114776AA151719Hs.95834ESTs 34.40
115009AA251561Hs.48689ESTs 30.20
115272AW015947 ESTs; Weakly similar32.60
to hypothetical
L1
115279AW964897Hs.290825ESTs 6.00
115302AL109719Hs.47578ESTs 12.00
115365AW976252Hs.268391ESTs 3.32
115559AL079707Hs.207443ESTs 48.00
115566AI142336Hs.43977ESTs 56.20
115683AF255910Hs.54650ESTs, Weakly similar31.d0
to (defline not
ava
1 115744AA418538Hs.43945ESTs; Highly similar 33.60
~ to dJ1178H5.3 (H.sa
115819AA486620Hs.41135Endomucin 2 74.40
115949AI478427Hs.43125ESTs 3.18
115965AA001732Hs.173233ESTs 388.80
116035AA621405Hs.184664ESTs 33.20
I 116049AA454033Hs.41644ESTs ~ 45.80
S
116081AI190071Hs.55278ESTs 3.57
116082AB029496Hs.59729ESTs 3.06
116213AA292105Hs.326740leucine rich repeat50.60
(in FLII) interaclin
116228AI767947Hs.50841ESTs; Weakly similar 3.85
to tuflelin [M.musc
116250N76712Hs.44829ESTs 6.00
116419AI613480Hs.47152ESTs; Weakly similar 30.00
to testicular tekti
116617D80761Hs.45220EST ' 2.27
116784AB007979Hs.301281tenascin R (restrictin;47.20
janusin)
116835N39230Hs.38218ESTs 41.20
116970AB023179Hs.9059KIAA0962 protein 11.00
117023AW070211Hs.102415ESTs 91.00
117027AW085208Hs.130093ESTs 49.40
917036H88908Hs.41192EST 32.60
117110AA160079Hs.172932ESTs ' 8.67
117209W03011Hs.306881ESTs 30.60
117325N23599Hs.43396ESTs 929
117454N29569Hs.44055ESTs 3.19
117475N30205Hs.93740ESTs 44.00
117543BE219453Hs.42722ESTs 16.00
35117567AW444761Hs.44565ESTs 12.00
117570N48649Hs.44583ESTs 11.00
117600N34963Hs.44676EST 3.74
117730N45513Hs.46608ESTs 6.00
117791N48325Hs.93956EST 9.00
117929N51075Hs.47191ESTs 29.20
117990AA446167Hs.47385ESTs 8.00
118224N62275Hs.48503EST 31.40
118244N62516Hs.48556ESTs 32.80
118357AL109667Hs.124154Homo Sapiens mRNA 2.40
full length insert
cDN
45118446N66361Hs.269121ESTs 2.28
118447N66399Hs.49193EST 30.80
118530N67900Hs.118446ESTs 3.10
118549N68163Hs.322954EST 3.41
118823W03754Hs.50813ESTs; Weakly similar 3.94
to long chain fatty
50118862W17065Hs.54522ESTs 3.56
118935AI979247Hs.247043KIAA0525 protein 33.00
118944A1734233Hs.226142ESTs; Weakly similar 11.43
to 1111 ALU SUBFAMI
118995N94591Hs.323056ESTs 14.00
119073BE245360Hs.279477ERG-21ERG-1; V-ets 52.60
avian erylhroblastosi
55119268T16335Hs.65325EST 31.40
119514W37937 Accession not listed 3.50
in Genbank
119824W74536Hs.184advanced glycosylation 2.75
end product-speci
119831AL1i7664Hs.58419DKFZP586L2024 protein 3.21
119861W78816Hs.49943ESTs; Moderately 33.80
similar to 1111
ALU SUB
119889W84346Hs.58671ESTs 30.03
119921W86192Hs.58815ESTs 29.00
120082H80286Hs.40111ESTs 3.80
120094AA811339Hs.124049ESTs 6.00
120132W57554Hs.125019Human lymphoid nuclear 36.60
protein (LAF-4)
65120378AA223249Hs.285728ESTs 12.00
120404A8023230.Hs.96427KIAA1013 protein 39.40
120504AA256837 ESTs 8.00
120512N55761Hs.194718ESTs 33.00
120667AA287740Hs.78335microtubule-associated 4.18
protein; RPIEB
fa
120777AA287702Hs.10031KIAA0955 protein 46.60
121082AA398722 ESTs 39.00
121191AA400205Hs.104447ESTs 41.60
121248AA400914Hs.97827EST 5.08
121363A1287280Hs.97933ESTs 12.00
75121366AI743515 ESTs 20.00
121483A1660332Hs.25274ESTs; Moderately 3.32
similar to putative
sev
121518AA412155 ESTs 30.20
121545AA412442Hs.9B132ESTs 2.29
121622AA416931Hs.126065ESTs 9.00
8~121665AA416556Hs.98234ESTs 34.80
121709AI338247Hs.98314Homo Sapiens mRNA; 34.80
cDNA DKFZp586L0120
(f
121730AI140683Hs.98328ESTs 38.80
121740AA421138Hs.98334EST 7.00
121772AI590770HS.110347Homo Sapiens mRNA 36.20
for alpha iniegdn
bin
85121821AL040235Hs.3346ESTs 3.61
98
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
121835AB033030Hs.300670ESTs 2.34
121841AA427794Hs.104864ESTs 2.61
121885AA934883Hs.98467ESTs 2.25
121888AA426429Hs.98463ESTs 2.92
121938AA428659Hs.98610ESTs 46.80
121950AA429515 EST 31.40
122030AA431310Hs.98724ESTs 34.40
122054AA431725Hs.98746EST 3.58
122211AA300900Hs.98849ESTs; Moderately 49.40
similar to bithoraxcid-
1 122233AA436455Hs.98872EST 29.80
~
122247AA436676Hs.98890EST 39.80
122253AA436703Hs.104936ESTs; Weakly similar 9,00
to hypothetical
pro
122266AA436840Hs.98907EST 3.60
122285AA436981Hs.121602EST 3.14
15122409AAd46830Hs.99081ESTs 30.80
122485AA524547Hs.160318phospholemman 2.65
122697AA420683Hs.98321Homo sapiens cDNA 15.00
FLJ14103 fis,
clone MA
122772AW117452Hs.99489ESTs 6.67
122831AI857570Hs.5120ESTs 3.37
122913A1638774Hs.105328ESTs 32.20
123049BE047680Hs.211869ESTs 41.80
123076AI345569Hs.190046ESTs 35.80
123136AW451999Hs.194024ESTs 2.58
123309N52937Hs.102679ESTs 19.00
123455AA353113Hs.112497ESTs 82.80
123691AA609579Hs.112724ESTs 3.95
123756AA609971Hs.112795EST 35.40
123802AA620448 Homo Sapiens clone58.00
24760 mRNA sequence
123837AI807243Hs.112893ESTs 32.40
123844AA938905Hs.120017olfactory receptor; 2.63
family 7; subfamily
123936NM_004673Hs.241519ESTs 29.00
123987C21171Hs.95497ESTs; Weakly similar 70.60
to GLUCOSE TRANSPOR
124013AI521936Hs.107149ESTs; Weakly similar28.40
to PTB-ASSOCIATED
S
124160840290Hs.124685ESTs 13.00
124205H77570Hs.108135ESTs 4.74
124226AA618527Hs.190266ESTs 2.35
124246H67680Hs.270962ESTs 29.40
124348AI796320Hs.10299ESTs 17.00
124358AW070211Hs.102415"yw35g11.s1 Morlon 3.07
Fetal Cochlea
Homo sa
124409AI814166Hs.107197ESTs 3.14
124442AW663632Hs.285625TATA box binding 2.48
protein (TBP)-associate
124468N51413Hs.109284ESTs 30.80
124479AB011130Hs.127436calcium channel; 6.03
voltage-dependent;
alph
124519AI670056Hs.137274ESTs; Weakly similar 2.50
to SPLICEOSOME
ASSO
45124711NM_004657Hs.26530serum deprivation 59.20
response (phosphatidyl
124866AI768289Hs.304389ESTs 8,00
1248748E550182Hs.127826ESTs 37.60
125097AW576389Hs.335774ESTs 10.00
125179AW206468Hs.103118ESTs 3.12
125200AW836591Hs.103156ESTs 2.79
125299T32982Hs.102720ESTs 34.20
125400AL110151Hs.128797DKFZP586D0824 protein29.00
125810H00083 aryl hydrocarbon 32.20
receptor-interacting
pr
126176BE242256Hs.2441KIAA0022 gene product 12.00
55126303D78841 HUM525A05B Human 33.60
placenta polyA+(TFuji
126403AW629054Hs.125976ESTs; Weakly similar35.80
to meialloproteasel
126507AL040137Hs.23964ESTs; Weakly similar 29.80
to HC1 ORF [M.muscu
126773AA648284Hs.187584ESTs 39.60
127307AW962712Hs.126712ESTs; Weakly similar28.80
to pIL2 hypothetica
127462AA760776Hs.293977aa59b04.s1 NCI-CGAP_GCB1 34.40
Homo sapiens c
127486AW002846Hs.105468ESTs 9.00
127572AA594027Hs.191788ESTs 2.36
127609X80031Hs.530ESTs 29.40
127832AW976035Hs.292396ESTs 37.20
65127898AA774725Hs.12B970ESTs 4.42
128073AW340720Hs.125983ESTs 38.40
128101AA905730Hs.128254ESTs 7.33
128149NM Hs.177576mannosyl (alpha-1;3-)-glycoprotein 2.58
012214 beta-
128212W27411Hs.336920glutathione peroxidase 3.09
3 (plasma)
128333W68800Hs.12126ESTs; Weakly similar 34.40
to LRB [H.sapiensj
128364N76462Hs.269152ESTs; Weakly similar 10.00
to ZINC FINGER
PROT
128426AI265784Hs.145197ESTs 4.31
128598AA305407Hs.102308potassium inwardly-rectifying31.20
channel; s
128634AA464918 ESTs; Moderately 41.60
similar to !!!!
ALU 5U8
128687AW271273Hs.23767ESTs 87.00
128726A1311238Hs.104476ESTs 4.02
128773NM Hs.1051granzyme B (granzyme 9.00
004131 2; cytotoxic T-lymp
128833W26667Hs.184581ESTs 3.76
128870H39537Hs.75309eukaryotic translation 2.66
elongation factor
128878825513Hs.10683ESTs 3.10
128885AF134803Hs.180141cofilin 2 (muscle) 11.00
128998W042d5Hs.107761ESTs; Weakly similar 3.21
to PUTATIVE RHOlRAC
129000AA744902Hs.107767ESTs; Moderately 3.68
similar to CaM-KII
inhi
129038AW156903Hs.108124ribosomal protein 3.17
L41
129098AW580945Hs.330466ESTs 34.60
99
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
129210AL039940Hs.202949KIAA1102 protein 4.09
129240AA361258Hs.237868interleukin 7 receptor2.29
129262BE222198Hs.109843ESTs 3.30
129301AF182277Hs.330780Human cytochrome 4.05
P450-IIB (hIIB3)
mRNA;
129331AW167668Hs.279772ESTs; Highly similar4.09
to CGI-38 protein
[
129381AW245805Hs.110903claudin 5 (transmembrane2.93
profein detefed
129565X77777Hs.198726vasoactive intestinal160.80
peptide receptor
1
129595009550Hs.1154oviductalglycoprotein10.00
1;120k0
129613AW978517Hs.172847ESTs; Weakly similar3.40
to collagen alpha
1
10129782AW016932Hs.104105EST 9.00
129950F07783Hs.1369decay accelerating 87.80
factor for complement
129958827496Hs.1378annexin A3 44.60
129959AL036554Hs.274463defensin; alpha 2.72
1; myeloid-related
segue
130160AA305688Hs.267695UDP-Gal:betaGIcNAc 42.20
beta 1;3-galactosyllr
15130259NM_000328Hs.1536f4retinitis plgmentosa2.54
GTPase regulator
130273AW972422Hs.153863MAD (mothers against51.60
decapentaplegic;
Dr
130312AF056195Hs.15430DKFZP586G1219 protein3.16
130436NM_001928Hs.155597Dcomponentofcomplement(adipsin)4.11
130523AA999702Hs.214507ESTs 4.77
130799AB028945Hs.12696ESTs 6.00
130885NM_005883Hs.20912adenomalous polyposis3.54
colt like
131002AL050295Hs.22039KIAA0758 protein 3.50
131012AL039940Hs.202949KIAA1102 protein 20.00
131031NM_001650Hs.288650aquaporin 4 41.20
25131061N64328Hs.268744ESTs; Moderately 31.40
similar to KIAA0273
[H.
131066AW169287Hs.22588ESTs 29.60
131082A1091121Hs.24621ESTs; Weakly similar9.00
B to zinc finger
prot
131087AF147709Hs.22824ESTs; Weakly similar3.86
to p160 myb-binding
131161AF033382Hs.23735potassium voltage-gated3.14
channel; subfami
30131179AA171388Hs.184482DKFZP586D0624protein3.80
131182AI824144Hs.23912ESTs 3.67
131205NM_003102Hs.2420superoxide dismutase2.98
3; extracellular
131277AA131466 ESTs 3.15
Hs.23767
131281AA251716Ns.25227ESTs 32.20
35131282X03350Hs,4 alcohol dehydrogenase3.44
3 (class I); gamma
131285AI567943Hs.25274ESTs; Moderately 6.40
similar to putative
sev
131355852804Hs.25956DKFZP564D206 protein8.00
131391AW085781Hs.26270ESTs 10.00
131461AA992841Hs.27263bulyrateresponsefactor2(EGF-response28.80
40131487F13036Hs.27373Homo Sapiens mRNA; 4.03
cDNA DKFZp56401763
(f
131517AB037789Hs.263395ESTs; Highly similar39.00
to semaphorin Vla
[
131545AL137432Hs.28564ESTs 11.00
131583AK000383Hs.323092ESTs; Weakly similar- 10.00
to dual specificity
131647AA359615Hs.30089ESTs 2.47
45131675H15205Hs.30509ESTs 3.06
131676A1126821Hs.30514ESTs 45.80
131708S60415Hs.30941calcium channel; 2.28
voltage-dependent;
beta
131717X94630Hs.3107CD97 antigen 3.78
131756AA443966Hs.31595ESTs 40.60
50131762AA744902Hs.107767ESTs; Moderately 3.67
similar to CaM-KII
inhi
131821AA017247Hs.164577ESTs 2.87
131839AB014533Ns.33010KIAA0633 protein 3.48
131861AL096858Hs.184245KIAA0929 protein 54.00
Msx2 interacting
nuclea
132015AI418006Hs.3731ESTs 49.20
S 132070BE622641Hs.38489ESTs 34.80
132242AA332697Hs.42721ESTs 2.68
132334AW080704Hs.45033lacrimal praline 4.66
rich protein
132476AL119844Hs.49476Homo Sapiens clone 34.20
TUAB Cri-du-chat
regi
132490NM Hs.4980LIM binding domain 2.66
001290 2
132533AI922988Hs.i72510ESTs 13.00
132598X80031Hs.530collagen;typelV; 30.60
alpha 3 (Goodpasture
132619H28855Hs.53447ESTs; Moderately 4.02
similar to kinesin
ligh
132652N41739Hs.61260ESTs 3.18
132726N52298Hs.55608ESTs; Weakly similar11.43
to cDNA EST yk48dg1
65133028851604Hs.300842ESTs 2.37
133071BE384932Hs.64313ESTs 2.27
133120NM Hs.65424letranecfin (plasminogen-binding2.63
003278 protein
133129AA42858Hs.65551ESTs 5.49
0
133147AA026533Ns.66interleukin 1 receptor6.20
like 1
70133151NM Hs.94896ESTs 3.69
014051
133213AA903424Hs.6786ESTs 31.40
133276AW978439Hs.69504ESTs 9.00
133377AJ131245Hs.7239SEC24 (S. cerevisiae)41.20
related gene famil
133407AF017987Hs.7306secreted frizzled-related50.20
protein 1
75133535AL134030Hs.284180protocadherin 2 3.72
(cadherin-like
2)
133537041518Hs.74602aquapodn 1 (channel-forming3.35
integral pr
133656BE149455Hs.75415Accession not listed2.65
in Genbank
133689NM-001872Hs.75572carboxypeplidase 90.80
B2 (plasma)
133779T58486Hs.222566ESTs 3.05
133978AF035718Ns.78061transcriptionfactor2l2.92
133985L34657Hs.78146plateletlendothelial3.45
cell adhesion molec
134000AW175787Hs.334841selenium binding 4.05
protein 1
134111AI372588Hs.8022TU3A protein 4.49
134185AA285136Hs.301914Homo sapiens mRNA; 3.27
cDNA DKFZp586K1220
(f
5 134204AI873257Hs.7994ESTs; Weakly similar40.80
to CGI-69 protein
[
100
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
134641A1092634Hs.156114protein tyrosine 3.76
phosphatase; non-recept
134677AA251363Hs.177711ESTs 32.20
134745NM Hs.89472angiotensin receptor15.00
000685 1B
134749T28499Hs.89485carbonic anhydraselV3.05
134786T29618Hs.89640angiopoietin 1 57.80
receptor; TEK
tyrosine k1
134825033749Hs.197764thyroid transcription 3.73
factor 1
134978AI829008Hs.333383ficolin (collagenlfibdnogen2.52
domain-coot
135010N50465Hs.92927ESTs 31.60
135053AW796190Hs.93678ESTs 3.21
1 135081AF069517Hs.173993RNA binding motif 28.80
~ protein 6
135091AA493650Hs.94367ESTs 4.24
135135AA775910Hs.95011syntrophin; beta 8.00
1 (dystrophin-associate
135203C15737Hs.269386ESTs 4.31
135236A1636208Hs.96901ESTs 43.00
I 135266841179Hs.97393Human mRNA for 6.42
S KIAA0328 gene;
partial cd
135346NM-000928Hs.992phospholipase A2; 3.82
group IB (pancreas)
135378AW961818Hs.24379potassium voltage-gated4.15
channel; shaker-
135387NM_001972Hs.99863elastase 2; neutrophil37.20
135388W27965Hs.99865EST 38.80
135402L12398Hs.99922dopamine receptor 4.21
D4
TABLE 2B shows the accession numbers for those primekeys lacking unigenelD's
far Table 2A. For each probeset we have listed the gene cluster number from
which the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Tools (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
Pkey: Unique Eos probeset identifier number
CAT number. Gene cluster number
3 o Accession. Genbank accession numbers
Pkey CAT number Accessions
10844743452 -7 AA079126
35108550120073_1 AA084867AA084996
108655127522_1 AA099960 AA113013
10239744371_ 1 041898
1263031525933 1 D78841 D78880
1258101554054
1 H00083 881062
103627_
2615-2 248513 248512
121366280401 1 A1743515 AA405617 AW276706
114609116777 1 AA079505 AA079537
115272172113_1 AW015947 AA211890 AA279425
108338112186 1 AA070773 AA070774
45108434114012_1 AA078899 AA078782 AA075788
123802genbank_AA&20448 AA620448
102310NOT_FOUND-entrez 033839 033839
102636entrez_U67092 067092
104776genbank_AA026349 AA026349
120504genbank_AA256837 AA256837
0
113502genbank_T89130T89130
108499genbank-AA083103 AA083103
101308entrez_L41390 L41390
108629genbanILAA102425 AA102425
5 103098221 215 M86361 226593 X02850 D13070 AE000659 M17649
5 M87869 M87871 X61077 M16286 AF018169 X61079 S59351
X60142 AF043169
103241entrez-X76223 X76223
103508entrez_Y10141 Y10141
103575entrez-226256 226256
119514NOT
FOUND entrez
W37937W37937
121082_
-
genbank-AA398722 AA398722
128634AA464918 at AA464918
105817genbank-AA397825 AA397825
121518genbanILAA412155 AA412155
114449genbank_AA020736 AA020736
65114648genbanILAA101056 AA101056
121950genbank_AA429515 AAd29515
107723genbank-AA015967 AA015967
1~1
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Table 3A shows 452 genes up-regulated in chronically diseased Lung relative to
normal lung. Chronically diseased lung samples represent chronic non-malignant
lung diseases
such as fibrosis, emphysema, and bronchitis. These genes were selected from
59680 probesets on the EosIAffymefrix Hu03 Genechip array. Gene expression
data for each
probeset obtained from this analysis was expressed as average intensity (AI),
a normalized value reflecting the relative level of mRNA expression.
J Pkey:Unique
Eos
probeset
identifier
number
ExAccn:Exemplar number, Genbank accession
Accession number
UnigenelD:
Unigene
number
Unigene
Title:
Unigene
gene
title
R1: 80th 0th
percentile percentile
of of
AI AI
for for
chronically normal
diseased lung
lung samples.
samples
divided
by
the
9
10R2: 80th
percentile
of
AI
for
chronically
diseased
lung
samples
divided
by
the
90th
percentile
of
normal
lung
samples,
squamous
cell
carcinomas
and
adenocarcinomas
R3: 70th
percentile
of
AI
for
chronically
diseased
lung
samples
minus
the
15th
percentile
of
AI
for
all
normal
lung,
chronically
diseased
lung
and
tumor
samples
dividedby
the
90th
percentile
of
normal
lung
samples,
squamous
cell
carcinomas
and
adenocarcinomas
minus
the
15th
percentile
of
AI
for
all
normal
lung,
chronically lung and tumor samples
diseased
15
Pkey ExAccnUnigenelDUnigeneTille Rt R2 R3
135423050531Hs.138751Human BRCA2 region, 12.40
mRNA sequence CG030
20135378AW961818Hs.24379MUM2 protein 2.13
135346NM_000928Hs.992phospholipase A2,
group IB (pancreas)
135235AW298244Hs.293507ESTs 12.40
135057090268Hs.93810cerebral cavernous 11.67
malformations 1
134951BE305081Hs.169358hypothetical protein 8.00
25134799M36821Hs.89690GR03 oncogene 8.20
134786T29618Hs.89640TEK tyrosine kinase,
endothelial (venous
134772NM Hs.163697glutamate receptor, 29.80
000829 ionotrophic, AMPA
4
134752BE246762Hs.89499arachidonate 5-lipoxygenase 1.93
134749T28499Hs.89485carbonic anhydraselV 2.07
30134696BE326276Hs.8861ESTs
134636NM_005582Hs.87205lymphocyte antigen 13.60
64 (mouse) homolog,
r
134627A1018768Hs.12482glyceronephosphate 1.92
0-acyltransferase
134622AW975159Hs.293097ESTs, Weakly similar 1.92
to A55380 faciogeni
134570066615Hs.172280SWI/SNF related, 13.20
matrix associated,
acti
35134561076421Hs.85302adenosine deaminase, 1.78
RNA-specific, B1
(h
134468NM_001772Hs.83731CD33 antigen (gp67) 6.20
134417NM Hs.82921solute carrier family
006416 35 (CMP-static act
134343D50683Hs.82028transforming growth
factor, beta recepto
134323BE170651Hs.8700deleted in liver
cancer 1
40134300NM_001430Hs.8136endothelial PAS domain
. protein 1
134299AW580939Hs.97199complement componentClqreceptor
134253X52075Hs.80738sialophorin (gpL115,20.60
leukosialin, CD43)
134182D52059Hs.7972KIAA0871 protein 12.20
133985L34657Hs.78146plateletlendothelial
cell adhesion molec
133978AF035718Hs.78061transcriptionfactor2l
133835A1677897Hs.76640RGC32 protein
133651A1301740Hs.173381dihydropyrimidinase-like
2
133633D21262Hs.75337nucleolar and coiled-body15.20
phosphprotein
133565AW955776Hs.313500ESTs, Moderately
similar to ALU7
HUMAN A
50133548AW946384Hs.178112DNA segment, single 1.77
copy probe LNS-CAIIL
133488AA335295Hs.74120adipose specific
2
133478X83703Hs.31432cardiac ankyrin repeat 2.08
preiein
133337AF085983Hs.293676ESTs 9.60
133200AB037715Hs.183639hypothetical protein 1.77
FLJ10210
55133153AF070592Hs.66170HSKM-B protein 30.60
133130AI128606Hs.6557zinc finger protein 22.60
161
133120NM Hs.65424tetranectin (ptasminogen-binding
003278 protein
132928AW168082Hs.169449protein kinase C, 13.80
alpha
132836AB023177Hs.29900KIAA0960 protein
60132799W73311Hs.169407SAC2 (suppresser 41.60
of actin mutations
2,
132742AA025480Hs.292812ESTs, Weakly similar40.40
to T33468 hypotheti
132548X12830Hs.193400interleukin 6 receptor 7.20
132476AL119844Hs.49476Homo sapiens clone 4.76
TUA8 Cri-du-chat
regi
132439AK001942Hs.4863hypothetical protein 1.88
DKFZp566A1524
65132240AB018324Hs.42676KIAA0781 protein 21.20
132210NM_007203Hs.42322A kinase (PRKA) anchor 1.99
protein 2
132199AL041299Hs,165084ESTs 15.20
131751T96555Hs.31562ESTs 1.76
131745AI828559Hs.31447ESTs, Moderately 27.80
similar to A46010
X-li
70131694NM Hs.3076MHC class II fransactivator 4.00
000246
131686NtvL012296Hs.30687GRB2-associated binding '
protein 2
131676AI126821Hs.30514ESTs 6.20
131629245794Hs.238809ESTs 21.40
131589C18825Hs.29191epithelial membrane
protein 2
75131536AA019201Ns.269210ESTs 9.40
131517AB037789Hs.263395sema domain, fransmembrane 3.59
domain (TM),
131355852804Hs.25956DKFZP564D206 protein 4.48
131253871802Hs.24853ESTs 15.00
131207AF104266Hs.242i2lafrophilin 1.75
80131156AI472209Hs.323117ESTs 1.84
131066AW169287Hs.22588ESTs 3.54
131061N64328Hs.268744KIAA1796 protein
131053AA348541Hs.296261guanine nucleotide 1.93
binding protein
(G pr
130895AA641767Hs.21015hypothetical protein16.60
DKFZp564L0864 simil
130762D84371Hs.1898paraoxonase 1 12.00
102
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
130657AW337575Hs.201591ESTs
130655A1831962Hs.17409cysteine-rich protein
1 (intestinal)
130589AL110226Hs.16441DKFZP434H204 protein 2.08
130562050402Hs.182611solute carderfamily 1.91
11 (proton-coupled
130555869743Hs.116774integdn, alpha 9.60
1
130365W56119Hs.155103eukaryotic translation11.60
initiation factor
130273AW972422Hs.153863MAD (mothers against 6.60
decapentaplegic,
Dr
130259NM-000328Hs.i53614retiniGs pigmentosa 1.91
GTPase regulator
130090H97878Hs.132390zinc finger protein21.20
36 (KOX 18)
10129958827496Hs.1378annexin A3 5.05
129898AI672731Hs.13256ESTs
129875AA181018Hs.13056hypoihe6calprotein18.60
FLJ13920
129699AB007899Hs.12017homologofyeastubiquitin-proteinligas
129626F13272Hs.111334ferrilin, light
polypeptide
I 129598N30436Hs.11556Homo Sapiens cDNA 22.63
S FLJ12566 fis,
clone NT
129593AI338247Hs.983i4Homo Sapiens mRNA;
cDNA DKFZp586L0120
(f
129565X77777Hs.198726vasoactive intestinal 2.53
peptide receptor
1
129527AA769221Hs.270847delta-tubulin 39.20
129402W72062Hs.11112ESTs 2.11
129385AA172106Hs.110950Rag C protein 15.20
129315NM-014563Hs.174038spondyloepiphyseal12.40
dysplasia, late
129312T97579Hs.110334ESTs, Weakly similar20.83
to 178885 serinellh
129240AA361258Hs.237868interleukin 7receptor 1.95
129210AL039940Hs.202949KIAA1102 protein
25129122AW958473Hs.301957nudix (nucleoside 4.20
diphosphate linked
mot
129057N90866Hs.276770CDW52 antigen (CAMPATH-1
antigen)
128946Y13153Hs.107318kynurenine 3-monooxygenase(kynurenine 5.20
3
128798AF015525Hs.302043chemokine (GC motif)
receptor-like
2
128789AW36857fiHs.13985icaveolin 2 2.24
3 128778AA504776Hs.186709ESTs, Weakly similar12.20
~ to 138022 hypothet
128766AW160432Hs.296460craniofacial development26.d0
protein 1
128631844238Hs.155546KIAA1080 protein; 1.78
Golgi-associated,
gamm
128624BE154765Hs.102647ESTs, Weakly similar 2.51
to TRHY-HUMAN
TRICH
128609NM Hs.102456survival of motor 16.00
003616 neuron protein
interac
35128603NM-004915Hs.10237ATP-binding cassette,12.80
sub-family G (WHIT
128598AA305407Hs.102308potassium inwardly-recUfying 4.00
channel, s
128458H55864Hs.56340ESTs
128061AF150882Hs.186877sodium channel, 17.20
voltage-gated,
type XII,
127968AA830201Hs.124347ESTs 21.30
4~127959A1302471Hs.124292Homo Sapiens cDNA:
FLJ23123 fis,
clone L
127944AI557081Hs.262476S-adenosylmethionine10.60
decarboxylase
1
127925AA805151Hs.3628mitogen-activated 13.40
protein kinase
kinase
127896AI669586Hs.222194ESTs 7.00
127859AA761802Hs.291559ESTs 14.00
,
45127817AA836641Hs.163085ESTs 14.00
127742AW293496Hs.180138ESTs 11.00
127628AI240102Hs.322430NDRG family, member11.10'
4
127609X80031Hs.530collagen, type
IV, alpha 3 (Goodpasture
127582AA908954Hs.130844ESTs 19.60
127543AK000787Hs.157392Homo Sapiens cDNA 15.d0
FLJ20780 fis,
clone CO
127535AA568424Hs.164450ESTs 17.50
127404A1379920Hs.270224ESTs 14.60
127396L31968Hs.187991DKFZP564A122 protein15.40
127374AA442797Hs.312110ESTs, Weakly similar14.60
to 138022 hypolhet
55127346AA203616Hs.44896DnaJ (Hsp40) homolog,21.00
subfamily B, membe
127340BE047653Hs.119183ESTs, Weakly similar15.80
to ZN91 HUMAN
ZINC
127307AW962712Hs.126712ESTs, Weakly similar
to AF1910201 E21G5
127242AW390395Hs.181301cathepsin S 22.60
127167AA625690Hs.190272ESTs 21.40
127046AA321948Hs.293968ESTs 41.20
126926AA480902Hs.137401ESTs 11.00
126900AF137386Hs.12701plasmolipin 1.78
126652AA399961 gb:zu68c01.r1 Scares 5.60
testis-NHT Homo
sap
126816AA248234 gb:csg2228.seq.F 12.20
Human fetal heart,
Lamb
65126812AB037860Hs.173933nuclearfactorllA 17.19
126666AA648886Hs.151999ESTs 13.57
126645AA316181Hs.61635six transmembrane 15.40
epithelial antigen
of
126592AI611153Hs.6093Homo Sapiens cDNA: 4.67
FLJ22783 fis,
clone K
126556AF255303Hs.112227membrane-associated18.00
nucleic acid binding
126433AA325606 gb:EST28707 Cerebellum16.77
II Homo sapiens
c
126299AW979155Hs.298275amino acid transporter14.60
2
126218AL049801Hs.13649Novel human gene 3.50
mapping to chomosome
13
126182AA721331Hs.293771ESTs 13.40
126177AW752782Hs.129750hypothetical protein18.20
FLJ10546
75126142H86261Hs.40568ESTs 14.00
126077M78772Hs.210836ESTs 16.59
125994A1990529Hs.270799ESTs 17.40
125934AA193325Hs.32646hypothetical protein13.00
FLJ21901
125847AW161885Hs.249034ESTs 49.57
125831H04043 gb:yj45c03.r1 Scares
placenta Nb2HP
Homo
125731861771Hs.26912ESTs 13.20
125676BE612918Hs.151973hypothetical protein11.20
FLJ23511
125561F78572Hs.22978ESTs, Weakly similar
to ALU4_HUMAN
ALU S
125552H09701Hs.278366ESTs, Weakly similar12.60
to 138022 hypotheti
85125489H49193Hs.124984ESTs,ModeratelysimilartoALU7_HUMANA33.40
103
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
125422AA903229Hs.153717ESTs 1.80
125331A1422996Hs.161378ESTs 38.00
125309T12411Hs.183745hypothetical protein18.20
FLJ13456
125167AL137540Hs.102541netrin 4 1.95
125139AW194933Hs.9788hypothetical protein 1.84
MGC10924 similar
to
125042T78906Hs.269432ESTs, Moderately 21.80
similar to ALU1
HUMAN
124711NM Hs.26530serum deprivation 10.60
004657 response (phosphatidyl
124631NM Hs.270594FLVCR protein 23.20
014053
124578N68321Hs.231500EST 21.43
10124574AL036596Hs.42322A kinase (PRKAj 1.77
anchor protein
2
124472N52517Hs.102670EST 37.20
124438BE178536Hs.11090membrane-spanning
4-domains, subfamily
A
124357N22401 gb:yw37g07.s1 Morton14.64
Fetal Cochlea Homo
124306AW973078Hs.293039ESTs 4.00
1 124214H58608Hs.151323ESTs
124097AW298235Hs.101689ESTs 27.20
123978T89832Hs.170278ESTs 2.03
123972T46848Hs.70337immunoglobulin superfamily, 6.00
member 4
123961AL050184Hs.21610DKFZP434B203 protein 1.79
123936NM_004673Hs.241519angiopoietin-like 15.80
1
123802AA620448 gb:ae58c09.s15tratagene 4.23
lung carcinoma
123734AA609861Hs.312447ESTs 4.20
123619AA602964 gb:no97c02.s1 NCI_CGAP_Pr233.60
Homo Sapiens
123596AA421130Hs.112640EST 10.93
123476AA384564Hs.108829ESTs 2.18
123340AA504264Hs.182937peplidylprolyl isomerase11.20
A (cyclophilin
123190AA489212Hs.105228EST 14.20
123136AW451999Hs.194024ESTs 7.00
123073AA485061Hs.105652ESTs 31.20
3 123055AA482005Hs.105102ESTs, Weakly similar 4.80
0 to reverse iranscri
122699AA456130Hs.301721KIAA1255 protein 5.00
122679AA811286Hs.192837ESTs, Weakly similar14.40
to ALU5 HUMAN ALU
S
122633NM_00154EiHs.34853inhibitor of DNA
binding 4, dominant
neg
122553AA451884Hs.190121ESTs 40.00
35122544AW973253Hs.292689ESTs 15.40
122485AA524547Hs.160318FXYD domain-containing 1.81
ion transport reg
122211AA300900Hs.98849ESTs,ModeratelysimilartoAF1615111H 12.10
122127AW207175Hs.106771ESTs 1.95
122011AA431082 gb:zw78a10.s15oares_testis_NHT 1.89
Homo sap
40121992AI860775Hs.98506ESTs 3.60
121989W56487Hs.193784Homo Sapiens mRNA; 2.01
cDNA DKFZp586K1922
(f
121835AB033030Hs.300670KIAA1204 protein 1.85
121726AF241254Hs.178098angictensin I converting12.43
enzyme (peptidy
121690AV660305Hs.110286ESTs 1.82
45121643AA640987Hs.193767ESTs
121633AA417011Hs.98175EST 14.00
121622AA416931Hs.126065ESTs 16.40
121497AA412031Hs.97901EST 11.20
121351AW206227Hs.287727hypothetical protein12.20
FLJ23132
121314W07343Hs.182538phospholipid scramblase 1.83
4
121242AA400857Hs.97509ESTs 22.40
121059AA393283 gb:zt74e03.r1 Soares14.80
testis_NHT Homo
sap
120934AA226198 gb:nc26a07.s1 NCI 21.20
CGAP_Pr1 Homo Sapiens
120755AA312934Hs.190745Homo sapiens cDNA: 1.79
FLJ21326 fis, clone
55120637AA811804 gb:ob39a05.s1 NCI-CGAP_GCB120.00
Homosapiens
120484AA253170Hs.96473EST 40.20
120336N85785Hs.181165eukaryolic translation 6.60
elongation factor
120266AI807264Hs.205442ESTs, Weakly similar16.80
to T34036 hypotheti
120132W57554Hs.125019ESTs 4.73
60120041AA830882Hs.59368ESTs 1.75
119996W88996Hs.59134EST 7.20
119970AA767718Hs.93581hypothetical protein11.20
FLJ10512
119861W78816Hs.49943ESTs, Weakly similar 3.78
to S65657 alpha-1G
119824W74536Hs.184advanced glycosylation
end product-speci
65119740AW021407Hs.21068hypothetical protein20.20
119271A1061118Hs.65328Fanconianemia,complementatfon15.20
group F
119221C14322Hs.250700tryptase beta 1
119126845175Hs.117183ESTs 12.60
119073BE245360Hs.279477ESTs
70118928AA312799Hs.283689activator of CREM 10.00
in testis
118901AW292577Hs.94445ESTs 3.96
118661AL137554Hs.49927protein kinase NYD-SP15 9.60
118607AI377444Hs.54245ESTs, Weakly similar10.40
to S65824 reverse
t
118449AI813865Hs.164478hypothetical protein 1.90
FLJ21939 similar
to
118416N66028Hs.491,05FKBP-associated 16.20
protein
118379N64491Hs.48990ESTs 4.00
118329N63520 gb:yy62f01.s1 Soares_multiple-sclerosis_ 6.60
118320N63451Hs.14i600ESTs, Weakly similar 3.80
to alternatively
s
118253AA497044Hs.20887hypothetical protein17.60
FLJ10392
118124N5696BHs.46707chromosome 21 open 14.00
reading frame 37
,
118056AB037746Hs.42768hypothetical protein 1.86
DKFZp76100113
118032N52802Hs.47544~ EST 5.00
117840T26379Hs.48802Homo Sapiens clone 4.00
23632 mRNA sequence
117404N39725Hs.15220zinc finger protein 1.90
106
$s117314N32498Hs.42829ESTs 14.20
104
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
117209W03011Hs.306881MSTP043 protein
117023AW070211Hs.102415Homo sapiens mRNA; 2.31
cDNA DKFZp586N0121
(f
116814H50834 gb:ypB6a10.s1Soaresfetalliverspleen20.20
116784AB007979Hs.301281Homo Sapiens mRNA, 3.51
chromosome 1 specific
116766AI608657Hs.95097ESTs 16.20
116712AW901618Hs.61935Homo Sapiens mRNA; 6.80
cDNA DKFZp7611071
(fr
116707H10344Hs.49050ESTs, Weakly similar18.60
to A Chain A, Human
116351AL133623Hs.82501similar to mouse 19.40
Xm1 I Dhm2 protein
116279AW971248Hs.291289ESTs,WeaklysimilartoALU1
FIUMANALUS
116166AL039940Hs.202949KIAA1102 protein 2.13
116152AL040521Hs.15220zinc finger protein 1.75
106
116117BE613410Hs.31575SEC63, endoplasmic 13.20
reGculum translocon
116107AL133916Hs.172572hypothetical protein30.11
FLJ20093
115965AA001732Hs.173233hypothetical protein 2.36
FLJ10970
I 115955AF263613Hs.44198intracellular membrane-associated18.20
S calciu
115844AI373062Hs.332938hypothetical protein18.57
MGC5370
115683AF255910Hs.54650junctionaladhesion 23.00
molecule 2
115673AA406341Hs.269908Homo sapiens cDNA 11.82
FLJ 11991 fis, clone
HE
115672AI889110Hs.73251ESTs 10.60
115566AH42336Hs.43977Human DNA sequence 1.76
from clone RP11-196N1
115313AA808001Hs.184411albumin 25.20
115279AW964897Hs.290825ESTs 8.00
115230AA278300Hs.124292Homo Sapiens cDNA: 1.80
FLJ23123 fis, clone
L
115110AK001671Hs.11387KIAA1453 protein 14.20
25 114999BE246481Hs.87856ESTs 19.20
114930AA237022Hs.188717ESTs 5.60
114922AA235672Hs.87491ESTs 3.60
114837BE244930Hs.166895ESTs 43.70
114769AA149060Hs.296100ESTs 11.00
114761AA143781Hs.126280hypotheticalprotein 14.00
FLJ23393
114736A1610347Hs.103812ESTs, Moderately 4.20
similar to ALU1
HUMAN A
114596AA310162Hs.169248cytochrome c 10.71
114518AW163267Hs.106469suppressorofvar1(S.cerevisiae)3-like20.40
114455H37908Hs.271616ESTs, Weakly similar20.40
to ALUB HUMAN ALU
S
3 114452AI369275Hs.243010Homo Sapiens cDNA 17.20
5 FLJ 14445 fis, clone
HE
114359NM-016929Hs.283021chloride intracellular 2.09
channel 5
114357841677Hs.6107Homo Sapiens cDNA 12.40
FLJ14839 fis, clone
OV
114251H15261Hs.21948ESTs 2.00
114138AW384793Hs.15740Homo Sapiens mRNA; 11.40
cDNA DKFZp434E033
(fr
40 114124W57554Hs.125019ESTs 6.04
113946AW083883Hs.37896Homo Sapiens cDNA 1.82
FLJ 13510 fis, clone
PL
113695796965Hs.17948ESTs, Weakly similar
to ALUB_HUMAN 7111
113606NM-013343Hs.278951NAG-7 protein 2.15
113590849642Hs.142447ESTs, Weakly similar 3.60
to ALU1 HUMAN ALU
S
45 113560791015Hs.268626ESTs 32.00
113552A1654223Hs.16026hypothetical protein
FLJ23191
113540AW152618Hs.16757ESTs
113502789130 gb:ye12d01.s1 Stratagene 8.35
lung (937210) H
113288A1076838Hs.12967ESTs 12.40
113252NM-004469Hs.11392c-fos induced growth 4.27
factor (vascular
en
113238845467Hs.189813ESTs
113203AA743563Hs.10305ESTs 21.20
113195H83265Hs.8881ESTs, Weakly similar 1.92
to S41044 chromosom
113089Td0707Hs.270862ESTs 14.33
55 113076AF033199Hs.8198zinc finger protein 6.00
204
113009723699Hs.7246ESTs 9.40
112937AI694320Hs.6295ESTs, Weakly similar 12.20
to 717248 hypotheti
112891703927Hs.293147ESTs, Moderately 10.57
similar to A46010
X-li
112794897018 gb:yq74bO8.s1 Soaresfetalliverspleen26.60
112691888708Hs.220647ESTs 15.33
112602AW004045Hs.203365ESTs 15.60
112366AF035318Hs.12533Homo Sapiens clone 15.40
23705 mRNA sequence
112210849645Hs.7004ESTs 14.00
112064AL049390Hs.22689Homo Sapiens mRNA; 13.00
cDNA DKFZp5B601318
(f
65 111998842379Hs.138283ESTs 11.00
111987NM_015310Hs.6763KIAA0942 protein 22.40
111803AA593731Hs,325823ESTs, Moderately 1.77
similar to ALU5_HUMAN
A
111737H04607Hs.9218ESTs 1.86
111605791061Hs.194178ESTs, Moderately 23.00
similar to PC4259
fern
70 111510807856Hs,16355ESTs 11.02
111341AL157484Hs.22483Homo Sapiens mRNA; 1.8B
cDNA DKFZp762M127
(fr
111280AA373527Hs.19385CGI-58 protein 18.40
111247AW058350Hs.16762Homo Sapiens mRNA;
cDNA DKFZp564B2062
(f
111232AI247763Hs.16928ESTs 27.60
75 110942863503Hs.28419ESTs 14.80
110924AW058463Hs.12940zinc-fingers and 24.71
homeoboxes 1
110837H03109Hs.10B920HT018 protein 2.18
110824AI767183Hs.26942ESTs 12.20
110776A8032417Hs.19545frizzled (Drosophila) 1.75
homolog 4
110576H60869Hs.37889ESTs 13.00
110369AK000768Hs.107872hypothetical protein 5.60
FLJ20761
110099844557Hs.23748ESTs 2.31
109984A1796320Hs.10299Homo Sapiens cDNA
FLJ13545 fis, clone
PL
109958AA001266Hs.133521ESTs 11.25
$s 109893AA884208Hs.30484ESTs 2.68
1~5
CA 02444691 2003-10-17
WO 443 PCT/US02/12476
02/086
109842AW818436Hs.23590solute tamer family23.83
16 (monocarboxylic
109837H00656Hs.29792ESTs, Weakly similar 3.91
to 138022 hypolheti
109796AI800515Hs.12024ESTs 17.20
109688841900Hs.22245ESTs 9.60
109648H17800Hs.7154ESTs 22.80
109613H47315Hs.27519ESTs
109550AW021488Hs.26981ESTs
109523AW193342Hs.24144ESTs 1.89
109472AK001989Hs.91165hypothetical protein 6.00
109355AA524525Hs.48297DKFZP586C1620 protein15.00
109260AW978515Hs.131915KIAA0863 protein 25.60
108781AA128654 gb:zn98g07.s1 Siratagene14.20
fetal retina 93
108663BE219231Hs.292653ESTs, Weakly similar11.00
to T26845 hypotheti
108573AA086005 gb:z184c04.s1 Stratagene26.00
colon (937204)
106480AL133092Hs.68055hypothetical protein
DKFZp43410428
108382NM-006770Hs.67726macrophage receptor 1.83
with collagenous
str
108174AA055632Hs.303070ESTs 15.20
108138AL049990Hs.51515Homo sapiens mRNA; 3.60
cDNA DKFZp564G1
1 2 (fr
108087AA045708Hs.40545ESTs 15.44
108048A1797341Hs.165195Homo Sapiens cDNA 11.40
FLJ14237 fis, clone
NT
108041AW204712Hs.61957ESTs
107997AL049176Hs.82223chordin-like 4.76
107994AA036811Hs.48469LIM domains containing
1
107922BE153855Hs.61460Ig superfamily receptor14.20
LNIR
107681BE379594Hs.49136ESTs,ModeratelysimilartoALU7_HUMANA51.80
107666AA010611Hs.60418EST 29.20
107332T87750Hs.183297DKFZP566F2124 protein10.73
107292BE166479Hs.4789Homo Sapiens serologically32.00
defined breas
107230A1034467Hs.34650ESTs 17.40
30 107168W57578Hs.237955R,4B7, member RAS 10.43
oncogene family
107160AA314490Hs.27669KIAA1563 protein 11.40
107054A1076459Hs.15978KIAA1272 protein
107029AF264750Hs.288971myeloidllymphoid 21.40
or mixed-lineage
leukem
106999H93281Hs.10710hypothetical protein35.80
FLJ20417
35 106954AF128847Hs.204038indolethylamineN-methyllransferase 1.76
106870AI983730Hs.26530serum deprivation
response (phosphatidyl
106865AW192535Hs.19479ESTs 13.40
106844AA485055Hs.158213sperm associated 7.13
antigen 6
106820NM Hs.12592period (Drosophila) 7.00
016831 homolog 3
40 106818AK002135Hs.3542hypothetical protein13.00
FLJ11273
106797AI76B801Hs.169943Homo Sapiens cDNA 2.05
FLJ13569 fis, clone
PL
106773AA478109Hs.188833ESTs
106747NM_007118Hs.171957triple functional 12.60
domain (PTPRF interact
106743BE613328Hs.2193Bhypotheticalprotein10.60
FLJ12492
45 106667AW360847Hs.16578ESTs
106605AW772298Hs.21103Homo Sapiens mRNA; 2.40
cDNA DKFZp564B076
(fr
106567AW450408Hs.86412chromosome 9 open 1.78
reading frame 5
106562AL031846Hs.i52151plakophilin4 1.76
106536AA329648Hs.23804ESTs, Weakly similar 2.19
to PN0099 son3
prat
50 106533AL134708Hs.145998ESTs 23.20
106507AA259068Hs.267819protein phosphatase15.20
1, regulatory (inhib
106490AA404265Hs.115537putative dipeptidase
106474BE383668Hs.42484hypothetical protein10.44
FLJ10618
106211AA428240Hs.126083ESTs 29.80
55 105986A8037722Hs.8707KIAA1301 protein 3.70
105894AI904740Hs.25691receptor (calcitonin) 1.94
activity modifying
105847AW964490Hs.32241ESTs, Weakly similar 1.75
to S65657 alpha-1
G
105803AW747996Hs.160999ESTs, Moderately 2.47
similar to A56194
ihrom
105731AA834664Hs.29131nuclearreceptorcoactivator210.71
60 105729H46612Hs.293815Homo Sapiens HSPC285
mRNA, partial cds
105688AI299139Hs.17517ESTs 23.40
105510242047Hs.283978Homo Sapiens PR0275137.20
mRNA, complete
cds
105101H63202Hs.38163ESTs 8.30
104989865998Hs.285243hypotheticalprotein 8.09
FLJ22029
65 104986AW088826Hs.117176poly(A)-binding 1.92
protein, nuclear
1
104969AI670947Hs.78406phosphatidylinositol-4-phosphate 5.40
5-kinas
104903AId36323Hs.31141Homo sapiens mRNA 7.60
for KIAA1568 protein,
104896AW015318Hs.23165ESTs 13.80
104865T79340Hs.22575Homo Sapiens cDNA:
FLJ21042 fis, clone
C
70 104825AA035613Hs.141883ESTs 1.87
104781AA099904Hs.21610DKFZP434B203 protein 1.93
104776AA026349 gb:zj99f01.s1 Soares-pregnant-uterus_NbH 10.20
104691U29690Hs.37744Homo sapiens beta-1 5.69
adrenergic receptor
104667AI239923Hs.30098ESTs 3.82
75 104404N58762 gb:EST00057 HE6W 4.20
Homo sapiens cDNA
clone
104392AA076049Hs.274415Homo Sapiens cDNA 27.20
FLJ10229 tis, clone
HE
104212A8002298Hs.173035KIAA0300 protein 1.91
104074AL162039Hs.31422Homo Sapiens mRNA; 11.20
cDNA DKFZp434M229
(fr
103749AL135301Hs.8768hypotheticalprotein10.86
FLJ10849
g 103645AW246253Ns.7043succinale-CoA ligase,12.00
0 GDP-forming, alpha
103554AI878826Hs.323469caveolin 1, caveolae ~ 1.80
protein, 22k0
103541AI815601Hs.79197CD83 antigen (activated
B lymphocytes,
1
103496Y09267Hs.132821tiavin containing
monooxygenase 2
103428BE383507Hs.78921A kinase (PRKA) 11.20
anchor protein
1
$s 103353X89399Hs.11927dRAS p21 protein 19.80
activator (GTPase
activa
106
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
103295X81479Hs.2375egF like module 3.60
containing, mucin-like,
103280084722Hs.76206cadherin 5, type
2, VE-cadherin
(vascula
103100005574Hs.184585LIM domain only 1.76
NM 2 (rhombotin-like
1)
103025_ Hs.123641protein tyrosine 2.15
NM phosphatase, receptor
002837 t
102698M18667Hs.1867progastricsin (pepsinogen
C)
102659BE245169Hs.211610CUG triplet repeat,11.00
RNA-binding protein
102580060808Hs.152981CDP-diacylglycerol 25.40
synthase (phosphatida
102417AA034127Hs.153487signal transducing 14.00
adaptor molecule
(SH3
102363NM Hs.198241amine oxidase, copper
003734 containing 3 (vasc
1 102302AA306342Hs.69171protein kinase Glike10.86
~ 2
102283AW161552Hs.83381guanine nucleogde
binding protein
11
102188020350Hs.78913chemokine (GX3-C) 7.40
receptor 1
102151T27013Hs.3132stereidogenic acute16.40
regulatory protein
101957L28824Hs.74101spleen tyrosine 15.40
kinase
15 101842M93221Hs.75182mannose receptor,
C type 1
101771NIv>_002432Hs.153837myeloid cell nuclear
differentiation
ant
101764AI198550Hs.81256S100 calcium-binding 1.78
protein A4 (calcium
101716AF050658Hs.2563tachykinin, precursor18.80
1 (substance K,
su
101678M62505Hs.2161complement component 2.22
5 receptor 1 (C5a
I
101447M21305 gb:Human alpha satellite504.80
and satellite 3
101383NM_000132Hs.79345coagulation factorVlll,procoagulantco 31.00
101346AI738616Hs.77348hydroxyprostaglandin 1.75
dehydrogenase 15-(N
101345NN[..005795Hs.152175calcitonin receptor-like
101336NM Hs.75678FBJ marine osteosarcoma 2.24
006732 viral oncogene
h
25 101330L43821Hs.80261enhanceroffilamentation
1 (cas-like do
101277BE297626Hs.296049microfibrillar-associated
protein 4
101262L35854 gb:Human dystrophin19.00
(dp140) mRNA, 5'
end
101168NM_005308Hs.211569G protein-coupled 2.01
receptor kinase
5
101102NM Hs.79059transforming growth
003243 factor, beta recepto
101088X70697Hs.553solute carrier family 7.52
6 (neurotransmilte
101066AW970254Hs.889Charot-Leyden crystal19.38
protein
100971BE379727Hs.83213fatty acid binding 1.91
protein 4, adipocyte
100893BE245294Hs.180789S164 protein 15.40
100770W25797.comp amyloid beta (A4) 11.20
Hs.177486 precursor protein
(pro
35 100716X89887Hs.172350HIR (histone cell 14.80
cycle regulation
defec
100555M69181 gb:Human nonmuscle 33.00
myosin heavy chain-B
100425NM_014747Hs.78748KIAA0237 gene product16.20
100408086640Hs.56045src homology three 4.00
(SH3) and cysteine
r1
100382083407Hs.156007Down syndrome critical 4.24
region gene 1-lik
4~ 100351064158 6.20
100299049493Hs.2171growth differentiation 21.20
factor 10
100134AA305746Hs.49macrophage scavengerreceptor1
100108009577Hs.76873hyaluronoglucosaminidase 1.79
2
100095297171Hs.78454myocilin, trabecular 5.40
meshwork inducible
45 loooss 11.29
TABLE 3B shows the accession numbers for those primekeys lacking unigenelD's
for Table 3A. For each probeset we have listed the gene cluster number from
which the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
50 similarity using Clustering and Alignment Tools (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
Pkey: Unique Eos probeset identifier number
55 CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accessions
6o
123619371681 1 AA602964 AA609200
126433127143_1 AA325606 AA099517
N89423
1258311522905 1 H04043 060988
060337
1268161 AA248234 AA090985
122973
126852_
136135-1 AA399961 AA128347
121059273450-1 AA393283 AA398628
120637200885 1 AA811804 AA809404
AA286907 AW977624
1220117617_ 2 AA431082
120934177521 1 AA226198 AA226513
AA383773
70 123802genbank-AA620448 AA620448
116814genbank-H50834 H50834
118329genbanILN63520 N63520
104404H58762 at H58762
104776genbank_AA026349 AA026349
75 113502genbank-T89130T89130
101262entrez L35854 L35854
108573genbank_AA086005 AA086005
101447entrez-M21305 M21305
124357genbank-N22401 N22401
$0 108781genbank-AA128654 AA128654
112794genbank_R97018 897018
100351entrez-064158 064158
100555tigr-HT2245 M69181
M81105 051039
g5
1~7
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Table 4A shows 202 genes up-regulated in samples from pafients treated with
chemotherapy or radiotherapy. These genes were selected from 59680 probesets
on the
EosIAffymetdx Hu03 Genechip array. Gene expression data for each probeset
obtained ham this analysis was expressed as average intensity (AI), a
normalized value reflecting
the relative level of mRNA expression.
Pkey:Unique
Eos
probeset
identifier
number
ExAccn:Exemplar
Accession
number,
Genbank
accession
number
UnigenelD: number
Unigene
UnigeneTitle:
Unigene
gene
title
Ri. average
of
AI
for
samples
from
patients
treated
with
chemotherapy
or
radiotherapy
divided
by
the
average
of
AI
for
normal
lung
samples'
1
O
Pkey ExAccnUnigenelDUnigene Title R1
100113NM_001269Ns.84746chromosome condensation27.20
1
100187D17793Hs.78183aldo-keto reductase 20.60
family 1, member
C3
100210D26361Hs.3104KIAA0042 gene product20.40
100225D28539Hs.167185glutamate receptor, 20.60
metabotropic 5
100269NM Hs'1189E2Ftranscriptionfactor329.40
001949
100438AA013051Hs.91417topoisomerase (DNA) 23.50
II binding protein
100877X80821Hs.27973KIAA0874 protein 35.56
1008938E245294Hs.180789S164 protein 43.40
101273211933Hs.182505POU domain, class 21.80
3, transcription
facto
101447M21305 gb:Human alpha satellite193.60
and satellite 3
101649AW959908Hs.1690heparin-binding growth38.40
factor binding pr
101724L11690Hs.620bullous pemphigoid 198.80
antigen 1 (2301240kD)
101748NM_001944Hs'1925desmoglein 3 (pemphigus78.60
vulgads antigen
101809M86849Hs.323733gap junction protein,162.20
beta 2, 26kD (coon
101879AA176374Hs.243886nuclear autoantigenic50.00
sperm protein (his
101915AF207881Hs.i55185cytosolic ovarian 26.00
carcinoma antigen
1
101973041514Hs.80120UDP-N-acetyl-alpha-D-galactosamine:polyp37.20
3 102025004045Hs.78934mutS (E. coli) homolog
0 2 (colon cancer,
102031004898Hs.2156RAR-related orphan 32.00
receptorA
102052NM_002202Hs.505ISL1 transcription 51.20
factor, LIMlhomeodoma
102391AA296B74Hs.77494deoxyguanosine kinase13.90
102420044060Hs.14427Homo Sapiens cDNA: 28.80
FLJ21800 fis, clone
H
102610065011Hs.30743preferentially expressed110.60
anfigen in mela
102829NM-006183Hs.80962neurotensin 116.80
103000NM_001975Hs.146580enolase 2, (gamma, 2.30
neuronal)
103036M13509Hs.83169matrix metalloprateinase181.40
1 (interstifial
103507AJ000512Hs.296323serumiglucocorticoid49.20
regulated kinase
103587BE270266Hs.821285T4 oncofetaltrophoblastglycoprotein86.60
104660BE298665Hs.1d846Homo Sapiens mRNA; 42.60
cDNA DKFZp564D016
(fr
104896AW015318Hs.23165ESTs 29.40
1050311AW503733Hs.9414KIAA1488 protein 21.50
105298BE387790Hs.26369hypothetical protein32.80
FLJ20287
105510242047Hs.283978Homo sapiens PR0275120.20
mRNA, complete cds
105667AA767526Hs.22030paired box gene 5 28.40
(B-cell lineage
specif
106073AL157441Hs.17834downstream neighbor 25.40
of SON
106205AW965058Hs.111583ESTs, Weakly similar32.00
to 138022 hypothefi
106516AL137311Hs.234074Homo Sapiens mRNA; 40.60
cDNA DKFZp76iG0212i
(
106533AL134708Hs.145998ESTs 59.80
106575AW970602Hs'105421ESTs 43.40
106654AW075485Hs.286049phosphoserine aminotransferase50.80
106851AI458623 gbak04g09'x1 NCI-CGAP_Lu2d53.40
Homo Sapiens
106995AB023139Hs.37892KIAA0922 protein 20.88
107332T87750Hs.183297DKFZP566F2124protein23.60
107532AA443473Hs.173684Homo sapiens mRNA; 57.20
cDNA DKFZp762G207
(fr
107922BE153855Hs.61dfi0Ig superfamilyreceptor49'00
LNIR
108609BE409857Hs.69499hypothetical protein19.67
108780AU076442Hs.117938collagen, type XVII,48.17
alpha 1
109166AA219691Hs.73625RAB6 interacfing, 59.20
kinesin-like (rabkines
109260AW978515Hs.131915KIAA0863 protein 28.60
109280AK001355Hs.279610hypothetical protein22.80
FLJ10493
109292AW975746Hs.188662KIAA1702 protein
109384AA219172Hs.86849ESTs 21.00
109415080736Hs.110826trinucleotide repeat31.60
containing 9
109445AA232103Hs.189915ESTs 24.20
109502AW967069Hs.211556hypothetical protein21.40
MGC5487
109633AW003785H5.170267ESTs 20.40
109786AI989482Hs.146286kinesin family member19.60
13A
109958AA001266Hs.133521ESTs 24.00
110920N47224Hs.20521HMT1 (hnRNP methyltransferase,28'40
S. cerevi
110924AW058463Hs.12940zinc-fingers and 36.00
homeoboxes 1
111084H44186Hs.15456PDZ domain containing61'20
1
111132AB037807Hs.83293hypothefical protein24.60
111229AW389845Hs.110855ESTs 27.20
111337AA837396Hs.263925LIS1-interacting 48.00
protein NUDE1, rat
homo
111987NM_015310Hs.6763KIAA0942 protein 37.80
112046AA383343Hs.22116CDC14 (cell division26.80
cycle 14, S. cerevi
112268W39609Hs.22003solute carrier family63.80
6 (neurolransmitte
112685887650Hs.33439ESTs, Weakly similar26.40
to ALU1 HUMAN ALU
112871AL110216Hs.12285ESTs, Weakly similar47.64
to 155214 salivary
112897AW206453Hs.3782ESTs 22.00
112973AB033023Hs.318127hypothetical protein65.00
FLJ10201
112992AL157425Hs.133315Homo Sapiens mRNA; 42.00
cDNA DKFZp761J1324
(f
113073N39342Hs.103042microtubule-associated55.40
protein 1B
108
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
113494T91451Hs.86538ESTs 22.80
113560T91015Hs.268626ESTs 22.80
113849AA457211Hs.8858bromodomain adjacent51.80
to zinc finger
doma
113950AI267652Hs.30504Homo Sapiens mRNA; 28.20
cDNA DKFZp434E082
(fr
114339AA782845Hs.22790ESTs 20.20
114365H42169Hs.18653hypothefical protein21.00
FLJ14627
114455H37908Hs.271616ESTs, Weakly similar25.80
to ALUB HUMAN ALU
S
114518AW163267Hs.106469suppressorofvarl(S.cerevisiae)3-like23.60
114824AA960961Hs.305953zinc finger protein27.20
83 (HPF1)
10114837BE244930Hs.166895ESTs 30.20
114974AW966931Hs.179662nucleosome assembly20.80
protein 1-like
1
115075AA814043Hs.88045ESTs 30.60
115084BE383668Hs.42484hypotheficalprotetn28.86
FLJ10618
115291BE545072Hs.122579hypotheticalprotein38.00
FLJ10461
1 115313AA808001Hs.184411albumin 22.60
115697031382Hs.63325transmembrane protease,173.60
serine 4
115909AW872527Hs.59761ESTs, Weakly similar27.77
to DAP1 HUMAN DEATH
116090AI591147Hs.61232ESTs 20.80
116107AL133916Hs.172572hypotheticalprotein164.20
FLJ20093
116399AA889120Hs.110637homeo box A10 38.00
117099H93699 gb:yv16a11.s15oaresfetalliverspleen21.60
117881AF161470Hs.260622butyrate-induced 49.40
transcript1
118091AW005054Hs.47883ESTs, Weakly similar22.40
to KCC1 HUMAN CALCI
118138AA374756Hs.93560Homo Sapiens mRNA 22.00
for KIAA1771 protein,
25118720N73515 gb:za49d07.s1 Soaresfetal20.00
liver spleen
118873AI824009Hs.44577ESTs 19.40
119126845175Hs.117183ESTs 111.20
119717AA918317Hs.57987B-cell CLUiymphoma 33.00
118 (zinc finger
pro
119940AL050097Hs.272531DKFZP586B0319 protein31.00
30120266A1807264Hs.205442ESTs, Weakly similar20.20
to T34036 hypotheti
120515AA258356 gb:zr59c10.s1 Soares25.00
NhHMPu S1 Homosapi
120859AA826434Hs.1619achaete-scute complex95.40
(Drosophila) homol
120983AA398209Hs.97587EST 105.20
121054AW976570Hs.97387ESTs 38.80
35121369AW450737Hs.128791CGI-09 protein 41.60
122335AA443258Hs.241551chloride channel, 30.80
calcium activated,
fam
122612AA974832Hs.128708ESTs 19.60
123130AAd87200 gb:ab19f02.s15tratagene33.20
lung (937210) H
123440AI733692Hs.112488ESTs 23.17
40123596AA421130Hs.112640ES7 23.00
123619AA602964 gb:no97c02.s1 NCI_CGAP_Pr228.80
Homo Sapiens
124006AI147155Hs.270016ESTs 77.60
124169BE079334Hs.271630ESTs 22.20
124281AI333756Hs.111801arsenate resistance42.20
protein ARS2
45124472N52517Hs.102670EST 32.60
124617AW628168Hs.152684ESTs 21.80
124631NM-014053Hs.270594FLVCR protein 30.40
124839855784Hs.140942ESTs 21.20
125186AA610620Hs.181244major histocompatibility42.80
complex, class
50125321T86652Hs.178294ESTs 27.00
125535NM Hs.22215secretogranin III 23.80
013243
125646AA628962Hs.75209protein kinase (CAMP-dependent,23.20
catalyti
125684AW589427Hs.i Homo Sapiens cDNA: 21.20
58849 FLJ21663 fis, clone
C
125724AL360190Hs,295978Homo Sapiens mRNA 48.80
full length insert
cDN
55125847AW161885Hs.249034ESTs 31.00
125934AA193325Hs.32646hypothetical protein21.20
FLJ21901
126077M78772Hs.210836ESTs 49.80
126299AW979155Hs.298275amino acid transporter21.80
2
126395AI468004Hs.278956hypotheticalprotein71.00
FLJ12929
60126433AA325606 gb:EST28707 Cerebellum23.20
II Homo Sapiens
c
126509847400Hs.23850ESTs 23.80
126538A8030656Hs.17377coronin, actin-binding23.10
protein, 1C
126666AA648886Hs.151999ESTs 36.00
126812AB037860Hs.173933nuclearfactorllA 20.80
6S126872AW450979 gb:Ul-H-B13-ala-a-12-0-Ul.s146.29
NCI-CGAP-Su
127046AA321948Hs.293968ESTs 22.80
127431AW771958Hs.175437ESTs, Moderately 30.00
similar to PC4259
fern
127489AA650250Hs.272076ESTs 20.80
127521AW297206Hs.164018ESTs 25.20
70127742AW293496Hs.180138ESTs 28.00
127925AA805151Hs.3628mitogen-activated 21.20
protein kinase
kinase
127930AA809672Hs.123304ESTs 20.54
127968AA830201Hs.124347ESTs 28.20
127987A1022103Hs.124511ESTs 19.60
75128116H07103Hs.286014Homo Sapiens, clone20.40
IMAGE:38672d3,
mRNA
128609NM_003616Hs.102456survival of motor 34.40
neuron protein
interac
128777AI878918Hs.10526cysteine and glycine-rich53.80
protein 2
128949AA009647Hs.8850a disintegrin and 23.00
metalloproteinase
doma
129168AI132988Hs.109052chromosome 14 open 37.60
reading frame 2
80129404AI267700Hs.317584ESTs 28.60
129527AA769221Hs.270847delta-lubulin ' 40.80
129574AA026815Hs.11463UMP-CMP kinase 31.20
129598N30d36Hs.11556Homo Sapiens cDNA 29.60
FLJ12566 fis, clone
NT
129785H19006Hs.18d780ESTs 72.20
129970AV655806Hs.296198chromosome 12 open 22.20
reading frame 4
109
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
130149AW067805Hs.172665methylenetetrahydrofolate29.60
dehydrogenase
130199248579Hs.172028a disintegrin and 27.60
metalloproteinase
doma
130441063630Hs.155637protein kinase, 28.36
DNA-activated,
catalytic
130466W19744Hs.180059Homo sapiens cDNA 20.20 '
FLJ20653 tis, clone
KA
130482AW409701Hs.1578baculoviral IAP 22.40
repeat-containing
5 (sur
130617M90516Hs.1674glutamine-fructose-6-phosphate19.60
transamin
130703877776Hs.18103ESTs 19.40
130732AW890487Hs.63984cadherin 13, H-cadherin21.40
(heart)
130867001072Hs.284239UDP glycosyltransferase110.00
NM 1 family, polype
1 131028_ Hs.2Z27CCAATIenhancer binding25.20
~ AI879165 protein (CIEBP),
131086AL035461Hs.2281chromogranin B (secretogranin40.60
1)
131284NM Hs.25272E1A binding protein24.60
001429 p300
131775AB014548Hs.31921KIAA0648 protein 21.00
131860BE3B3676Hs.334Rho guanine nucleotide33.40
exchange factor
(
15 131945NM Hs.35120replication factor 60.80
002916 C (activator 1)
4 (37
132040NM_001196Hs.315689Homo sapiens cDNA: . 20.40
FLJ22373 fis, clone
H
132084NM Hs.3886karyophedn alpha 29.40
002267 3 (importin alpha
4)
132389AA310393Hs.190044ESTs 32.40
132437AA152106Hs.4859cyclin L ania-6a 27.40
132550AW969253Hs.170195bone morphogenelic 75.60
protein 7 (osteogenic
132617AF037335Hs.5338carbonic anhydrase 31.36
XII
132632AU076916Hs.5398guanine monphosphate32.40
synthetase
132672W27721Hs.54697Cdc42 guanine exchangefactor(GEF)23.40
9
132742AA025480Hs.292812ESTs, Weakly similar61.20
to T33468 hypotheti
25 132771Y10275Hs.56407phosphoserine phosphatase22.33
133070092649Hs.64311a disintegrin and 23.50
metalloproteinase
doma
133153AF070592Hs.66170HSKM-B protein 30.00
133181X91662Hs.66744twist(Drosophila)homolog23.80
(acrocephalos
133282AA449015Hs.286145SR87 (suppressor 51.60
of RNA polymerase
B, ye
133350AI499220Hs.71573hypothetical protein33.00
FLJ10074
133592AV652066Hs.75113general transcription82.00
factor IIIA
133658AA319146Hs.75426secretogranin II
(chromogranin C)
133865AB011155Hs.170290discs, large (Drosophila)69.33
homolog 5
134032NM Hs.78589serine (or cysteine)33.20
005025 proteinase inhibito
35 134125NM Hs.50421KIAA0203 gene product31.60
014781
134158015174Hs.79428BCL2ladenovirus 30.60
E1B l9kD-interacting
pro
134321BE538082Hs.8172ESTs, Moderately 23.40
similar to A46010
X-tin
134367AA339449Hs.82285phosphoribosylglycinamide49.20
formyltransfer
134570066615Hs.172280SWIISNF related, 20.20
matrix associated,
acti
134753NM Hs.173135dual-specificity 20.80
006482 tyrosine-(Y)-phosphoryl
135002AA448542Hs.251677G antigen 7B 37.60 '
135029H58818Hs.187579hydroxysteroid (17-beta)53.40 '
dehydrogenase
135047AL134197Hs.93597cyclin-dependent 31.60
kinase 5, regulatory
su
135345X53655Hs.99171neurotrophin 3 28.80
45
TABLE 4B shows the accession numbers for those primekeys lacking unigenelD's
for Table 4A. For each probeset we have listed the gene cluster number from
which the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Tools (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
S 5 Accession: Genbank accession numbers
Pkey CAT number Accessions
123619 371681 1 AA602964 AA609200
126433 127143 1 AA325606 AA099517 N89423
126872 142696-1 AW450979 AA136653 AA136656 AW419381 AA9B4358 AA492073 BE168945
AA809054 AW238038 BE011212 BE011359
BE011367 BE011368 BE011362 BE011215 BE011365 BE011363
106851 322947 1 A1458623 AA639708 AA485409 822065 AA485570
118720 genbank_N73515 N73515
65 120515 genbanl~AA258356 AA258356
117099 321871 1 H93699 H97976 H80036
101447 entrez_M21305 M2i305
123130 genbank-AA487200 AA487200
11~
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Table 5A shows 680 genes up-regulated in squamous cell carcinoma or
adenocarcinoma lung tumors relative to normal lung and chronically diseased
lung. These genes were
selected from 59680 probesets on the EosIAffymetdx Hu03 Genechip array. Gene
expression data for each probeset obtained from this analysis was expressed as
average
intensity (AI), a normalized value reflecting the relative level of mRNA
expression.
Pkey: Unique Eos probeset identifier number
ExAccn: ExempIarAccession number, Genbank accession number
UnigenelD: Unigene number
Unigene Titie: Unigene gene title
R1: 70th percentile of AI for squamous cell carcinoma and adenocarcinoma lung
tumor samples divided by the 90th percentile of AI for normal and chronically
1 ~ diseased lung samples.
R2: 80th percentile of AI adenocarcinoma lung tumor samples divided by the
90th percentile of AI for normal and chronically diseased lung samples.
R3: 80th percentile of AI squamous cell carcinoma lung tumor samples divided
by the 90th percentile of AI for normal and chronically diseased lung samples.
R4: 80th percentile of AI adenocarcinoma lung tumor samples divided by the
80th percentile of AI for squamous cell carcinoma lung tumor samples.
R5: 70th percentile of AI for squamous cell carcinoma and adenocarcinoma lung
tumor samples minus the 15th percentile of AI for all normal lung, chronically
15 diseased lung and tumor samples divided by 90th percentile of AI for normal
and chronically diseased lung samples minus the 15th percentile of AI for all
normal lung, chronically diseased lung and tumor samples
Pkey ExAccnUnigenelDUnigeneTitle R1 R2 R3 R4 R5
2o
100035 AFFX control: GAPDH6.76
100036 AFFX control: GAPDH5.77
100037 AFFX control: GAPDH5.75
100071A28102 Human GABAa receptor8.00
alpha-3 subunit
100114X02308Hs.82962thymidylate syntheiase5.71
100154H60720Hs.81892KIAA0101 gene product3.84
100187D17793Hs.78183aldo-keto reductase3.33
family 1, member
C3
100188AW247090Hs.57101minichromosome 4.52
maintenance deficient
(S.
100202BE294407Hs.99910phosphofructokinase,5.49
platelet
100216AA489908Hs.1390proteasome (prosome,5.67
macropain) subunit,
100269NM Hs.1189E2F transcription 2.55
001949 factor 3
100287AU076657Hs.1600chaperonin containing5.66
TCPt, subunit
5 (e
100297AU077258Hs.182429protein disulfide 3.81
isomerase-related
prat
100330AW410976Hs.77152minichromosome 4.50
maintenance deficient
(S.
100335AW247529Hs.6793platelet-activating5.07
factor acetylhydrcla
100360W70171Hs.75939uridine monophosphate4.82
kinase
100372NM Hs.184339KIAA0175 gene product3.79
014791
100474NM Hs.300280amylase, alpha 15.65
000699 2A; pancreatic
100486T19006Hs.10842RAN, member RAS 5.49
oncogene family
100491D56i65Hs.275163non-meiastatic 4.17
cells 2, protein
(NM23Bj
100516D90278Hs.l1 carcinoembryonic 7.20
antigen-related
cell ad
100522X51501Hs.99949prolactin-induced 14.20
protein
100559NM Hs.1640collagen, type 3.10
000094 VII, alpha 1 (epidermolys
100576X00356Hs.37058calcitoninlcalcitonin-related9.30
polypeptid
45 100629AA015693Hs.21291mitogen-activated 20.60
protein kinase
kinase
100661BE623001Hs.132748Homo sapiens ribosomal3.85
protein L39 mRNA,
100677AA353686Hs.57813zinc ribbon domain8.60
containing,1
100696D14887Hs.121686general franscripticn10.00
factor IIA,1 (37k
100709N26539Hs.100469myeloidllymphoid 24.80
or mixed-lineage
leukem
100761BE208491Hs.2951i2KIAA0618 gene product7.60
100830AC004770Hs.4756flap structure-specific7.99
endonuclease 1
100867014622 gb:Human transketolase-like10.20
protein gene
100902M16029Hs.287270ret proto-oncogene8.00
(multiple endocrine
n
100906AU076916Hs.5398guanine monphosphate5.16
synthetase
55 100960J00124Hs.117729keratin 14 (epidermolysis2.57
bullosa simple
101045J05614 gb:Human proliferating4.69
cell nuclear anti
101061NM_000175Hs.180532glucose phosphate 4.19
isomerase
101071L02840Hs,84244potassium voltage-gated12.91
channel, Shab-re
101124L10343Hs.112341protease inhibitor3.12
3, skin-derived
(SKAL
101175082671Hs.36980melanoma antigen, 3.50
family A, 2
101181BE262621Hs.13798macrophage migration5.69
inhibitory factor
(
101204L24203Hs.82237ataxia-telangiectasia4.08
group D-associated
101210L29301Hs.2353apioid receptor, 6.40
mu 1
101216AA284166Hs.84113cyclin-dependent 2.53
kinase inhibitor
3 (CDK
65 101228AA333387Hs.82916chaperonin containing7.90
TCP1, subunit
6A (
101233AL135173Hs.878sorbitoldehydrogenase4.45
101273211933Hs.182505POU domain, class 8.50
3, transcription
facto
101342052112Hs.182018interleukin-1 receptor-associated4.17
kinase
101346AI738616Hs.77348hydroxyprostaglandin21.89
dehydrogenase
15-(N
101369NM_000892Hs.1901kallikrein B, plasma12.80
(Fletcher factor)
1
101396BE267931Hs.78996proliferating cell3.24
nuclear antigen
101431BE185289Hs.1076small proline-rich7.90
protein 1B (cornifln)
101448NM Hs.195850keratin 5 (epidermolysis8.31
000424 bullosa simplex
101462AL035668Hs.73853bone morphogenetic38.80
protein 2
75 101466BE262660Hs.170197glutamic-oxaloacetic4.01
transaminase 2,
mit
101484AA053486Hs.20315interferon-induced12.00
protein with tetraUi
101502M26958 gb:Human parathyroid10.50
hormone-related
pro
101505AA307680Hs.75692asparagine synthetase4.46
101526NM Hs.154721aconitase 1, soluble4.02
002197
g0 101535X57152Hs.99853fibrillarin 4.65
101577M34353Hs.1041v-ros avian UR2 9.09
sarcoma virus
oncogene h
101649AW959908Hs.1690heparin-binding 54.00
growth factor
binding pr
101663NM_003528Hs.2178H28 histone family,5.59
member A
101664AA436989Hs.121017H2A histone family,7.00
member A
g5 101669L24498Hs.80409growth arrest and 7.60
DNA-damage-inducible,
111
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
101695M69136Hs.135626chymase 1, mast 4.79
cell
10f72dL11690Hs.620bullous pemphigoid15.21
antigen 1 (230I240kD)
101748NM-001944Hs.1925desmoglein 3 (pemphigus55.50
vulgaris antigen
101759M80244Hs.184601solute carrier 4.10
family 7 (cationic
amino
101771NM Hs.153837myeloid cell nuclear 18.57
002432 differentiation
ant
101804M86699Hs.169840TTK protein kinase4.50
101809M86849Hs.323733gap junction protein,140.00
beta 2, 26kD (coon
101833AU076442Hs.117938collagen, type 2.56
XVII, alpha 1
101842M93221Hs.75182mannose receptor, 12.80
C type 1
1 101851BE260964Hs.82045midkine (neurite 5.88
~ growth-promoting
factor
102002NM_002484Hs.81469nucleotide binding 7.80
protein 1 (E.coli
Min
102039ALi Hs.306098aldo-keto reductase 4.35
34223 family 1, member
C1
102072009410Hs.78743zinc finger protein 7.40
131 (clone pHZ-10)
102083T35901Hs.75117interleukin enhancer 5.12
binding'factor
2, 4
15 102111L36196Hs.81884sulfotransferase 12.00
family, cytosolic,
2A,
102123NM-001809Hs.1594centromere protein6.20
A (l7kD)
102154017760Hs.75517laminin, beta 3 2.62
(nicein (125kD),
kalinin
102193AL036335Hs.313secreted phosphoprotein5.85
1 (osleopontin,
102217AA829978Hs.301613JTV1gene 6.18
2~ 102224NM_002810Hs.148495proteasome (prosome,. 4.49
macropain) 26S
subu
102234AW163390Hs.278554heterochromatin-like 5.80
protein 1
102251NM Hs.41706DEADIH (Asp-Glu-Ala-AspIHis)4.50
004398 box polypep
102305AL043202Hs.90073chromosome segregation 5.15
1 (yeast homology
102330BE298063Hs.77254chromobox homolog 4.17
1 (Drosophila
HP1 beta
25 102340037055Hs.278657macrophage stimulating 9.33
1 (hepatocyte
gro
102348037519Hs.87539aldehyde dehydrogenase8.87
3 family, member
102368039817Hs.36820Bloom syndrome 15.91
102394NM_00381&Hs.2442a disintegrin and 19.20
metalloproteinase
doma
102404Ntv> Hs.79141vascular endothelial 14.00
005429 growth factor
C
3~ 102537_ Hs.50477RAB27A, member 12.00
057094 RAS oncogene family
102581AU077228Hs.77256enhancerofzeste 4.57
(Drosophila) homolog
2
102605A1435128Hs.181369ubiquitin fusion 3.98
degradation 1-like
102610065011Hs.30743preferentially 77.50
expressed antigen
in mela
102623AW249285Hs.37110melanoma antigen, 12.50
family A, 9
35 102642AA205847Hs.23016G protein-coupled 22.00
receptor
102654AV649989Hs.24385Human hbc647 mRNA 12.00
sequence
102659BE245169Hs.211610CUG triplet repeat, 12.80
RNA-binding protein
102669071207Hs.29279eyes absent (Drosophila)6.50
homolog 2
102672072066Hs.29287retinoblastoma-binding8.50
protein 8
40 102687NM_007019Hs.93002ubiquitin carrier 9.24
protein E2-C
102696BE540274Hs.239forkhead box M1 5.54
102768082321 gb:Homo Sapiens 6.60
clone 14.98 mRNA
sequenc
102781BE258778Hs.108809chaperonin containing 3.78
TCP1, subunit
7 (e
102784085658Hs.61796transcription factor 4.26
AP-2 gamma (activat
45 102824090916Hs.82845Homo Sapiens cDNA: 14.40
FLJ21930 fis,
clone H
102829NM_006183Hs.80962neurotensin 8.00
102888AI346201Hs.76118ubiquitin carboxyl-terminal 5.50
esterase L1
102892BE440042Hs.83326matrix metalloproteinase 6.70
3 (stromelysin
102913NM_002275Hs.80342keratin 15 4.64
102935BE561850Hs.80506small nuclear ribonucleoprotein2.93
polypept
102951X15218Hs.2969v-ski avian sarcoma 11.40
viral oncogene
homol
102983BE387202Hs.118638non-metastatic 7.26
cells 1, protein
(NM23A)
103023AW500470Hs.117950multifunctional 3.01
polypeptide similar
to S
103036M13509Hs.83169matrix metalloproteinase27.90
1 (interstitial
55 103038AA926960Hs.334883CDC28 protein kinase 8.79
1
103060NM_005940Hs.155324matrix metalloproteinase 4.27
11 (stromelysin
103099AI693251Hs.8248NADH dehydrogenase 9.80
(ubiquinone) Fe-S
pro
103119X63629Hs.2877cadherin 3, type 4.05
1, P-cadherin
(placenta
103168X53463Hs.2704glutathione peroxidase3.07
2 (gastrointestin
103185NM_006825Hs.74368lransmembrane protein 5.62
(63kD), endoplasmi
103192M22440Hs.170009transforming growth 7.40 '
factor, alpha
103223BE275607Hs.1708chaperonin containing 4.70
TCP1, subunit
3 (g
103242X76342Hs.389alcohol dehydrogenase 100.00
7 (class IV),
mu o
103316X83301Hs.324728SMA5 9.80
65 103375NM Hs.54416sine oculis homeobox9.71
005982 (Drosophila) homolo
103376AL036166Hs.323378coated vesicle 14.00
membrane protein
103385NtuL007069Hs.37189similar to ratHREV107 11.00
103391X94453Hs.114366pyrroline-5-carboxylate2.93
synlhetase (glut
103404BE394784Hs.78596proteasome (prosome, 5.15
macropain) subunit,
103430BE564090Hs.20716translocase of 3.98
inner mitochondria)
membr
103446X98834Hs.79971sat (Drosophila)-like 21.40
2
103476Y07701Hs.293007aminopeptidase 13.00
puromycin sensitive
103477AJ011812Hs.119018transcriptionfactor 6.40
NRF
103478BE514982Hs.38991S100 calcium-binding5.02
protein A2
75 103515Y10275Hs.56407phosphoserine phosphatase10.50
103558BE616547Hs.2785keratin 17 6.41
103580AA328046Hs.46405polymerase (RNA) 3.84
II (DNA directed)
polyp
103587BE270266Hs.821285T4 oncofetal trophoblast78.50
glycoprotein
103594AI368680Hs.816SRY (sex determining6.51
region Y)-box
2
103636NM Hs.2407POU domain, class 3.50
006235 2, associating
factor
103768AF086009 gb:Homo Sapiens 4.48
full length insert
cDNA
103841AA3f Hs.38178hypothetical protein 8.00
4821 FLJ23468
103847AF219946Hs.102237tubby super-family 10.40
protein
103913AW967500Hs.133543ESTs 15.60
$5 104094AA418187Hs.330515ESTs 6.60
112
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
104150AL122044Hs.331633hypotheticalprotein26.00
DKFZp566N034
104257BE560621Hs.9222estrogen receptor 6.80
binding site associate
104261AW2d8364Hs.5409RNA polymerase I 3.98
subunit
104331AB040450Hs.279862cdk inhibitor p21 6.80
binding protein
104415BE410992Hs.258730heme-regulated initiation10.29
factor 2-alpha
104558856678Hs.88959hypothetical protein4.21
MGC4816
104590AW373062Hs.83623nuclear receptorsubfamily15.79
f, group I, m
104658AA360954Hs.27268Homo Sapiens cDNA: 17.40
FLJ21933 fis, clone
H
104660BE298665Hs.14846Homo Sapiens mRNA; 6.40
cDNA DKFZp564D016
(Fr
1 104689AA420450Hs.292911ESTs, Highly similar6.55
~ to S60712 band-6-pr
104754AI206234Hs.155924cAMP responsive 10.00
element modulator
104758BE560269Hs.7010NPD002 protein 4.47
104971BE311926Hs.15830hypothetical protein2.87
FLJ12691
105011BE091926Hs.16244mitotic spindle 3.83
coiled-coil related
prot
1 105012AF098158Hs.9329chromosome 20 open 2.86
S reading frame 1
105026AA809485Hs.124219hypotheticalprotein11.00
FLJ12934
105076A1598252Hs.37810hypothetical protein5.01
MGC14833
105132AA148164Hs.247280HBV associated factor3.99
105143AI368836Hs.24808ESTs, Weakly similar11.00
to 138022 hypotheti
105158AW976357Hs.234545hypothetical protein16.00
NUF2R
105175AA305384Hs.25740ER01 (S. cerevisiae)-like4.32
105200AA328102Hs.246d1cytoskeleton associated3.00
protein 2
105264AA227934 gb:zr57e08.s1 Soares10.00
NhHMPu_S1 Homo
sapi
105298BE387790Hs.26369hypothetical protein3.69
FLJ20287
105409AW505076Hs.301855DiGeorge syndrome 9.20
critical region
gene 8
105460AW296078Hs.271721Homo Sapiens, clone7.80
IMAGE:4179986,
mRNA,
105667AA767526Hs.22030paired box gene 4.12
5 (B-cell lineage
specif
105743BE2d6502Hs.9598sema domain, immunoglobulin3.82
domain (1g),
105782H09748Hs.57987B-cell CLLllymphoma27.00
11 B (zinc finger
pro
3 105848AW954064Hs.24951ESTs 7.60
~
105891055984Hs.289088heat shock 90kD 4.14
protein 1, alpha
106019AF221993Hs.46743McKusick-Kaufman 16.80
syndrome
106069BE566623Hs.29899ESTs, Weakly similar23.40
to 602075 transcrip
106073AL157441Hs.17834downstream neighbor9.50
of SON
35 106126AA576953Hs.22972hypothetical protein6.00
FLJ13352
106159AK001301Hs.3487hypothetical protein3.95
FLJ10439
106220D61329Hs.32196mitochondrial ribosomal6.04
protein L36
106260A1097144Hs.5250ESTs, Weakly similar13.20
to ALU1 HUMAN ALU
S
106300Y10043Hs.19114high-mobility group5.02
(nonhistone chromoso
106307AA436f74Hs.37751ESTs, Weakly similar6.60
to putative p150
(
106318AA025610Hs.9605cleavage and polyadenylation5.04
specific fa
106341AF191020Hs.5243hypothetical protein,7.25
estradiol-induced
106440AA449563Hs.151393glutamate-cysteine 13.80
ligase, catalytic
sub
106481D61594Hs.17279lyrosylprotein sulfotransferase4.75
1
45 106586AA243837Hs.57787ESTs 10.84
106605AW772298Hs.21103Homo Sapiens mRNA; 45.60
cDNA DKFZp5648076
(fr
106654AW075485Hs.286049phosphoserine aminotransferase28.00
106785Y15227Hs.20149deleted in lymphocytic3.00
leukemia,1
106813C05766Hs.181022CGI-07 protein 11.40
106895AK001826Hs.25245hypotheticalprotein6.00
FLJ11269
106913A1219346Hs.86178M-phase phosphoprotein6.56
9
106919AW043637Hs.21766ESTs, Weakly similar4.27
to ALU5_HUMAN ALU
S
107054A1076459Hs.15978KIAA1272 protein 34.80
107059BE61d410Hs.2304dRAD51 (S. cerevisiae)4,71
homolog (E colt
Re
55 107098AI823593Hs.27688ESTs 24.80
107104AU076640Hs.15243nucleolar protein 7.05
1 (120kD)
107129AC004770Hs.4756flap structure-specific2.60
endonuclease 1
107198AV657225Hs.9846KIAA1040 protein 19.20
107203D20426Hs.41639programmed cell 7.60
death 2
107217AL080235Hs.35861DKFZP586E1621 protein9.50
107284NM_005629Hs.187958solute carrier family2.71
6 (neurotransmitte
107318T74445Hs.5957Homo Sapiens clone 8.71
24416 mRNA sequence
107516X57152Hs.99853fibrilladn 4.33
107529BE515065Hs.296585nucleolar protein 4.00
(KKEID repeat)
65 107728AA019551Hs.294151Homo Sapiens, clone10.80
IMAGE:3603836,
mRNA,
107851AA022953Hs.61172EST 8.00
107901L42612Hs.335952keratin 6B 3.40
107922BE153855Hs.61460Ig superfamily receptor2.88
LNIR
107932AW392555Hs.18878hypothetical protein7.50
FLJ21620
70 108015AW298357Hs.49927protein kinase NYD-SP1523.40
108056AA043675Hs.62633ESTs 12.80
-108075A1867370Hs.139709hypotheticalprotein12.80
FLJ12572
108187BE245374Hs.27842hypolheticalprotein7.00
FLJ11210
108296N31256Hs.161623ESTs 6.60
75 108305AA071391 gb:zm61e06.r1 Stratagenefibroblast(93711.80
106393AA0752f1 gb:zm86a08.r1 Stratagene11.80
ovarian cancer
108480AL133092Hs.68055hypothetical protein20.80
DKFZp43410428
108554AA084948 gb:zn13b09.s1 Stratagene6.40
hNT neuron (937
108573AA086005 gb:z184c04.s1 Stratagene25.40
colon (937204)
108584AA088326Hs.120905Homo Sapiens cDNA 9.60
FLJ11448 fls, clone
HE
108597AK000292Hs.278732hypotheticalprotein14.60
FLJ20285
108695AB029000Hs.70823KIAA1077 protein 3.00
108699AA121514Hs.70832ESTs 10.00
108700AA121518Hs.193540ESTs, Moderately 11.00
similar to 2109260A
B c
g5 108780AU076442Hs.117938collagen, type XVII,11.21
alpha 1
113
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
108810AW295647Hs.71331hypothetical protein8.50
MGC5350
108816AA130884Hs.270501ESTs, Moderately 7.40
similario ALU2
HUMAN
108857AK001468Hs.62180anillin (Drosophila4.00
Scraps homology,
act
108860AA133334Hs.129911ESTs 6.09
108937AL050107Hs.24341transcriptional 3.00
co-activator with
PDZ-bi
109010NM_OD7240Hs.44229dual specificity 2.69
phosphatase 12
109121BE389387Hs.49767NADH dehydrogenase 4.53
(ubiquinone) Fe-S
pro
109166AA219691Hs.73625RAB6 interacting, 10.513
kinesin-like (rabkines
109227AA766998Hs.85874Human DNA sequence 9.00
from clone RP11-16L21
10109415U80736Hs.110826trinucleotide repeat51.40
containing 9
109418AI866946Hs.161707ESTs 11.00
109454AA232255Hs.295232ESTs, Moderately 17.60
similar to A46010
X-li
109502AW967069Hs.211556hypothetical protein9.d9
MGC5487
109543AA564994Hs.222851ESTs 12.67
15109648H17800Hs.7154ESTs 10.40
109680AB037734Hs.4993KIAA1313 protein 33.20
109700F09609 gb:HSC33H092 normalized16.00
infant brain cDN
109704AI743880Hs.12876ESTs 11.00
109792849625 gb:yg61f03.s1 Soares12.60
infant brain 1NIB
H
1099818E546208Hs.26090hypotheticalprotein4.00
FLJ20272
109998AL042201Hs.21273transcriptionfactor7.80
NYD-sp10
110039H11938Hs.21907histone acetyltransferase7.00
110156AA581322Hs.4213hypothetical protein4.24
MGC16207
110500AA907723Hs.36962ESTs 4.50
110551AW450381Hs.14529ESTs 8.60
110561AA379597Hs.5199HSPC150 protein 3.06
similar to ubiquitin-con
110854BE612992Hs.27931hypothetical protein6.80
FLJ10607 similar
to
1108136AW274992Ns.72249three-PDZ containing8.80
protein similar
to
110916BE178102Hs.24349ESTs fi.80
111003N52980Hs.83765dihydrofolate reductase16.80
111337AA837396Hs.263925LIS1-interacting 2.54
protein NUDE1,
rat homo
111434801608Hs.142736ESTs 9.80
111439A1476429Hs.19238ESTs 10.40
111540U82670Hs.9786zinc finger protein15.40
275
35111597811499Hs.189716ESTs 9.20
111895T80581Hs.12723Homo Sapiens clone 6.80
25153 mRNA sequence
111929AF027208Hs.112360prominin (mouse)-like14.67
1
112054843590 gb:yc85g02.s1 Soares10.80
infant brain 1
NIB H
112210849645Hs.7004ESTs 10.20
40112244A8029000Hs.70823KIAA1077 protein 2.99
112382859904 gb:yh07g12.s1 Soares6.60
infant brain 1NIB
H
112392860763Hs.193274ESTs, Moderately 7.10
similar to 157588
HSrel
112442AA280174Hs.285681Williams-Beuren 3.00
syndrome chromosome
regi
112539870318Hs.339730ESTs 37.20
45112772AI992283Hs.35437ESTs, Moderately 14.60
similar 10138026
MLN 6
112869BE261750Hs.4747dyskeratosis congenita4.83
1, dyskerin
112935871449Hs.268760ESTs 2.73
112970AA694010Hs.6932Homo Sapiens clone 12.00
238D9 mRNA sequence
112973A8033023Hs.318127hypotheticalprotein11.50
FLJ10201
112992AL157425Hs.133315Homo sapiens mRNA; 10.89
cDNA DKFZp761J1324
(f
113063W15573Hs.5027ESTs, Weakly similar15.00
to A47582 B-cell
gr
113073N39342Hs.103042microtubule-associated15.31
protein 1B
113078T40444Hs.118354CAT56 protein 7.00 ,
113238845467Hs.189813ESTs 41.20
55113591T91881Hs.200597KIAA0563 gene product9.40
113702T97307 gb:ye53h05.s1 Soares25.00
fetal liver spleen
113844AI369275Hs.243010Homo Sapiens cDNA 13.91
FLJ14445 fis, clone
HE
113984896696Hs.35598ESTs 7.80
114073844953Hs.22908Homo Sapiens mRNA; 7.20
cDNA DKFZp434J1027
(f
114162AF155661Hs.22265pyruvate dehydrogenase3.42
phosphatase
114208AL049466Hs.7859ESTs 6.74
114251H15261Hs.21948ESTs 33.20
114285844338Hs.22974ESTs 13.20
114313H18456Hs.27946ESTs 10.00
65114339AA782845Hs.22790ESTs 7.80
114407BE539976Hs.103305Homo sapiens mRNA; 4.14
cDNA DKFZp434B0425
(f
114560AI452469Hs.165221ESTs 9.80
114699AA127386 gb:zn90d09.r1 Stratagene7.60
lung carcinoma
114767AI859865Hs.154443minichromosome maintenance3.21
deficient (S
70114793AA158245 gb:zo76c03.s1 SUatagene6.00
pancreas(93720
114833A1417215Hs.87159hypothetical protein11.40
FLJ12577
115047BE270930Hs.82916chaperonin containing4.31
TCP1, subunit 6A
(
115060AF052693Hs.198249gap junction protein,4.03
beta 5 (connexin
3
115097AA256213Hs.72010ESTs 35.40
75115113AA256460 gb:zr81a04.s1 Soares-NhHMPu-S115.20
Homosapi
115123AA256641Hs.236894ESTs, Highly similar4.19
to S02392 alpha-2-m
115134AW968073Hs.194331ESTs, Highly similar12.40
to A55713 inositol
115291BE545072Hs.122579hypotheticalprotein25.00
FLJ10461
115347AA356792Hs.334824hypothetical protein7.00
FLJ14825
115414AA662240Hs.283099AF15q14 protein 3.25
115522BE614387Hs.333893c-Myc target JP01 3.68
115536AK001468Hs.62180anillin (Drosophila10.50
Scraps homology,
act
115566AI142336Hs.43977Human DNA sequence 24.40
from clone RP11-196N1
115645AI207410Hs.69280Homo Sapiens, clone4.17
IMAGE:3636299,
mRNA,
115648AW016811Hs.234478Homo Sapiens cDNA: 6.00
FLJ22648 fis, clone
H
114
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02/086443
115652BE093589Hs.38178hypothetical protein3.81
FLJ2346B
115697D31382Hs.63325transmembrane protease,62.14
serine 4
115793AA424883Hs.70333hypothefical protein 11.80
MGC10753
115816BE042915Hs.287588Homo Sapiens cDNA 9.71
FLJ13675 fis, clone
PL
115892AA291377Hs.50831ESTs 27.40
115906A1767756Hs.82302Homo sapiens cDNA 2.53
FLJ14814 fis, clone
NT
115909AW872527Hs.59761ESTs, Weakly similar11.82
to DAP1 HUMAN DEATH
115965AA001732Hs.173233hypothetical protein 34.29
FLJ10970
115978AL035864Hs.69517cDNA for differentially 8.23
expressed C016
g
1 115985AA447709Hs.268115ESTs, Weakly similar3.00
~ to T08599 probable
116090Ai591147Hs.61232ESTs 5.17
116096AA682382Hs.59982ESTs 8.20
116127AF126743Hs.279884DNAJ domain-containing10.60
116157BE439838Hs.44298mitochondria) ribosomal 5.82
protein 517
15 116190AI949095Hs.67776ESTs, Weakly similar 4.08
to T22341 hypotheti
116278NM_003686Hs.47504exonuclease 1 9.50
116335AK001100Hs.41690desmocollin 3 3.67
116496AW450694Hs.21433hypothetical protein7.00
DKFZp547J036
116503AI925316Hs.212617ESTs 12.60
116674A1768015Hs.92127ESTs 32.00
116929AA586922Hs.80475polymerase (RNA) 7.60
II (DNA directed)
polyp
116973AI702054Hs.166982phosphatidylinositol9.80
glycan, class F
116993AI417023Hs.40478ESTs 10.20
117079H92325 gb:ys85f05.s1 Soares 15.20
retina N2b4HR Homo
25 117317AI263517Hs.43322ESTs 13.d0
117326N23629Hs.241420Homo Sapiens mRNA 20.60
for KIAA1756 protein,
117396W20128Hs.296039ESTs 10.60
117412N32536Hs.42645ESTs 16.00
117519N32528Hs.146286kinesin family member 9.11
13A
117693AW179019Hs.112110mitochondria) ribosomal 4.01
protein L42
117721N46100Hs.93939EST 19.80
117881AF161470Hs.260622butyrate-induced 2.71
transcript1
117903AA768283Hs.47111ESTs 17.80
117992A1015709Hs.172089Homo sapiens mRNA; 4.17
cDNA DKFZp58612022
(f
35 118013AI674126Hs.94031ESTs 10.60
118017AI813444Hs.d2197ESTs 8.82
118186N22886Hs.42380ESTs 7.00
118325AI868065Hs.166184intersectin 2 13.80
118367N64269Hs.48946EST 6.14
118368N64339Hs.48956gap junction protein,3.14
beta 6 (connexin
3
118472AL157545Hs.42179bromodomain and 12.40
PHD finger containing,
3
118709AA232970Hs.293774ESTs 12.20,
119025BE003760Hs.55209Homo sapiens mRNA; 4.50
cDNA DKFZp434K0514
(f
119027AF086161Hs.114611hypotheficalprotein3.22
FLJ11808
45 119052810889 gb:yf38d02.s1 Soaresfetalliverspleen9.60
119164AF221993Hs.46743McKusick-Kaufman 6.60
syndrome
119186AI979147Hs.101265hypothetical protein 10.80
FLJ22593
119243T12603 gb:CHR90123 Chromosome 9.44
9 exon II Nomo
so
119490AA195276Hs.263858ESTs, Moderately 11.80
similar to 834087
hypot
119499AI918906Hs.55080ESTs 14.80
119599W45552 gb:zc26d03.s1 Soares12.60
senescent-fibroblas
119780NM_016625Hs.191381hypothetical protein17.00
1191345W79123Hs.58561G protein-coupled 13.50
receptor 87
119941AA699485Hs.58896ESTs 8.00
119994AA642402Hs.59142ESTs 7.73
120102W67353Hs.170218KIAA0251 protein 39.60
120104AK000123Hs.180479hypothetical protein2.91 '
FLJ20116
120294AK000059Hs.153881Homo Sapiens NY-REN-628.20
antigen mRNA, par
120486AW368377Hs.137569tumor protein 63 8.73
kDa with strong
homolog
120599AA80d448Hs.104463ESTs 7.00
120699AI683243Hs.97258ESTs, Moderately 10.00
similar to S29539
ribos
120715AA292700 gbzs59a06.s1 NCI 9.40
CGAP-GCB1 Homo
sapiens
120821Y19062Hs.96870staufen (Drosophila, 13.80
RNA-binding protein
120859AA826434Hs.1619achaete-scute complex9.00
(Drosophila) homol
65 120880AA360240Hs.97019EST 15.60
120983AA398209Hs.97587EST 27.66
121034AL389951Hs.271623nucleoporin 50kD 20.80
121121AA399371Hs.189095similar to SALL1 22.80
(sat (Drosophila)-like
121313AA4D2713Hs.97872ESTs 10.00
121369AW450737Hs.128791CGI-09 protein 25.71
121376AA448103Hs.187958solute carrier family 5.42
6 (neurotransmi8e
121476AA412311Hs.97903ESTs 8.30
121509AA868939Hs.97888ESTs 8.59
121553AA412488Hs.48820TATA box binding 18.50
protein (TBP)-associat
75 121753AK000552Hs.323518WD repeat domain 7.00
5
121838AA425680Hs.98441'ESTs 10.40
121857BE387162Hs.280858ESTs, Highly similar6.00
to A35661 DNA excis
121991AA430058Hs.98649EST 12.20
122089AW016543Hs.98682hypothetical protein8.60
FKSG32
$0 122105AW241685Hs.98699ESTs 6.14
122163AA435702Hs.98829EST 10.40
122318AA429743 gb:zv60b05.r1 Soares 18.20
testis_NHT Homo
sap
122335AA443258Hs.241551chloride channel, 13.50
calcium acfivated,
fam
122338AA443311Hs.98998ESTs 4.80
122414A1313473Hs.99087ESTs, Weakly similar8.00
to S47073 finger
pr
115
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122512AF053305Hs.98658budding uninhibited8.80
by benzimidazoles
1
122516AA449352Hs.99217ESTs 9.40
122702A1220089Hs.99439ESTs 9.20
122852AI580056Hs.98992ESTs 10.40
122925AW268962Hs.111335ESTs 6.80
123005AW369771Hs.52620integrin, beta 8 12.60
123044AK001035Hs.130881B-cell CLLnymphoma 5.35
11A (zinc finger
pro
123160AA488687Hs.284235ESTs, Weakly similar6.06
to 138022 hypotheG
123315AA496369 gb:zv37d10.s1 Soares12.40
ovary tumor NbHOT
H
1 123329247542Hs.179312small nuclear RNA 11.80
~ activating complex,
po
123497AA765256Hs.135191ESTs, Weakly similar12.00
to unnamed protein
123518AL035414Hs.21068hypothetical protein13.00
123519AW015887Hs.112574ESTs 12.20
123614AK000492Hs.98806hypotheticalprotein7.80
15 123616AA680003Hs.109363Homo Sapiens cDNA: 10.60
FLJ23603 fis, clone
L
123673BE550112Hs.158549ESTs, Weakly similar23.00
1o T2D3 HUMAN TRANS
123727A1083986Hs.282977hypothetical protein7.00
FLJ13490
123731AA609839 gb:ae62fOt.s1 Stratagene9.80
lung carcinoma
123752AA227714Hs.179703KIAA0129 gene product3.50
123900AA621223Hs.112953EST 12.80
124006A1147155Hs.270016ESTs 97.00
124059BE387335Hs.283713ESTs, Weakly similar3.02
to S64054 hypotheti
124069AF134160Hs.7327claudin 1 27.80
124191T96509Hs.248549ESTs, Moderately 35.80
similar to 565657
alpha
124273AA457211Hs.8858bromodomain adjacent7.20
to zinc finger
doma
124297AL080215Hs.102301Homo Sapiens mRNA; 11.00
cDNA DKFZp586J0323
(f
124305AW963221 gb:EST375294 MAGE 16.00
resequences, MAGH
Homo
124676AI360119.compHs.181013 phosphoglycerate 6.08
mutase 1 (brain)
124874BE550fHs.127826RaIGEF-like protein 21.00
82 3, mouse homolog
124904AK000483Hs.93872KIAA1682 protein 9.40
124969AI650360Hs.100256ESTs 10:80
125000T58615Hs.110640ESTs 9.80
125201AA693960Hs.103158ESTs, Weakly similar7.60
to T33296 hypolheU
125266W90022Hs.186809ESTs, Highly similar6.59
to LCT2-HUMAN LEUKO
35 125299T32982Hs.102720ESTs 9.57
125356A1057052Hs.133554ESTs, Weakly similar 14.00
to 2195-HUMAN ZINC
125370AA256743Hs.134158Homo Sapiens, Similar8.20
to KIAA0092 gene
p
125418AA777690Hs.188501ESTs 13.20
125433AL162066Hs.54320hypothetical protein21.40
DKFZp762D096
125437AI609449Hs.140197ESTs 6.96
125446BE219987Hs.166982phosphatidylinositol8.80
glycan, class F
125711AA305800Hs.5672hypothetical protein 11.20
AF140225
125756BE174587Hs.289721growth arrest specific 4.31
lranscdpt 5
125757AI274906Hs.166835ESTs, Highly similar 15.60
to 1814460A p53-ass
45 125769BE270266Hs.821285T4 oncofetaltrophoblastglycoprotein3.20
125839AW836261Hs.337717ESTs 8.20
125850W85858Hs.99804ESTs 2.65
125875H14480 gb:ym18b09.r1 Soares7.40
infant brain 1N18
H
125924BE272506Hs.82109syndecan 1 4.23
125972A1927475Hs.35406ESTs, Highly similar 3.98
to unnamed protein
126034H60340 gb:yr39b04.r1 Soares 10.60
fetal liver spleen
126327AA432266Hs.44648ESTs 11.60
126345N49713 gb:yv23fO6.s1 Soaresfetalliverspleen6.67
126435AW614529Hs.285847CGI-19 protein 10.60
126487AA283809Hs.184601solute carrier family 4.38
5 7 (cationic amino
126521AI475110Hs.203933ESTs 6.60
126522W31912 gb:zc76d03.s1 Pancreatic 14.80
Islet Homo sapi
126543AL035864Hs.69517cDNA for differentially 4.01
expressed C016
g
126567AA058394Hs.57887ESTs, Weakly similar7.80
to KIAA0758 protein
126605AA676910 gb:zj65h07.s1 Soares 11.60
fetal liver_spleen-
126627AA497044Hs.20887hypothetical protein 14.60
FLJ10392
126628N49776Hs.170994hypothetical protein6.00
MGC10946
126737AW976516Hs.283707Homo Sapiens cDNA: 2.92
FLJ21354 fis, clone
C
126795AW975076Hs.172589nuclear phosphoprotein7.50
similar to S. cer
65 126802AW805510Hs.97056hypothetical protein11.60
FLJ21634
126892AF121856Hs.284291sorting nexin 6 3.50
126928AA480902Hs.137401ESTs 22.83
126979AA210954 gb:zq89h10.r1 Slratagene 11.80
hNT neuron (937
126986AI279892Hs.46801sorting nexin 14 11.60
126992AI809521. gb:wf30e03.x1 Soares-NFLLT-GBC_S1 20.80
Homo s
127066825066 gb:yg42c07.r1 Soares 27.60
infant brain 1
NIB H
127099AA347668 gb:EST54026 Fetal 21.60
heart II Homo Sapiens
127139AA830233Hs.293585ESTs 11.20
127209AA305023Hs.81964SEC24 (S. cerevisiae)3.10
related gene famil
75 127221BE062109Hs.241551chloride channel, 2.76
calcium activated,
fam
127225AA315933Hs.120879ESTs 16.80
127313AK002014Hs.47546Homo Sapiens cDNA 14.00
FLJ 11458 fis,
clone HE
127444AW978474Hs.7560Homo sapiens mRNA 13.60
for KIAA1729 protein,
127500AW971353Hs.162115ESTs 11.20
127524AI243596Hs.94830ESTs, Moderately 7.80
similar to T03094
A-kin
127540N45572Hs.105362Homo Sapiens, clone3.53
MGC:18257, mRNA,
com
127599AA613204Hs.150399ESTs 13.80
127609X80031Hs.530collagen, type IV, 28.00
alpha 3 (Goodpasture
127662W80755Hs.8294KIAA0196 gene product 19.80
127668A1343257Hs.139993ESTs 11.20
116
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127746Ai239495Hs.120189ESTs , 14.18
127812AA741368Hs.291434ESTs 4.50
127817AA836641Hs.163085ESTs 24.60
127959A1302471Hs.124292Homo Sapiens cDNA: 9.20
FLJ23123 fis, clone
L
127960AI613226Hs.41569phosphatidic acid 16.83
phosphatase type
2A
127969F06498Hs.93748Homo Sapiens cDNA 13.60
FLJ14676 fis, clone
NT
128015221169Hs.334659hypothetical protein7.00
MGCi4139
128027AI433721Hs.164153ESTs 37.40
128077A1310330Hs.128720ESTs 9.60
1 128166NM_006147Hs.11801interferon regulatory9.24
~ factor 6
128226AI284940Hs.289082GM2 ganglioside 19.00
activator protein
128305AI954968Hs.279009matrix Gla protein 10.40
128341AA191420Hs.185030ESTs 9.00
128527AA504583Hs.101047transcription factor4.30
3 (E2A immunoglobul
1 128539846163Hs.258618ESTs 12.60
128568H129i2Hs.274691adenylate kinase 4.56
3
128572AA933022Hs.256583interleukin enhancer10.00
binding factor
3, 9
128777AI878918Hs.10526cysteine and glycine-rich16.80
protein 2
128781N71826Hs.105465small nuclear ribonucleoprotein4.48
polypept
128796AJ000152Hs.105924defensin, beta 2 8.12
128920AA622037Hs.166468programmed cell 4.62
death 5
128924BE279383Hs.26557plakophilin 3 4.04
128971H05132Hs.107510ESTs 12.60
129008AL079648Hs.301088ESTs 8.80
129041BE382756Hs.169902solute carrier family6.05
2 (facilitated
glu
129075BE250i62Hs.83765dihydrofolatereductase2.59
129105AI769160Hs.108681Homo Sapiens brain ~ 6.67
tumor associated
prot
129189AB023179Hs.9059KIAA0962 protein 8.00
129229AF013758Hs.109643polyadenylate binding4.00
protein-interactin
129241AI878857Hs.109706hematological and 4.06
neurological expressed
129300W94197Hs.110165ribosomal protein 2.55
L26 homolog
129404AI267700Hs.3175B4ESTs 18.00
129457X61959Hs.207776aspar<ylglucosaminidase6.50
129466L42583Hs.334309keratin 6A 12.94
35 129494AI148976Hs.112062ESTs 11.00
129605AF061812Hs.115947keratin 16 (focal 4.46
non-epidermolylic
palm
129641AI911527Hs.11805ESTs 12.00
129665AW163331Hs.118778KDEL (Lys-Asp-Glu-Leu)4.70
endoplasmic relic
129703BE388665Hs.179999Homo sapiens, clone4.02
IMAGE:3457003,
mRNA
129720AA156214Hs.12152APMCF1 protein 5.71
129748M16707Hs.123053H4 histone, family 3.50
2
129890AI868872Hs.282804hypotheticalprotein4.21
FLJ22704
129896BE295568Hs.13225UDP-Gal:betaGIcNAc 2.56
beta 1,4- galactosylt
129945BE514376Hs.165998PAI-i mRNA-binding 4.03
protein
45 130010AA301116Hs.142838nucleolarphosphoproteinNopp347.00
130026T40480Hs.332112EST 6.40
130080X14850Hs.147097H2A histone family,4.65
member X
130149AW067805Hs.172665methylenetetrahydrofolate2.74
dehydrogenase
130285AA063546Hs.75981ubiquitin specific 7.40
protease 14 (tRNA-gua
130441U63630Hs.155637protein kinase, 3.91
DNA-activated,
catalytic
130482AW409701Hs.1578baculoviral IAP 4.87
repeat-containing
5 (sur
130500AB007913Hs.158291KIAA0444 protein 9.60
130524U89995Hs.159234forkhead box E1 13.40
(thyroid transcription
f
130541X05608Hs.211584neurofilament, light8.20
polypeptide (68kD)
55 130553AF062649Hs.252587piluitarytumor-transforming6.06
1
130567AA383092Hs.1608replication protein7.00
A3 (l4kD)
130577M69241Hs.162insulin-like growth3.04
factor binding
prote
130627BE003054Hs.1695matrix metalloproteinase3.87
12 (macrophage
130648AI458165Hs.17296hypothetical protein16.20
MGC2376
130697L29472Hs.1802major histocompa6bility17.80
complex, class
130744H59696Hs.18747POP7 (processing 5.28
of precursor, S.
cerevi
130800AI187292Hs.19574hypothetical protein4.43
MGC5469
130867NM Hs.284239UDP glycosyllransferase16.84
001072 1 family, polype
130869J03626Hs.2057uridine monophosphate4.92
. synthetase (orotat
65 130925AF093419Hs.169378multiple PDZdomain 9.60
protein
130994W17044Hs.327337ESTs 12.40
131028A1879165Hs.2227CCAATIenhancer binding10.21
protein (CIEBP),
131031NM Hs.288650aquaporin 4 9.80
001650
131041T15767Hs.22452Homo Sapiens mRNA 9.60 '
for KIAA1737 protein,
131058W28545Hs.10151dhypothetical protein17.00
FLJ10342
131090AI143139Hs.2288visinin-like 1 2.74
131112H15302Hs.168950Homo sapiens mRNA; 8.80
cDNA DKFZp566A1046
(f
131148AW953575Hs,303125p53-induced protein3.12
PIGPC1
131185BE280074Hs.23960cyclin B1 3.07
75 131200BE540516Hs.293732hypothetical protein3.07
MGC3195
131219W25005Hs,24395small inducible 2.87
cytokine subfamily
B (Cy
131257AW339037Hs.24908ESTs 14.67
131375AW293165Hs.143134ESTs 19.20
131460NM_003729Hs.27076RNA 3'-terminal 3.50
phosphate cyclase
131476AI521663Hs.334644hypothetical protein15.00
FLJ 14668
131510BE245374Hs.27842hypothefical protein7.80
FLJ11210
131646BE302464Hs.30057MRS2 (S. cerevisiae)-like,7.00
magnesium hom
131786BE000971Hs.306083Novel human gene 2.65
mapping to chomosome
22
131839A8014533Hs.33010KIAA0633 protein 35.20
85 131843AA192315Hs.184062putative Rab5-interacting4.11
protein
117
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131877J04088Hs.156346lopoisomerase (DNA)19.00
II alpha (170kD)
131885BE502341Hs.3402ESTs 6.48
131921AA456093Hs.34720ESTs 8.40
131945NM Hs.35120replication factor 56.00
002916 C (activator 1)
4 (37
131958NM_014062Hs.3566ART-4 protein 3.82
131965W79283Hs.35962ESTs 3.03
132000AW247017Hs.36978melanoma antigen, 9.80
family A, 3
132040NM_001196Hs.315689Homo Sapiens cDNA: 3.30
FLJ22373 fis, clone
H
132109AW190902Hs.40098cysteine knot superfamily21.00
1, BMP antagon
1 132114NM_006152Hs.40202lymphoid-restricted 8.40
~ membrane protein
132162AA315805Hs.94560desmoglein 2 12.25
132164AI752235Hs.41270procollagen-lysine,2.70
2-oxoglutarate
5-dio
132180NM Hs.418fibroblast activation2.71
004460 protein, alpha
132181AW961231Hs.16773Homo sapiens clone 3.83
TCCCIA00427 mRNA
sequ
15 132182NM_014210Hs.70499ecotropic viral 13.20
integration site
2A
132231AA662910Hs.42635hypothetical protein9.50
DKFZp434K2435
132277AK001745Hs.184628hypothetical protein4.50
FLJ 10883
132328NM-014787Hs.44896DnaJ (Hsp40) homolog, 9.20
subfamily B, membe
132394AK001680Hs.30488DKFZP434F091 protein 19.80
132424AA417878Hs.48401ESTs, Moderately 8.60 .
similar to ALUB
HUMAN A
132528T78736Hs.50758SMC4 (structural 27.40
maintenance of
chromoso
132543BE568452Hs.5101protein regulator 4.38
ofcytokinesis1
132544L19778Hs.51011H2A histone family, 7.00
member P
132550AW969253Hs.170195bone morphogenetic 2.64
protein 7 (osteogenic
25 132552BE621985Hs.296922thiopurine S-melhyltransferase 15.83
132581AK000631Hs.52256hypothetical protein 6.60
FLJ20624
132617AF037335Hs.5338carbonic anhydrase 4.95
XII
132638AI796870Hs.54277DNA segment on chromosome 8.20
X (unique) 992
132653215008Hs.54451laminin, gamma 2 4.38
(nicein (100kD),
kalini
3 132669W38586Hs.293981guanine nucleotide 4.36
~ binding protein
(G pr
132710W74001Hs.55279serine (or cysteine)4.60
proteinase inhibito
132771Y10275Hs.56407phosphoserine phosphatase3.71
132799W73311Hs.169407SAC2 (suppressor 9.48
of actin mutations
2,
132833U78525Hs.57783eukaryotic translation 5.83
initiation factor
132892AW834050Hs.9973tensin 12.00
132906BE613337Hs.234896geminin 3.09
132959AW014195Hs.61472ESTs, Weakly similar 3.67
to YAE6-YEABT HYPOT
132962AA576635Hs.6153CGI-48 protein 3.50
132990X77343Hs.334334transcription factorAP-26.18
alpha (activat
40 132994AA112748Hs.279905clone H00310 PR00310p13.19
133000AL042444Hs.62402p211Cdc421Rac1-activated2.96
kinase 1 (yeast
133050X73424Hs.63788propionyl Coenzyme 2.55
A carboxylase,
beta p
133083BE244588Hs.6456chaperonin containing 4.00
TCP1, subunit 2
(b
133086L17131Hs.139800high-mobility group 8.96
(nonhistone chromoso
45 133134AF198620Hs.65648RNA binding motif 4.28
protein SA
133155M58583Hs.662cerebellin 1 precursor 10.80
133181X91662Hs.66744twist (Drosophila) 3.00
homolog (acrocephalos
133204BE267696Hs.254105enolase 1,(alpha) 4.63
133412U41493Hs.73112guanine nucleotide 12.50
binding protein
(G pr
133421AF134160Hs.7327claudin 1 2.85
133451AW970026Hs.73818ubiquinol-cylochrome 4.66
c reductase hinge
p
133453AI659306Hs.73B26protein tyrosine 6.80
phosphatase, non-recept
133504NM-004415Hs.74316desmoplakin (DPI, 6.14
DPII)
133506BE562958Hs.74346hypothetical protein 4.55
MGC14353
55 133615M62843Hs.75236ELAV (embryonic 17.80
lethal, abnormal
vision,
133627NM-002047Hs.75280glycyl-tRNA synthetase 4.85
133649U25849Hs.75393acid phosphatase 6.34
1, soluble
133669NM_006925Hs.166975splicing factor, 14.00
argininelsedne-rich
5
133749L20852Hs.10018salute carrier family 6.11
20 (phosphate tran
133776BE268649Hs.177766ADP-ribosyltransferase 4.91
(NAD+; poly (ADP-
133865AB011155Hs.170290discs, large (Drosophila)3.07
homolog 5
133946AJ001258Hs.173878NIPSNAP, C. elegans, 4.60
homolog 1
133973N55540Hs.78026ESTs, Weakly similar 13.00
to similar to ankyr
134047BE262529Hs.78771phosphoglycerate 3.85
kinase 1
134098BE513171Hs.79086mitochondrial ribosomal2.56
protein L3
134107NM_005629Hs.187958solute carrier family 8.20
6 (neurotransmitte
134112AW449809Hs.79150chaperonin containing 4.08
TCP1, subunit 4
(d
134158U15174Hs.79428BCL2ladenovirus 31.00
E1B l9kD-interacting
pro
134160T98152Hs.79432fibrillin 2 (congenital 2d.60
contractural ara
134168AA398908Hs.181634Homo Sapiens cDNA: 6.71
FLJ23602 fis, clone
L
134185AA285136Hs.301914neuronal specific 14.74
transcription factor
D
134201L35035Hs.79886ribose 5-phosphate 8.40
isomerase A (ribose
5
134272X76040Hs.278614protease,serine,l5 4.50
134276BE083936Hs.80976antigen identified 9.00
by monoclonal antibod
75 134353AL138201Hs.82120nuclear receptor 16.40
subfamily 4, group
A, m
134367AA339449Hs.82285phosphodbosylglycinamide2.80
formyltransfer
134380AU077143Hs.179565minichromosome maintenance4.68
deficient (S.
134423H53497Hs.83006CGl-139 protein 3.84
134469AA279661Hs.83753small nuclear ribonucleoprotein 5.81
polypept
134470X54942Hs.83758CDC28 protein kinase 4.21
2
134498AW246273Hs.84131threonyl-IRNA synthetase 7.30
134502BE148534Hs.84168UV-B repressed sequence, 13.60
HUR 7
134510NM_002757Hs.250870mitogen-ac8vated 9.70
protein kinase
kinase
134548N95406Hs.333495Deleted in split-handisplit-foot ' 4.63
1 regio
85 134654AK001741Ns.8739hypothetical protein6.00
FLJ10879
118
CA 02444691 2003-10-17
WO 43 PCT/US02/12476
02/0864
134724AF045239Hs.321576ring finger protein 12.00
22
134743AA0441fi3Hs.89463potassium large 4.00
conductance calcium-ac6
134781AA374372Hs.89626parathyroid hormone-like 25.20
hormone
134806AD001528Hs.89718spermine synlhase 4.58
134853BE268326Hs.902805-aminoimidazole-4-carboxamide 4.79
ribonucle
134859D26488Hs.90315KIAA0007 protein 6.20
134891851083Hs.90787ESTs 7.40
134960BE246400Hs.285176acetyl-Coenzyme 4.00
A transporter
134993BE409809Hs.301005purine-rich element 4.48
binding protein
B
1 135047AL134197Hs.93597cyclin-dependent 9.50
~ kinase 5, regulatory
su
135080AI7fi1180Hs.94211rcdl (required 5.00
for cell differentiation,
135103NM-003428Hs.9450zinc finger protein 11.00
84 (HPF2)
135145AW014729Hs.95262nuclear factor 4.01
related to kappa
B bindin
135184U13222Hs.96028forkhead box 41 7.00
15 135242AI583187Hs.9700cyclin Ei 13.50
135286AW023482Hs.97849ESTs 6.46
135289AW372569Hs.9788hypothetical protein 8.80
MGC10924 similar
to
135355AK001652Hs.99423ATP-dependent RNA 10.00
helicase
135371NM_006025Hs.997protease, serine, 8.00
22
135393L11244Hs.99886complementcomponent4-binding 14.60
protein,
TABLE 5B shows the accession numbers for those primekeys lacking unigenelD's
for Table 5A. For each probeset we have listed the gene cluster number from
which the
cligonucleolides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
25 similarity using Clustering and Alignment Tools (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accessions
1170791621717H92325 T97125
1
35 124305242183 AW963221 AA344B70AA3d4871 H93331
1
10150218202 M26958
-6
109792754958 849625 F10674
1
1260341598157_1H60340 N91637
10276844641 U82321 H66077
1
1263451653833_1N49713 N49819 W03810
1270661703458825066 820144 820145 243845
1
127099244301 AA347fi68 AW956810 244271 F07065 F07064 813506
1
1192431774795T12fi03 T12604
1
1258751566433H14480 N98295
1
45 1120541538292843590 F10439
1
126979171411 AA210954 AA211007
1
126992880655-1A1809521 H12174 242556
122318292419 AA429743 AA442754
1
114699135322 AA127386 815644 AA127404
1
114793- AA158245 AA158235
0 150742_1
108305111550_1AA071391 AA069892 AA069891
108393113411 AA075211 AA075245 AA075126 AA074946
1
100867tigr-HT4586U14622
123731genbank-AA609839
AA609839
S 109700genbankF09609
5 F09609
120715genbank_AA292700
AA292700
113702genbanl~T97307T97307
115113genbank_AA256460
AA256d60
101045entrez J05614
J05614
108554genbank-AA084948
AA084948
108573genbank_AA086005
AA0B6005
119052149538_1810889 810888
126522416020 W31912 A1167491
1
126605439280 AA676910 AA778853 AA778865 W86800
1
65 10376846922-1Wd2667 AI580740 AI690440 AI561350 AW467906 AW151450
AIB25927 AL041716 AI885600 AI7d2213 AW24B624 AI955498
AA033947
AA845593 AI623711 N68583 C00064 AA193567 AW083868
AW163216 AA191595 AA522778 AI628008 AI915518 AA843508
AI926195
AA176265 AW167963 AA992115 W93647 AW103572 AI862994
AI342059 AA911719 AA176155 AA024712 AA069988 AA205591
AI591107
AI199673 AI811766 AI275832 AI422233 AI191852 A1096682
AI580124 AI683612 AA582453 AA927559 AA486415 T32414
A1084978 H44849
H44848 H20477 T91695 W47039 AA070055 AA024795 AA328855
AA379248 AA379330 AA385580 W25920 W03688 AA448359
AA093881
AW362477 AA089997 AI350265 W93479 N99688 AA932257
AW351469 H68590 AA663402 AA069771 AW087986 AI858420
AA600214
AI970774 AI857712 AI683081 AI885584 AW131150 AI567981
AW002714 AW189973 AW075495 AW168303 AA953714 AW516881
AI357375
AI566663 AW512676 AI570580 A1023690 AA448216 A1079853
AI422707 AA779516 AW026972 AW130082 AW162307 AW438646
AA709332
AW192394 AI167350 AI217879 AI129152 AA719509 AI350480
AA663418 A1003634 AW118546 AA180261 AA442833 AI268625
AA8B8881
A1038759 AA846723 AI248770 AA993694 AI280335 AI885107
AW518649 AA641563 AA995835 AA582521 AI276744 AA436478
A1017360
75 AI620763 AI859887 N73926 A1076327 AI741615 AI160617
AW172819 AI492005 AA677429 AA996334 AI693771 AI950039
AI245629 AI288515
AI866186 T93293 AA173262 AA599779 AI6B0092 AW439316
A1084555 AI272672 AI583507 AW473219 AA738132 AW473283
AI367492
AA995410 AI68962d AA206353 A1033095 A1040382 AA873630
AI22107d AI93d840 AI418680 AA844306 894503 AA773520
AA8d3169
AA219425 AA629658 AI811719 AW411275 AI590981 W37907
AI591178 AI6B4051 AA983238 AA669347 AA976239 AA704570
AI628339
AI884391 AI241580 A1003539 AW176687 AA009650 N34566
AI333493 AI186070 AA070827 AA411683 AI280884 AA872023
AA207255
AA021576 N71953 AI885888 AW076039 T15777 AI537673
AW248048 H09554 W93480 W47001 AW079114 AA063160
AA757453 860788
AI859431 H20478 AA218882 AA757465 AA100995 AI864135
AI934209 AA070503 H47008 AA219646 W61039 W93907
AW385050 W37967
W78028 AA189007 AA479136 893650 AA442312 T30287 AA847628
AA180262 AA009649 C03892 AW1494fi4 AA310963 AA219693
AA069747 829207 AA094784 AA293615 AA447848 AI9841
fi7 N90393 C05097 N56499 AW292351 AW149681 AW473258
AA629322 A1004409
AW105577 AI954937 AI811070 AA902422 AW514437 AA535460
AA916877 AW517122 AA974657 AA975649 AW517130 AW517129
F31737
W07688 AA193fi45 AA378994 AA489273 F32267 W39303
AA021181 N86810 AA406524 AA062553 AA436801 H08985
H15979 N40310
119
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
AA436789
AA232172
AW360778
W25862
860282
AA436530
AA378894
AA187461
AI940535
AA604210
AA089514
AA360421
N88243
N8428i
AA209340
N56174
N88374
AA191088
AW247691
AA249013
AA093111
AA972536
AW298594
AA375893
T12139
W28186
AW243849
AI288629
AA843996
W15260
AI188286
AW248079
815836
119599genbank-W45552
W45552
112382genbank
859904
859904
105264genbank-AA227934AA227934
100071entrez-A26102
A28102
123315714071-i
AA496369
AA496646
Table
6A
shows
99
genes
up-regulated
nonsmokers
with
lung
cancer
relative
to
smokers
with
lung
cancer.
These
genes
were
selected
from
59680
probesets
on
the
EosIAffymetdx
Hu03
Genechip
array.
Gene
expression
data
for
each
probeset
obtained
from
this
analysis
was
expressed
as
average
intensity
(AI),
a
normalized
value
reflecting
the level of
relativemRNA expression.
Pkey: Unique
Eos probeset
idenflfler
number
ExAccn:ExemplarAccession
number,
Genbank
accession
number
UnigenelD:Unigene
number
Unigene
Title:
Unigene
gene
title
R1: average for samples from smokers
of AI with adenocarcinoma
for samples
from non-smokers
with adenocarcinoma
divided
by the
90th percentile
of AI
R2: average by
of AI the
for samples 90th
from non-smokers percentile
with squamous of
cell carcinoma AI
divided for
samples
from
smokers
with
squamous
cell
carcinoma
Pkey ExAccn UnigeneTille R1 R2
UnigenelD
100971BE379727 fatty acid binding 3.64
Hs.83213 protein 4, adipocyte
101174L17330 pre-TINK cell associated15.00
Hs.280 protein
101296Y12490 thyroid hormone receptorinteractorl1 2.46
Hs.85092
101304AA001021 thyroid hormone receptor 12.00
Hs.6685 inleractor 8
101806AA586894 S100 calcium-binding 2.68
Hs.112408 protein A7 (psorias
101972582472 gb:beta-pot=DNA polymerase 2.11
beta {exon a
102274U30930 UDP glycosyltransferase7.50
Hs.158540 8 (UDP-galactose
102394NM 003816 a disintegrin and 7.50
Hs.2442 metalloproteinase
doma
102832U92015 gb:Human clone 14378913.50
defective mariner
103010X52509 tyrosine aminotransferase9.50
Hs.161640
103439X98266 gb:H.sapiensmRNAforligaselikeprotei 2.50
103563L02911 activin A receptor, 9.00
Hs.150402 type I
103857A1076795 lacrimal proline rich 3.94
Hs.45033 protein
104239AB002367 doublecortin and CaM 13.50
Hs.21355 kinase-like 3
104590AW373062 nuclear receptor subfamily 12.66
Hs.83623 1, group I, m
104907AA055829 ESTs, Weakly similar 16.50
Hs.196701 to ALU1 HUMAN ALU
106131BE514788 SNARE protein 2.17
Hs.296244
106672H47233 ESTs 7.00
Hs.30643
1061372T56887 KIAA1134 protein 11.50
Hs.18282
106960AA156238 ESTs 2.38
Hs.32501
106971243846 Homo Sapiens mRNA; 9.50
Hs.194478 cDNA DKFZp43401572
(f
107982AA035375 ESTs, Weakly similar 2.95
Hs.57887 to KIAA0758 protei
108562AA100796 gb:zm26cO6.s1 Stratagene16.50
pancreas (93720
108599A8018549 MD-2 protein 13.00
Hs.69328
108663BE219231 ESTs, Weakly similar 2.40
Hs.292653 to T26845 hypotheti
109247AA314907 ESTs 7.00
Hs.85950
109630844607 ESTs 5.00
Hs.22672
110193A1004874 Homo Sapiens mRNA; 12.50
Hs.310764 cDNA DKFZp434M082
(fr
110234H24458 EST 16.50
Hs.32085
110644894207 ESTs, Highly similar 8.00
Hs.268989 to type II CALMIAF1
110886AW274992 three-PDZcontaining 17.00
Hs.72249 protein similar to
111057T79639 ESTs 16.50
Hs.14629
111950AF071594 Wolf-Hirschhorn syndrome11.00
Hs.110457 candidate 1
112291853972 ESTs 3.00
Hs.26026
112956243784 ankyrin 3, node of 2.79
Hs.75893 Ranvier (ankyrin
G)
113009T23699 ESTs 4.50
Hs.7246
113060BE564162 hypothetical protein 9.79
Hs.250820 FLJ14827
113073N39342 microtubule-associated32.50
Hs.103042 protein 18
113074AK001335 protein tyrosine phosphatase,receptort 3.82
Hs.31137
113121T48011 EST 2.21
Hs.8764
113125AA968672 hypothetical protein 19.50
Hs.8929 FLJ11362
113757AA703095 ESTs 2.65
Hs.18631
f 13848W52854 hypotheflcal protein 6.00
Hs.27099 FLJ23293 similar
to
113884AI333076 chromosome 12 open 6.00
Hs.28529 reading frame 2
113936W17056 nuclear receptor subfamily 4.63
Hs.83623 1, group I, m
114875AA235609 Homo sapiens mRNA; 7.00
Hs.236443 cDNA DKFZp564N1063
(
114987AA251016 EST 6.00
Hs.87808
115460AW958439 ESTs 2.27
Hs.38613
115722W9i892 ESTs 9.00
Hs.59609
116261AA481788 ESTs 9.50
Hs.190150
116830H61037 ESTs, Weakly similar 8.50
Hs.70404 to ALU2_HUMAN ALU
116970AB023179 KIAA0962 protein 7.50
Hs.9059
117178H98675 ESTs 2.68
Hs.269034
117757AF088019 EST 7.50
Hs.46732
118283AA287747 ESTs, Weakly similar 16.50
Hs.173012 to A46010 X-linked
$0 118384AF217525 Down syndrome cell 2.50
Hs.49002 adhesion molecule
118657AI822106 ESTs 2.39
Hs.49902
120328AA923278 ESTs, Weakly similar 3.50
Hs.290905 to protease [H.sapi
120404AB023230 KIAA10f3 protein 7.00
Hs.96427
120524AA261852 ESTs 6.00
Hs.192905
120688AW207555 Homo Sapiens cDNA: 17.92
Hs.97093 FLJ23004 fis, clone
L
120
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
121558AA412497 gb:zi95g12.s1 Snares 2.95
tesfis-NHT Homo
sap
121676H56037Hs.108146ESTs 10.00
121936A1024600Hs.98612ESTs 15.00
121938AA428659Hs.98610ESTs 14.00
$ 122177AA435789Hs.98833EST 8.93
123442AA299652Hs.111496Homo sapiens cDNA 13.04
FLJ 11643 fis, clone
HE
123551AA608837 gb:af03h12.s1 Snares11.50
testis-NHT Homo
sap
123756AA609971Hs.112795EST 1f.00
123861AA620840 gb:af89g01.s1 Snares 2.50
lesfis_NHT Homo
sap
124371N24924Hs.188601ESTs 6.50
127477BE328720Hs.280651ESTs 4.33
127591A1190540Hs.131092ESTs 3.02
128252AA455924Hs.192228ESTs 7.00
128426AI265784Hs.145197ESTs 2.08
1$ 128925867419Hs.21851Homo sapiens cDNA 2.11
FLJ12900 fis, clone
NT
128945AI990506Hs.8077Homo sapiens mRNA; 10.00
cDNA DKFZp547E184
(fr
129105AI769160Hs.108681Homo sapiens brain 15.50
tumor associated
prot
129235AW977238Hs.126084KIAA1055 protein 4.25
129506A8020684Hs.11217KIAA0877 protein 6.50
129595009550Hs.1154oviductal glycoprotein 10.00
1,120kD (mucin 9
130160AA305688Hs.267695UDP-Gal:betaGIcNAc 20.00
beta 1,3-galaclosyltr
130340D82326Hs.239106solute carrier family11.50
3 (cystine, dibasi
131220AB023194Hs.300855KIAA0977 protein 17.50
131430AI879148Hs.26770fatty acid binding 6.10
protein 7, brain
2$ 132114NM-006152Hs.40202lymphoid-restricted 6.15
membrane protein
132458AA935315Hs.d8965Homo sapiens cDNA: 5.56
FLJ21693 fis, clone
C
132647NM-006927Hs.54432sialyltransferase 7.50
48 (beta~galactosidase
132655D49372Hs.54460small inducible cytokine 2.53
subfamily A (Cy
132682A1077500Hs.54900serologically defined 2.50
colon cancer anlig
132747AA345241Hs.55950ESTs, Weakly similar 2.83
to KIAA1330 protein
132812850333Hs.92186Lemon coiled-coil 3.82
protein
133337AF085983Hs.293676ESTs 5.00
133876AL134906Hs.771phosphorylase, glycogen; 3.00
liver (Hers dis
134119AW157837Hs.79226fasciculation and 2.06
elongation protein
zet
3$ 134464AA302983Hs.239720CCR4-NOT transcripfion 2.27
complex, subunit
134542M14156Hs.85112insulin-like growth 11.50
factor 1 (somatomedi
135002AA448542Hs.251677G antigen 7B 87.00
135305AA203555Hs.98288Homo sapiens cDNA 6.50
FLJ14903 fis, clone
PL
TABLE 6B show the accession numbers for those primekeys lacking unigenelD's
for Table 6A. For each probeset we have listed the gene cluster number from
which the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Tcols (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
4$ "Accession" column.
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
$ O Accession: Genbank accession numbers
Pkey CAT number Accessions
108562 36375 1
AA100796
AF020589
AA074629
AA075946
AA100849
AA085347
AA126309
AA079311
AA079323
AA085274
$ $ 10343935330 1 N41124
X98266
123551 genbank-AA608837AA608837
123861 genbank_AA620840AA620840
102832 entrez 092015
092015
101972 entrez S82472
S82472
60 121558genbank_AA412497AA412497
121
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Table 7A shows 98 genes down-regulated in non-smokers with lung cancer
relative to smokers with lung cancer. These genes were selected from 59660
probesets on the
EosIAffymetrix Hu03 Genechip array. Gene expression data for each probeset
obtained from this analysis was expressed as average intensity (AI), a
normalized value reflecting
the relative level of mRNA expression.
J Pkey:Unique
Eos
probeset
identifier
number
ExAccn:Exemplar
Accession
number,
Genbank
accession
number
UnigenelD: number
Unigene
Unigene gene
Title; Title
Unigene
R1: 90th
percentile
of
AI
for
samples
from
smokers
with
adenocarcinoma
divided
by
the
average
of
AI
for
samples
from
non-smokers
with
adenocarcinoma.
1 R2: 90th
~ percentile
of
AI
for
samples
from
smokers
with
squamous
cell
carcinoma
divided
by
the
average
of
AI
for
samples
from
non-smokers
with
squamous
cell
carcinoma.
Pkey ExAccnUnigenelDUnigeneTitle R1 R2
15 100187D17793Hs.78183aldo-keto reductase 164.10
family 1, member
C3
100380D82343Hs.18551neuroblasfoma (nerve 77.40
tissue] protein
100576X00356Hs.37058calcitoninicalcilonin-related102.40
polypeptid
100971BE379727Hs.83213fatty acid binding 463.80
protein 4, adipocyte
101046K01160 (NONE) 672.00
2~ 101066AW970254Hs.889Charot-Leyden crystal66.00
protein
101175U82671Hs.36980melanoma antigen, 77.20
family A, 2
101497W05150Hs.37034homeo box A5 62.80
101663NM Hs.2178H2B histone family,78.00
003528 member Q
101677NM Hs.1012complement component186.20
000715 4-binding protein,
25 101745M88700Hs.150403dopa decarboxylase 80.08
(aromatic L-amino
act
101941S77583 gb:HERVK101HUMMTV 99.20
reverse transcriptase
102125NM-006456Hs.288215sialyltransferase 103.10
102242U27185Hs.82547relinoic acid receptor67.00
responder (tazaro
102340U37055Hs.278657macrophage stimulating71.60
1 (hepatocyte gro
102369U39840Hs.299867hepatocyte nuclear 69.70
factor 3, alpha
102457NM Hs.2359dual specificity 153.00
001394 phosphatase 4
102669U71207Hs.29279eyes absent (Drosophila) 65.70
homolog 2
102796AL079646Hs.107019symplekin; Huntingtin 58.80
interacting protei
102829NM Hs.80962neurotensin 268.80
006183
35 103207X72790 gb:Human endogenous70.00
retrovirus mRNAfor
103242X76342Hs.389alcohol dehydrogenase 212.10
7 (class IV), mu
o
103260X78416Hs.3155casein, alpha 130.70
103351X89211 gb:H.sapiensDNAforendogenousretrovir64.60
104212AB002298Hs.173035KIAA0300 protein 66.80
104252AF002246Hs.210863cell adhesion molecule63.80
with homology to
104258AF007216Hs.5462solute carrier family94.40
4, sodium bicarbon
105024AA126311Hs.9879ESTs 68.20
106260A10971ddHs.5250ESTs, Weakly similar 74.60
to ALU1 HUMAN ALU
S
106440AA449563Hs.151393glutamate-cysteine 71.10
ligase, catalytic
sub
45 106566BE298210 gb:601118016F1 NIH-MGC_1773.20
Homo Sapiens c
106605AW772298Hs.21103Homo sapiens mRNA; 83.80
cDNA DKFZp564B076
(fr
106614AA648459Hs.335951hypothetical protein 62.30
AF301222
106654AW075485Hs.286049phosphoserine aminotransferase 202.40
106999H93281Hs.10710hypothetical protein 89.60
FLJ20417
108700AA121518Hs.193540ESTs, Moderately 66.40
similar to 2109260A
B c
108810AW295647Hs.71331hypothetical protein 95.50
MGC5350
108857AK001468Hs.62180anillin (Drosophila 63.40
Scraps homology,
act
109597AA989362Hs.293780ESTs 85.00
109691T65568Hs.12860ESTs 58.70
55 109704AI7d3880Hs.12876ESTs 60.60
110942863503Hs.28419ESTs 76.40
111722823924Hs.23596EST 74.60
112891T03927Hs.293147ESTs, Moderately 64.80
similar to A46010
X-li
112992AL157425Hs.133315Homo Sapiens mRNA; 76.70
cDNA DKFZp761J1324
(f
113073N39342Hs.103042microtubule-associated 120.20
protein 1B
114251H15261Hs.21948ESTs 127.20
115230AA278300Hs.124292Homo Sapiens cDNA: 174.00
FLJ23123 fis, clone
L
115291BE545072Hs.122579hypothetical protein 91.00
FLJ10461
115815AW905328Hs.180842ribosomal protein 66.40
L13
65 115909AW872527Hs.59761ESTs, Weakly similar 226.60
to DAP1 HUMAN DEATH
115965AA001732Hs.173233hypothefical protein82.80
FLJ10970
116107AL133916Hs.172572hypolheticalprotein 361.60
FLJ20093
116552D20508Hs.164649hypothetical protein69.00
DKFZp434H247
116571D45652 gb:HUMGS02848 Human64.20
adult lung 3' direct
118466N66741 gb:yz33gO8.s1 Morton 63.50
Fetal Cochlea Homo
120484AA253170Hs.96473EST 81.60
120983AA398209Hs.97587EST 81.10
121034AL389951Hs.271623nucleoporin 50kD 66.20
121423AW973352Hs.290585ESTs 64.40
75 122553AAd51884Hs.190121ESTs 60.d0
122946AI71B702Hs.308026major histocompatibility188.60
complex, class
123130AA487200 gb:ab19f02.s1 Stratagene 80.20
lung (937210) H
124472N52517Hs.102670EST 71.00
124526N6209fiHs.293185ESTs, Weakly similar 104.90
to JC7328 amino
act
0 125489H49193Hs.124984ESTs, Moderately 72.00
similar to ALU7-HUMAN
A
125731861771Hs.26912ESTs 69.90
125747NM_002884Hs.865RAP1A, member of 69.00
RAS oncogene family
126020H79863Hs.114243ESTs 62.40
126547U47732Hs.84072transmembrane 4 62.80
superfamily member
3
126966838438Hs.182575solute comer family 60.10
15 (H+Ipeptide
tra
122
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127472AA761378Hs.192013ESTs 70.20
127610AA960867Hs.150271ESTs, Highly similar64.00
to unnamed protein
127742AW293496Hs.180138ESTs 85.20
127987A1022103Hs.124511ESTs 96.60
128233AW889132Hs.11916ribokinase 78.90
128420AA650274Hs.41296fibronecfln leucine 106.90
rich transmembrane
p
128766AW160432Hs.296460craniofacial development66.80
protein 1
129014AW935187Hs.170162KIAA1357 protein 58.53
129215AB040930Hs.126085KIAA1497 protein 64.20
1 130090H97878Hs.132390zinc finger profein63.80
~ 36 (KOX 18j
130385AW067800Hs.155223slanniocalcin 2 139.60
130732AW890487Hs.639B4cadherin 13, H-cadherin 64.60
(heart)
131025AB040900Hs.6189KIAA1461 protein 64.40
131241BE501914Hs.24654Homo Sapiens cDNA 76.20
FLJ11640 fis,
clone HE
15 131775A8014548Hs.31921KIAA0648 protein 97.80
132240AB018324Hs.42676KIAA0781 protein 71.00
132856NM_001448Hs.58367glypican 4 88.40
132977AA093322Hs.301404RNA binding motif 133.20
protein 3
133749L20852Hs.10018solute carrier 59.30
family 20 (phosphate
tran
2~ 133818AI110684Hs.7645fibrinogen, B beta341.00
polypeptide
134264AF149297Hs.8087NAG-5 protein 64.30
134265M83772Hs.80876flavin containing 232.53
monooxygenase
3
134346X84002Hs.82037TATA box binding 66.00
protein (TBP)-associate
134395AA456539Hs.8262lysosomal-associated 75.80
membrane protein
2
25 135047AL134197Hs.93597cyclin-dependent 108.30
kinase 5, regulatory
su
135056N75765Hs.93765lipoma HMGIC fusion71.40
partner
135309AI564123Hs.42500ADP-ribosylation 70.40
factor-like 5
3 ~ TABLE 78 shows the accession numbers for those primekeys lacking
unigenelD's far Table 7A. For each probeset we have listed the gene cluster
number from which the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were cNsiered based on
sequence
similarity using Clustering and Alignment Tools (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
3 S Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
4o Pkey CAT number Accessions
103207 30635 -4 X72790
106566 120358_1 BE298210 A1672315 AW086489 BE298417 AA455921 AA902537 8E327124
814963 AA085210 AW274273 A1333584 A1369742 A1039658
AI885095 AI476470 AI287650 Ai885299 AI985381 AW592624 AW340136 AI266556
AA456390 AI310815 AA484951
116571 genbank-D45652 D45652
45 118466 genbanl~,N66741 N66741
101046 enirez_K01160 K01160
101941 entrez-S77583 S77583
103351 entrez X89211 X89211
50 123130 genbank_AA487200 AA487200
123
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WO 02/086443 PCT/US02/12476
Table 8A shows 1720 genes either up or down-regulated in lung tumors or
chronically diseased lung relafive to a broad collection of over 40 disflnct
normal body tissues.
Chronically diseased lung samples represent chronic non-malignant lung
diseases such as fibrosis, emphysema, and bronchifis. These genes were
selected from 39494
probesets on the EosIAifymetrix Hu02 Genechip array. Gene expression data for
each probeset obtained from this analysis was expressed as average intensity
(AI), a
normalized value reflecting the relative level of mRNA expression.
Pkey:Unique
Eos
probeset
idenfifier
number
ExAccn:ExempIarAccession
number,
Genbank
accession
number
UnigenelD: number
Unigene
Unigene gene
Tifle:Unigene title
R1: 70th ung tumors divided
percentile by 90th percentile
of of AI for normal
AI lung
for
l
R2: 70th
peroentile
of
AI
for
chronically
diseased
Jung
divided
by
90th
percentile
ofAl
for
normal
lung
Pkey ExAccnUnigenelDUnigeneTitle R1 R2
I 300097AI916973Hs.213603ESTs 5.46 4.69
S
300117AW189787Hs.147474ESTs 0.58 0.56
300197AI686661Hs.218286ESTs 4.26 5.44
300201AI308300 gbaa90cO6.x1 NCI_CGAP_Bm200.62 0.83
Homo sapien
300225AI989963Hs.197505ESTs 1.68 1.75
300247AW274682Hs.16i394ESTs 1.08 2.28
300256AI469095Hs.298241Transmembrane protease,0.86 1.00
serine 3
300337AI707881Hs.202090ESTs 5.80 9.09
300362242308 gb:HSCOF8121 normalized4.18 12.78
infant brain cDN
300374AI859947Hs.314158ESTs 2.99 4.38
25 300387AW270150Hs.254516ESTs 1.50 2.53
300440AI421541Hs.146164ESTs 3.98 5.25
300441810367Hs.307921EST, Weakly similar3,18 6.80
to 2232-HUMAN ZINC
F
300449AI362967Hs.132221hypothetical protein0.43 0.62
FLJ12401
300469AW135830Hs.233955hypothetical protein0.16 0.83
FLJ20401
300552X85711Hs.21838hypothetical protein4.10 9.75
FLJ11191
300627W27363 gb:ab37d01.r1 Stratagene4.60 12.60
HeLa cell s3 93
300630AW118822Hs.128757ESTs 2.91 5.86
300716AI216113Hs.126280hypothetical protein1.00 0.92
FLJ23393
300738AI623332Hs.130541KIAA1542 protein 1.82 1.71
35 300777AA235361Hs.96840KIAA1527 protein 4.48 8.22
300790AI492471Hs.188270ESTs 1.29 1.18
300832A1688147Hs.220615ESTs, Weakly similar5.51 8.56
to T03829 transcrip
300836244942Hs.22958calcium channel 4.90 6.34
alpha2-delta3 subunit
300838AI582897Hs.192570hypothetical protein1.70 2.81
FLJ22028
300878AW449802Hs.285901Homo Sapiens cDNA 4.56 7.91
FLJ20428 fis, clone
KA
300897AI890356Hs.127804ESTs, Weakly similar2.23 1.58
to T17233 hypotheti
300926AA504860 gb:ab03a10.s1 Stratagene2.13 3.50
fetal retina 93
300960A1041019Hs.15245dESTs 2.74 4.46
300961AW204069Hs.312716ESTs, Weakly similar1.00 1.00
to unnamed protein
45 300962AA593373Hs.293744ESTs 1.46 1.51
300967AA565209Hs.269439ESTs 0.39 1.30
300987AW450840Hs.148590ESTs, Weakly similar1.49 1.08
to AF2088461 BM-00
300988AI927208Hs.208952ESTs 0.16 0.37
301050AW136973Hs.288516ESTs, Weakly similar3.23 1.94
to S69890 mitogen
t
50 301098AA677570Hs.185918ESTs 6.76 14.28
301157AA729905Hs.231916ESTs 3.16 8.85
301162AI142118Hs.129004ESTs 1.68 7.18
301170AA737594Hs.247606ESTs 4.40 6.42
301192AI808751Hs.121188ESTs 6.38 11.59
55 301193AA758115Hs.128350ESTs, Weakly similar4.35 7.78
to JC5423 2-hydroxy
301267AW297762Hs.255690ESTs 1.56 1.61
301281AA843986Hs.190586ESTs 2.19 1.78
301341AI819198Hs.208229ESTs 0.76 0.76
301382AA912839Hs.163369ESTs 1.00 1.81
60 301407AW450466Hs.126830ESTs 1.48 1.51
301452AA975688Hs.159955ESTs 0.51 1.46
301483AW272467Hs.254655Unfitted 2.40 5.02
301494AI678034Hs.131099ESTs 2.79 3.41
301521AI733621Hs.133011zinc finger protein0.67 0.67
117 (HPF9)
65 301531A1077462Hs.134084ESTs 2.52 3.76
301580AI878959Hs.73737splicing factor, 7.41 11.92
argininelserine-rich
1
301676243570Hs.27453ESTs, Moderately 8.31 10.70
similar to 601251
Rar p
301690F05865Hs.108323ubiquifln-conjugating2.70 4.22
enzyme E2E 2 (homo
301718F07744Hs.7987DKFZP434F162 protein4.20 8.78
301799AA384252Hs.286132D15F37 (pseudagene)5.93 7.04
301804AA581004Hs.62180anillin (Drosophila1.70 0.76
Scraps homology,
act
301822X17033Hs.271986integrin, alpha 1.58 1.36
2 (CD498, alpha
2 subuni
301846820002Hs.6823hypotheflcal protein1.00 1.00
FLJ10430
301868T71508Hs.13861ESTs, Weakly similar2.88 5.49
to pH sensifive
max
75 301882T78054 gb:yc97g09.r1 Soares2.28 3.80
infant brain 1NIB
H
301905AI991127Hs.117202ESTs 1.00 1.00
301948AA344647Hs.116724aldo-keto reductase5.28 2.28
family 1, member
B11
301960AW070252Hs.27973KIAA0874 protein 5.38 6.48
302011T91418Hs.125156transcriptional 3.03 3.42
adaptor 2 (ADA2,
yeast,
302016N40834Hs.23495hypothefical protein1.00 1.25
FLJ11252
302041NM-001501Hs.129715gonadotropin-releasing0.71 0.99
hormone 2
302072AJ238381Hs.132576paired box gene 1.60 1.71
9
302094AI286176Hs.6786ESTs 0.52 1.20
302095AW044300Hs.137506Homo Sapiens BAC 2.75 4.93
done RP11-120J2
from 7
g5 302148AW269618Hs.23244ESTs 3.04 3.87
124
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WO PCT/US02/12476
02/086443
302155A1088485Hs.144759ESTs 0.45 1.15
302201AJ006276Hs.159003transient receptor 0.33 0.84
potential channel
6
302202AF097159Hs.159140UDP-Gal:betaGIcNAc 0.52 0.94
beta 1,4-galactosylt
302206AI937193Hs.41143phosphoinositide-specific2.76 3.65
phospholipase
302209AF047445Hs.159297killer celllectin-like1.00 1.00
receptorsubfami
302235AL049987Hs.i66361Homo Sapiens mRNA; 1.fi81.50
cDNA DKFZp564F112
(fr
302290AL117607Hs.175563Homo Sapiens mRNA; 1.00 2.11
cDNA DKFZp564N0763
(f
302328AA354849Hs.23240Homo sapiens cDNA 9.38 13.08
FLJ13496 fis, clone
PL
302346AL039101Hs.194625dynein, cytoplasmic,3.27 7.24
light intermediate
1 302360AJOi090tHs.198267mucin 4, iracheobronchial2.54 f.88
~
302384Y08982Hs.202676synaptonemal complex1.00 0.91
protein 2
302406086751Hs.211956CD3-epsilon-associated2.63 2.67
protein; antisens
302409AF155156Hs.218028adaptor-related 5.82 9.34
protein complex
4, epsil
302423AB028977Hs.225974KIAA1054 protein 3.66 3.18
15 302432AL080068Hs.272534Homo sapiens mRNA; 2.44 6.77
cDNA DKFZp564J062
(fr
302435AF092047Hs.227277sine oculis homeobox0.44 0.84
(Drosophila) homolo
302437AB024730Hs.227473UDP-N-acetylglucosamine:a-1,3-D-mannosid4.18 5.64
302455AA356923Hs.240770nuclear cap binding1.85 0.92
protein subunit
2, 2
302472AA317451Hs.6335SWIISNF related, 2.04 2.13
matrix associated,
acti
20 302476AF182294Hs.241578U6 snRNA-associated1.44 1.89
Sm-like protein
LSmB
302489T80660Hs.230424Homo sapiens cDNA 0.51 1.10
FLJ13540 fis, clone
PL
302490AA885502Hs.187032ESTs 2.64 4.87
302562AJ005585Hs.48956gap junction protein,5.34 2.68
beta 6 (connexin
3
302566AA085996Hs.248572hypotheticalprotein1.00 1.21
FLJ22965
25 302630AB029488Hs.272100SMS3protein 0.52 1.2d
302634AB032953Hs.173560odd Ozlten-m homolog1.00 1.00
2 (Drosophila,
mous
302638AA463798Hs.102696MCT-1 protein 1.56 1.02
302647X57723Hs.198273NADH dehydrogenase 2.72 6.85
(ubiquinone) 1
beta s
302655AJ227892Hs.146274ESTs 1.00 4.32
302656AW293005Hs.70704Homo sapiens, clone2.97 0.93
IMAGE:2823731,
mRNA,
302668AA580691Hs.180789S1fi4 protein 0.80 0.95
302679H65022 gb:yu66g11.r1 Weizmann1.68 5.04
Olfactory Epithet
302680AW192334Hs.38218ESTs 2.70 7.98
302697AJ001408 gb:Homo Sapiens 4.25 8.13
mRNA for immunoglobulin
35 302705009060 gb:Human immunoglobulin3.91 8.68
heavy chain, V-r
302711L08442 gb:Human autonomously2.20 2.73
replicating sequen
302719W69724Hs.288959hypothetical protein0.54 1.02
FLJ20920
302742L12069 gb:Homo Sapiens 4.28 11.57
(clone WR4.10VH)
anti-th
302755AW384815Hs.149208KIAA1555 protein 1.57 2.38
302771H98476Hs.42522ESTs 2.94 4.68
302789AJ245067 gb:HomosapiensmRNAforimmunoglobulin3.49 6.31
302795AJ245313Hs.272838hypothetical protein0.80 2.74
FLJ10494
302802Y08250 gb:H.sapiens mRNA 1.13 0.77
for variable region
of
302803AA442824Hs.293961ESTs, Moderately 3.14 10.68
similar to putative
DNA
45 302812N31301Hs.152664hypothetical protein3.04 8.24
FLJ20051
302847X98940 gb:H.sapiens rearranged1.80 1.92
Ig heavy chain
(
302885AL137763Hs.132127hypothetical protein1.00 1.00
LOC57822
302943AI581344Hs.127812ESTs, Weakly similar0.53 0.67
to T17330 hypolheti
302977AW263124Hs.315111hypolheticalprotein2.45 2.62
FLJ12894
303006AF078950Hs.24139Homo Sapiens cDNA: 4.88 8.61
FLJ23137 fis, clone
L
303011AF090405 gb:Homo Sapiens 1.41 1.86
clone 2A1 scFV
anitbody
303013F07898Hs.2889fi8RA822A, member RAS 1.51 1.19
oncogene family
303061AF151882Hs.27693peptidylprolyl isomerase0.72 0.76
(cyclophilin)-I
303077AF163305 gb:H.sapiens T-cell1.17 3.90
receptor mRNA
55 303090AA443259Hs.146286klnesin family member4.08 6.46
13A
303091AF192913Hs.130683zinc finger protein2.50 4.37
180 (HHZ168)
303094AF195513Hs.278953Pur-gamma 5.38 8.38
303095AF202051Hs.134079NM23-HS 3.26 4.08
303131AW081061Hs.103180DC2 protein 2.02 1.83
303195AA082211Hs.233936myosin, light polypeptide,1.32 3.95
regulatory, n
303196AA082298Hs.59710ESTs 0.77 0.53
303216AA581439Hs.152328ESTs 0.24 0.63
303222AA333538Hs.204501hypothetical protein3.56 6.22
FLJ10534
303234AA132255Hs.143951ESTs 2.28 3.17
65 303251AW340037Hs.115897protocadherin 12 0.38 1.02
303295AA205625Hs.208067ESTs 2.30 1.00
303297T80072Hs.13423Homo Sapiens clone 1.86 4.46
244613 mRNA sequence
303316AF033122Hs.14125p53 regulated PA26 0.10 0.80
nuclear protein
303467AA398801Hs.323397ESTs 4.54 9.65
303506AA340605Hs.105887ESTs, Weakly similar0.09 0.04
3o Homolog of rat
Z
303552AA359799Hs.224662ESTs, Weakly similar1.00 1.72
to unnamed protein
303598AA382814 gb:EST96097 Testis 4.96 9.14
I Homo sapiens
cDNA 5
303637AF056083Hs.24879phosphatidic acid 2.06 2.02
phosphatase type
2C
303655AA504702Hs.258802ATPase, (Na+)IK+ 1.00 1.24
transporting, beta
4 po
75 303756AI738488Hs.115838ESTs 1.08 1.43
303856AA96B589Hs.180532glucose phosphateisomerase1.76 1.31
303893N88597Hs.113503karyophedn (importin)2.30 2.57
beta 3
303907AW46777dHs.171880polymerase (RNA) 3.10 5.79
II (DNA directed)
polyp
303946AW474196Hs.306637Homo Sapiens cDNA 5.06 11.86
FLJ12363 fis, clone
MA
303978AW513315 gb:xo43c12.x1 NCI_CGAP_Utt5.14 7.31
Homo Sapiens
303981AW513804Hs.278834ESTs, Weakly similar2.83 4.06
to ALUt HUMAN ALU
S
303990AW515465 gb:xu71a11.x1 NCI-CGAP-KidB1.15 2.35
Homo Sapiens
303998AW516449 gb:xt68f05.x1 NCI 2.20 9.35
CGAP Ut2 Homc Sapiens
303999AW516611 gb:xp70b11.x1 NCI 4.85 6.28
CGAP_Ov39 Homo
Sapiens
$s 304006AW517947 gb:xt66h02.x1 NCI-CGAP-Ut23.21 4.07
Homo Sapiens
125
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WO PCT/US02/12476
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304008AW518198Hs.3297ribosomal protein 6.5011.08
S27a
304009AW518206Hs.181165eukaryotic translation1.883.27
elongation factor
304024T03036 gb:F821B7 Fetal 2.153.55
brain, Stratagene
Homo s
304026.T03160 gb:F826F2 Fetal 5.8811.80
brain, Stratagene
Homo s
304028T03266 gb:FB7C1 Fetal brain,5.5913.46
Stratagene Homo
la
304036T16855Hs.244621ribosomal protein 6.5514.43
S14
304046T54803 gb:yb42d06.s1 SUatagene6.1812.19
fetal spleen (9
304061T61521 gb:yb73gOt.s1 Stratagene2.648.23
ovary (937217)
304063T62536 gb:yc04c12.s1 Stratagenelung0.531.61
(937210) H
1 304097825376Hs.177592ribosomal protein, 6.4911.67
~ large, Pi
304114878946 gb:yi87g02.s1 Soares2.904.18
placenta Nb2HP
Homo
304122H28966 gb:ym31a06.s1 Soares1.002.76
infant brain 1N18
H
304155H68696 gb:yr78bO6.s1 Soaresfetal0.791.18
liver spleen
304203N56929 gb:yy82dO8.s1 Soares4.2811.34
multiple sclerosis
15 304234W81608 gbzd88h06.s1 Soares_fetal6.4711.03
heart_NbHH19W
304267AA064862Hs,73742ribosomal protein, 1.341.16
large, PO
304270AA069711Hs.297753vimentin 3.405.40
304287AA079286Hs.78466proteasome (prosome,2.93d.42
macropain) 26S
sub
304348AA179868 gb:zp38g12.si Slratagene3.9810.96
muscle 937209 H
2~ 304415AA290747Hs.169476glyceraldehyde-3-phosphate3.325,99
dehydrogenase
304430AA347682 gb:EST54044 Fetal 1.001.00
heart II Homo sapiens
304456AA411240 gbzv26g05.s1 Soares_NhHMPu_S11.423.33
Homo sapi
304521AA464716 gb:zx82c11.s1 Soares2.181.15
ovary tumor NbHOT
H
304526AA476427 gb:zx02c05.s1 Soares5.3814.11
total-fetus Nb2HF8_
25 304542AA482602Hs.169476glyceraldehyde-3-phosphate4.168.23
dehydrogenase
304546AA486074Hs.297681serine (or cysteine)0.551.20
proteinase inhibito
304607AA513322 gb:nh85e08.s1 NCI 1.952.10
CGAP_Brl.1 Homo
sapien
304640AA524440Hs.111334ferritin, light 2.102.83
polypeptide
304650AA527489Hs.3463ribosomal protein 3,3312.62
S23
304735AA576453 gb:nm75h11.s1 NCI_CGAP1.330.88
Co9 Homo Sapiens
304760AA580401 gb:nn13g09.s1 NCI-CGAP_Co123.688.14
Homo Sapiens
304849AA588157Hs.13801KIAA1685 protein 2.773.70
304917AA602685Hs.284136PR02047 protein 7.1611.01
304921AA603092Hs.297753vimentin 2.474.24
35 304966AA613893Hs.282435ESTs ' 6.7811.66
304987AA618044Hs.300697immunoglobulin heavy0.901.23
constant gamma
3 (G
305016AA626876 gb:zu89hO6.s1 Soares6.4610.17
testis_NHT Homo
sap
305034AA630128 gb:a699c04.s1 Stratagenelung1.001.00
(937210) H
305072AA641012 gb:nr72a12.s1 NCI_CGAP_Pr245.6811.59
Homo Sapiens
305111AA644187Hs.303405ESTs 1.481.37
305148AA654070 gb:nt01gOB.s1 NCI_CGAP_Lym31.764.61
Homo Sapiens
305159AA659166Hs.275668EST, Weakly similar1.002.15
to EF1 D-HUMAN
ELONG
305190AA665955 gb:ag57di2.s1 Gessler5.318.14
Wilms tumor Nomo
s
305232AA670052Hs.169476glyceraldehyde-3-phosphate0.781.18
dehydrogenase
45 305235AA670480 gb:ag37e01.s1 Jia 3.118.66
bone marrow stroma
Hom
305245AA676695Hs.81328nuclear factor of 4.387.53
kappa light polypeptid
305312AA700201 gb:zj44f07.s1 Soares2.132.66
fetal liver-spleen_
305322AA701597Hs.163019EST 1.201.40
305394AA720942Hs.300697immunoglobulin heavy1.160.68
constant gamma
3 (G
305413AA724659 gb:ai10f08.s1 Soares~arathyroid-tumor-N5.869.87
305447AA737856 gb:nx10cO8.s1 NCI 2.212.86
CLAP GC3 Homo Sapiens
305476AA745664Hs.287445hypotheticalprotein3.366.54
FLJ11726
305483AA748030Hs.303512EST 1.002.02
305528AA769156 gb:nz12e05.s1 NCI 6.449.10
CGAP_GCB1 Homo
Sapiens
55 305612AA782347Hs.272572hemoglobin, alpha 0.190.79
2
305614AA782866 gb:aj09h02.s1 Soares_parathyroid1.001.00
tumor-N
305616AA782884Hs.275865ribosomal protein 7.5710.20
S18
305637AA806124 gb:oe29a12.s1 NCI_CGAP-Pr254.7812.42
Homo Sapiens
305639AA806138 gb:oe29c12.s1 NCI 0.890.70
CGAP Pr25 Homo
Sapiens
305650AA807709 gb:nw31e04.s1 NCI-CGAP_GCBO 8.71
Homo sapiens4.49
305690AA813477 gb:ai67a05.s1 Soares4.919.40
testis_NHT Homo
sap
305726AA828156Hs.73742ribosomal protein, 0.190.81
large, PO
305728AA828209 gb:of34a02.s1 NCI_CGAP5.129.29
Kid6 Homo Sapiens
305759AA835353 gb:ak72bO6.s1 Barstead1.664.11
spleen HPLRB2 Nom
65 305792AAB45256 gb:akB4a08.s1 Barstead2.34d.25
spleen HPLRB2 Nom
305864AA864374Hs.73742ribosomal protein, 0.301.40
large, PO
305901AA872968 gb:oh63h08.s1 NCI_CGAP2.105.21
Kid5 Homo Sapiens
305910AA875981 gb:nx21h02.s1 NCI 0.321.01
CGAP_GC3Homosapiens
306015AA897116 gb:am08b07.s1 Soares-NFL_T-GBC_S1.56 1.12
Homo s1
306017AA897221Hs.109058ribosomal protein 5.217.90
S6 kinase, 90kD,
polyp
306020AA897630Hs.130027EST 1.966.59
306063AA906316 gb:ok03g03.s1 Soares_NFL_T_GBC_S17.3820.69
Homos
306065AA906725 gb:ok78g02.s1 NCI 7.1913.48
CGAP_GC4 Homo Sapiens
306104AA910956 gb:ok85h11.s1 NCI 6.509.13
CGAP Kid3 Homo
Sapiens
75 306109AA911861 gb:og21a07.s1 NCI-CLAP-PNS14.215.25
Homosapiens
306148AA917409Hs.288036tRNA isopentenyipyrophosphate2.202.70
transferal
306242AA932805 gb:oo60g04.s1 NCI_CGAP_Lu52.845.35
Homo Sapiens
306288AA936900 gb:oi53h05.s1 NCI 1.601.12
CGAP_HN3 Homo Sapiens
306325AA953072Hs.210546interleukin 21 receptor1.652.26
306353AA961382Hs.275865ribosomal protein 3.786.32
S18 .
306375AA968650Hs.27601EST, Moderately 4.305.74
B similar to JC4662
ribos
306396AA970223 gb:op09d05.s1 NCI_CGAP_Kid60.952.45
Homo Sapiens
306428AA975110Hs.191228hypothetical protein3.194.10
FLJ20284
306442AA976899 gb:oq35e09.s1 NCI 4.677.44
CGAP-GC4 Homo Sapiens
$5 306446AA977348 gb:oq72e12.s1 NCI-CGAP-Kid63.926.27
Homo Sapiens
126
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306458AA978186 gb;op33cO6.s1 Soares3.355.77
NFL-T_GBC-S1 Homo
s
306467AA983508Hs.163593ribosomal protein 3.725.37
L18a
306510AA988546 gb:or84d07.s1 NCI_CGAP-Lu51.001.00
Homo Sapiens
306555AA994304Hs.276083EST, Weakly similar6.6110.91
to RL23 HUMAN 60S
R
306557AA994530 gb:ou57e08.s1 NCI-CGAP16.2031.83
Br2 Homo sapiens
306572AA995686 gb:os25c12.s1 NCI_CGAP2.516.52
ICid5 Homo Sapiens
306582AA996248 gb:os18c10.s1 NCI 1.423.13
CGAP_Kid5 Homo
Sapiens
306598A1000320Hs.i69476glyceraldehyde-3-phosphate4.918.68
dehydrogenase
306605A1000497Hs.119500ribosomal protein, 1.968.60
large P2
1~ 306656A1004024 gb:ou11b07.xiSoares_NFL_T-GBC-S1Nomos0.110.45
306676A1005603Hs.284136PR02047 protein 9.5617.28
306686A1015615 gb:ov29f10.x1Soares1.863.60
testis-NHTHomo
sap
306702A1022565Hs.307670EST 1.471.19
306728A1027359Hs.272572hemoglobin, alpha 1.282.83
2
15 306751A1032589 gb:ow70h12.s1 Soares3.915.21
fetal liver-spleen_
306767A1038963Hs.249118ESTs 3.336.06
306892A1092465 gb:qa75hi2.x1 Soares3.777.46
fetal_heart NbHHI9W
306897A1093967 gb:qa33cO6.s1 Soares2.122.85
NhHMPu S1 Homo
sapi
306956AI125111 gb:am66f03.s1 Barstead6.1010.52
spleen HPLRB2 Nom
306958AI125152 gb:am55e09.x1 Johnston1.721.56
frontal cortex
No
307035AI142774Hs.119122ribosomal protein 2.004.70
Ll3a
307041AI144243 gb:qb85b12.x1 Soares9.1212.56
fetal heart-NbHHI9W
307091AI167439 gb:ox70hO6.s1 Soares_NhHMPu-St4.888.52
Homo sapi
307181AI189251 gb:qc99gO6.x1 Soares3.556.44
pregnant-uterus_NbH
25 307297AI205798Hs.111334ferdtin, light polypeptide2.464.65
307317AI208303Hs.147333EST 5.6410.13
307327AI214142Hs.246381CD68 antigen 3.185.15
307382AI223158Hs.147885ESTs 2.023.73
307410A1241715Hs.77039ribosomal protein 0.720.48
S3A
307415AI242118 gb:qh92b02.x1 Soares2.383.51
NFL-T_GBC-S1 Homo
s
307423AI243206Hs.179573collagen, type I, 2.605.44
alpha 2
307426AI243364 gb;qh30g11.x1 Soares3.187.67
NFL_T_GBC-S1 Homo
s
307517AI275055 gb:q172d03.x1 Soares1.001.00
NhHMPu S1 Homo
sapi
307551AI281556 gb;qu52f11.x1 NCI-CGAP_Lym6Homosapiens3.4011.20
35 307561AI282207 gb:qp65a12.x1 Soares4.7415.51
fetal lung-NbHL19W
307608AI290295 gb:qm01f02.x1 Soares_NhHMPu-S13.507.19
Homo sapi
307657AI306428Hs.298262ribosomal protein 1.762.44
S19
307691AI318285 gbab17b01.x1 NCI_CGAP-Ov371.591.31 '
Homo Sapiens
307701AI318583Hs.276672EST, Weakly similar1.902.13
to RL6 HUMAN 60S
RI
307718AI333406Hs.83753small nuclear ribonucleoprotein0.450.99
polypept
307730AI336092 gb:qt43b07.x1 Soares1.510.99
fetal lung_NbHLI9W
307760AI342387 gb:qt27f07.xi Soares-pregnant_uterus-NbH1.001.00
307764A1342731 gb:qo26a07.x1 NCI 4.5212.58
CGAP_Lu5 Homo Sapiens
307783AI347274 gbac05d02.x1 NCI 1.421.00
CGAP_Co16 Homo
Sapiens
45 307796AI350556 gb:qt18f09.x1 NCI 6.579.61
CGAP_GC4Homosapiens
307807AI351799 gb:qt09d02.x1 NCI-CGAP3.387.68
GC4 Homo Sapiens
307808AI351826 gb:qt09g03.x1 NCI 0.330.86
CGAP_GC4 Homo sapiens
307820AI355761 gb:qt94a11.x1 NCI 7.9421.57
CGAP_Col4 Homo
Sapiens
307830AI358722Hs.276737EST, Weakly similar2.053.32
to R5HU22 ribosomal
50 307852AI365541 gb:qz08g05.x1 NCI 3.185.21
CGAP_CLL1 Homosapiens
307902AI380462 gbag02h05.x1 NCI-CGAP3.134.99
CLL1 Homo Sapiens
307997AI434512Hs.181165eukaryotic translation1.003.01
elongation factor
308002AI435240Hs.283442ESTs 5.8612.64
308011A1439473 gbai60a08.x1 NCI_CGAP3.795.83
Lym12 Homo sapien
55 308023AI452732Hs.251577hemoglobin, alpha 0.380.88
1
308041AI458824Hs.169476glyceraldehyde-3-phosphate4.366.06
dehydrogenase
308059A1468938Hs.276877EST, Weakly similar1.801.98
to RL10_HUMAN 60S
R
308085AI474135Hs.i81165eukaryotic translation3.384.14
elongation factor
308101AI475950Hs.181165eukaryotic translation1.303.87
elongation factor
GD 308106AI476803 gbaj77e12.x1 Soares-NSF 8.72
F8_9W-OT_PA-P S2.38
308122AI480123Hs.309411EST 2.703.86
308154AI500600 gban93d08.x1 NCI 0.661.33
CGAP_Ut2 Homo Sapiens
308171AI523632Hs.298766ESTs, Weakly similar2.484.86
to schlafen4 [M.mu
308211AI557029Hs.278572anaplasGc lymphoma 2.432.14
kinase (Ki-1)
65 308213AI557041 gb:PT2.1 12 E04.r 3.343.79
tumor2 Homo Sapiens
cD
308216AI557135 gb:PT2.1 13_H06.r 4.614.78
tumor2 Homo Sapiens
cD
308219AI557246 gb:PT2.1 15_D07.r 4.877.94
tumor2 Homo Sapiens
cD
308271AI567844Hs.252259ribosomal protein 2.406.35
S3
308319AI583983Hs.181165eukaryotic Uansiation2.453.33
elongation factor
308362AI613519Hs.105749KIAA0553 protein 1.241.41
308413AI636253Hs.196511ESTs 3.164.82
308450AI660B60Hs.96840KIAA1527 protein 1.792.68
308464AI672425Hs.277117EST, Moderately 4.878.27
similar to 138055
myosi
308588AI718299 gb:as51g12.x1 Barstead3.905.64
aorta HPLRB6 Homo
75 308599AI719893 gb:as47d07.x1 Barstead3.325.12
aorta HPLRB6 Homo
308615AI738593Hs.101774hypothetical protein3.112.36
FLJ23045
308643AI745040 gbar19a12.x1 NCI-CGAP-Ov233.983.69
Homo sapiens
308673AI760864 gb:wi09c10.x1 NCI-CLAP-CLLi0.820.99
Homo Sapiens
308697AI767143 gb:wi97a07.x1 NCI-CGAP_Kid122.765.59
Homo sapien
308762AI807405Hs.259408ESTs 3.176.30
308778AI811109 gbar04c11.x1 NCI 1.001.00
CGAP_Ov23 Homo
Sapiens
308782AI811767Hs.2186eukaryotic translation2.945.15
elongation factor
308808AI818289 gb:wk52c01.x1 NCI-CGAP-Pr224.d18.34
Homo Sapiens
308823AI824118Hs.217493annexin A2 1.851.92
g 308875A1832332 gb:at48g03.x1 Barstead2.523.80
colon HPLRB7 Homo
127
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308879AI832763Hs.75968ihymosin, beta 4, 3.38 7.96
X chromosome
308886AI833240 gb:at76d10.x1 Barstead3.06 2.65
colon HPLRB7 Homo
308898AI858845 gb:w132d10.x1 NCI 2.45 3.44
CGAP_Ut1 Homo Sapiens
308934AI865023Hs.i77phospha6dylinositol4.14 6.76
glycan, class H
308966AI870704 gb:w147h01.x1 NCI 1.00 1.00
CGAP_Ut1 Homo Sapiens
308979AI873111 gb:w152h05.x1 NCI 7.15 11.10
CGAP-Brn25 Homo
sapien
309045AI910902 gbaq39f01.x1 NCI 0.61 0.59
CGAP Ut1 Homosapiens
309051AI911975 gb:wd78d01.x1 NCI 1.78 4.42
CGAP-Lu24 Homo
Sapiens
309069AI917366Hs.78202SWIISNF related, 3.27 5.88
matrix associated,
act
1 309083AI922426Hs.119598ribosomal protein 2.39 3.34
~ L3
309105A1925503Hs.265884ESTs 5.54 17.78
309122AI928178 gb:wo95a11.x1 NCI 1.00 2.92
CGAP_Kidl1 Homosapien
309128AI928816Hs.180842ribosomal protein 1.38 5.55
L13
309164AI937761 gb:wp84b09.x1 NCI 2.43 3.11
CLAP-Brn25 Homo
sapien
15 309177AI951118 gb:wx63g05.x1 NCI-CGAP-Br180.81 0.97
Homo Sapiens
309288AI991525Hs.299426ESTs d.86 7.46
309299AW003478 gb:wq66cO6.x1 NCI_CGAP_GC64.36 9.43
Homo Sapiens
309303AW004823 gb:ws93a08.x1 NCI-CGAP-Co32.88 7.54
Homo Sapiens
309411AW085201Hs.244144EST 4.30 7.14
2~ 309437AW090702Hs.278242tubulin, alpha, 2.49 3.11
ubiquitous
309459AW117645Hs.65114keratin 18 2.88 4.55
309476AW129368 gb:xe14b05.x1 NCI 2.08 6.60
CGAP_Ut4 Homo sapiens
309499AW136325Hs.279771Homo Sapiens clone 2.82 3.55
PP1596 unknown
mRNA
309529AW150807Hs.181357laminin receptor d.78 3.95
1 (67kD, ribosomal
pro
25 309532AW151119 gb:xg33e10.x1 NCI 1.18 4.40
CGAP_Ut1 Homosapiens
309626AW192004Hs.297681serine (or cysteine)4.46 12.06
proteinase inhibit
309641AW194230Hs.253100EST, Moderately 1.47 1.39
similar to GHHU
Ig gamm
309675AW205681Hs.253506EST, Moderately 5.68 15.20
similar to ATPN
HUMAN A
309693AW237221Hs.181357laminin receptor 1.00 1.00
1 (67kD, ribosomal
prot
309695AW238011Hs.295605mannosidase, alpha,5.45 9.61
class 2A, member
2
309700AW241170Hs.179661tubulin, beta polypeptide1.41 1.25
309747AW264889 gb:xq36h02.x1 NCI 5.00 8.35
CGAP_Lu28 Homo
Sapiens
309769AW272346 gb:xs13c10.x1 NCI_CGAP5.76 11.90
Kidl1 Homo sapien
309782AW275156Hs.156110immunoglobulin kappa0.42 0.69
constant
35 309783AW275401Hs.254798EST 1.00 d.11
309799AW276964 gb:xp58h01,x1 NCI-CGAP_Ov391.68 1.44
Homo Sapiens
309866AW299916 gb:xs44c01.x1 NCI 3.02 5.04
CGAP Kidl1 Homo
sapien
309903AW339071Hs.300697immunoglobulin heavy1.05 1.18
constant gamma
3 (G
309923AW340684 gb:hd05gO8.x1 Soares-NFL_T_GBC2.30 3.67
S1 Homo s
309928AW341418 gb:hd08c03.x1 Soares-NFL-T-GBC7.41 13.71 '
S1 Homos
309931AW341683 gb:hdl3dOt.x1 Soares-NFL_T_GBC_S11.20 12.70
Homo s
309933AW341936 gb:hb73f10.x1 NCI 4.90 18.29
CGAP Ut2 Homo Sapiens
309964AW449111Hs.257111hypothetical protein1.99 3.07
MGC3265
310002AI439096Hs.323079Homo Sapiens mRNA; 0.20 0.47
cDNA DKFZp564P116
(fr
45 310096AW136822Hs.172824ESTs, Weakly similar1.51 1.22
to 848013 proline-r
310098AI685841Hs.161354ESTs 0.31 0.76
310109A1203094Hs.148633ESTs 2.06 5.83
310112AW197233Hs.147253ESTs 2.92 3.55
310115AI611317Hs.223796ESTs 1.25 0.84
50 310121AW195642Hs.148901ESTs 1.00 2.71
310146AI206614Hs.197422ESTs 9.50 15.31
310193AI627653Hs.147562ESTs 2.85 4.18
310255AW450439Hs.i53378ESTs 4.26 10.63
310261AI240483Hs.201217ESTs 3.28 4.40
55 310264A1915771Hs.74170metallothionein1E(functional)0.26 0.86
310275AI242102Hs.213636ESTs 5.43 8.19
310282AI243332Hs.156055ESTs 3,15 8.06
310290AW013815Hs.149i03ESTs 2.19 3.12
310333AI253200Hs.145402ESTs 1.17 1.91
310346A1261340Hs.145517ESTs 4.81 9.95
310385A1263392Hs.156151ESTs 5.96 7.79
310443AW119018Hs.i64231ESTs 2.90 4.63
310444AW196632Hs.252956ESTs 0.85 1.01
310446AI275715Hs.145926ESTs 2.18 3.85
65 310468A1984074Hs.196398ESTs 3.39 5.19
310477AI948801Hs.171073ESTs 1.00 1.0D
310512AW275603Hs.200712ESTs 3.87 8.12
310514AI681145Hs.160724ESTs 3.30 7.33
310524AW082270Hs.12496ESTs, Highly similar0.72 1.d4
to AC0048361 simil
310547AI302654Hs.208024ESTs 3.26 3.46
310584A1653007Hs.156304ESTs 2.39 4.08
310608AI962234Hs.i96102ESTs 5.60 6.d9
310624AI341594 gb:Human endogenous4.91 9.09
relrovirus H proteas
310636AI814373Hs.164175ESTs 1.85 1.71
75 310648AI347863Hs.156672ESTs 0.17 0.69
310694AI654370Hs.157752Homo Sapiens mRNA 5.40 13.22
full length insert
cDN
310695AI472124Hs.157757ESTs 4.82 6.27
310714A1418446Hs.157882ESTs 1.76 3.51
310722AI989803Hs.157289ESTs 1.14 6.85
310756AI916560Hs.158707ESTs 8.46 13.01
310764AI376769Hs.167172ESTs 4.76 7.37
310848AI459554Hs.161286ESTs 2.84 1.96
310851AW291714Hs.221703ESTs 1.00 2.32
310854AI421677Hs.161332ESTs 6.37 7.94
85 310858AI871000Hs.161330ESTs 6.07 9.84
128
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310864AI924558Hs.161399ESTs 0,87 0.78
310875T47764Hs.132917ESTs 1.00 3.63
310896AW157731Hs.270982ESTs, Moderately 7.07 16.68
similar to ALUl-HUMAN
A
310922AW195634Hs.170401ESTs 1.00 1.00
310955A1560210Hs.263912ESTs 10.0817.66
310957AW190974Hs.196918ESTs 2.18 3.18
311000A1521830Hs.171050ESTs 3.06 6.64
311012AW298070Hs.241097ESTs 1.23 3.77
311034A1564023Hs.311389ESTs, Moderately 2.44 2.09
similar to PT0375
natur
1 311074AW290922Hs.199848ESTs 6.04 14.19
0
311134A1990849Hs.196971ESTs 3.54 6.96
311174AW450552Hs.205457pedaxin 0.65 0.95
311187A1638374Hs.224189ESTs 2.46 2.78
311220A1656040Hs.196532ESTs 1.10 2.52
1 311230A1989808Hs.197663ESTs 1.41 1.75
311236A1653378Hs.197674ESTs 2.18 2.11
311242AW016812Hs.200266ESTs 0.63 5.11
311258A1671221Hs.199887ESTs 1.00 1.41
311277AW072813Hs.27086BESTs, Moderately 2.56 1.94
similar to ALU4-HUMAN
A
2~311294AA826425Hs.291829ESTs 1.04 2.69
311308F12664Hs.49000ESTs 1.96 6.70
311351A1682303Hs.201274ESTs 4.77 9.38
311390AW392997Hs.202280ESTs 2.80 6.06
311405AW290961Hs.201815ESTs 3.80 11.66
25311409AI698839 gb:wd31f02.x1 Soares-NFL-T_GBC-S13.84 6.94
Homos
311420AI936291Hs.209867ESTs 5.30 12.56
311443A1791521Hs.192206ESTs 4.39 6.09
311467A1934909Hs.175377ESTs 1.00 1.04
311479A1933672Hs.211399ESTs 2.76 5.61
311488857390Hs.301064arfaptin 1 2.50 5.73
311495AW300077Hs.221358ESTs 3.63 6.09
311511AW444568Hs.210303ESTs 2.00 2.87
311534AW130351Hs.243549ESTs 0.31 1.33
311537A1805121Hs.211828ESTs 3.69 5.85
35311543A1681360Hs.201259ESTs 1.73 1.34
-
311551AW449774Hs.296380POM (POM121 rat 3.31 6.12
homology and ZP3
fusion
311557AI819230Hs.211238interleukin-1 homolag1.00 1.00
1
311558244432Hs.63128KIAA1292 protein 2.25 3.41
311559AW008271Hs.265848similar to rat myomegalin2.68 5.90
311563AI922143Hs.211334ESTs 2.39 3.32
311586A1827834Hs.211227ESTs 2.47 3.85
311616AW450675Hs.212709ESTs ~ 1.00 1.00
311621AI924307Hs.213464ESTs 4.16 6.74
311635A1928456Hs.213081ESTs 2.17 3.76
45311668AW193674Hs.240044ESTs 2.60 3.12
311672811807Hs.20914hypothetical protein2.79 5.18
FLJ23056
311683AW183738Hs.232644ESTs 0.19 0.96
311700849601Hs.171495retinoic acid receptor,6.28 8.83
beta
311714AW131785Hs.246831ESTs, Weakly similar5.00 8.17
to CIKG HUMAN VOLTA
311735AW294416Hs.144687Homo Sapiens cDNA 0.96 0.72
FLJ12981 fis, clone
NT
311743T99079Hs.191194ESTs 1.00 1.95
311783A1682478Hs.13528hypothetical protein0.16 0.77
FLJ14054
311785A1056769Hs.133512ESTs 1.34 3.97
~
311799AA780791Hs.14014ESTs, Weakly similar8.52 13.32
to KIAA0973 protein
55311819AW265275Hs.254325ESTs 3.56 3.91
311823A1089422Hs.131297ESTs 1.40 1.72
311877AA349893Hs.85339G protein-coupled 0.95 0.91
receptor39
311886AA522738Hs.132554ESTs 0.88 0.87
311896AW206447 gb:Ul-H-811-afg-g-02-0-ULs11.66 1.13
NCI CGAP_Su
60311910N28365Hs.22579Homo Sapiens clone 1.66 2.30
CDABP0036 mRNA
sequen
311923T60843Hs.189679ESTs 0.42 2.63
311933AI597963Hs.118726ESTs 1.88 3.02
311959T67262Hs.124733ESTs 2.02 2.33
311960AW440133Hs.189690ESTs 3.87 6.62
65311967AI382726Hs.182434ESTs 5.80 8.1d
311975AA804374Hs.272203Homo Sapiens cDNA 0.98 3.26
FLJ20843 fis, clone
AD
312005T78450Hs.i3941ESTs 0.12 1.39
312028T78886Hs.284450ESTs 3.78 4.92
312046A1580018Hs.268591ESTs 4.11 7.32
312056T83748Hs.268594ESTs 2.36 3.08
312064AA676713Hs.191155ESTs 3.34 5.28
312088AW303760Hs.13685ESTs 1.60 1.15
312093T91809Hs.121296ESTs 0.68 0.85
312094278390 gb:HSZ78390 Human 3.05 4.48
fetal brain S.
Meter-E
75312097AI352096Hs.112180zinc finger protein4.52 9.70
148 (pHZ-52)
312118T85332Hs.178294ESTs 2.40 2.60
312128A1052609Hs.17631Homo Sapiens cDNA 2.39 3.53
FLJ20118 fis, clone
CO
312147T89855Hs.195648ESTs 0.67 1.03
312175AA953383Hs.127554ESTs 5.85 10.60
312179A1052572Hs.269864ESTs 2.41 3.32
312201A1928365Hs.91139solute carrier family0.24 0.89
1 (neuronallepithe
312207H90213Hs.191330ESTs 2.20 4.55
312220N74613 gb:za55a07.s1 Soaresfetailiverspleen4.28 11.13
3f2252A1128388Hs.143655ESTs 1.64 1.57
$s312304AA491949Hs.269392ESTs 0.12 2.47
129
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
312318AW235092Hs.143981ESTs 3.46 5.69
312319AA216698Hs.180780TERA protein 5.78 4.46
312321866210Hs.186937ESTs 0.44 1.74
312331AA825512Hs.289101glucose regulated 3.73 5.96
protein, 58kD
312339AA524394Hs.165544ESTs 3.07 0.95
312363A1675558Hs.181867ESTs 10.0816.73
312375A1375096Hs.172405cell division cycle2.78 3.71
27
312376852089Hs.i72717ESTs 1.00 1.00
312389A1863140 gbaz43h12.x1 NCI 2.37 3.98
CGAP-Brn52 Homo
sapien
1 312437AA995028 gb:RC4-BT0629-120200-011-b104.06 5.41
0 BT0629 Homo
312440A1051133Hs.133315Homo sapiens mRNA; 1.00 1.00
cDNA DffFZp761J1324
(f
312451859989Hs.176539ESTs 4.96 10.04
312458A1i67637Hs.146924ESTs 1.11 1.00
312507A1168177Hs.143653ESTs 5.89 8.24
15312520AI742591Hs.205392ESTs 3.30 8.92
312548AI566228Hs.159426hypothetical protein1.38 1.65
PR02121
312564H21520Hs.35088ESTs 0.40 0.77
312583AI193122Hs.124141ESTs 0.13 0.94
312599AI865073Hs.125720ESTs 3.75 5.29
312602AA046451Hs.165200ESTs 6.78 12.93
312645H52121Hs.193007ESTs 0.38 1.13
312666AI240582Hs.214678ESTs 0.96 2.03
312689AW450461Hs.203965ESTs 0.21 0.61
312817H75459Hs.233425ESTs 1.51 0.85
312846AW152104Hs.200879ESTs 8.93 13.78
312873AI690071Hs.283552ESTs, Weakly similar4.20 6.23
to unnamed protein
312893A1016204Hs.172922ESTs 2.67 3.15
312902AW292797Hs.130316ESTs, Weakly similar1.19 0.71
to T2D3-HUMAN TRANS
312925N90868Hs.271695ESTs 2.50 4.25
3 312936AI68f581Hs.121525ESTs 1.00 1.17
0
312975A1640506Hs.293119ESTs, Weakly similar2.30 4.80
to ALU7 HUMAN ALU
S
312978N24887Hs.292500ESTs 0.80 1.05
312980AA497043Hs.115685ESTs 3.12 3.60
312984N25871Hs.177337ESTs 2.03 2.13
3 313000A1147412Hs.146657ESTs 5.52 8.42
313029AA731520Hs.170504ESTs 0.96 1.39
313039A1419290Hs.149990ESTs, Weakly similar6.46 13.20
to unnamed protein
313049AW293055Hs.119357ESTs 6.44 10.73
313056AI651930Hs.135684ESTs 1.51 2.04
40313058D81015Hs.125382ESTs 0.25 1.50
313070AI422023Hs.161338ESTs 8.56 11.60
313097A1676164Hs.204339ESTs 3.72 4.56
313130AW449171Hs.168677ESTs 3.26 5.06
313136N59284Hs.288010ESTs 0.49 1.36
45313153A1240838Hs.132750ESTs 5.36 5.52
313210N74077Hs.197043ESTs 0.30 0.66
313236AW238169Hs.83513ESTs, Weakly similar5.16 8.76
to ALU1 HUMAN ALU
S
313239W19632Hs.124170ESTs 1.00 3.87
313265N93466Hs.12i764ESTs, Weakly similar0.74 2.06
to testicular tekii
5 313267A1770008Hs.129583ESTs 0.23 1.30
0
313275A1027604Hs.159650ESTs 6.68 9.57
313290A1753247Hs.29643Homo Sapiens cDNA 1.34 1.07
FLJ 13103 fis,
clone NT
313292AI362991Hs.202121ESTs, Weakly similar2.00 4.32
to env protein
[H.s
313325AI420611Hs.127832ESTs 1.20 2.27
5 313357AW074848Hs.201501ESTs 4.02 5.33
5
313393A1674685Hs.200141ESTs 1.36 2.84
313399AW376889Hs.194097ESTs 2.58 5.26
313414A1241540Hs.132933ESTs 6.57 15.07
313417AA741151Hs.137323ESTs 0.63 3.01
60313457AA576052Hs.193223Homo Sapiens cDNA 2.78 4.70
FLJ11646 fis, clone
HE
313499AI261390Hs.146085tfIAA1345 protein 0.91 2.37
313516AA029058Hs.135145ESTs 3.41 7.08
313556AA628517Hs.118502ESTs 0.23 0.70
313569A1273419Hs.135146hypothetical protein1.8B 1.00
FLJ13984
65313570AA041455Hs.209312ESTs 0.73 2.27
313638A1753075Hs.104627Homo Sapiens cDNA 1.00 1.72
FLJ10158 fis, clone
HE
313662AA740151Hs.130425ESTs 0.20 1.42
'
313671W49823Hs.104613RP42 homolog 1.00 1.00
313672AW468891Hs.122948ESTs 3.46 5.80
70313690A1493591Hs.78146plateletlendothelial0.51 0.97
cell adhesion molec
313711AA398070Hs.133471ESTs 0.18 1.01
313723AA070412 gb:zm68c10.s1 Stratagene1.08 1.03
neuroepithelium
313726AI744687Hs.257806ESTs 2.13 2.99
313774AW136836Hs.144583ESTs 1.38 1.19
75313784AA910514Hs.134905ESTs 3.88 5.78
313790AW078569Hs.177043ESTs 0.22 2.06
313832AW271022Hs.133294ESTs 1.15 0.91
313834AW418779Hs.114889ESTs 0.68 3.14
313835AI538438Hs.159087ESTs 5.74 8.88
$0313852H18633Hs.123641protein tyrosine 0.16 1.14
phosphatase, receptort
313854AW470806Hs.275002ESTs 2.09 4.06
313865AA731470Hs.163839ESTs 3.41 4.09
313871AWd71088Hs.145950ESTs 5.28 6.83
313883AI949384 gb:nu76d01.s1 NCI-CGAP_AIv12.90 10.91
Homo Sapiens
g5313915AI969390Hs.i63443Homo Sapiens cDNA 1.00 1.00
FLJ11576 fis, clone
HE
130
CA 02444691 2003-10-17
WO 6443 PCT/US02/12476
02/08
313926AW473830Hs.171442ESTs 3.40 4.11
313948AW452823Hs.135268ESTs 5.77 9.15
313978A1870175Hs.13957ESTs 0.46 0.75
313983A1829133Hs.226780ESTs 4.10 6.40
314035AA164199Hs.270152ESTs 5.86 7.90
314037AW300048Hs.275272ESTs 1.00 3.79
314040AA166970Hs.118748ESTs 7.60 11.33
'
314067AW293538Hs.51743KIAA1340 protein 1.86 1.21
314103A1028477Hs.132775ESTs 2.90 5.29
1 314107AA806113Hs.189025ESTs 2.00 1.66
~
314113AA218986Hs.118854ESTs 0.91 4.17
314124AW118745Hs.9460Homo Sapiens mRNA; 2.53 3.32
cDNA DKFZp547C244
(fr
314126AA226d31 gb:nc18b12.s1 NCf_CGAP_Pri3.13 5.08
Homosapiens
314128AA935633Hs.194628ESTs 2.90 6.35
1 314151AA236163Hs.202430ESTs 4.15 6.45
314184AW081795Hs.233465ESTs 3.44 4.65
314192AW290975Hs.118923ESTs 1.00 1.23
314244AL036450Hs.103238ESTs 2.88 3.67
314253AA278679Hs.189510ESTs 4.98 7.16
314262AW086215Hs.246096ESTs 0.36 1.94
314320AA811598Hs.275809ESTs 3.34 5.66
314332AL037551Hs.95612ESTs ~ 2.85 2.09
314335AA287443Hs.142570Homo sapiens clone 4.35 4.78
24629 mRNA sequence
314340AW304350Hs.130879ESTs, Moderately 0.77 0.86
similar to putative
p15
314351AA292275Hs.193746ESTs 3.07 3.77
314376A1628633Hs.32d679ESTs 4,10 6.11
314443AA827125Hs.192043ESTs 6.20 13.67
314458A1217440Hs.143873ESTs 0.58 2.49
314466AA767818Hs.122707ESTs 2.53 2.62
3~314478A1521173Hs.125507DEAD-box protein 3.94 5.65
314482AL043807Hs.134182ESTs 1.30 1.44
314506AA833655Hs.206868Homo Sapiens cDNA 3.28 3.47
FLJ14056 fis, clone
HE
314519Rd2554Hs.210862T-box,brain,l 3.12 6.16
314529AL046412Hs.202151ESTs 3.43 6.87
35314546AW007211Hs.16131hypothetical protein1.38 1.00
FLJ12876
314562AI564127Hs.143493ESTs 2.29 5.27
314579AW197442Hs.116998ESTs 3.87 5.75
314580AW451832Hs.255938ESTs, Moderately 0.10 0.71
similar to KIAA1200
pro
314585AA918474Hs.216363ESTs 1.08 1.40
314589AW384790Hs.153408Homo Sapiens cDNA 1.00 1.00
FLJ10570 fis, clone
NT
314592AA435761Hs.192148ESTs 0.90 2.60
314603AA418024Hs.270670ESTs 4.56 6.29
314604AA946582Hs.8700deleted in liver 3.42 3.92
cancer 1
314606AA418241Hs.188767ESTs 2.97 4.55
45314648AA878419 gb:EST391378 MAGE 1.36
resequences, MAGP
Homo1.d2
314699A1038719Hs.132801ESTs 3.66 4.97
314701A1754634Hs.131987ESTs 0.03 0.90
314710A1669131Hs.290989EST 3.40 7.52
314750A1095005Hs.135174ESTs 2.80 6.54
314767AW135412Hs.164002ESTs 3.20 4.26
314801AA481027Hs.109045hypothetical protein1.00 1.00
FLJ10498
314817AI694i39Hs.192855ESTs 0.91 0.99
314835AI281370Hs.76064ribosomal protein 5.75 7.44
L27a
314852AI903735 gb:MR-BT035-200199-0311.68 4.34
BT035 Homo sapien
55314853AA729232Hs.153279ESTs D.60 1.85
314940AW452768Hs.162045ESTs 10.1016.20
314941AA515902Hs.i30650ESTs 0.31 1.02
314943A1476797Hs.184572cell division cycle2.18 0.37
2, G1 1c S and
G2 to
314955AA521382Hs.192534ESTs 2.59 3.90
314973AW273128Hs.300268ESTs 1.05 1.25
315004AA527941Hs.325351EST 5.64 13.63
315006A1538613Hs.298241Transmembrane protease,0.52 1.78
serine 3
315033AI493046Hs.146133ESTs 2.46 1.00
315035A1569d76Hs.177135ESTs 0.34 1.33
65315056AI202703Hs.152414ESTs 2.10 2.64
315069AI821517Hs.105866ESTs 1.00 1.30
315071AA552690Hs.152423Homo Sapiens cDNA: 1.78 1.00
FLJ21274 fis, clone
C
315073AW452948Hs.257631ESTs 1.17 1.52
315078AA568548Hs.190616ESTs 3.00 3.79
315080AA744550Hs.136345ESTs 1.00 1.00
315120AA564991Hs.269477ESTs 0.64 1.44
315175A1025842Hs.152530ESTs 0.61 1.91
315193A1241331Hs.131765ESTs 1.06 0.97
315196AA972756Hs.44898Homo Sapiens clone 0.48 1.96
TCCCTA00151 mRNA
sequ
75315200AI808235Hs.307686EST 3.76 9.40
315254AI474433Hs.179556ESTs 5.37 9.36
315353AW452608Hs.279610hypothetical protein1.00 1.30
FLJ10493
315397AA218940Hs.137516fidgetin-like 1 3.36 2.24
315403AW362980Hs.163924ESTs 2.04 5.23
315431AA622104Hs.184838ESTs 2.36 8.04
315454A1239473 gb:qh36f02.x1 Soares_NFL-T_GBC_S73.46 7.64
Homos
315455AW393391Hs.156919ESTs 3.78 5.76
315473A1681671Hs.312671ESTs, Moderately 0.89 2.15
similar to OVCA1
315483AW512763Hs.222024transcription factor2.32 1.96
BMAL2
5 315526AI193048Hs.128685ESTs 1.67 1.78
131
CA 02444691 2003-10-17
WO 6443 PCT/US02/12476
02/08
315530At200852Hs.127780ESTs 1.05 1.01
315541A1168233Hs.123159sperm associated 0.85 0.56
antigen 4
315552AW445034Hs.256578ESTs 1.00 2.22
315562AA737415Hs.152826ESTs 2.66 2.48
315577AW513545Hs.17283hypolhe6cal protein2.20 2.25
FLJ10890
315587AI268399Hs.140489ESTs 1.00 1.04
315589AW072387Hs.158258Homo sapiens mRNA; 0.14 1.05
cDNA DKFZp434B1272
(f
315623AA364078Hs.258189ESTs 7.44 12.56
315634AA837085Hs.220585ESTs 0.50 1.40
1 315668AA912347Hs.136585ESTs 0.43 1.22
~
315677A1932662Hs.164073ESTs 0.60 1.39
315706AW440742Hs.155556hypothetical protein2.18 3.77
FLJ20202
315707AI418055Hs.161160ESTs 2.88 2.63
315730H25899Hs.201591ESTs 0.11 0.60
15 315745AI821759Hs.191856ESTs 3.50 7.25
315791AA678177 gb:zi15a05.s1 Soares_fetal_liver_spleen_1.78 2.63
315801AA827752Hs.266134ESTs 4.31 6.23
315820A1652022Hs.258785ESTs 2.35 3.01
315878AA683336Hs.189046ESTs 2.12 2.64
2~ 315905AI821911Hs.209452ESTs 1.03 1.97
315923A1052789Hs.133263ESTs 2.63 5.06
315954AW276810Hs.254859ESTs, Moderately 1.21 0.85
similar to ALU5_HUMAN
A
315978AA830893Hs.119769ESTs 3.09 3.41
316001AI248584Ns.190745Homo sapiens cDNA: 2.20 6,82
FLJ21326 fis, clone
C
25 316011AW516953Hs.201372ESTs 0.35 1.63
316012AA764950Hs.119898ESTs 6.56 8.13
316040A1983409Hs.189226ESTs 5.69 10.69
316048AI720759Hs.224971ESTs 2.84 10.45
316076AW297895Hs.116424ESTs 0.30 1.05
3 396124AI308862Hs.167028ESTs 1.00 1.43
~
316151A1806016Hs.156520ESTs 5.80 9.03
316187AW518299Hs.192253ESTs 1.20 3.96
316204AA731509Hs.120257ESTs 4.92 6.94
316232AW297853Hs.251203ESTs 1.48 1.60
35 316275Ai671041Hs.292611ESTs, Moderately 5.86 12.14
similar to ALU1
HUMAN A
316291AW375974Hs.156704ESTs 2.73 2.69
316303AA740994Hs.209609ESTs 1.53 1.26
316344AA744518Hs.120690EST's 3.66 8.34
316346A1028478Hs.157447ESTs 3.51 6.69
316365A1627845Hs.210776ESTs 2.50 4.33
316380A1393378Hs.164496ESTs 1.16 2.16
316470AA809902Hs.243813ESTs 5.40 10.34
316509AA767390Hs.291766ESTs 2.46 2.89
316514AA768037Hs.291671ESTs 4.70 6.04
45 316519AI929097 gb:od10c11.s1 NCI_CGAP_GC814.41 9.70
Homo sapiens
316609AW292520Hs.122082ESTs 1.00 2.89
316633AI125586Hs.127955ESTs 2.61 3.72
316700AW172316Hs.252961ESTs, Weakly similar3.46 4.fi4
to ALU1 HUMAN ALU
S
316711AI743721Hs.285316ESTs, Moderately 4.45 6.95
similar to ALU7_HUMAN
A
316713A1090671Hs.134807hypothetical protein0.30 2.40
FLJ12057
316715AI44026fiHs.170673ESTs, Weakly similar0.20 1.45
to AF1267801 retin
316787AW369770Hs.130351ESTs 4.05 5.53
316809AA825839Hs.202238ESTs 2.25 3.62
316811AA922060Hs.132471ESTs 1.00 1.32
316812AW135045Hs.232001ESTs 3.28 4.70
5
316818AA827176Hs.124316ESTs 0.67 1.81
316824AA837416Hs.124299ESTs 3.53 6.00
316827A1380429Hs.172445ESTs 0.72 1.56
316891AW298119Hs.202536ESTs 1.64 2.97
316951AA134365Hs.57548ESTs ~ 1.45 1.08
316970AA8fi0172Hs.132406ESTs 1.00 1.53
316971AA860212Hs.170991ESTs 1.08 1.96
316990AA861611Hs.130643ESTs 5.44 10.04
317001AI627917Hs.233694hypothetical protein3.56 4.37
FLJ11350
65 317008AW051597Hs.143707ESTs 0.69 1.37
317051AA873253Hs.126233ESTs 6.18 12.72
317128AA97137dHs.125674ESTs 1.87 2.66
317129H12523Hs.78521Homo sapiens cDNA: 4.12 6.64
FLJ21193 fis, clone
C
317137AW341567Hs.125710ESTs 2.82 5.12
317196A1348258Hs.153412ESTs 1.98 2.51
317212A1866468Hs.148294ESTs 1.86 2.83
317223AW297920Hs.130054ESTs 0.83 1.57
317224D56760Hs.93029sparclosteoneclin, 2.74 0.86
cwcv and kazal-like
d
317266AA906289Hs.203614ESTs 1.00 1.00
75 317282A1807444Hs.176101ESTs 2.60 4.21
317285AW370882Hs.222080ESTs 1.96 3.49
317302AA908709Hs.1355fi4ESTs 7.16 8.32
317304AW449899Hs.130184ESTs 1.38 2.28
317320AA927151Hs.130452ESTs 3.58 8.13
go 317413AW341701Hs.126622ESTs 2.08 4.92
317417AA918420Hs.145378ESTs 3.06 4.79
317452AA972965Hs.135568ESTs 4.22 9.21
317519A1859695Hs.126860ESTs 1.88 4.15
317521A1824338Hs.126891ESTs 3.12 4.55
g 317529A1916517Hs.126865ESTs 2.73 3.34
5
132
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
317570AI733361Hs.127122ESTs 1.00 2.43
317571AA938663Hs.199828ESTs 5.20 11.95
317598AW206035Hs.192123ESTs 0.33 1.56
317627AI346110Hs.132553ESTs 1.50 1.39
317650AI733310Hs.127346ESTs 0.48 1.46
317659AA961216Hs.127785ESTs 4.18 7.14
317674AW294909Hs.132208ESTs 2.92 3.20
317686AA969051Hs.187319ESTs 1.00 1.01
317692AI307659Hs.174794ESTs 5.33 9.59
1 317701AI674774Hs. ESTs 1.00 1.00
~ f
28014
317711AI733015Hs,272189ESTs 5.13 7.81
317722A1733373Hs.128119ESTs 2.50 6,03
317756AA973667Hs.128320ESTs 1.59 1.30
317777A1143525Hs.47313KIAA0258 gene product1.00 2.48
~
15317799A1498273Hs.128808ESTs 1.78 2.11
317803AA983251Hs,128899ESTs 0.80 1.06
317821AI368158Hs.70983PTPL1-associated 0.17 0.68
RhoGAP 1
317848AI820575Hs.129086Homo Sapiens cDNA 5.30 8.16
FLJ12007 fis, clone
HE
317850N29974Hs.152982hypothetical protein1.30 2.28
FLJ13117
20317861AW341064Hs.i29119ESTs 2.18 5.93
317865AI298794Hs.129130ESTs 4.48 8.20
317869AW295184Hs.129142deoxyribonuclease 0.44 0.99
II beta
317881AI827248Hs.224398Homo Sapiens cDNA d.06 2.23
FLJ11d69 fis, clone
HE
317890AI915599Hs.129225ESTs 4.68 7.48
25317899AI952430Hs.150614ESTs, Weakly similar3.14 3.37
to ALU4_HUMAN ALU
S
317986A1005163Hs.201378ESTs, Weakly similar0.28 1.66
to 712545 hypotheti
318001AW235697Hs.130980ESTs 5.12 9.97
318016A1016694Hs.256921ESTs 1.86 4.50
318023AW243058Hs.131155ESTs 2.92 5.22
3 318054AW449270Hs.232140ESTs 3.92 6.37
~
318068A1024540Hs,131574ESTs 1,21 1.27
318117A1208304Hs.250114ESTs 0.86 1.17
318187A1792585Hs.133272ESTs, Weakly similar5.90 6.98
to ALUC_HUMAN 7777
318223A1077540Hs.134090ESTs 1.05 0.90
35318240A1085377Hs.143610ESTs 3.10 2.40
318255A1082692Hs.134662ESTs 0.02 1.05
318266AI554341Hs.271443ESTs 6.12 10.55
318330A1093840Hs.143758ESTs 4.98 7.90
318369AI493501Hs,170974ESTs 2.46 5.62
318428A1949409Hs.194591ESTs 0.77 0.45
318458AI149783Hs.158438ESTs 3.54 d.92
318467A1151395Hs.144834ESTs 4.56 5.62
318473AI939339Hs.146883ESTs 2.08 4.05
' 318476A1693927Hs.265165ESTs 4.22 8.07
45318487AI167877Hs.143716ESTs 1.47 1.05
318488AI217431Hs.144709ESTs 1.40 4.14
318491726477Hs.22883ESTs, Weakly similar1.84 1.90
to ALUB HUMAN ALU
S
318499725451 gb:PTHl188 HTCDL1 2.58 5.20
Homo Sapiens cDNA
5'13
318537AA377908Hs.13254ESTs 3.26 4.18
318538N28625Hs.74034Homo Sapiens clone 0.35 1.07
24651 mRNA sequence
318547820578Hs.90431ESTs 3.22 4.60
318552818364Hs.90363ESTs 4.87 9.06
318575855102Hs.107761ESTs, Weakly similar1.91 1.98
to unnamed protein
3185110734571Hs.49007poly(A) polymerase 2.74 6,22
alpha
55318587AA779704Hs.168830Homo sapiens cDNA 0.85 2.46
FLJ12136 fis, clone
MA
318596AI470235Hs.172698EST 4.88 4.93
318622Td8325Hs.237658apolipoprotein A-II4.80 12,51
318629N25163Hs.8861ESTs 0.39 1.04
318637AA243539Hs.9196hypothetical protein1.72 3.57
3186413777141Hs.184411albumin 6.27 9.91
318650AA393302Hs.176626hypothetical protein3.96 8.84
EDAG-1
318671AA188823Hs.299254Homo Sapiens cDNA: 1.53 0.81
FLJ23597 fis, clone
L
318679756115Hs.10336ESTs 1.00 2.19
318711A1936475Hs.101282Homo Sapiens cDNA: 3.05 3.18
FLJ21238 fis, clone
C
65318725AI962487Hs.242990ESTs 1.08 2.46
318728230201Hs.291289ESTs, Weakly similar0.77 1.33
to ALU1 HUMAN ALU
S
318740NM Hs.77729oxidised low density0.25 1.49
002543 lipoprotein (lectin
318776824963Hs.23766ESTs 1.00 3.01
318784H00148Hs.5181proliferation-associated2.70 3.86
2G4, 38kD
70318816F07873Hs.21273ESTs 3.90 7.13
318865H10818 gb:ym04f10.r1 Soares2.25 3.56
infant brain 1N18
H
318879856332Hs.18268adenylate kinase 1.78 5.00
5
318881243224Hs.124952ESTs 4.79 14.13
318894F08138Hs.7387DKFZP56d8116 protein5.31 7.00
75318901AW368520Hs.301528L-kynureninelalpha-aminoadipate1.03 0.91
aminotra
318925243577Hs.21470ESTs 2.23 3.80
318936A1219221Hs.308298ESTs 1.86 7.16
318982244140Hs.269622ESTs 5.84 9.79
318986244186Hs.169161ESTs, Highly similar1.00 1.00
to MAON HUMAN NADP-
319041244720Hs.98365ESTs, Weakly similar3.38 6.11
to weak similarity
319103H05896Hs.4993KIAA1313 protein 1.00 1.07
319170813678Hs.285306putative selenocysteine3.79 5.03
lyase
319196F07953Hs.16085putative G-protein 1.00 2.98
coupled receptor
319199F07361Hs.13306ESTs 3.53 5.66
319242F11472Hs.12839ESTs 5.87 7.26
133
CA 02444691 2003-10-17
WO 443 PCT/US02/12476
02/086
319263T65331Hs.81360Homo Sapiens cDNA: 1.81 1.57
FLJ21927 fis, clone
H
319267F11802Hs.6818ESTs 1.10 4.72
319270813474Hs.290263ESTs 4.80 10.40
319279T65094Hs.12677CGI-147 protein 1.50 2.11
319282AA461358Hs.12876ESTs 1.00 1.00
319289W07304Hs.79059transforming growth0.18 0.68
factor, beta recepto
319291W86578Hs.285243hypothetical protein0.26 0.62
FLJ22029
319293F12119Hs.12583ESTs 3.13 4.50
319312245481 gb:HSC20E041 normalized1.10 1.00
infant brain cDN
1 319370H54254Hs.325823ESTs, Moderately 0.16 0.73
~ similar to ALU5_HUMAN
A
319391806304Hs.13911ESTs 1.26 2.43
319396H67130Hs.301743ESTs 0.70 0.76
319398AA359754Hs.191196ESTs 2.45 3.59
319407805329 gb:ye91 b04.r1 Soares2.00 3.54
fetal liver spleen
15319425T82930 gb:yd39f07.r1 Soares4.28 8.81
fetal liver spleen
319433806050Hs.191198ESTs 6.15 14.13
319437AA282420Hs.111991ESTs, Weakly similar3.26 5.68
to Y48A5A.1 [C.eleg
319466AI809937Hs.116417ESTs 1.76 5.65
319471806546Hs.19717ESTs 4.29 4.84
319480806933Hs.184221ESTs 1.00 1.00
319484T91772 gb:yd52a10.s1 Soaresfetalliverspleen2.81 4.88
319486AI382429Hs.250799ESTs 2.08 2.82
319508T99898Hs.270104ESTs, Moderately 2.80 4.39
similar to ALUS_HUMAN
A
319523T69499Hs.191184ESTs 1.55 3.25
25319545883716Hs.14355Homo Sapiens cDNA 1.65 1.19
FLJ13207 fis, clone
NT
319546809692 gb:yf23b12.r1 Soares5.11 8.54
fetal liver spleen
319552AA096106Hs.20403ESTs 1.89 3.36
319582T82998Hs.250t54hypotheticalprotein3.48 d.82
FLJ12973
319586D78808Hs.283683chromosome 8 open 0.26 0.82
reading frame 4
3~319604811679Hs.297753vimentln 1.68 3.d1
319609AW247514Hs.12293hypothetical protein3.06 4.24
FLJ21103
319611H14957 gb:ym19c10.r1 Soares2.76 4.24
infant brain 1NIB
H
319653AA770183Hs.173515uncharacterized 2.51 3.55
hypothalamus protein
HTO
319657819897Hs.106604ESTs 5.32 7.68
35319658813432Hs.167481syntrophin, gamma 3.35 5.00
1
319661H08035Hs.21398ESTs, Moderately 5.18 12.55
similar to A Chain
A, H
319662H06382Hs.21400ESTs 1.58 1.56
319708815372Hs.22664ESTs 1.00 1.22
319742T77668Hs.21162ESTs 2.48 3.13
4~319748818178Hs.295866Homo Sapiens mRNA; 3.02 4.85
cDNA DKFZp434N1923
(f
319772876633Hs.22646ESTs 4.36 11.61
319788AA321932Hs.117414KIAA1320 protein 2.56 3.68
319805892857Hs.271350likely ortholog 4.63 6.56
of mouse polydom
319812N74880Hs.264330N-acylsphingosine 0.63 1.32
amidohydrolase
(acid c
45319834AA071267 gb:zm61g01.r1 Stratagenefibroblast(9370.30 0.94
319878T78517Hs.13941ESTs 3.99 6.44
319882AA258981Hs.291392ES7s ' 5.09 7.36
319912T77559Hs.94109Homo Sapiens cDNA 3.24 3.21
FLJ 13634 fis,
clone PL
319935H79460Hs.271722ESTs, Weakly similar4.40 9.42
to ALU1_HUMAN ALU
S
319944T79248Hs.133510ESTs 3.31 5.39
319947AA160967Hs.14479Homo Sapiens cDNA 2.90 4.95
FLJ14199 fis, clone
NT
319962H06350Hs.135056Human DNA sequence 1.81 1.57
from clone RP5-850E9
320007AA336314 gb:EST40943 EndomeUial3.42 6.29
tumor Homo sapie
320018T83263 gb:yd40h09.r1 Soaresfetal2.77 5.14
liver spleen
55320030H63789Hs.296288ESTs, Weakly similar4.10 6.69
to KIAA0638 protein
320032AI699772Hs.292664ESTs, Weakly similar3.27 3.27
to A46010 X-linked
320040AA233671Hs.87164hypothetical protein1.81 1.64
FLJ14001
320047T86564Hs.302256EST 3.38 7.36
320063AA074108Hs.120844FOXJ2forkheadfactor5.90 16.73
320096H58138Hs.117915ESTs 2.08 4.47
320099AW411307Hs.114311CDC45 (cell division1.00 1.00
cycle 45, S.cerevis
320112T92107Hs.188489ESTs 2.27 2.06
320140H94179Hs.119023SMC2 (structural 1.00 1.00
maintenance of
chromoso
320188AW419200Hs.172318ESTs 1.26 1.00
65320193AA831259Hs.17132ESTs 2.58 6.23
320195862203Hs.24321Homo Sapiens cDNA 2.85 4.53
FLJ12028 fis, clone
HE
320199878659Hs.29792ESTs 0.40 0.94
320203AL049227Hs.124776Homo Sapiens mRNA; 0.84 1.18
cDNA DKFZp564Ni
116 (f
320219AA327564Hs.127011tubulointerstitial 1.00 1.17
nephritis antigen
320220AF054910Hs.127111tektin 2 (testicular)0.18 1.09
320225AF058989Hs.128231G antigen, family 5.26 13.75
B,1 (prostate associa
320231H03139Hs.24683ESTs 1.59 1.93
320260NM Hs.131924G protein-coupled 1.38 4.56
003608 receptor 65
320267AL049337Hs.13257tHomo Sapiens mRNA; 1.00 1.92
cDNA DKFZp564P01fi
(fr
75320268H06019Hs.151293Homo Sapiens cDNA 5.58 5.70
FLJ 10664 fis,
clone NT
320322AF077374Hs.139322small proline-dch 1.41 1.01
protein 3
320325AI167978Hs.139851caveolin 2 0.05 0.67
320330AF026004Hs.141660chloride channel 2.17 1.26
2
320339H10807Hs.281434Homo sapiens cDNA 1.81 2.32
FLJ14028 fis, clone
HE
320388H16065Hs.31286ESTs 1.00 3.22
320402822291Hs.23368Homo sapiens clone 1.41 1.36
FLC0578 PR02852
mRNA,
320413AA203711Hs.173269ESTs 2.31 3.61
320432862786Hs.124136ESTs 11.2520.78
320436AA253352Hs.293663ESTs 2.22 3.49
320438W24548Hs.5669ESTs 3.53 8.14
134
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
320448AI240233Hs.80887v-yes-1 Yamaguchi 1.423.46
sarcoma viral related
320451826944Hs.180777Homo Sapiens mRNA; 0.870.81
cDNA DKFZp564M0264
(f
320484AA094436Hs.296267follistatin-like 0.651.18
1
320499832555Hs.24321Homo Sapiens cDNA 3.447.15
FLJ12028 fis, clone
HE
320514A8007978Hs.158278KIAA0509 protein 6.4413.62
320521N31464Hs.24743hypothetical protein1.481.04
FLJ20171
320526AW374205Hs.111314ESTs 3.667.87
320527834672Hs.324522ESTs 3.165.63
320536AA331732Hs.137224ESTs 2.835.83
1 320556AF054177Hs.14570hypothetical protein1.281.00
~ FLJ22530
320564AF056209Hs.159396peptidylglycine 1.220.81
alpha-amidating
monooxyg
320587244524Hs.167456Homo Sapiens mRNA 1.842.44
full length insert
cDN
320635854159Hs.80506small nuclear ribonucleoprotein1.006.25
polypept
320639AA243258Ns.7395hypolheficalprotein2.fi02.30
FLJ23182
15 320648N48521Hs.26549Homo sapiens mRNA 1.001.53
for KIAA1708 protein,
320651AA489268Hs.111334ferritin, light 0.140.79
polypeptide
320664AI904216Hs.91251hypothetical protein5.028.84
FLJ11198
320676AA132650Hs.300511ESTs 3.635.37
320683859291Hs.26638ESTs, Weakly similar0.371.31
to unnamed protein
320689AA334609Hs.171929ESTs, Weakly similar1.271.02
to A54849 collagen
320696AW135016Hs.172780ESTs 3.534.60
320714A1445591 gb:yq04a10.r1 Soaresfetalliverspleen1.060.85
320727U96044Hs.181125immunoglobulin lambda1.351.49
locus
320771AI793266Hs.117176poly(A)-binding 0.040.82
protein, nuclear
1
320794AA281993Hs.91226ESTs 2.964.33
320822AF100780Hs.194679WNT1 inducible signaling0.100.79
pathway protein
320824AF120274Hs.194689artemin 1.161.11
320830AJ132445Hs.266416claudin 14 1.061.75
320843AA317372Hs.34744Homo Sapiens mRNA; 1.361.47
cDNA DKFZp547Cf
36 (fr
3 320849D60031Hs.34771ESTs 5.307.49
~
320853AI473796Ns.135904ESTs 1.001.00
320896AB002155Hs.271580uroplakin 1B 5.902.55
320921894038Hs.199538inhibin, beta C 2.201.17
-
320927AI205786Hs.213923ESTs 0.181.d6
35 320957A1878933Hs.92023core histone macroH2A2.21.672.18
320997H22544 gb:yn69f11.r1 Soaves3.263.62
adult brain N2b5HB5
321045W88483Hs.293650ESTs 2.254.55
321046H27794Hs.269055ESTs 2.694.25
321052AW372884Hs.240770nuclear cap binding2.142.56
protein subunit
2, 2
40 321059A1092824Hs.126465ESTs 1.690.53
321062887955Hs.241411Homo Sapiens mRNA 2.765.20
full length insert
cDN
321067AF131782Hs.241438Homo Sapiens clone 4.797.41
24941 mRNA sequence
321102AA018306 gb:ze40dO8.r1 Soaves1.794.27
retina N2b4HR Homo
321130H43750Hs.125494ESTs 1.003.14
45 321142A1817933Hs.298351ASPL protein 8.7315.36
321155AA336635Hs.99598hypothetical protein3.045.03
MGC5338
321158AA700289 gb:yu76f11.r1 Soaresfetalliverspleen4.628.39
321170N53742Hs.172982ESTs 2.214.46
321199AW385512 gb:yy56d10.s1 Soaves5.698.01
multiple sclerosis
321206H54178Hs.226469Homo Sapiens cDNA 4.007.32
FLJ 12417 fis,
clone MA
321225AL080073Hs.251414Homo Sapiens mRNA; 4.174.63
cDNA DKFZp5fi4B1462
(f
321236AW371941Hs.18192Ser/Arg-related 1,001.00
nuclear matrix
protein (
321244AF068654 gb:Homo Sapiens 2.189.13
isolate AN.1 immunoglobu
321270883560 gb:yv76c06.s1 Soaves3.805.26
fetal liver spleen
55 321317AI937060Hs.6298KIAA1151 protein 1.811.65
321318AB033041Hs.137507KIAA1215 protein 1.001.00
321325A8033100Hs.300646KIAA protein (similar0.440.93
to mouse paladin)
321342AA127984Hs.222024transcription factor4.944.93
BMAL2
321356893443Hs.271770ESTs 3.104.66
321418A1739161Hs.161075ESTs 2.282.54
321420A1368667Hs.132743ESTs 1.130.97
321430U05890 gb:H.sapiens (DIG3)2.423.35
mRNA for immunoglobu
321453N50080Hs.82845Homo Sapiens cDNA: 1.603.11
FLJ21930 fis, clone
H
321467X13075 gb:Human2a12mRNAforkappa-immunoglobu0.420.72
65 321468AA514198Hs.38540ESTs 2.466.50
321491H706fi5Hs.292549ESTs 1.001.25
321498AW295517Hs.255436ESTs 3.196.24
321504W02356Hs.268980ESTs 2.283.86
321510AA703650Hs.255748ESTs 2.143.94
321513H84972Hs.108551ESTs 2.785.37
321516AI382803Hs.159235. 3.067.19
ESTs
321565A1525773Hs.266514hypotheticalprotein4.897.82
FLJ11342
321577H84260 gb:ys90g04.r1 Soaves1.001.73
retina N2b5HR Homo
321581AA019964Hs.28803ESTs 4.886.73
75 321582AA143755Hs.21858trinucleotide repeat1.002.08
containing 3
321587H95531 gb:ys76e02.r1 Soaves2.264.52
retina N2b4HR Homo
321626AA295430Hs.96322hypotheticalprolein1.953.83
FLJ23560
321628H87064Hs.161051ESTs,ModeratelysimilartoALU6_HUMANA0.471.02
321642AW085917Hs.247084ESTs 1.521.38
321669H95404Hs.294110ESTs 2.172.45
321687AA625149 gb:af70c12.r1 Soaves-NhHMPu-S14.316.95
Homo sapi
321688H97646Hs.123158Homo Sapiens cDNA 2.823.28
FLJ12830 fis, clone
NT
321693AA700017Hs.173737vas-related C3 botulinum0.511.0B
toxin substrate
321700N55160Hs.1672fi0ESTs 4.577.46
g5 321701AW390923Hs.42568ESTs 1.001.00
135
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
321709N25847Hs.108923RAB38, member RAS 1.00 i.00
oncogene family
321710N35682Hs.259743ESTs 2.97 5.26
321775AI694875Hs.202312Homo Sapiens clone 1.00 1.00
N11 NTera2D1 teratoca
321777AI637993Hs.202312Homo Sapiens clone 1.68 0.45
N11 NTera2D1 teratoca
321779N42729Hs.163835ESTs 0.90 0.90
321829081993Hs.8966tumor endothelial 2.69 3.89
marker 8
321646AA281594Hs.87902ESTs 5.11 7.64
321879AL109670Hs.302809ESTs 6.49 9.58
321883AA426494Hs.46901KIAA1462 protein 0.28 0.95
1 321899N55158Hs.29468ESTs 0.39 0.95
~
321911AF026944Hs.293797ESTs 6.20 10.76
321949849202Hs.181694EST 4.62 10.51
321955AI651866Hs.195689ESTs 2.89 5.47
321956AL110177Hs.132882ESTs 0.32 1.25
15 321987AL133612Hs.272759KIAA1457 protein 1.00 1.83
321991AL133627Hs.158923Homo sapiens mRNA; 4.00 6.47
cDNA DKFZp434K0722
(f
322002AA328801Hs.84522ESTs 2.10 3.48
322035AL137517Hs.306201hypothet(cal protein1.00 1.90
DKFZp56401278
322044AW340926 gb:xy51b10.x1 NCI_CGAP_Lu34.13.20 9.67
Homosapie
322057N92197Hs.154679synaptotagmin 1 1.55 1.07
322060A1341937 gb:qt10e03.x1 NCI_CGAP_GC44.59 7.68
Homo Sapiens
322070U80769Hs.210322Homo Sapiens mRNA 2.78 4.52
for KIAA1766 protein,
322083AF074982Hs.226031ESTs, Highly similar3.10 5.52
to KIAA0535 protein
322091AI819863Hs.i06243ESTs 1.59 f.75
322125893901 gb:yq16c12.r1 Soaresfetalliverspleen2.06 5.27
322130898978Hs.117767ESTs 10.1216.49
322147AF085919Hs.114176ESTs 0.94 0.64
322166AF085958 gb:yr88b03.r1 Soares4.09 6.67
fetal liver spleen
322173H52567 gb:yt85d04.r1 Soares_pineal_gland_N3HPG3.46 4.85
30 322178H56535 gb:yt88g03.r1 Soares_pineal_gland0.44 2.54
N3HPG
322179H92891 gb:yl94c02.s1 Soares_pineal~land_N3HPG4.52 7.50
322186H67346Hs.269187ESTs 0.15 0.98
322196W87895Hs.211516ESTs 2.20 5.04
322212AF087995Hs.134877ESTs 3.42 4.84
35 322221AI890619Hs.179662nucleosome assembly0.82 2.14
protein 1-like
1
322277AI640193Hs.226389ESTs 3.62 3.98
322278AF086283 gb:zd46f01.r1 Soares1.00 1.00
fetal_heart-NbHHI9W
322284AI792140Hs.49265ESTs 0.66 2.76
322288AL037273Hs.7886pellino (Drosophila)0.71 0.70
homolog 1
40 322320AF086419 gb:zd78d03.r1 Soares2.02 2.76
fetal_hearf-NbHHI9W
322336AA308526Hs.76152decorin 2.92 4.44
322339Wi7348 gb:zb18c07.x5 Soares8.50 11.56
fetal_lung_NbHLI9W
322366AW404274Hs.122492hypothetical protein0.61 1.34
322372W25624Hs.153943ESTs 7.37 12.07
45 322374AI394663Hs.122116ESTs, Moderately 4.78 10.50
similar to Osf2
[M.musc
322378AF064819Hs.201877DESC1 protein 1.00 1.00
322388AI815730Hs.247474hypothetical protein7.09 8.49
FLJ21032
322416AA223183Hs.298442adaptor-related 3.20 5.80
protein complex
3, mu 1
.
322419AA248987Hs.14084ring finger protein1.64 1.57
7
322425W37943Hs.34892KIAA1323 protein 0.83 1.00
322431AA069222Hs.141892ESTs 3.96 5.22
322d50AA040131Hs.25144ESTs 5.18 12.67
322465AA137152Hs.286049phosphosedne aminotransferase3.41 2.23
322467AF116826Hs.180340putative protein-tyrosine1.00 1.30
kinase
55 322473AA744286Hs.266935tRNA selenocysteine1.75 2.03
associated protein
322509T52172Hs.302213ESTs 1.00 2.27
322523W80398Hs.193197ESTs 2.75 5.49
322527AF147359 gb:Homo Sapiens 1.25 1.27
full length insert
cDNA
322560AI916847Hs.270947ESTs 4.57 8.81
322566W87285Hs.269587ESTs 1.00 1.42
322585AA837622 gbzh69c01.r1 Soares4.18 6.94
fetal liver_spleen_
322635AA679084 gb:zh90h08.r1 Soares2.40 4.85
fetal_liver_spleen_
322641AA007352Hs.256042ESTs 2.94 4.64
322653AI828854Hs.258538strialin, calmodulin-binding0.48 0.38
protein
65 322664AA011522 gb:zi03g07.r1 Soares1.92 2.18
fetal liver_spleen
322687AI110759 gb:AF074666 Human 4.14 6.75
fetal liver cDNA
libra
322692AA0181Hs.60843potassium voltage-gated3.50 5.00
i7 channel, shaker-
322694AI110872Hs.279812PR00327 protein 1.80 1.72
322708AF113674Hs.283773clone FLB1727 1.00 3.43
322712AA021328Hs.23607hypotheticalprotein3.28 3.86
FLJ11109
322766AW068805Hs.288467Homo Sapiens cDNA 1.63 1.53
FLJ12280 fis, clone
MA
322770AA045796Hs.122682ESTs 1.53 1.06
322794AI608591Hs.38991S100 calcium-binding12.061.94
protein A2
322810AI962276Hs.127d44ESTs 4.09 6.90
75 322818AW043782Hs.293616ESTs i.20 1.63
322820AI377755Hs.120695ESTs 0.21 1.93
322872AA827228Hs.126943ESTs 2.04 1.63
322882AW2d8508Hs.279727Homo sapiens cDNA 5.26 1.22
FLJ14035 tis, clone
HE
322887AI986306Hs.86149phosphoinositol 2.80 2.24
3-phosphate-binding
prot
322913AI733737Hs.68837ESTs 2.38 6.61
322926A1825940Hs.211192ESTs 4.02 5.79
322929A1365585Hs.146246ESTs 0.30 1.14
322968A1905228Hs.83484SRY (sex determining2.06 1.13
region Y)-box 4
322971C15953Hs.212760hypotheticalprotein1.18 2.00
FLJ13649
g5 322981AA493252Hs.159577ESTs 2.28 2.61
136
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
322968C18727Hs.171941ESTs 0.39 2.00
323003AI733859Ns.149089ESTs 3.28 1.00
323013AA134042Hs.191451ESTs 3.38 5.68
323025AL157565Hs.315369Homo Sapiens cDNA: 0.06 1.10
FLJ23075 fis, clone
L
323032AW244073Hs.145946ESTs 10.1821.27
323052821124Hs.85573Homo sapiens DC29 1.46 1.90
mRNA, complete
cds
323064AL119341Hs.49359Homo Sapiens mRNA; 3.08 5.64
cDNA DKFZp547E052
(fr
323098AI700025Hs.270471ESTs 2.31 4.49
323102AL119913Hs.163615ESTs 5.38 11.64
10323155AL135041 gb:DKFZp762K2310 2.38 5.56
r1762 (synonym:
hmel2)
323176AW071648Hs.82101pleckstrin homology-like1.06 1.41
domain, family
323191AA195600Hs.301570ESTs 0.73 1.24
323225AA205654Hs.24790KIAA1573 protein 5.25 11.95
323232AA148722Hs.224680ESTs 0.45 1.35
15323266AW003362Hs.243886nuclear autoantigenic1.71 1.83
sperm protein (his
323281AI697556Hs.292659ESTs 1.24 3.21
323283AA2560i4Hs.86682Homo sapiens cDNA: 12.6615.05
FLJ21578 fis, clone
C
323314AA226310Hs.191501ESTs 4.42 9.61
323316AL134620Hs.280175ESTs 2.98 5.93
323334A1336501Hs.77273ras homolog gene 1.98 3.30
family, member
A
323338874219Hs.23348S-phase kinase-associated1.62 1.00
protein 2 (p45
323348AA233056Hs.191518ESTs 1.00 1.07
323351AA704103Hs.24049ESTs 1.43 1.68
323359AA234172Hs.137418ESTs 0.34 1.18
25323360AA716061Hs.161719ESTs 3.01 3.71
323405AW139550Hs.115173ESTs 1.90 8.81
323420AI672386Hs.263780ESTs 0.29 1.01
323434AW081455Hs.120219ESTs 2.27 1.92
323445AA253103Hs.135569ESTs, Weakly similar0.43 0.80
to NEUROD [H.sapien
3 323449AA282865Hs.284153Fanconi anemia, 3.19 3.85
~ complementation
group A
323492H00978Hs.20887hypotheticalprotein2.70 3.20
FLJ10392
323501AA182461Hs.84520ESTs 2.04 3.31
323505A1652287 gb:EST382593 MAGE 3.08
resequences, MAGK
Homo2.21
323515AA282274Hs.256083ESTs 2.69 3.40
35323541A1185116Hs.104613RP42homolog 1.20 1.09
323545AI814405Hs.224569ESTs 1.25 1.55
323635863117Hs.9691Homo Sapiens cDNA: 0.27 0.72
FLJ23249 fis, clone
C
323675AA984759Hs.272168tumor differenliahy3.70 5.80
expressed 1
323678AL042121Hs.20880ESTs 3.33 5.10
323691AA317561Hs.145599ESTs 1.00 1.00
323693AW297758Hs.249721ESTs 2.01 1.54
323746AW298611Hs.12808MARK 4.11 5.53
323774AA329806Hs.321056Homo Sapiens mRNA; 2.06 3.70
cDNA DKFZp586F1322
(f
323856AA355264Hs.267604hypotheticalprotein3.42 8.13
FLJ10450
45323857T18988Hs.293668ESTs 5.97 12.51
323870AA341774Hs.i29212ESTs 3.17 4.52
323876AL042492Hs.147313ESTs 0.36 1.00
323885AA344308Hs.128427Homo Sapiens BAC 2.31 3.33
clone RP11-335J18
from
323911AL043212Hs.92550ESTs 4.38 5.41
323919AA862973Hs.220704ESTs 5.80 10.20
323972A1869964Hs.182906ESTs 3.10 5.14
324005AA610011Hs.208021ESTs 5.34 10.07
324036A1472078Hs.303662ESTs 1.00 5.03
324055AA528794Hs.128644ESTs 0.86 1.00
55324063AW292740Hs.272813dual oxidase 1 0.45 0.91
324072AA381829 gb:EST94855 Activated2.82 5.12
T-cells I Homo
sap
324092AW269931Hs.202473Homo Sapiens cDNA: 2.40 2.52
FLJ22278 fis, clone
H
324095AW377983Hs.298140Homo Sapiens cDNA: 1.32 4.30
FLJ22502 tis, clone
H
324129AI381918Hs.285833Homo Sapiens cDNA: 1.40 1.77
FLJ22135 fis, clone
H
324132AW504860Hs.288836hypothetical protein4.2d fi.21
FLJ12673
324214AA412395Hs.225740ESTs 6.96 10.69
324227AA295552Hs.28631Homo Sapiens cDNA: 0.81 0.53
FLJ22141 tis, clone
H
324266AL047634Hs.231913ESTs 2.42 4.05
324275AA429088Hs.98523ESTs 3.62 5.38
65324281AL048026Hs.124675ESTs, Weakly similar0.14 0.70
to T14742 hypotheti
324290AA432032Hs.304420ESTs 3.71 4.34
324303AL118754 gb:DKFZp761P19i0_r10.95 0.91
761 (synonym:hamy2)
324312A1198841Hs.128173ESTs 4.06 5.91
324325AL138153Hs.300410ESTs 5.86 8.25
324338AL138357Hs.145078regulator of differentiation0.87 1.25
(in S. pomb
324341AW197734Hs.99807ESTs, Weakly similar1.28 1.00
to unnamed protein
324343AW452016Hs.293232ESTs 2.54 3.46
324371AA452305Hs.270319ESTs 5.85 8.36
324382AW502749Hs.24724MFH-amplified sequences0.76 1.64
with leucine-ric
75324384AA453396Hs.127656KIAA1349 protein 2.88 5.69
324385F28212Hs.284247KIAA1491 protein 1.81 1.99
324388A1924963Hs.306206hypothetical protein1.00 1.00
FLJ11215
324432AA464510Hs.152812ESTs 2.73 2.17
324497AW152624Hs.136340ESTs, Weakly similar0.71 1.90
to unnamed protein
324510AI148353Hs.287425Homo Sapiens cDNA 1.00 1.00
FLJ11569 fis, clone
HE
324580AA492588 gb:ng99c08.s1 NCI 2.18 3.50
CGAP_Thy1 Homo
Sapiens
324582AA506935Hs.t32036ESTs, Weakly similar5.96 11.36
to ALU1 HUMAN ALU
S
324633AA572994Hs.325489ESTs 2.92 d.22
324640AW295832Hs.134798ESTs, Moderately 5.48 11.74
similar to TTL
MOUSE TU
324675AW014734Hs.157969ESTs 0.39 0.73
137
CA 02444691 2003-10-17
WO 6443 PCT/US02/12476
02/08
324699AW504732Hs.21275hypothetical protein0.93 0.93
FLJ11011
324747AA603532Hs.130807ESTs 1.57 1,81
324748AA657457Hs.292385ESTs 1.55 1.34
324801AI819924Hs.14553sterol 0-acyltransferase1.00 6.56
(acyl-Coenzyme
324804AI692552 gb:wd73f12.x1 NCI-CGAP1.00 7.53
Lu24 Homo Sapiens
324828AA843926Hs.124434ESTs 2.00 3.25
324855AW152305Hs.122364ESTs 2.74 3.43
324866AI541214Hs.46320Small proline-rich 1.07 0.95
protein SPRK [human,
324871AW297755Hs.271923Homo Sapiens cDNA: 1.68 1,21
FLJ22785 fis, clone
K
1~ 324886AA806794Hs.13151iESTs 2.56 5.fif
324889D31010 gb:HUML12147 Human 2.20 4.65
fetal lung Homo
sapie
324948AW383618Hs.265459ESTs, Moderately 5.28 7.05
similar to ALU2-HUMAN
A
324953AI264628Hs.125428ESTs 3.37 5.51
324958AA625076Hs,132892protocadherin 20 5.12 9.81
15 324988T06997Hs.121028hypothetical protein2.52 1.08
FLJ10549
325024F13254Hs.78672laminin, alpha d 5.24 10.22
325105H97109Hs.105421ESTs 1.00 1.00
325108AA401863Hs,22380ESTs 1.99 2.14
325114D83901Hs.315562ESTs 2.73 3.17
325146A1064690Hs.171176ESTs 1.86 3.41
325149D61117Hs.i87646ESTs 0.42 0.93
325187AI653682Hs.197812ESTs 6.50 11.31
325228 6.18 15.76
325235 2,64 4.12
25 325328 2.87 4.42
325340 0.29 0.33
325367 16.5624.29
325373 0.63 1.22
325389 0.88 1.05
3 325436 5.75 14.14
0
325471 8.46 17.82
325498 3.32 6.42
325557 5.51 8.28
325559 7.48 21.40
3 325560 4.08 6.25
325569 4.20 5.24
325585 1.10 1,13
325587 1.00 1.00
325597 2.98 13.40
325639 0.78 0.78
325685 0.46 0.66
325686 0.95 1.55
325735 4.48 9.20
325739 0.59 0.88
45 325740 2.42 6.61
325792 7.88 9.83
325819 4.74 7.18
325883 . 2.02 2.64
325895 7.78 15.98
325925 2.04 10.60
325932 4.18 7.36
325941 3.66 9.03
325969 0.61 0.80
325971 4.88 7.42
5 326025 0.55 1.07
5
326046 7.21 14.72
326099 3.60 5.98
326108 1.27 1.06
326163 3.27 5.70
326165 0.45 1.11
326189 0.13 0.45
326204 5.60 9.00
326230 7.00 12.01
326274 1.00 8.09
65 326360 9.86 15.35
326393 0.52 0.77
326505 1.00 1.42
326515 1.24 5.84
326589 9.20 13.49
326592 2.77 4.01
326605 2.01 2.53
326692 1.00 1.00
326693 1.00 1.31
326720 0.19 0.65
75 326742 2.34 7.20
326770 0.25 0.83
326818 3.09 4.56
326936 2.08 3.45
326964 0.41 1.70
8~ 326983 2.02 3.80
326991 1.09 1.20
327036 1.00 8.04
327040 3.05 4.22
327053 3.55 6.31
8 327075 1.59 1.40
5
138
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
327085 2.50 12.57
327130 5.38 8.04
327156 3.74 6.58
327220 1.28 1.54
327224 6.56 12.91
327288 2.61 5.40
327321 2.42 3.11
327332 6.62 10.58
327361 2.69 4.41
1 327377 2.0d 6.72
~
327396 2.61 4.50
327414 1.00 8.01
327442 5.91 9.65
327467 6.58 18.01
1 327473 3.79 7.48
327483 4.08 8.87
327562 0.68 2.86
327568 1.00 2.00
327606 2.06 3.61
20327611 5.90 14.26
327642 4.06 8.74
327654 1.05 2.08
327734 1.00 1,00
327775 1.46 11.79
327796 3.47 5.65
327840 3.26 6.64
327940 5.84 15.58
327984 0.36 1.50
328004 1.87 1.42
3 328021 0.42 0.59
0
328068 2.83 4.68
328100 3.04 5.39
328101 3.54 5.20
328113 0.72 0.91
3 328157 5.58 5.16
5
328196 .5.76 11.13
328197 5.98 10.58
328264 3.11 4.88
328299 2.20 3.06
328342 1.49 1.94
328365 1,00 1.00
328369 4.40 7,36
328381 1.86 4.93
328451 5.51 7.56
45328481 0.13 0.72
328500 2.71 3.97
328530 5.41 7,62
328600 3.14 10.68
328608 4.56 8.17
328616 2.24 11.91
328623 3.04 5.46
328632 0.70 1.19
328664 3.48 6.80 .
328666 10,42 26.47
5 328698 9.68 14.56
5
328700 2,74 10.22
328708 0.15 0.57
328735 6.23 8.91
328743 3.62 6.54
328806 0.22 0.78
328861 3.68 10.54
328908 5.42 16,36
328933 2.02 5.29
328934 1.73 4.45
65328949 3.34 5.41
329005 2.88 7.26
329011 2.52 3.72
329033 1.00 1.03
329037 5.07 8.16
70329067 1.98 2.41
329134 2.24 3.25
329157 2,30 11.04
329178 2.64 5.02
329192 6.41 15.27
75329194 0.31 0.79
329204 1.60 3.75
329224 2.99 6.11
329228 0.83 0.83
329286 0.63 1.01
329337 1.00 1.00
329541 0.76 1.68
329560 1.34 2.02
329588 1.68 2.22
329643 4.18 11.77
329703 1.00 1.00
139
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WO PCT/US02/12476
02/086443
329764 5.78 15.50
329816 . 2.09 5.44
329860 3.13 10.77
329993 7.83 14.21
330020 5.58 13.12
330036 3.32 5.57
330052 4.31 7.97
330085 1.34 1.76
330088 4.70 12.46
1 330093 0.44 1.06
0
330100 3.47 4.83
330106 2.14 3.61
330107 3.17 6.87
330120 5.61 11.89
1 330123 4.50 12.74
330208 1.55 7.62
330263 13.1023.38
330300 2.81 4.98
330313 3.00 4.41
20330366 0.67 0.76
330372 4.76 11.82
330385AA449749Hs.182971karyopherin alpha 2.14 2.15
5 (importin alpha
6)
330397D14659Hs.154387KIAA0103 gene product0.40 1.15
330468L10343Hs.112341protease inhibitor 1.11 0.94
3, skin-derived
(SKAL
330472L24203Hs.82237ataxia-telangiectasia1.67 1.17
group D-associated
330478L38486Hs.296049microtibrillar-associated0.46 1.07
protein 4
330493M27826Hs.267319endogenous retroviralprotease1.07 0.95
330495M31328Hs.71642guanine nucleotide 0.97 0.96
binding protein
(G pr
330506M61906Hs.6241phosphoinosilide-3-kinase,regulatorysu0.17 3.66
30330512M80563Hs.81256S100 calcium-binding0.60 1.06
protein A4 (calcium
330537019765Hs.2110zinc finger protein2.81 2.07
9 (a cellular retrov
330547032989Hs.183671iryptophan 2,3-dioxygenase3.91 1.49
330551039840Hs.299867hepatocyte nuclear 1.15 1.03
factor 3, alpha
330568056244 (NONE) 2.83 4.79
35330599090437 gb:Human RP1 homolog2.08 1.54
mRNA, 3'0T8 region
330601090916Hs.82845Homo Sapiens cDNA: 0.89 1.35
FLJ21930 fis, clone
H
330605X02419Hs.77274plasminogen activator,1.87 1.55
urokinase
330609X04741Hs.76118ubiquitin carboxyl-terminal1.83 1.30
esterase L1
330617X53587Hs.85266integrin, beta 4 1.54 1.15
40330630X78669Hs.79088reticulocalbin 2, 1.39 1.19
EF-hand calcium
bindin
330644Y07755Hs.38991S100 calcium-binding3.83 1.13
protein A2
330650268228Hs.2340junction plakoglobin1.25 0.95
330660AA347868Hs.139293ESTs, Weakly similar15.5029.07
to ALU7_HUMAN ALU
S
330692AA017045Hs.6702ESTs 1.00 1.00
45330707AA133891Hs.293690ESTs 0.20 1.35
330715AA233707Hs.11571Homo Sapiens cDNA 0.12 1.40
FLJ11570 fis, clone
HE
330717AA233926Hs.52620integrin, beta 8 6.62 5.42
330722AA243560Hs.34382ESTs 1.4D 1.65
330740AA297746Hs.22654Homo Sapiens voltage-gated0.27 2.04
sodium channe
50330742AA400979Hs.25691receptor (calcitonin)0.44 0.90
activity modifying
330744AA406142Hs.12393dTDP-D-glucose 4,6-dehydratase0.71 3.23
330751AA428286Hs.29643Homo Sapiens cDNA 1.66 1.52
FLJ 13103 fis,
clone NT
330760AA448663Hs.30469ESTs 0.52 0.90
330763AA450200Hs.274337hypothetical protein0.37 0.97
FLJ20666
5 330786D60374Hs.49136ESTs, Moderately 0.78 0.84
5 similar to ALU7_HUMAN
A
330790T48536Hs.105807ESTs 0.23 3.17
330814AA015730Hs.265398ESTs, Weakly similar0.37 2.07
to transformation-r
330827AA040332Hs.12744ESTs 1.60 1.00
330844AA063037Hs.66803ESTs 0.93 1.16
60330901AA157818Hs.267319endogenous retroviral1.02 1.03
protease
330931F01443Hs.284256hypothetical protein0.24 0.88
FLJ14033 similar
to
330952H02855Hs.29567ESTs 0.08 1.31
330961H10998Hs.7164a disintegrin and 1.29 1.26
metalloproteinase
doma
330968H16568Hs.23748ESTs 0.48 0.96
65331014H98597Hs.30340hypothetical protein0.29 0.74
KIAA1165
331046N66563Hs.191358ESTs 0.99 8.56
331060N75081Hs.157148Homo Sapiens cDNA 1.24 1.00
FLJ11883 fis, clone
HE
331099836671Hs.83937hypothe6calprotein 0.75 1.03
331108841408Hs.21983ESTs 1.00 2.75
70331131854797 gb:yg87b07.s1 Soares6.04 10.68
infant brain 1N18
H
331135861398Hs.4197ESTs 0.80 0.96
331170T23461Hs.i59293ESTs 2.63 4.29
331180T32446Hs.6640Human DNA sequence 1.78 2.71
from PAC 75N13
on chr
331183T40769Hs.8469ESTs 1.00 3.01
75331203T82310 (NONE) 1.70 3.80
331271AA059347Hs.82226glycoprotein (Uansmembrane)1.20 3.19
nmb
331306AA252079Hs.63931dachshund (Drosophila)0.31 1.30
homolog
331327AA281076Hs.109221ESTs 2.09 2.41
331341AA303125Hs.23240Homo Sapiens cDNA 0.72 2.43
FLJ 13496 fis,
clone PL
331359AA416979Hs.46901KtAA1462 protein 0.09 0.91
331363AA421562Hs.91011anterior gradient 1.02 0.87
2 (Xenepus laevis)
hom
331378AA448881Hs.49282hypothetical protein1.03 1.23
FLJ11088
331384AA456001Hs.93847NADPH oxidase 4 1.40 1.00
331402AA505135Hs.d4037ESTs 1.80 3.93
85331422F10802Hs.163628ESTs, Moderately 1.65 1.89
similar to ALU7-HUMAN
140
CA 02444691 2003-10-17
WO 443 PCT/US02/12476
02/086
331490N32912Hs.26813CDA14 2.48 1.73
331531N51343 gb:yz15g04.s1 Soares0.98 1.68
multiple-sclerosis
331547N54811 gb:od74f04.s1 NCI-CGAP-Ov23.80 5.75
Homo Sapiens
331578N67960Hs.249989ESTs 0.11 0.67
331589N71027Hs.152618ESTs 1.09 1.38
331608N89861Hs.112110PTD007 protein 0.93 0.76
331614N92293Hs.240272EST 0.17 1.34
331668W69707Hs.58030EST 2.24 3.82
331671W72033Hs.194695ras homolog gene 1.00 1.24
family, member
I
1 331676W79834Hs.58559ESTs, Weakly similar0.06 1.07
~ to rhotekin [M.musc
331681W85712Hs.119571collagen, type III,8.72 4.27
alpha 1 (Ehlers-Danl
331692W93592Hs.152213wingless-type MMTV 0.94 0.54
integration site
fami
331717AA190888Hs.153881Homo Sapiens NY-REN-621.57 1.34
antigen mRNA, par
331718AA191404Hs.104072ESTs 6.80 11.77
1 331811AA404500Hs.301570ESTs 1.10 1.00
331820AA405970Hs.97996transcription termination0.73 0.59
factor, mitoc
331831AA412031Hs.97901EST 2.77 4.08
331852AA418988Hs.98314Homo Sapiens mRNA; 0.23 0.93
cDNA DKFZp586L0120
(f
331943AA453418Hs.21275hypotheGcalprolein 0.36 1.88
FLJ11011
331969AA460702Hs.82772collagen, type XI, 1.00 1.00
alpha 1
331990AA478102Hs.139631ESTs 3.04 3.87
332002AA482009Hs.105104ESTs 1.19 0.78
332027AAd89671Hs.65641hypothetical protein1.27 1.03
FLJ20073
332029AA489697Hs.145053ESTs 0.30 1.62
25332033AA489840Hs.251014EST 2.30 3.70
332048AA496019Hs.201591ESTs 0.17 0.52
332071AA598594Hs.205293KIAA1211 protein 1.35 1.23
332074AA599012 gb:ae41e11.s1 Gessler0.19 2.00
Wilms tumor Nomo
s
332083AA600200Hs.155546KIAA1080 protein; 0.31 1.18
Golgi-associated,
gamm
332085AA600353Hs.173933nuclear factor IIA 0.30 1.50
332125AA609861Hs.312447ESTs 0.22 0.62
332177F10812Hs.101433ESTs 8.21 18.03
332180H03348Hs.7327claudin 1 2.27 1.57
332185H10356Hs.101689ESTs 0.09 1.18
3 332203H49388Hs.317769EST 8.05 5.02
5
332232N48891Hs.101915Stargardt disease 0.78 0.85
3 (autosomal dominant)
332240N54803Hs.324267ESTs, Weakly similar0.96 1.23
to putative p150
[
332261N70294Hs.269137ESTs 2.40 3.74
332275808838Hs.26530serum deprivation 0.27 0.75
response (phosphatidyl
40332280838100Hs.146381RNA binding motif 0.39 1.88
protein, X chromosome
332299869250Hs.21201pectin 3; DKFZP566808465.24 12.76
protein
332304874041Hs.101539ESTs 1.44 3.18
332314T25862Hs.101774hypothetical protein0.68 1.32
FLJ23045
332384M11433Hs.101850retinol-binding 1.71 0.88
protein 1, cellular
45332434N75542Hs.289068Homo Sapiens cDNA 0.43 0.86
FLJ 11918 fis,
clone HE
332445T63781Hs.11112ESTs 0.68 1.00
332453L00205Hs.111758keratin 6A 31.541.00
332458M33493Hs.250700tryptase beta 1 0.51 1.00
332504AA053917Hs.15106chromosome 14 open 0.79 1.24
reading frame 1
332525M17252Hs.278430cytochrome P450, 0.98 1.70
subfamily XXIA
(steroid
332530M31682Hs.1735inhibin, beta B 0.88 0.66
(activin AB beta
polypep
332535N20284Hs.19280cysteine-rich motor0.22 1.46
neuron 1
332539AA412528Hs.20183ESTs, Weakly similar0.93 1.49
to AF1647931 prote
332559M13955Hs.166189cytokeratin 2 0.35 1.13
5 332563N92924Hs.274407protease, serine,161.00 1.00
5 (thymus)
332565AA234896Hs.25272E1A binding protein0.36 1.05
p300
332594AA279313Hs.3239methyl CpG binding 0.53 0.59
protein 2 (Rett
syndr
332634S38953Hs.283750tenascin XA 0.38 1.16
332638AA283034Hs.50640JAK binding protein1.00 1.70
332640AA417152Hs.5101protein regulator 6.15 1.16
ofcytokinesisl
332654AA001296Hs.288217hypothetical protein1.50 2.73
MGC2941
332665AA223335Hs.63788propionyl Coenzyme 1.20 0.91
A carboxylase,
beta p
332692AA496035Hs.247926gap junction protein,0.17 1.12
alpha 5, 40kD (con
332716L00058Hs.79070v-myc avian myeiocyfomafosis1.00 1.44
viral oncog
65332736L13773Hs.114765myeloidllymphoid 1.00 1.81
or mixed-lineage
leukem
332758X93921Hs.296938dual specificity 0.53 0.78
phosphatase 7
332781AA233258Hs.247112hypothetical protein1.44 1.56
FLJ10902
332792 1.70 1.19
332816 1.85 2.47
332858 1.04 1.57
332906 3.48 8.04
332911 1.00 1.00
332912 1.06 4.40
332922 1.00 1.00
75332956 0.42 0.88
332959 1.96 6.34
332982 0.56 0.99
332984 0.30 0.78
332998 1.47 2.01
g 333058 0.47 1.38
o
333097 2.14 3.19
333121 2.76 3.70
333122 1.92 1.21
333123 1.85 1.39
g 333138 0.47 0.52
5
141
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333139 1.88 0.84
333140 0.21 0.64
333221 1.51 1.11
333260 0.75 1.01
333380 6.68 15.75
333387 4.56 12,61
333512 5.05 8.01
333524 2.28 3.98
333585 2.31 1.53
1 333603 2.23 1.17
~
333604 2.51 1.58
333618 0.52 0.98
333627 1.44 1.36
333628 1.90 1.90
1 333650 1.85 2.10
333678 1.85 2.35
333750 2,18 5.67
333763 1.99 2.fi0
333767 1.02 0.96
333768 1.78 1.65
333769 2.15 2,13
333772 1.46 2.53
333777 1.00 1.42
3338d6 2.99 4.50
25 333884 0.47 0.94
333887 0.50 1.00
333891 0.43 0.89
333892 0.51 0.91
333904 0.26 1.13
333906 0.55 0.98
333948 1.70 2.15
333954 0.37 1.09
333966 8.10 14.30
333968 0.63 1.38
3 334061 4.24 12.30
5
33409d 1.30 12.03
334113 4.55 8.63
334161 0.82 1.59
334183 0.47 0.76
4~ 334187 1.36 3.70
334219 0.69 1.04
334222 1.88 1.70
334223 4.72 3.14
334239 0.79 0.62
45 334255 0.45 1.10
334333 1.00 3.56
334378 3.98 5.76
334382 1.50 1.31
334492 3.59 4.75
334562 5.94 15.40
334588 8.14 19.53
334616 1.55 1.56
334633 5.16 8.07
334648 0.59 2.13
5 334787 3.70 7.15
5
334866 8.13 10.60
334891 0.32 1,14
334933 1.00 3.84
334934 4.01 7.43
334945 1.04 2.96
334967 0.29 1.14
334990 1.50 1.39
335015 5.88 18.65
335093 0.55 1.75
65 335120 4.31 8.01
335125 0.38 1.97
335179 1.24 1,98
335188 0.46 1.47
335211 1.61 1.42
335288 0.73 0.97
335289 0.20 0,26
335361 2.18 1.58
335379 0.50 0.71
335414 3.64 14,94
75 335416 2.93 3.98
335496 0.96 0.91
335497 1.71 1.92
335548 i.15 2.40
335551 . 3.22 10.54
335558 3.42 4.89
335586 5.50 12.75
335619 2.99 3.07
335620 3.80 8.29
335621 0.28 0.57
335682 0.46 1.17
142
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335686 2.55 3.81
335755 2.24 1.07
335784 0.20 0.97
335814 1.13 1.48
335815 2.45 3.51
335823 1.00 4.16
335835 0.49 1.70
335851 1.66 1.39
335868 2.98 6.43
1 335896 0.98 0.99
~
335936 12.10 21.93
335948 1.00 1.64
335983 1.00 4.21
335995 0.37 1.17
1 336021 1.04 0.84
336034 11.40 23.54
336038 1.19 1.21
336066 0.54 1.63
336107 0.95 0.70
20 336205 3.13 6.29
336275 3.2D 10.10
336292 2.34 3.09
336331 1.00 1.00
336419 0.65 0.79
2S 336632 2.33 2.16
336633 2.55 2.23
336634 2.19 2.03
336635 2.69 2.48
336636 2.13 1.83
3 336637 2.43 2.24
~
336638 2.31 2.03
336659 0.60 1.31
336675 0.31 1.18
336684 1.50 1.14
3 336694 4.74 7.10
5
336716 4.43 6.37
336721 2.20 0.74
336798 1.64 2.14
336900 6.14 12.73
40 336948 1.00 1.00
337028 1.30 2.09
337043 4.01 11.53
337046 1.67 1.84
337054 2.78 7.35
45 337128 7.20 16.14
337162 3.45 5.34
337183 5.72 11.41
337184 3.72 5.90
337192 1.27 1.06
337194 1.88 1.68
337229 0.22 1.03
337268 1.00 3.31
337299 3.23 5.14
337325 2.76 3,72
55 337389 5.80 10.42
337493 2.06 6.30
337497 7.88 20.29
337500 3.80 4.48
337549 1.66 2,31
337603 1.27 8.54
337605 5.76 7.16
337671 0.73 0.97
337755 1.54 0.92
337786 5.07 9.73
65 337809 6.18 12,87
337862 3.78 12.97
337871 2.66 8.16
337958 0.26 1.34
338008 1.48 1.12
338033 2.38 14.59
338083 0.65 2.16
338110 1.00 1.61
338112 5.86 8.25
338145 1.70 1.97
75 338148 8.07 18.19
338158 1.30 4.55
338161 2.58 3.57
338179 1.00 1.00
338182 3.32 4.63
338189 1.00 3.34
338197 0.99 1.69
338199 d.58 7.62
338215 6.01 15.85
338279 0.53 0.95
g5 338316 20.58 38.66
143
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338322 3.23 7.39
338357 4.10 11.39
338359 10.12 21.59
338366 0.69 1.02
338374 0.40 1.18
338414 0.47 1.06
338418 6.12 13.86
338469 3.09 5.11
338501 6.28 10.32
1 338506 6.97 12.41
~
338523 3.10 5.84
338549 1.70 2.70
338561 0.79 0.81
338662 1.72 1.46
I 338671 0.17 0.91
S
338676 2.10 ~ 15.86
338726 1,20 1.09
338779 0.12 0.57
338804 0.99 1.67
338836 1.00 1.00
338871 4.30 9,81
338872 5.02 12.81
338879 0.23 1.12
338937 6.55 12.26
338966 1.76 5.42
338993 1.00 2.40
339047 5.26 10.81
339100 5.10 6.88
339114 1.00 1.70
339121 1,00 3.75
339170 10.36 19.67
339229 4.06 13.48
339264 2.64 3.83
339293 1.73 1.94
3
TABLE 88 shows the accession numbers for those Pkeys in Table 8A lacking
unigenelD's. For each probeset we have listed the gene cluster number from
which the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Tools (DcubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
4O "Accession~column.
Pkey: Unique Eos probeset identifier number
CAT number: Geno cluster number
45 Accession: Genbank accession numbers
Pkey CAT number Accessions
322044187363AW340926 AA249063 N86075
1
32206044320Ai341937 AW003063 034725 AA904742
1
32143042705X57414 X57415
1
32146743034X13075 X13076
1
32212546779_1893901 AF075073 893902
32216646861H69434 AF085958 H69846
1
32217346873H52567 H52557 AF085970 H52164
1
5 322178- H56535 AF085980 H56712
S 46882
1
32217946685-1H92891 AF085982 H92777
3215771615102-1H84849 H84252 H84260 H86664 H85320
3215671615333H95531 H95521 H8d529
1
313723111953AA070412 AA102346 AA081885
1
6O320997627492H22544 H46842 A1204929
1
32227847271W69304 AF086283 ta69200
1
321687218439-fAA625149 AA313030 AA313052 H97463
313883129439AA665089 AA135130 AA484059 AA102419
1 AW877765
32232047422W79150 AF086419
1
65322339814584A1668646 A1734214 W17348
1
314648293660-1AW979268 AA878419 AA431342 AA431628
300201682222A1308300 A1308296
1
30689725196_A1093967
2
323155979809AL120701 AL135041 AL121524
1
32252738927_1AF147359 T58511 T58560
322585473768W88919 W89125
2
3003621574395-1242308 H23514
32263582296AA005129 AA679084 AA694399
1
32266485042_1AA011522 AA702841 AA011691 AA330797
7 315454360580A1239464 A1239473 AA625812 A1208703
5 1
32268737372_1AF074666 A1110759 AF090902
314852327472A1903735 AA491283 A1694953 AW976903
1 AA761362
307783697809AI347274 AW844024
1
324072269032AA381722 AA381829 AW963906 AW963902
1 AA381242
300627_ AA488472 W27363 AA317053 BE082689
221345_1AW967036 BE079872
323505196389AW970512 AA280251 A1652287 BE466438
1 A1650725 AA551854 AA281574 AW571481
315791403558AA678177 AA677034
1
324303233842AL118754 AA333202 H38001
1
316519442885AA847835 AA768376
1
g 300926333127_1AA504860 AA504911
5
144
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324580328264_1AA492588 AA492498 AA492571
301882275067T78054 T79888 AA398185
1
324804398093-1A1692552 A1393343 A1800510 A1377711 F24263 AA661876
3248891515978_1D31010 D30991 D31168 D31166 D31465
30269743219AJ001409 AJ001410
1
30271145419_1L08442 D51348
3027d2458-39Li20fii
318499364430T25451 AA585296 AA585305
1
31062434624088896 088898 AA916056 T03285 A1341594 A1359534
4 A1634031 088897
1 302847458 X98941 X98942 X98943 X98953 X98949
~ 105
30412277271H28966
-5
303598270283AA382814 AA402411 AA412355
1
311409837264-1A1696839 A1909260 A1909259
312094797889278390 T97427
1
153193121540116245481 F12393 T74437
1
3194071688823_1805329 801555 808276
3194251689571T82930 802424 T85145
1
320007229683_1AA336314 T82938 AA327744 AW967388 AA639967 T10753
3200181815987T83263 T85731 T85730
1
2~3194841691553-1T91772 807257 807098
3188651535937H10818 F07831 243072
1
3122201671607_1N74613 T98756 T98589
319546243305-1809692 809414 AA346353
312389902067_1A1863140 W80703 843474
3196111566863H14957 856522 811908
1
312437291472-1BE080180 AW827313 AW231970 AA995028 AA428584 AW872716
AW892508 AW854593 AA578441 AW975234 AA664937 AA984131
AA528743 AA552874 AA564758 AW063245 AI267534 AW070190
AW893483 AA770330 AA906928 AA906582 AA758746 AA551717
AW063311 AA429538
3118961 AW206447 AI248530 A1084433 AI400976 816553
579192
319834_ AA071267 T65940 T64515 AA071334
112523_1
32110280531AA018306 H38925 AA001221
1
321158410938_1H79670 H47798 AA700289
321199212379_1N34524 AA305071 AW954803 AA502335 A1433430 A1203597
AW026670 AW265323 AW850787 AA317554 AW993643 AW835572
AW385512 AI334966 W32951 H62656 H53902 888904 AW835732
3 30552828632=AA769156
3
3212701662057-1N59537 N78278 883560
314126177666_1AA226431 AA226569 AA488748
320714743644891883 A1445591
1
306442AA976899
40306446AA977348
306d58AA978186
306510AA988546
306557AA994530,
306572AA995686
45306582AA996248
306656A1004024
306686A1015615
306751A1032589
308011A1439473
5 306892A1092465
0
308106A1476803
308154A1500600
306956A1125111
306958A1125152
5 308213A1557041
5
308216A1557135
308219A1557246
306588A1718299
308599A1719893
60308643A1745040
308673A1760864
308697A1767143
308778A1811109
308808A1818289
65308875A1832332
308886AI833240
308898A1858845
308966A1870704
308979A1873111
30301141689AF090405 AF090407 AF090406
1
30307744060-1AF163305 AF163307 AF163303
305016AAfi26876
305034AA630128
305072AA641012
75305148AA654070
305190AA665955
303978AW513315
303990AW515465
303998AW516449
303999AW516611
305235AA670480
305312AA700201
305413AA724659
305447AA737856
32124429327-1AF068654 AF068656 AF068655
145
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305614 AA782866
305637 AA806124
305639 AA806138
305650 AA807709
305690 AA813477
305728 AA828209
305759 AA835353
305792 AA845256
307041 A1144243
1 0 307091 A1167439
307181 A1189251
305901 AA872968
305910 AA875981
307415 A1242118
1 5 307426 A1243364
307517 A1275055
307551 A1281556
307561 A1282207
307608 A1290295
307691 A1318285
307730 A1336092
307760 A1342387
307764 A1342731
307796 A1350556
309045 A1910902
309051 A1911975
307807 A1351799
307808 A1351826
307820 A1355761
307852 A1365541
309122 A1928178
309164 A1937761
309177 A1951118
307902 A1380462
3 5 309299 AW003478
309303 AW004823
309476 AW129368
309532 AW151119
309747 AW264889
4~ 309769 AW272346
309799 AW276964
309866 AW299916
302679 311853_1 H65022 AA186889
309923 AW340684
45 309928 AW341418
309931 AW341683
309933 AW341936
302705 31765_1 009060 009061
302789 34161 1 AJ245067 AJ245070
304006 AW517947
304024 T03036
304026 T03160
304028 T03266
304046 T54803
5 304061 T61521
304063 T62536
302802 34487-1 Y08250 Y08245
304114 878946
304155 H68696
304203 N56929
304234 W81608
304348 AA179868
304430 AA347682
304456 AA411240
65 304521 AA464716
304526 AA476427
304607 AA513322
304735 AA576453
304760 AA580401
7O 306015 AA897116
306063 AA906316
306065 AA906725
306104 AA910956
306109 AA911861
75 306242 AA932805
306288 AA936900
306396 AA970223
330568 NOT_FOUND_entrez 056244
330599 15323 -12 090437
331131 genbank_R54797 854797
331203 NOT_FOUND_entrez T82310
331531 genbank_N51343 N51343
331547 467396 1 AA828597 N54811
$s 332074 genbank_AA599012 AA599012
146
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TABLE 8C shows the genomic position for those Pkeys in Table 8A lacking
unigene ID's and accession numbers. For each predicted exon, we have listed
the genomic
sequence source used for prediction. Nucleotide locations of each predicted
exon are also listed.
J Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham I. et al." refers to the publication entitled
"fhe DNA
sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495.
Strand: indicates DNA strand from which exons were predicted.
1 O Nt-position: Indicates nucleotide positions of predicted exons.
Pkey Ref Sfrand Nt_position
332792Dunham, Plus 73381-73768
I. et.al.
332816Dunham, Plus 359844-360030
I. et.al.
1 332906Dunham,l.et.al.Plus 1923101-1923205
332911Dunham, Plus 1961767-1961858
I. et.al.
332912Dunham, Plus 1962120-1962246
I. et,al.
332922Dunham,l.et.al.Plus 2009620-2009738
332956Dunham, Plus 2510528-2510658
I. et.al.
332959Dunham, Plus 2518145-2518213
I. et.al.
333138Dunham,l.et.al.Plus 3369205-3369323
333139Dunham,l.et.al.Plus 3369495-3369571
333221Dunham, Plus 3978070-3978187
I. et.al.
333380Dunham, Plus 4904775-4904846
I. et.al.
333387Dunham,l.et.al.Plus 4910935-4910997
333512Dunham,h Plus 5560510-5560564
et,al.
333524Dunham, Plus 5612620-5612780
I. et.al.
333585Dunham,l.et.al.Plus 6234778-6234894
333618Dunham,l.et.al.Plus 6562391-6562566
333627Dunham, Plus 6620564-6620903
I. et.al.
333628Dunham, Plus 6629004-6629233
I. et.al.
333650Dunham, Plus 6796852-6797128
I. et.al.
333678Dunham, Plus 7068223-7068288
I. et.al.
333750Dunham,l.et.al.Plus 7608165-7608234
35 333763Dunham, Pius 7692491-7692630
I. et.al.
333767Dunham, Plus 7694407-7694623
I. et.al.
333768Dunham, Plus 7695440-7695697
I. et.al.
333769Dunham,l.et.al.Plus 7696625-7696707
333772Dunham,l.et.al.Plus 7706773-7706902
40 333777Dunham, Plus 7746805-7746916
~ I, et.al.
333846Dunham, Plus 8008623-8008757
I. et.al.
333684Dunham,l.et.al.Plus 8153960-8154161
333887Dunham, Plus 8154882-8155025
I. et.al.
333891Dunham, Plus 8156437-8156709
(. et.al.
45 333892Dunham,l.et.al.Plus 8156825-8157001
333948Dunham, Plus 8583497-8583627
I. et.al.
333954Dunham, Plus 6563186-6563335
I. et.al.
333966Dunham,l.et.al.Plus 8655643-8655626
333968Dunham, Plus 8661004-8681241
I. et.al.
50 334061Dunham, Plus 9686941-9687077
I. et.al.
334094Dunham, Plus 9889953-9890105
I. et.al.
334113Dunham,l.et.al.Plus 10282459-10282597
334161Dunham, Plus 10599033-10599180
I. et.al.
334219Dunham, Plus 12716160-12716384
I. et.al.
5 334239Dunham, Plus 13056569-13056693
S I. et.al.
334333Dunham, Plus 13603544-13603657
I. et.al.
334378Dunham, Plus 13907239-13907370
I. et.al.
334382Dunham,l,Plus 13915866-13916036
et.al.
334562Dunham, Plus 14987847-14987940
I. et.al.
334588Dunham,l.et.al.Plus 15032740-15032817
334616Dunham, Plus 15176123-15176470
I. et.al.
334633Dunham, Plus 15333206-15333305
I. et.al.
334866Dunham, Plus 18872214-18672317
I. et.al.
334891Dunham,l.et.al.Plus 19299770-19299944
65 334934Dunham,l.et.al.Plus 20103970-20104058
335015Dunham, Plus 20682792-20682945
I. et.al.
335120Dunham, Plus 21436286-21436384
I. et.al.
335125Dunham, Plus 21441390-21441471
I. et.al.
335179Dunham, Plus 21634405-21634526
I. et.al.
335188Dunham,I.et.al.Plus 21669118-21669328
335211Dunham,l.et.al.Plus 21774611-21774680
335361Dunham, Plus 22807292-22807445
I. et.al.
335379Dunham, Plus 22899306-22899420
1. et.al.
335414Dunham,l.et.al.Plus 23235546-23235664
75 335416Dunham,l.et.al.Plus 23237354-23237465
335496Dunham, Plus 24164386-24164545
I. et.al.
335497Dunham,l.et.al.Plus 24167666-24167869
335558Dunham, Plus 24740167-24740347
I. et.al.
335586Dunham, Plus 24990333-24990497
I. et.al.
335686Dunham,l.et.al.Plus 25439839-25439920
335784Dunham, Plus 25942710-25942792
I. et.al.
335823Dunham,l.et.al.Plus 26365925-26366004
335983Dunham, Plus 27938968-27939070
I. et.al.
335995Dunham, Plus 28009044-28009184
I. et.al.
g5 336021Dunham, Plus 28686482-28686559
I. et.al.
147
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336034Dunham, Plus 29014404-29014590
I. et.al.
336038Dunham, Plus 29022983-29023165
I. et.al.
336107Dunham,l.et.al.Plus 29987731-29987869
336632Dunham, Plus 963890.985529
I. et.al.
336633Dunham, Plus 985591-986221
I. et.al.
336634Dunham,l.et.al.Plus 986296-986670
336635Dunham,l.et.al.Plus 987908-988364
336636Dunham, Plus 988418-989185
. I. et.al.
336637Dunham, Plus 969276-990813
I. et.al.
336638Dunham, Plus 991906-993240
I. et.al.
336659Dunham,l.et.al.Plus 1896402-1896478
336694Dunham,l.et.al.Plus 2420546-2420616
336721Dunham,l.et.al.Plus 3371522-3371586
336900Dunham,l.et.al.Plus 10236423-10236523
336948Dunham, Plus 12692290-12692381
I. et.al.
337028Dunham,l.et.al.Plus 16644817-16644942
337054Dunham,l.Plus 17821742-17821922
et.al.
337162Dunham,l.et.al.Plus 23478943-23479145
337183Dunham,l.et.al.Plus 23943606-23943696
337184Dunham, Plus 23973949-23974016
1. et.al.
337268Dunham,l.et.al.Plus 28011979-28012034
337299Dunham, Plus 29022656-29022775
I. et.al.
337389Ounham,l.et.al.Plus 31401509-31401579
337493Dunham, Plus 33330760-33330981
I. et.al.
337549Dunham, Plus 34474472-3dd74531
I. et.al.
337755Dunham, Plus 3971764-3971900
I, et.al.
337809Dunham,l.et.al.Plus 4449069-4449193
337871Dunham,l.et.al.Plus 5443027-5443101
337958Dunham, Plus 6969162-6969270
I. et.ai.
338008Dunham,l.et.al.Plus 7697068-7697236
338033Dunham, Plus 8092128-8092271
I. et.al.
338110Dunham,l.et.al.Plus 10384481-10384621
338112Dunham,l.et.al.Plus 10391398-10391600
338145Dunham, Plus 11386629-11386692
i. et.al.
35 338148Dunham, Plus 11448985-11449085
I. et.al.
338179Dunham, Plus 12808775-12808833
I. et.al.
338197Dunham,l.et.al.Plus 13638107-13638181
338279Dunham,l.et.al.Plus 16168944-16169091
338316Dunham, Plus 17089711-17089988
I. et.al.
4~ 338322Dunham, Plus 17132477-17132547
I. et.ai.
338357Dunham,l.et.al.Plus 18062184-18062402
338359Dunham,l.et.al.Plus 18074402-18074501
338366Dunham,i.et.al.Plus 18252026-18252189
338374Dunham, Plus 18371200-18371282
I. et.al.
45 338414Dunham,l.et.al.Plus 19345573-19345660
338418Dunham,l.et.al.Plus 19435506-19435596
338501Dunham,l.et.al.Plus 21244713-21244828
338506Dunham, Plus 21221871-21221953
I. et.al.
338523Dunham, Plus 21509763-21509864
I. et.al.
5 338662Dunham,l.et.al.Plus 24404720-24404899
0
338804Dunham,l.et.al.Plus 27236005-27236108
338836Dunham,l.et.al.Plus 27792166-27792272
338879Dunham,l.et.al.Plus 28410653-28410734
338937Dunham,l.et.al.Plus 29160655-29160725
5 338993Dunham,l.et.al.Plus 30077787-30078184
S
339047Dunham,l.et.al.Plus 30760793-30760968
339100Dunham,l.et.al.Plus 31141580-31141765
339114Dunham,l.et.al.Plus 31456454-31456519
339121Dunham, Plus 31583467-31583536
I. et.al.
339170Dunham,l.et.al.Plus 32216399-32216527
339293Dunham,i.et.al.Plus 33223671-33223819
332858Dunham,l.et.al.Minus 1339607-1339397
332982Dunham,l.et.al.Minus 2626296-2628109
332984Dunham, Minus 2632606-2632457
I. et.al.
65 332998Dunham,I.et.al.Minus 2711704-2711565
333058Dunham,l.et.al.Minus 3028925-3028811
333097Dunham, Minus 3204124-3204036
I. et.al.
333121Dunham,l.et.al.Minus 3308446-3308358
333122Dunham,l.et.al.Minus 3309596-3309531
333123Dunham,l.et.al.Minus 3310817-3310749
333140Dunham,l.et.al.Minus 3377220-3376309
333260Dunham,l.et.al.Minus 4308400-4308304
333603Dunham,l.et.al.Minus 6466335-6465727
333604Dunham, Minus 6467090-6d&6768
I. et.ai.
75 333904Dunham, Minus 8217374-8217261
I. et.al.
333906Dunham,l.et.al.Minus 8218238-8218063
334183Dunham, Minus 11832582-11832508
I. et.al.
334187Dunham,l.et.al.Minus 11921456-11921205
334222Dunham,l.et.al.Minus 12732417-12732289
334223Dunham,l.et.al.Minus 12734365-12734269
334255Dunham,l.et.ai.Minus 13200776-13200692
334492Dunham,i.et.al.Minus 14478333-14478172
334648Dunham,l.et.al.Minus 15363301-15363222
334787Dunham,l.et.al.Minus 16299093-16298937
334933Dunham, Minus 20078117-20077991
I. et.al.
14~
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
334945Dunham, Minus 20138885-20138637
I. et.al.
334967Dunham,l.et.al.Minus 20173311-20173218
33499DDunham, Minus 20341159-20341087
I. et.al.
335093Dunham, Minus 21297367-21297214
I. et.al.
335288Dunham, Minus 22304275-22303770
I. et.al.
335289Dunham, Minus 22305950-22305708
I, et.al.
335548Dunham,l.et.al.Minus 24662773-24662673
335551Dunham,l.et.al.Minus 24679828-24678961
335619Dunham, Minus 25082677-25082498
I. et.al.
1 335620Dunham, Minus 25092561-25092434
~ I. et.al.
335621Dunham, Minus 25098878-25098767
I. et.al.
335682Dunham, Minus 25421215-25421093
l, et.ai.
335755Dunham,l.et.al.Minus 25763806-25763747
335614Dunham,l.et.al.Minus 26320043-26319845
I 335815Dunham, Minus 26320518-26320421
S I. et.al.
335835Dunham, Minus 26393311-26393245
I. et.al.
335851Dunham, Minus 26604863-26604742
I. et.al.
335868Dunham,l.et.al.Minus 26711437-26711300
335896Dunham, Minus 26977639-26977558
I. et.al.
335936Dunham,l.et.al.Minus 27360474-27360400
335948Dunham,l.et.al.Minus 27555924-27555788
336066Dunham,l.et.al.Minus 29241080-29240842
336205Dunham,l.et.al.Minus 30477456-30477311
336275Dunham,l.et.al.Minus 32086675-32086536
336292Dunham,l.et.al.Minus 32818035-32817927
336331Dunham, Minus 33594527-33594371
I. et.al.
336419Dunham,l.et.al.Minus 34052568-34052445
336675Dunham, Minus 2020758-2020664
I, et.al.
336684Dunham, Minus 2158060-2157993
I, et.al.
336716Dunham, Minus 3259952-3259862
I. et.al.
336798Dunham,l.et.al.Minus 5888954-5888757
337043Dunham,l.et.al.Minus 17407330-17407251
337046Dunham,l.et.al.Minus 17610892-17610821
337128Dunham,l.et.al.Minus 22215251-22215034
35 337192Dunham, Minus 24591853-24591771
I. et.al.
337194Dunham, Minus 24610510-24610359
!. et.al.
337229Dunham, Minus 26716579-26716481
I, et.al.
337325Dunham,l.et.al.Minus 30015948-30015800
337497Dunham,l.et.ai.Minus 33371317-33371258
337500Dunham, Minus 33376212-33376158
I. et.al.
337603Dunham, Minus 1299296-1299194
1. et.al.
337605Dunham,l.et.al.Minus 1346555-1346397
337671Dunham,l. Minus 3260634-3260547
et.al.
337786Dunham, Minus 4133203-4133081
I. et.al.
337862Dunham, Minus 5347658-5347550
I. et.al.
338083Dunham,l.et.al.Minus 9318438-9318301
338158Dunham,l.et.al.Minus 11794465-11794343
338161Dunham, Minus 12124716-12124658
I. et.al.
338182Dunham, Minus 12824919-12824827
I. et.at.
338189Dunham,l.et.al.Minus 12878594-12878478
338199Dunham,l.et.al.Minus 13760865-13760780
338215Dunham,l.et.al.Minus 14055447-14055355
338469Dunham, Minus 20520387-20520242
I. et.al.
338549Dunham, Minus 22049171-22049081
I. et.al.
338561Dunham, Minus 22311966-22311856
I. et.al.
338671Dunham, Minus 24508421-24508346
I. et.al.
338676Dunham, Minus 24637427-24637369
I. et.al.
338726Dunham, Minus 25926206-25925618
I. et.al.
338779Dunham, Minus 27030151-27029795
I. et.al.
J~ 338871Dunham, Minus 28301708-28301611
I. et.al.
338872Dunham,l, Minus 28300921-28300790
et.al.
338966Dunham,l.et.al.Minus 29614876-29614749
339229Dunham,l.et.al.Minus 32722330-32722199
339264Dunham,l.et.al.Minus 32975145-32975053
)S 3252286381940 2630-2694
Plus
3252356381943 162154-162264
Minus
3295883962484 1169-1619
Plus
3295603962491 2095-2990
Plus
3295413983503 2765-3059
Minus
3253285866875 86780-86854
Plus
3253406017033 166656.166619
Minus
3253735866920 1136686-1136777
Minus
3253675866920 922881-922958
Minus
3253895866921 239672-239759
Plus
3254365866939 29778-29907
Minus
3254985866967 173372-173930
Plus
3254716017034 289268-289342
Minus
3255578056302 50921-51050
Plus
3255596249595 118590-119172
Minus
3255606249595 133794-133981
Minus
3255696249599 79927-80217
Plus
3255876682462 126724-126967
Plus
3255856682462 73476-73574
Plus
3255975866992 1065020-1065089
Plus
3256395867002 253525-253608
Plus
149
CA 02444691 2003-10-17
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02/0864
3257395867038Minus205138-205269
3257405867038Minus207533-207690
3257926469828Minus1018-1176
'
3257356552447Minus269122-269190
3256856682468Plus117397-117483
3256866682468Plus118337-118439
3258196682490Minus130314-130370
3297646048195Minus109733-109968
3297036065793Minus139994-140138
1 3296436448539Plus53403-53537
0
3298166624888Minus70296-70423
3298606687260Minus163474-163605
3258835867087Plus22498-22663
3258955867097Plus358317-358476
1 3259255867124Plus115749-115962
3259325867127Plus7369-7441
3259415867133Minus64228-64402
3259695867153Plus101911-102081
3259715867153Plus105841-106035
203299934567166Minus101307-101434
3300206671887Plus172397-172491
3261635867168Minus7831-8035
3262745867171Minus410289-410404
3260255867176Plus70854-70915
ZS3260465867182Minus62668-62825
3260995867186Minus661381-661510
3261085867187Minus23784-23903
3261655867208Minus62787-62929
3261895867212Plus69288-69413
3 3262045867218Minus148088-148200
0
3262305867230Minus301868-301972
3300524567182Plus352560-352963
3300366042048Plus117120-117216
3263605867293Plus13627-13844
3 3265895867320Plus22760-22919
5
3263935867341Plus41702-41841
3265055867435Minus8818-8949
3265155867439Plus36683-36809
3265926138928Plus23689-23828
403301076015249Minus100091-100282
3301066015249Minus99443-99778
3301006015253Plus21166-21301
3300936015278Plus1043-1199
3300886015293Plus37517-37638
453300856015302Minus59613-59770
3301206671864Minus127553-127656
3301236671869Minus35311-35406
3267425867611Minus95187-95248
3266055867637Plus24656-24749
5 3268186117831Minus15199-15309
0
3267206552456Plus84525-84677
3267706598307Minus513603-513668
3266926682502Plus117697-117899
3266936682502Minus335002-335095
5 3269835867657Minus16023-16581
5
3269915867660Plus18147-18339
3269366004446Minus10217-10357
3269646469836Plus75340-75456
3270406531965Plus783670-783817
603270536531965Plus2247267-2247437
3270756531965Plus4041318-4041431
3270856531965Plus4734947-4735069
3270366531965Plus319951-320040
3271306531976Plus20247-22343
653271565866841Minus2462-2620
3272885667481Plus48583-48773
3273325867516Minus56361-56532
3272205867525Minus65707-65781
3272245867534Plus188468-188544
703273216249562Minus99745-99836
3273616552412Minus61013-62130
3273965867743Plus8702-8820
3274145867750Plus102461-102586
3274425867759Plus111483-111618
753274675867772Plus88030-88151
3274735867775Plus75101-75181
3274835867783Plus181573-181662
3273775867793Minus37610-37676
3275625867804Minus343989-344474
3275685867811Minus46152-46287
3276066004463Plus200262-200495
3276115867868Minus175063-175392
3276425867891Minus2513-2743
3276545867910Minus97564-97710
8 3277345867940Minus31003-31583
5
150
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02/0864
3277755867964Minus130791-130871
3277965867982Plus85267-85405
3278406249578Minus73065-73206
3302086013599Plus66517-66931
3302636671884Minus101503-101634
3280045867993Minus157407-157887
3281015868020Plus289920-290014
3281005868020Minus263545-263635
3281135868024Minus80378-80491
1 3281575868064Plus73326-73615
~
3281965868080Minus16551-16729
3281975868081Minus42133-42438
3279405868197Minus95240-95428
3279845868216Plus66611-66677
1 3280215902482Plus713478-714590
3280686117819Plus253903-254022
3282646381912Plus55086-55404
3303002905862Minus3246-3302
3286085868222Minus87770-87953
3286005868229Minus38889-40010
3286165868239Plus293920-294224
3286235868246Minus120020-120126
3286325868247Plus76734-76853
3286665868254Minus778-901
25 3286985868264Minus625555-625633
3287005868264Plus764089-764203
3287085868271Minus68114-68854
3287355868289Plus89389-89455
3287435868289Plus274638-274726
3288065868324Plus29408-29684
3282995868366Minus149708-149889
3283425868383Plus59955-60094
3283655868387Minus270724-270798
3283695868388Plus75371-75583
35 3283815868392Plus662758-662848
3284515868425Minus217275-217336
3284815868449Minus8987-9180
3285005868464Plus59098-59481
3285305868482Plus334973-335406
3286646004473Plus1193739-1193866
3288616381928Minus108317-108403
3289085868493Plus117002-117059
3289335868500Plus771755-771889
3289345868500Plus846342-846448
45 3289496456765Minus43552-43619
3303136042030Minus33642-33775
3290055868542Plus85470-85673
3303662944106Plus151837-151914
3303726580495Minus317461-317688
3290335868561Minus5390-5479
3290375868562Minus32466-32562
3290675868591Minus146417-147652
3291345868679Plus29959-30018
3291575868687Minus145940-146155
5 3291785868704Plus179177-179463
5
3291925868716Plus166936-167020
3291945868716Minus304450-304559
3292045868720Minus3050-3190
3292245868728Plus27422-27664
3292285868728Minus50118-50287
3292885868771Plus25554-26299
3293375868806Minus467155-467222
3290116682532Plus48658-48741
151
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TABLE 9A: Potential Therapeutic, Diagnostic and Prognostic targets for Therapy
of Lung Cancer
Table 9A shows about 1312 genes up-regulated in lung tumors (including
squamous cell carcinomas, adenocarcinomas, small cell carcinomas,
granulomatous and carcinoid
tumors) relative to normal body tissues. These genes were selected from about
59680 probesets on the Eos/Affymetrix Hu03 Genechip array.
Table 98 show the accession numbers for those Pkey's lacking UnigenelD's for
table 9A. For each probeset we have listed the gene cluster number from which
the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Toots (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
1 O "Accession" column.
Table 9C show the genomic positioning for those Pkey's lacking Unigene ID's
and accession numbers in table 9A. For each predicted exon, we have listed the
genomic
sequence source used for prediction. Nucleotide locations of each predicted
axon are also listed.
15Pkey:Unique Eos probeset identifier
number
ExAccn:ExempIarAccession number, Genbank
accession number
UnigenelD:
Unigene
number
Unigene
Title:
Unigene
gene
title
R1: Average of lung tumors (including
squamous cell carcinomas, adenocarcinomas,
small cell carcinomas, granulomatous
and carcinoid tumors) divided
by the
2~ average of normal lung samples
R2: Average of non-malignant lung
disease samples (including
bronchitis, emphysema, fibrosis,
atelectasis, asthma) divided
by the average of normal lung
samples
Pkey ExAccn UnigenelD UnigeneTitle R1 R2
400195NM_007057':Homo Sapiens ZW10 1.00 1.00
interactor
25400205NM_006265':Homo sapiens RAD21 15.80 396.00
(S. pombe)
400220Eos Control 2.28 2.84
400277Eos Control 7.68 9.72
400285Eos Control 1.00 1.00
400288X06256 Hs.149609 integrin, alpha1.04 2.24
(fibronectin receptor,
400289X07820 Hs.2258 matrix metalloproteinase132.454.00
(slromelysin
400298AA032279 Hs.61635 six lransmembrane43.86 74.00
epithelial antigen of
400301X03635 Hs.1657 estrogen receptorl1.00 1.00
400303AA242758 Hs.79136 LIV-1 protein,1.75 1.65
estrogen regulated
400328X87344 Hs.180062 transporter 0.87 1.80
2, ATP-binding cassette, sub
35400419AF084545 Target 156.55253.00
400512NM_030878':Homo Sapiens cytochrome1.00 2.00
P450,
400517AF242388 lengsin 3.67 87.00
400560NM_030878':Homo Sapiens cytochrome1.00 1.00
P450,
400664NM_002425:Homo Sapiens matrix 20.26 45.00
metallopro
400665NM_002425:Homo Sapiens matrix 1.36 1.07
metallopro
400666NM_002425:Homo sapiens matrix 3.26 3.22
metallopro
400749NM_003105':Homo Sapiens sortilin-related1.00 91.00
400763Target Exon 7.63 24.00
401027Target Exon 1.00 1.00
45401093012000586*:gi~6330167~dbj~BAA86477.1~1.00 155.00
(A
401203Target Exon 1.00 86.00
401212012000457':gi~7512178~pir~~T303371.00 400.00
polypr
401411ENSP00000247172':HYPOTHETICAL 1.00 72.00
126.2 kDa
401435014000397*:gi~7499898~pir~~T33295f.00 6d.00
hypath
401464AF039241 hislone deacetylase 3.82 49.00
5
401714ENSP00000241802*:CDNA FLJ11007 2.02 40.00
FIS, CLON
401747Homo sapiens keratin 17 (KRT17)128.4368.00
401760Target Exon 1.74 35.00
401780NM 005557':Homo Sapiens keratin26.47 10.50
16 (foca
55401781Target Exon 10.33 4.61
401785NM 002275':Homo Sapiens keratin4.13 2.70
(KRT1
401797Target Exon 1.44 2.10
401961NM_021626:Homo Sapiens serine 1.41 1.86
carboxypep
401985AF053004 class I cytokine receptor1.00 177.00
401994Target Exon 61.84 47.00
402075ENSP00000251056':Plasma membrane1.00 1.00
calcium
402260NM 001436':Homo sapiens fibrillarin1.56 1.39
(FBL
402265Target Exon 2.09 35.00
402297Target Exon 1.00 92.00
65402408NM 030920':Homo Sapiens hypothetical28.87 13.00
pro
40242001000823*:gi[10432400(emb~CAC10290.1~1.00 1.44
(A
402674Target Exon 7.44 243.00
402802NM-001397:Homo Sapiens endothelin1.00 70.00
convey
402994NM_002463':Homo Sapiens myxovirus1.37 1.43
(influ
403137NM-005381':Homo Sapiens nucleolin1.00 19.00
(NCL),
403306NM_006625 lransmembrane protein1.00 43.00
(63kD), endoplasmi
403329Target Exon 1.00 61.00
403381ENSP00000231844*:Ecotropic virus1.00 119.00
integra
403478NM_022342:Homo Sapiens kinesin 28.13 136.00
protein 9
40348503001813*:gi~12737279~ref~XP-012163.120.23 76.00
k
403627Target Exon 6.30 29.33
403715Target Exon 1.30 35.00
404044ENSP00000237855*:DJ398G3.2 (NOVEL1.00 54.00
PROTEI
404076NM 016020':Homo Sapiens CGI-75 14.29 91.00
protein (
404101C8000950:gi~423560~pir~~A47318 1.00 1.00
RNA-bindi
404140NM 006510:Homo Sapiens retflnger1.42 1.44
protei
404165ENSP00000244562:NRH dehydrogenase1.00 54.00
[quino
404185Target Exon 1.00 117.00
404210NM 005936:Homo sapiens myeloidllymphoid5.93 13.77
404253NM_021058':Homo Sapiens H2B 1.00 1.00
histone fami
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404287 " 06001909:gi~704441jdbj~BAA18909.1~29.71 42.00
(0298
404298 06001238':gi~121715~spjP26697~GTA3-CHICK1.30 1.00
404347 TargetExon 1.00 1.00
404440 NM_021048:Homo Sapiens1.00 15.00
melanoma anflgen,
404721 NM-005596':Homo 1.00 60.00
Sapiens nuclear
factor I
404794NM_000078 cholesteryl ester 1.07 1.38
transfer protein,
plas
404854 Target Exon 1.61 2.01
404877 NM_005365:Homo Sapiens1.00 1.00
melanoma anflgen,
404927 Target Exon 1.00 1.00
1 404996 Target Exon 1.00 1.00
~
405449 CY000047*:gi~11427234pefIXP_009399.1j1.00 1.00
z
405568 NM 031413':Homo 1.00 78.00
Sapiens cat eye
syndrome
405572 Target Exon 0.76 1.14
405646 012000200:gi~4557225pefINP-000005.1]1.01 1.28
al
15405676BE336714 cytochrome c-1 1.13 2.89
405770 NM 002362:Homo Sapiens45.52 37.00
melanoma antigen,
405932 015000305:gij3806122jgb[AAC69198.1j1.99 1.99
(AFO
406137 NM_000179':Homo 2.77 2.38
Sapiens mutS (E.
colt) h
406360 Target Exon 1.00 35.00
406399 NM_003122':Homo 1.00 39.00
Sapiens serine
protease
406467 Target Exon 1.00 1.00
406621X57809Hs.181125tmmunoglobulin lambda1.41 1.74
locus
406642AJ245210 gb:Homo sapiens 2.16 3.91
mRNA for immunoglobulin
406663024683Hs.293441immunoglobulinheavyconstantmu2.07 2.93
25406671AA129547Hs.285754met proto-oncogene 15.00 51.00
(hepalocyte growth
fa
406673M34996Hs.198253major histocompaflbility0.98 3.09
complex, class
406676X58399Hs.81221Human L2-9 transcript1.30 1.53
of unrearranged
im,
406678077534 gb:Human clone 1A111.33 1.45
immunoglobulin
varia
406685M18728 gb:Human nonspecific1.46 2.85
crossreacting antig
3 406687M31126Hs.272822pregnancy specific 8.61 8.50
~ beta-1-glycoprotein
9
406690M29540Hs.220529carcinoembryonic 226.37 350.00
anflgen-related
cell ad
406698X03068Hs.73931major histocompatibilily1.01 2.52
complex, class
406815AA833930Hs.288036tRNA isopentenylpyrophosphate20.25 32.00
transferas
406851AA609784 major htstocompalibility0.75 1.91
complex, class
35406964M21305 gb:Human alpha satellite38.15 1114.00
and satellite 3
406967M24349 gb:Human parathyroid1.00 1.00
hormone-like protet
406974M57293 gb:Human parathyroid9.00 1.00
hormone-related
pep
407103AA424881Hs.256301hypothetical protein1.77 1.10
MGC13170
407128883312Hs.237260EST 1.00 1.00
407137T97307 gb:ye53h05.s1 Soaresfetalliverspleen142.70 135.00
407168845175Hs.117183ESTs 2.16 18.00
407239AA076350Hs.67846leukocyte immunoglobulin-like1.10 1.57
receptor,
407242M18728 gb:Human nonspecific1.12 2.85
crossreacting antig
407244M10014Hs.75431fibrinogen, gamma 3.24 15.38
polypeptide
45407289AA135159Hs.203349Homo Sapiens cDNA 3.53 3.68
FLJ12149 fis, clone
MA
407300AA102616Hs.120769gb:zn43e07.s1 Stratagene19.74 73.00
HeLa cell s3 93
407366AF026942Hs.271530gb:Homo Sapiens 0.06 8.25
cig33 mRNA, partial
sequ
407378AA299264Hs.57776ESTs, Moderately 1.00 26.00
similar to 138022
hypot
407430AF169351 gb:Homo Sapiens 1.00 25.00
protein tyrosine
phospha
407453AJ gb:Homo Sapiens 1.00 75.00
132087 mRNA for axonemal
dynetn
407577AW131324Hs.246759hypothetical protein1.00 1.00
MGC12538
407634AW016569Hs.136414UDP-GIcNAc:betaGal 111.20 228.00
beta-1,3-N-acetylgluc
407710AW022727Hs.23616ESTs 1.00 28.00
407720AB037776Hs.38002KIAA1355 protein 1.89 1.31
55407746AK001962 hypothetical protein1.00 1.00
FLJ11100
407756AA116021Hs.38260ubiquifln specific 4.51 5.00
protease 18
407758050915Hs.38365KIAA0125 gene product1.00 28.00
407782AA608956Hs.112619ESTs, Moderately 0.97 1.14
similar to PURKINJE
CEL
407788BE514982Hs.38991S700 calcium-binding7.88 3.83
protein A2
407790A1027274Hs.288941Homo Sapiens cDNA 3.63 42.00
FLJ14866 fis, clone
PL
407811AW190902Hs.40098cysteine knot superfamily89.96 109.00
1, BMP antagon
407839AA045144Hs.161566ESTs 173.91 108.00
407944834008Hs.239727desmocollin 2 111.30 70.00
408000L11690Hs.620bullous pemphigoid 151.17 8.00
anflgan 1 (2301240k0)
65408031AA081395Hs.42173Homo sapiens cDNA 9.91 93.00
FLJ10366 fis, clone
NT
408063BE086548Hs.42346calcineurin-binding195.78 231.00
protein calsarcin-1
408070AW148852 gb:xf05d05.x1 NCI_CGAP_Bm351.00 1.00
Homo sapien
406101AW968504Hs.123073CDC2-related protein37.84 61.00
kinase 7
408122AI432652Hs.42824hypothelicalprotein0.85 1.71
FLJ10718
408212AA297567Hs.43728hypothetical protein5.88 7.91
408243Y00787Hs.624inlerleukin 8 4.27 9.98
408349BE546947Hs.44276homeo box 010 3.79 3.46
408353BE439838Hs.44298mitochondria) ribosomal1.88 1.65
protein S17
408354AI382803Hs.159235ESTs 1.00 73.00
75408369838438Hs.i solute carrier family1.41 16.50
82575 15 (H77? transport
408380AF123050Hs.44532diubiquifln 15.19 37.22
408482NM_000676Hs.45743adenosine A2b receptor1.65 1.19
408522AI541294Hs.d6320Small proline-rich 1.98 1.24
protein SPRK [human,
408536AW381532Hs.135188ESTs 1.55 1.50
408545AW235405Hs.253690ESTs 1.00 1.00
408572AA055611Hs.226568ESTs, Moderately 1.00 44.00
similar to ALU4_HUMAN
A
408633AW963372Hs.46677PR0200D protein 107.16 56.00
408660AA525775 ESTs, Moderately 1.00 1.00
similar to PC4259
ferci
408761AA057264Hs.238936ESTs, Weakly similar52.24 141.00
to (defline not
ova
85408771AW732573Hs.47584potassium voltage-gated3.05 109.00
channel, delayed
153
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
408783AF192522Hs.47701NPC1 (Niemann-Pick 1.02 1.07
disease, type C1,
gen
408790AW580227Hs.47860neurotrophic tyrosine41.19 61.00
kinase, receptor,
408805H69912Hs.48269vaccinia related 24.67 45.00
kinase 1
408841AW438865Hs.256862ESTs 1.00 58.00
d08873ALD46017Hs.182278calmodulin 2 (phosphorylase1.00 89.00
kinase, delt
408908BE296227Hs.250822serinellhreonine 7.76 1.00
kinase 15
408992AA059325Hs.71642guanine nucleotide 1.00 1.00
binding protein
(G pr
408996AI979168Hs.344096glycoprotein (transmembrane)3.71 5.50
nmb
409015BE389387Hs.49767NM 004553:Homo sapiens1.44 1.24
NADH dehydrogenas
1 409038T97490Hs.50002small inducible 4.28 5.32
~ cytokine subfamily
A (Cy
409041AB033025Hs.50081Hypothetical protein,112.42 195.00
XP_051860 (KIAA119
409077AA401369Hs.190721ESTs 1.00 17.00
409093BE243834Hs.50441CGI-04 protein 2.02 1.93
409103AF251237Hs.112208RAGE-1 protein 80.44 40.00
I 409142AL136877Hs.50758SMC4 (structural 14.87 6.00
S maintenance of
chromoso
409187AF154830Hs.50966carbamoyl-phosphate1.00 1.00
synthetase 1, miloch
409228A1654298Hs.271695ESTs, Weakly similar1.22 1.00
to 2109260A B cell
409234AI879419Hs.27206ESTs 1.00 1.00
409268AA625304Hs.187579ESTs 11.90 23.00
409269AA576953Hs.22972hypothetical protein1.00 1.00
FLJ13352
409361NM_005982Hs.54416sine oculis homeobox168.91 35.00
(Drosophila) homolo
409404BE220053Hs.f29056ESTs 1.00 1.00
409420215008Hs.54451laminin, gamma 2 79.7d 96.00
(nicein (100kD),
kalini
409430821945Hs.346735splicing factor, 1.45 2.10
argininelserine-rich
5
25409446AI561173Hs.67688ESTs 1.00 4.00
409506NM_006153Hs.54589NCK adaptor protein3.97 28.00
1
409522AA075382 gb:zm87b03.s1 Stratagene15.98 141.00
ovarian cancer
409582AA401369Hs.190721ESTs 1.00 17.00
409632W74001Hs.55279serine (orcysteine)292.12 79.00
proteinase inhibito
409705M37762Hs.56023brain-derivedneuroUophic1.00 82.00
factor
409719AI769160Hs.108681Homo sapiens brain 1.00 1.00
tumor associated
prot
409731AA125985Hs.56145thymosin, beta, 0.12 18.12
identified in neuroblast
409744AW675258Hs.56265Homo Sapiens mRNA; 20.75 51.00
cDNA DKFZp586P2321
(f
409757NM_001898Hs.123114cyslatin SN 22.46 15,80
35409866AW502152 gb:Ul-HF-BROp-ajr-f-11-0-ULr11.00 1.00
NIH MGC_5
409893AW247090Hs.57101minichromosome maintenance1.50 1.09
deficient (S.
409902AI337658Hs.156351ESTs 25.92 50.00
d09935AW511413Hs.278025ESTs 2.63 2.11
409956AW103364Hs.727inhibin, beta A 2.17 4.01
(activin A, aclivin
AB a
4~409958NM Hs.57697hyaluronan synthase0.91 2.07
001523 1
410001A8041036Hs.57771kallikrein 11 1.04 2.28
410032BE065985 gb:RC3-BT0319-120200-014-a091.00 58.00
BT0319 Homo
410037AB020725Hs.58009KIAA0918 protein 1.00 34.00
410044BE566742Hs.58169highly expressed 1.00 1.00
in cancer, rich
in leuc
45410048W76467Hs.58218praline oxidase 1.03 1.44
homolog
410076T05387Hs.7991ESTs 1.12 1.50
410102AW248508Hs.279727Homo sapiens cDNA 9.89 1.00
FLJ 14035 fis,
clone HE
410153BE311926Hs.15830hypothetical protein1.00 1.00
FLJ12691
410166AK001376Hs.59346hypothetical protein1.00 1.00
FLJ10514
410193AJ132592Hs.59757zinc fingerprotein28142.01 51.00
410274AA381807Hs.61762hypoxia-inducible 1.72 1.32
protein 2
410309BE043077Hs.278153ESTs 1.00 2.00
410340AW182833Hs.112188hypothetical protein32.0(1 75.00
FLJ13149
410348AW182663Hs.95469ESTs 1.00 1.00
55410407X66839Hs.63287carbonic anhydrase 1.40 1.11
IX
410418D31382Hs.63325transmembrane protease,d.30 2.03
serine 4
410438AB037756Hs.45207hypothetical protein1.00 18.00
KIAA1335
410553AW016824Hs.255527hypothefical protein1.34 1.04
MGC14128
410555W27235Hs.64311a disintegrin and 23.99 1.41 '
metalloproteinase
doma
d10561BE540255Hs.6994Homo Sapiens cDNA: 10.04 1.00
FLJ22044 fis, clone
H
410681AW246890Hs.65425calbindin 1, (28kD)10.88 18.92
410781AI375672Hs.165028ESTs 1.00 57.00
411027AF072099Hs.67846leukocyte immunaglobulin-like1.62 3.78
receptor,
411074X60435Hs.68137adenylate cyclase 1.00 1.15
activating polypeptide
65411089AA456454 cell division cycle1.56 1.58
2-like 1 (PITSLRE
pr
411152BE069199 gb:OV3-BT0379-010300-105-g031.00 84.00
BT0379 Homo
411248AA551538Hs.334605Homo Sapiens cDNA 1.82 1.45
FLJ14408 fis, clone
HE
411252AB018549Hs.69328MD-2 protein 7.32 12.74
4112638E297802Hs.69360kinesin-like 6 (mitofic3.44 2.55
centromere-assoc
70411365M76477Hs.2890B2GM2 ganglioside 1.35 2.02
acfivator protein
411402BE297855Hs.69855NRAS-related gene 1.00 46.00
411573AB029000Hs.70823KIAA1077 protein 11.40 11.35
411579AC005258Hs.70830U6 snRNA-associated1.08 1.90
Sm-like protein
LSm7
411617AA247994Hs.90063neurocalcin delta 1.74 2.57
75411732AA059325Hs.71642guanine nucleotide 1.02 1.00
binding protein
(G pr
411773NM Hs.72026protease, serine, 1.34 2.19
006799 21 (testisin)
411789AF245505Hs.72157Adlican 2.19 2.79
411800N39342Hs.103042microtubule-associaied23.34 34.00
protein 1B
411945AL033527Hs.92137v-myc avian myelocytomatosis1,00 8.00
viral oncog
412115AK001763Hs.73239hypothefical protein2.07 1.64
FLJ10901
412140AA219691Hs.73625RAB6 interacting, 118.48 92.00
kinesin-like (rabkines
412276BE262621Hs.73798macrophage migrafion1.98 1.49
inhibitory factor
(
412464T78141Hs.22826ESTs, Weakly similar1.16 1.34
to 155214 salivary
412530AA766268Hs.266273hypothetical protein41.52 84.00
FLJ13346
g 412537AL031778 nuclear transcription17.90 55.00
factor Y, alpha
154
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
412659AW753865Hs.74376olfactomedin related14.65 47.00
ER localized protei
412719AW016610Hs.816ESTs 382.d6 128.00
412723AA648459Hs.335951hypothetical protein54.90 1.00
AF301222
412811H06382 ESTs 1.00 11.00
412817AL037159Hs.746i9proteasome (prosome,1.63 1.42
macropain) 26S
subu
412863AA121673Hs.59757zinc finger protein17.63 56.00
281
412924BE018422Hs.75258H2A histone family,1.00 22.00
memberY
413004T35901Hs.75117interleukin enhancer2.19 2.05
binding factor
2, 4
413011AW068115Hs.821biglycan 1.22 1.88
1 413048M93221Hs.75182mannose receptor, 0.30 6.23
~ C type 1
413063AL035737Hs.75184chitinase 3-like 3.43 8.71
1 (cartilage glycoprote
413129AF292100Hs.104613RP42 homolog 4.67 4.77
413142M81740Hs.75212ornithine decarboxylase1.92 2.59
1
413223AI732182Hs.191866ESTs 5.73 27.00
15413248T64858Hs.21433hypothetical protein0.99 1.06
DKFZp547J036
413273075679Hs.75257stem-loop (histone)1.00 18.00
binding protein
413278BE563085Hs.833interferon-stimulated1.10 1.09
protein,15 kDa
413281AA861271Hs.222024transcription factor95.94 69.00
BMAL2
413364BE536218Hs.137516fidgetin-like 1 1.00 1.00
413385M34455Hs.840indoleamine-pyrrole0.95 2.09
2,3 dioxygenase
413409AI638418Hs.1440DEADIH (Asp-Glu-Ala-AspIHis)1.00 1.00
box polypep
413453AA129640Hs.128065ESTs 1.00 31.00
413527BE250788Hs.179882hypothefical protein1.06 1.46
FLJ124d3
413554AA319146Hs.75426secretogranin II 79.15 114.00
(chromogranin C)
25413573AI733859Hs.149089ESTs 1.00 1.00
413582AW295647Hs.71331hypothetical protein8.80 10.00
MGC5350
413597AW302885Hs.117183ESTs 1.00 1.00
413690BE157489 gb:RCt-HT0375-120200-011-e061.00 1.00
HT0375 Homo
df369fAB023173Hs.75478ATPase, Class VI, 3.16 2.32
type 118
413719BE439580Hs.75498small inducible 2.86 9.52
cylokine subfamily
A (Cy
413753017760Hs.75517laminin, beta 3 144.10 108.00
(nicein (125k0),
kalinin
413801M62246Hs.35406ESTs, Highly similar1.00 17.00
to unnamed protein
413833215005Hs.75573centromere protein 1.00 1.00
E (312k0)
413882AA132973Hs.184492ESTs 64.24 148.00
35d13926AA133338Hs.54310ESTs 1.00 67.00
413943AW294416Hs.144687Homo Sapiens cDNA 43.42 42.00
FLJ12981 fis, clone
NT
413995BE048146Hs.75671syntaxin 1A (brain)1.23 1.11
414035Y00630Hs.75716serine (or cysteine)2.02 2.51
proteinase inhibito
414142AW368397Hs.334485Homo Sapiens cDNA 1.00 102.00
FLJ14438 fis, clone
HE
414180AI863304Hs.120905Homo Sapiens cDNA 6.92 77.00
FLJ 11448 fis,
clone HE
414245BE148072Hs.75850WAS protein family,1.00 1.00
member 1
414275AW970254Hs.8B9Charot-Leyden crystal1.00 59.00
protein
414317BE263280Hs.75888phosphogluconate 1.52 1.73
dehydrogenase
414334AA824298Hs.21331hypothetical protein1.78 1.72
FLJ10036
45414341080004Hs.75909KIAA0182 protein 33.90 151.00
414368W70171Hs.75939uridine monophosphate171.60 97.00
kinase
414416AWd09985Hs.76084hypothetical protein2.32 1.85
MGC2721
414430AI346201Hs.76118ubiquitin carboxyl-terminal226.15 66.00
esterase L1
414570Y00285Hs.76473insulin-like growth1.64 1,98
factor 2 receptor
414618AI204600Hs.96978hypothetical protein1.87 72.00
MGC10764
414675879015Hs.296281interleukin enhancer1.51 1.39
binding factor
1
414683S78296Hs.76888hypothetical protein43.61 64.00
MGC12702
414696AF002020Hs.76918Niemann-Pick disease,28.63 71.00
type C1
414711AI310440Hs.288735Homo sapiens cDNA 14.86 42.00
FLJ13522 fis, clone
PL
S 414718H95348Hs.107987ESTs 1.00 5.00
414732AW410976Hs.77152minichromosome maintenance1.64 1.44
deficient (S.
414747030872Hs.77204centromere protein 65.01 74.00
F (3501d00kD, mitosin
414761AU077228Hs.77256enhancer of zeste 130.35 121.00
(Drosophila) homolog
2
414774X02419Hs.77274plasminogen activator,2.24 2.19
urokinase
60414806014694Hs.77329phosphatidylserine 1.63 1.53
synthase 1
414809AI434699Hs.77356transferrin receptor1.97 2.60
(p90, CD71)
414812X72755Hs.77367monokine induced 3.48 10.60
by gamma interferon
414825X06370Hs.77432epidermal growth 103.22 143.00
factor receptor
(avian
414839X63692Hs.77462DNA (cytosine-5-)-methyltransferase1.80 1.69
1
65414883AA926960 CDC28 protein kinase14.29 10.06
1
414907X90725Hs.77597polo (Drosophia)-like1.95 2.20
kinase
414914049844Hs.77613ataxia telangiectasia3.00 2.90
and Rad3 related
414945BE076358Hs.77667lymphocyte antigen 1.02 1.21
6 complex, locus
E
414972BE263782Hs.77695KIAAODOS gene product1.00 1.0D
415014AW954064Hs.24951ESTs 1.42 2.84
415091AL044872Hs.779103-hydroxy-3-methylglutaryl-Coenzyme1.00 30.00
A sy
415138C18356Hs.295944tissue factor pathway34.72 107,00
inhibitor 2
415227AW821113Hs.72402ESTs f.87 49.00
415238837780Hs.21422ESTs 1.00 1.00
75415263AA948033Hs.130853ESTs 1.00 1.00
415295841450Hs.6546ESTs 1.00 1.00
415339NM_015156Hs.78398KIAA0071 protein 51.18 166.00
415669NM_005025Hs.18589serine (or cysteine)30.84 63.00
proteinase inhibito
415674BE394784Hs.78596proteasome (prosome,1.48 1.39
macropain) subunit,
415709AA649850Hs.278558ESTs 1.00 1.00
415735AA704162Hs.120811ESTs, Weakly similar1.00 72.00
70138022 hypotheti
415799AA653718Hs.22584iDKFZP434D193 protein6.23 31.00
415817088967Hs.78867protein tyrosine 24.30 1.00
phosphatase, receptor-t
415857AA866115Hs.127797Homo Sapiens cDNA 32.51 35.00
FLJ 11381 fis,
clone HE
415989AI267700 ESTs 78.89 1.00
155
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
416018AW138239Hs.78977proprotein convertase1.00 1.00
subtilisinlkexin
t
416065BE267931Hs.78996proliferating ceU 3.35 2.32
nuclear antigen
416111AA033813Hs.79018chromatin assembly 39.03 3.00
factor 1, subunit
A (
416177AA174069Hs.187607ESTs 1.00 9.00
416178A1808527Hs.192822serologically defined3.83 3.76
breast cancer anti
416208AW291168Hs.41295ESTs, Weakly similar3.67 1.00
to MUC2~HUMAN MUCIN
416209AA236776Hs.79078MAD2 (mitotic arrest9.70 1.00
deficient, yeast,
h
416239AL038450Hs.48948ESTs 83.87 129.00
416250AA581386Hs.73452hypotheticalprotein1.96 2.12
MGC10791
1 416322BE019494Hs.79217pyrroline-5-carboxylate2.08 1.73
~ reductase 1
416423H54375Hs.268921ESTs 1.00 89.00
416448L13210Hs.79339lectin, galactoside-binding,1.28 1.54
soluble, 3
416498033632Hs.79351potassium channel, 27.29 67.00
subfamily K, member
1
416658003272Hs.79432fibrillin 2 (congenital53.29 51.00
contractural ara
~
15416661AA634543Hs.79440IGF-II mRNA-binding9.96 5.00
protein 3
416722AA354604Hs.122546hypotheticalprotein3.68 33.00
- FLJ23017
416819077735Hs.80205pim-2 oncogene 1.59 1.84
416936N21352Hs.42987ESTs, Weakly similar1.00 1.00
to S21348 probable
417034NM Hs.80962neurolensin 1.00 1.00
006183
417061AI675944Hs.188691Homo sapiens cDNA 32.95 156.00
FLJ12033 fis, clone
HE
417079065590Hs.81134interleukin 1 receptor3.91 4.93
antagonist
417218AA129547Hs.285754metprolo-oncogene(hepatocyte1.00 51.00
growthfa
417233W25005Hs.24395small inducible 3.38 2.05
cytokine subfamily
B (Cy
417308H60720Hs.81892KIAA0101 gene product82.94 25,36
25417315A1080042Hs.180450ribosomal protein 106.61 121.00
S24
417324AW265494 ESTs 1.20 1.28
417366BE185289Hs.1076small proline-rich 8.97 3.27
protein 1B (cornitin)
417389BE260964Hs.82045midkine (neurite 2.59 1.82
growth-promoting
factor
417428N87579Hs.278871gb:LL2030F Human 1.00 52.00
fetal heart, Lambda
ZAP
417433BE270266Hs.821285T4 oncofetal trophoblast304.75 173.00
glycoprotein
417466AI681547Hs.59457hypotheticalprotein1.24 1.34
FLJ22127
417512A1979168Hs.344096glycoprotein (transmembrane)2.14 5.50
nmb
417515L24203Hs.82237ataxia-telangiectasia2.66 1.68
group D-associated
417542J04129Hs.82269progesiagen-associated1.28 1.35
endometrial prote
3S417576AA339449Hs.82285phosphoribosylglycinamideformyltransfer42.76 51.00
417715AW969587Hs.86366ESTs 6.35 2.75
417720AA205625Hs.208D67ESTs 113.31 56,00
417791AW965339Hs.111471ESTs 39.98 16.00
417830AW504786Hs.122579hypothetical protein2.61 31.00
FLJ 10461
417866AW067903Hs.82772collagen, type XI, 2.35 2.44
alpha 1
417900BE250127Hs.82906CDC20 (cell division1.52 1.11
cycle 20, S. cerevi
417933X02308Hs.82962thymidylate synihetase4.74 2.55
417944AU077196Hs.82985collagen, type V, 3,61 5.21
alpha 2
417975AA641836Hs.30085hypothetical protein12.49 38.00
FLJ23186
45417991AA731452Hs.190008ESTs 1.00 26.00
418004037519Hs.87539aldehyde dehydrogenase3.02 2.12
3 family, member
418007M13509Hs.83169matrix metalloproteinase187.59 1.00
1 (interstitial
418054NM Hs.83354lysyl oxidase-like 2.85 2.63
002318 2
418057NM Hs.83363coagulation factorVlll-associated(intr1.54 1.69
012151
418113AI272141Hs.8348dSRY (sex determining6.82 5.22
0 region Y)-box 4
418140BE613836Hs.83551microfibrillar-associated1.26 1.46
. protein 2
418203X54942Hs.83758CDC28 protein kinase134.19 144.00
2
418207C14685Hs.34772ESTs 1.00 1.0D
418216AA662240Hs.283099AF15q14 protein 64.66 61.00
55418236AW994005Hs.337534ESTs 18.53 147.00
418249H89226Hs.34892KIAA1323 protein 30.53 106.00
418281009550Hs.1154oviductal glycoprotein1.00 3.00
1,120kD (mucin
9
418283S79895Hs.83942cathepsin K (pycnodysostosis)3.96 5.16
~
418300AI433074Hs.86682Homo sapiens cDNA: 3.18 2.91
FLJ21578 fis, clone
C
418322AA284i66Hs.84113cyclin-dependent 11.96 6.68
kinase inhibitor
3 (CDK
418327070370Hs.84136paired-like homeodomain9.23 2.22
transcription fa
d18345AJ001696Hs.241407serine (or cysteine)1.00 1.00
proteinase inhibito
418379AA218940Hs.137516fidgetin-like 1 21.68 44.00
418397NM Hs.84746chromosome condensation1.00 8.00
001269 1
65418403D86978Hs.84790KIAA0225 protein 16.91 18.98
418462BE001596Hs.85266integrin, beta 4 1.56 1.16
418478038945Hs.1174cyclin-dependent 3.22 2.38
kinase lnhibilor
2A (me
418506AA084248Hs.85339G protein-coupled 2.66 2.22
receptor 39
418526BE019020Hs.85838solute carrier family2.04 2.21
16 (monocarboxylic
418538BE2d4323Hs.85951exportin, tRNA (nuclear1.33 37.00
export receptor
418543NM_005329Hs.85962hyaluronan synthase1.04 1.23
3
418574N28754 M-phase phosphoprotein48.60 85.00
9
418592X99226Hs.284153Fanconi anemia, 18.24 26.00
complementation
group A
418641BE243136Hs.86947a disintegrin and 1.19 1.41
melalloproteinase
doma
75418661NM_001949Hs.1189E2F transcription 29.05 d3.00
factor 3
418663AK001100Hs.4i690desmocollin3 112.17 19.00
418678NM_001327Hs.87225cancedtestis antigen1.18 1.10
418686236830Hs.87268annexin A8 1.54 1.98
418689AI360883Hs.274448hypotheticalprotein1.19 1.04
FLJ11029
418712242183 gb:HSCOBF041 normalized1.00 12.00
infant brain cDN
418727AA227609Hs.94834ESTs 1.00 49.00
418738AW388633Hs.6682solute carver family49.85 1.00
7, (cationic amino
418819AA228776Hs.191721ESTs 1.00 140.00
418830BE513731Hs.88959hypothetical protein20.97 23.00
MGC4816
g5418882NM_004996Hs.89433ATP-binding cassette,57.09 35.00
sub-family C (CFTR
156
CA 02444691 2003-10-17
WO 43 PCT/US02/12476
02/0864
418971AA360392Hs.87113ESTs 1.00 12.00
418973AA233056Ns.1915i8ESTs 4.89 28.00
419078M93119Hs.89584insulinoma-associated' 1.0010.00
1
419079AW014836Hs.18844ESTs 1.09 1.98
419080AW150835Hs.18878hypothetical protein2.06 1.68
FLJ21620
419088AI538323'Hs.52620integdn, beta 8 15.60 51.00
419092J05581Hs.89603mucin 1, Uansmembrane1.11 1.83
419121AA374372Hs.89626parathyroid hormone-like1.00 1.00
hormone
419171NM-002846Hs.89655protein tyrosine 1.10 1.14
phosphatase, receptor
t
1 419183060669Hs.89663cytochrome P450, 1.00 1.00
~ subfamily XXIV (vitamin
419216AU076718Hs.164021small inducible cytokine3.18 2.43
subfamily B (Cy
419288AA256106Hs.87507ESTs 1.00 34.00
419335AW960146Hs.284137hypothetical protein1.00 8.00
FLJ12888
419354M62839Hs.1252apolipoprotein H 22.63 54.00
(beta-2-glycoprotein
I)
15419359AL043202Hs.90073chromosome segregation2.50 1.98
1 (yeast homology
419423D26488Hs.90315KIAA0007 protein 1.00 7.00
419443D62703 gb:HUM316G10B Clontech1.00 12.00
human aorta polyA
419452033635Hs.90572PTK7 protein tyrosine1.64 1.84
kinase 7
419474AW968619Hs.155849ESTs 13.63 62.00
419485AA489023Hs.99807ESTs, Weakly similard.27 2.26
to unnamed protein
419488AA316241Hs.90691nucleophosminlnucleoplasmin3.66 3.63
3
419502AU076704 fibrinogen, A alpha 13.05 115.00
polypeptide
419539AF070590Hs.90869Homo Sapiens clones 74.60 117.00
24622 and 24623
mRNA
419556029615Hs.91093chitinase 1 (chitolriosidase)1.47 4.98
419569AI971651Hs.91143jagged 1 (Alagille 1.00 4.00
syndrome)
419594AA013051Hs.91417topoisomerase (DNA) 94.30 94.00
II binding protein
419703AI793257Hs.128151ESTs 15.26 50.00
419721NM Hs.28B650aquapodn 4 1.00 191.00
001650
df9729AA586442Hs.2f411gb:no53a03.s1 NCI 1.00 59.00
CGAP_SS1 Homosapiens
419741NM-007019Hs.93002ubiquitin carrier 2.02 1.08
protein E2-C
419745AF042001Hs.93005slug (chicken homology,1.00 1.00
zinc finger prot
419752AA249573Hs.152618ESTs, Moderately 29.87 77.00
similar to ZN91
HUMAN Z
419839024577Hs.93304phospholipase A2, 50.99 214.00
group VII (platelet-ac
419936AI792788 gb:o191d05.y5 NCI-CGAP-Kid51.00 1.00
Homo Sapiens
35419937A8040959Hs.93836DKFZP434N014protein 1.64 2.47
419983W55956Hs.94030Homo Sapiens mRNA; 15.72 94.00
cDNA DKFZp586E1624
(f
420005AW271106Hs.133294ESTs 3.15 1.43
420047A1478658Hs.94631brefeldin A-inhibited12.45 39.00
guanine nucleotide
420058AK001423Hs.94694Homo sapiens cDNA 1.00 117.00
FLJ10561 fis, clone
NT
420162BE378432Hs.95577cyclin-dependentkinase1.43 1.21
4
420251AW374968Hs.348112Human DNA sequence 2.35 3.23
from clone RP5-110367
420259AF004884Hs.96253calcium channel, 0.77 1.15
voltage-dependent,
PlQ
420281AI623693Hs.323494ESTs 45.04 54.00
420309AW043637Hs.21766ESTs, Weakly similar49.22 31.00
to ALU5 HUMAN ALU
5
45420332NM_001756Hs.1305serine (orcysteine) 0.05 2.82
proteinase inhibito
420380AA640891Hs.102406ESTs 0.99 2.74
420462AF050147Hs.97932chondromodulinlprecursor1.00 1.00
420520AK001978Hs.98510similar to rab11-binding49.74 133.00
protein
420552AK000492Hs.98806hypothetical protein94.65 88.00
420560AW207748Hs.59115ESTs 1.00 17.00
420610A1683183Hs.99348distal-less homeo 1.00 13.00
box 5
420689H79979Hs,88678ESTs 50.09 95.00
420721AA927802Hs.159471ZAP3 protein 1.00 31.00
420759T11832Hs.127797Homo Sapiens eDNA 1.00 48.00
FLJ 11381 fis, clone
HE
55420783AI659838Hs.99923lectin, galactoside-binding,3.04 1.25
soluble, 7
420900AL045633Hs.44269ESTs 2.24 7.00
420931AF044197Hs.100431small inducible cytokine1.00 8.00
B subfamily (Cy
421002AF116030Hs.100932transcription factor1.00 27.00
17
421027AA761198Hs.55254ESTs 2.87 38.00
421037AI684808Hs.197653ESTs 1.00 46.00
421041N36914Hs.14691ESTs, Moderately 1.00 98.00
similar to 138022
hypot
421073NM-004689Hs.101448metastasis associated1.34 1.46
1
421110AJ250717Hs.1355cathepsin E 119.47427.00
421133AA401369Hs.190721ESTs 1.10 17.00
421150AI913562Hs.189902ESTs 1.45 1.63
421155H87879Hs.102267lysyloxidase 1.00 15.00
421307BE539976Hs.103305Homo sapiens mRNA; 1.37 1.10
cDNA DKFZp434B0425
(f
421316AA287203Hs.324728SMA5 1.00 21.00
421379Y15221Hs.103982small inducible cytokine1.92 3.94
subfamily B (Cy
421451AA291377Hs.50831ESTs 5.89 14.00
421474076362Hs.104637solute carrier family1.46 1.76
1 (glutamate traps
421506BE302796Hs.105097lhymidine kinase 1.56 1.08
1, soluble
421508NM_004833Hs.105115absent in melanoma 5.11 5.23
2
421515Y11339Hs.105352GaINAc alpha-2, 6-sialyltransferase1.00 3.00
I, I
75421524AA312082Hs.105445GDNF family receptor2.63 10.58
alpha 1
421526AL080121Hs.105460DKFZP56400823 protein1.46 1.86
421552AF026692Hs.105700secreted frizzled-related30.21 50.32
protein 4
421574AJ000152Hs.105924defensin, beta 2 1.67 1.74
421582AI910275 trefoil factor 1 1.23 1.00
(breast cancer,
estroge
421633AF121860Hs.106260sorting nexin 10 1.00 116.00
421659NM_014459Hs.106511protocadherin 17 0.05 6.33
421677H64092Hs.38282ESTs 1.31 1.42
421753BE314828Hs.107911ATP-binding cassette,1.41 1.20
sub-family B (MDRI
421773W69233Hs.112457ESTs 1.12 1.14
g5421777BE562088Hs.108196HSPC037protein 1.97 1.29
157
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
421800AA298151Hs.222969ESTs 1.03 1.30
421817AF146074Hs.108660ATP-binding cassette,1.88 1.59
sub-family C (CFTR
421896N62293Hs.45107ESTs 11.84 22.80
421928AF013758Hs.109643polyadenylate binding45.89 90.00
protein-interactin
421931NM Hs.1440gamma-aminobutyric 1.13 1.49
000814 acid (GABA) A recepto
421948L42583Hs.334309keratin 6A 51.83 20.25
421975AW961017Hs.6459hypothetical protein1.17 1.15
FLJ11856
422026080736Hs.110826trinucleotide repeat1.00 52.00
containing 9
422094AF129535Hs.272027F-box only protein 67.61 62.00
5
1 422095A1868872Hs.282804hypotheticalprotein 4.37 2.34
~ FLJ22704
422109573265Hs.1473gastrin-releasing 4.18 95.50
peptide
422128AW881145 gb:OVO-OT0033-010400-182-a0740.89 71.00
OT0033 Homo
422129AU076635Hs.1478serine (or cysteine)1.13 1.38
proteinase inhibito
422134AW179019Hs.112110mitochondrial ribosomal41.59 96.00
protein L42
I 422158L10343Hs.112341protease inhibitor 2.37 1.10
S 3, skin-derived
(SKAL
422168AA586894Hs.112408S100 calcium-binding3.29 1.68
protein A7 (psorias
422278AF072873Hs.114218frizzled (Drosophila)4.93 5.73
homolog 6
422282AF019225Hs.114309apolipoprotein L 1.49 1.71
422283AW411307Hs.114311CDC45 (cell division25.99 10.91
cycle 45, S.cerevis
422310AA316622Hs.98370cytochrome P450, 1.54 1.41
subfamily IIS, polypept
422311AF073515Hs.114948cylokine receptor-like1.15 1.78 ,
factor 1
422330D30783Hs.115263epiregulin 1.00 112.00
422364AF067800Hs.115515Gtype (calcium dependent,9.39 60.00
carbohydrate-
422406AF025441Hs.116206Opa-interacting protein18.33 53.00
5
25422424AI186431Hs.296638prostate differentiation1.71 3.21
factor
422440NM-004812Hs.116724aldo-keto reductase 47.53 32.00
family 1, member
810
422487.AJ010901Hs.198267mucin 4, iracheobronchial73.68 35.54
422511AU076442Hs.117938collagen, type XVII,173.97 26.00
alpha 1
422515AW500470Hs.117950multifunctional polypeptide4.68 2.92
similar to S
422656AI870435Hs.1569LIM homeobox protein1.00 1.00
2
422737M26939Hs.119571collagen, type III, 3.89 4.55
alpha 1 (Ehlers-Danl
422756AA441787Hs.119689glycoprotein hormones,1.05 1.46
alpha poiypeptide
422765AW409701Hs.1578baculoviral IAP repeat-containing3.88 1.53
5 (sur
422809AK001379Hs.121028hypothetical protein99.56 53.00
FLJ10549
3 422867L32137Hs.1584cartilage oligomeric1.69 3.17
matrix protein (pse
422938NM Hs.1594centromere protein 70.46 61.00
001809 A (l7kD)
4229568E545072Hs.122579ECT2 protein (Epithelial77.74 3.00
cell transforms
422960AW890487Hs.63984cadherin 13, H-cadherin5.88 8.55
(heart)
422963AA401369Hs.190721ESTs 171.41 17.00
422976AU076657Hs.1600chaperonin containing2.12 1.62
TCP1, subunit 5
(e
422981AF026445Hs.122752TATA box binding 10.49 35.00
protein (TBP)-associate
422986AA319777Hs.221974ESTs 12.40 32.47
423034AL119930 gb:DKFZp761A092_r1 16.41 60.00
761(synonym:hamy2)
423049X59373Hs.188023ESTs, Moderately 1.00 1.00
similar to HXDA_HUMAN
H
45423081AF262992Hs.123159sperm associated 1.82 2.96
antigen 4
423184NM_004428Hs.1624ephrin-A1 1.14 1.53
423217NM Hs.1640collagen, type VII, 2.14 1.69
000094 alpha 1 (epidermolys
423248AA380177Hs.125845ribulose-5-phosphate-3-epimerase7.18 14.00
423309BE006775Hs.126782sushi-repeatprotein 21.90 64.00
423361AWi70055Hs.47628ESTs 1.00 1.00
423453AW450737Hs.128791CGI-09 protein 55.52 66.00
423511AF036329Hs.i29715gonadotropin-releasing0.88 1.17
hormone 2
423516AB007933Hs.129729ligand of neuronal 1.76 5.40
niUic oxide synthase
423551AA327598Hs.233785ESTs 3.54 4.33
55423554M90516Hs.1674glutamine-fructose-6-phosphatetransamin1.00 50.00
423575C18863Hs.163443Homo Sapiens cDNA 38.88 70.00 '
FLJ11576 fis, clone
HE
423624AI807408Hs.166368ESTs 1.00 67.00
423634AW959908Hs.1690heparin-binding growth76.02 1.00
factor binding pr
423642AW452650Hs.157148hypothetical protein19.14 58.00
MGC13204
423662AA642452Hs.130881B-cell CLUlymphoma 3.61 13.57
11A (zinc finger
pro
423673BE003054Hs.1695matrix metalloproteinase240.73 40.00
12 (macrophage
423698AA329796Hs.1098DKFZp434J1813 protein1.00 59.00
423725AJ403108Hs.132127hypothetical protein4.20 1.00
LOC57822
423761NM Hs.132576paired box gene 9 1.00 1.00
006194
65d23787AJ295745Hs.236204nuclear pore complex7.i8 6.64
protein
423816AF151064 hypothetical protein1.00 44.00
423826020325Hs.1707cocaine- and amphetamine-regulated1.00 1.00
bans
d23849AL157425Hs.133315Homo Sapiens mRNA; 1.00 1.00
cDNA DKFZp761J1324
(f
423887AL080207Hs.134585DKFZP434G232 protein1.00 1.00
423934089995Hs.159234forkhead box E1 (thyroid31.33 31.00
transcription f
423954AW753164Hs.288604KIAA1632 protein 5.81 10.87
423961D13666Hs.136348osteoblast specific 3.55 3.30
factor 2 (fasciclin
424012AW368377Hs.137569tumor protein 63 233.42 68.00
kDa with strong
homolog
424016AW163729Hs.6140hypothetical protein0.93 1.01
MGC15730
75424028AF055084Hs.153692Homo Sapiens cDNA 21.30 52.00
FLJ14354 fis, clone
Y7
424046AF02786fiHs.138202serine (or cysteine)1.00 1.00
proteinase inhibito
424086AI351010Hs.102267lysyloxidase 21.91 70.00
424098AF077374Hs.139322small proline-rich 137.82 54.00
protein 3
424120T80579Hs.290270ESTs 1.00 1.00
424165AW582904Hs.142255islet amyloid polypeptide1.00 34.00
424200AA337221 gb:EST41944 Endometrial13.06 48.00
tumor Homo sapie
424279L29306Hs.1718i4tryptophan hydroxylase(tryptophan1.00 1.00
5-mon
424308AW975531Hs.154443minichromosome maintenance164.58 87.00
deficient (S.
424326NM Hs.145296disinlegrin protease53.72 302.00
014479
85424340AA339036Hs.7033ESTs 0.86 1.15
I5~
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
424351BE622117Hs.145567hypothetical protein 0.93 1.03
424364AW38322fiHs.201189ESTs, Weakly similar 7.02 3.24
to 601763 atrophin-
424381AA285249Hs.146329protein kinase Chk2 95.55 92.00
424411NM Hs.146549crystallin,betaA2 1.63 3.25
005209
424420BE614743Hs.146688prostaglandin E synthase1.63 1.33
424441X14850Hs.147097H2A histone family, 1.82 1.29
member X
424502AF242388Hs.149585lengsin 1.00 1.00
424503X06256Hs.149609integrin, alpha 5 1.02 2.24
(fibroneclin receptor,
424513BE385864Hs.149894mitochondria! iranslational1.00 17.00
initiation f
1 424539L02911Hs.150402Activin A receptor, 32.46 108.00
~ type I (ACVR1) (ALK
424568AF005418Hs.150595cytochrome P450, subfamily3.40 2.58
XXVIA, polyps
424602AK002055Hs.151046hypothetical protein 31.87 25.00
FLJ11193
424629M90656Hs.151393glutamate-cysteine 3.56 2.37
ligase, catalytic
sub
424645NM Hs.151449KIAA0535 gene product1.00 1.00
0146132
15424687J05070Hs.151738matrix metalloproteinase2.12 2.23
9 (gelatinase B
424717AW992292Hs.152213wingless-type MMTV 1.00 1.00
integration site
fami
424834AK001432Hs.153408Homo Sapiens cDNA 56.19 12.00
FLJ10570 fis, clone
NT
424840D79987Hs.153479extra spindle poles, 2.65 1.30
S. cerevisiae, homo
424867A1024860Hs.153591Not56 (D. melanogaster)-like1.23 1.05
protein
424905NM-002497Hs.153704NIMA (never in mitosis21.35 1.00
gene a)-related k
424979D87989Hs.154073UDP-galactose transporter1.36 1.35 ,
related
424999AW953120 gb:EST365190 MAGE 1.24 1.41
resequences, MAGB
Homo
425048H05468Hs.164502ESTs 1.00 11.00
425057AA826434Hs.1619achaete-scute complex7.46 87.00
(Drosophila) homol
25425081X74794Hs.154443minichromosome maintenance2.52 3.82
deficient (S.
425118AU07fi611Hs.154672methylene tetrahydrofolate4.84 4.03
dehydrogenase
425159NM_004341Hs.154868carbamoyl-phosphate 3.62 2.73
synlhetase 2, aspart
425202AW962282Hs.152049ESTs, Weakly similarl01380221.00 53.00
hypotheti
425234AW152225Hs.165909ESTs, Weakly similar 100.7744.00
to 138022 hypotheti
425236AW067800Hs.155223stanniocalcin 2 3.30 2.90
425245AI7517fi8Hs.155314KIAA0095 gene product1.91 2.32
425247NM_005940Hs.155324matrix metalloproleinase1.41 1.49
11 (stromelysin
425266J00077Hs.155421alpha-fetoprotein 1.00 68.00
425274BE281191Hs.155462minichromosome maintenance1.97 1.63
deficient (m3
35425322Ufi3630Hs.155637protein kinase, DNA-activated,141.49123.00
catalytic
425349AA425234Hs.79886ribose 5-phosphate 1.00 84.00
isomerase A (ribose
5
425371D49441Hs.155981mesothelin 0.87 1.59
425397J04088Hs.156346topoisomerase (DNA) 14,90 5.76
II alpha (170kD)
425420BE536911Hs.234545hypothetical protein 1.00 1.00
NUF2R
425424NM Hs.157199ELKL motif kinase 10.58 9.74
004954
425483AF231022Hs.158159FATtumorsuppressor(Drosophila)1.74 1.40
homolo
425566AW162943Hs.250618UL16 binding protein 1.49 1.14
2
425580L11144Hs.1907galanin 53.29 233.00
425650NM_001944Hs.1925desmoglein 3 (pemphigus33.45 1.00
vulgaris antigen
45425692D90041Hs.155956N-acetyltransferase 1.00 55.00
1 (arylamine N-acety
425695NM-005401Hs.159238protein tyrosine phosphatase,1.00 10.00
non-recept
425734AF056209Hs.159396peptidylglycine alpha-amidating1.00 41.00
monooxyg
425776U25128Hs.159499parathyroid hormone 1.00 48.00
receptor 2
425810AI923627Hs.31903ESTs 27.39 98.00
425811AL039104Hs.159557karycpherin alpha 1.99 1.58
2 (RAG cohort 1,
impor
425849A1077288Hs.296323serum/glucocorticoid 71.16 3.42
regulated kinase
4251152AK001504Hs.159651death receptor 6, 1.35 1.34
TNF superfamily member
426067AA401369Hs.190721ESTs 1.01 17.00
426088AF038007Hs.166196ATPase, Class I, type26.26 47.00
8B, member 1
55426215AW067800Hs.i55223stanniocalcin 2 1.91 2.90
426227Ufi7058Hs.154299Human proteinase activated22.40 25.00
receptor-2 mR
426269H15302Hs.168950Homo Sapiens mRNA; 1.00 1.00
cDNA DKFZp566A1046
(f
426283NM_003937Hs.169139kynureninase (L-kynurenine91.39 229.00
hydrolase)
426329AL389951Hs.271623nucleoparin 50kD 4.34 4.08
426427M86699Hs.169840TTK protein kinase 7.02 1.00
426432AF001601Hs.169857paraoxonase 2 1.16 1.68
426440BE382756Hs.169902solute tamer family 2.59 1.71
2 (facilitated glu
426459AF151812Hs.169992hypothetical 43.2 1.56 1.66
Kd protein
426471M22440Hs.170009transforming growth 20.60 26.00
factor, alpha
65426496D31765Hs.170114KIAA0061 protein 9.81 22.00
426501AA401369Hs.190721ESTs 19.23 17.00
426514BE616633Hs.170195bone morphogenetic 103.7441.00
protein 7(osleogenic
426536A1949749Hs.44441ESTs 4.65 23.00
426572AB037783Hs.170623hypothetical protein 1.00 43.00
FLJ11183
426682AVfi60038Hs.2056UDP glycosyltransferase160.068.00
1 family, polyps
426691NM_006201Hs.171834PCTAIRE protein kinase1.51 1.35
1
426746J03626Hs.2057uridine monophosphale2.13 1.68
synthetase (orotat
426752X69490Hs.172004titin 0.02 5.14
426784U03749Hs.172216chromogranin A (parathyroid1.72 1.71
secretary pr
7S426807AA385315Hs.156682ESTs 1.30 1.64
426612AF105365Hs.172613solute carver family 1.47 1.53
12 (potassiumichlo
426814AF036943Hs.172619myelin transcription 1.00 1.00
factor 1-like
426831BE296216Hs.172673S-adenosylhomocysteine1.51 1.25
hydrolase
426897AA401369Hs.190721ESTs 141.5617.00
426925NM_001196Hs.315689Homo Sapiens cDNA: 32.61 38.00
FLJ22373 fis, clone
H
426935NM-000086Hs.172928collagen, type I, 2.65 3.16
alpha 1
42&964AA393739Hs.28741fiHomo Sapiens cDNA 1.97 3.49
FLJ11439 fis, clone
HE
426966AI493134 sclerostin 1.00 1.00
426991AK001536 Homo sapiens cDNA 3.39 2.28
FLJ10674 fis, clone
NT
g5427099AB032953Hs.173560odd Ozllen-m homolog 4.24 17.00
2 (Drosophila, mows
159
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
427239BE270447Hs.174070ubiquitin carrier 1.58 1.05
protein
427260AA663848 gb:ae70bO6.s1 Stralagene1.34 1.60
schizo brain S1
427281AA906147Hs.102869ESTs 1.00 66.00
427335AA448542Hs.251677G anfigen 7B 51.83 4.00
427354T57896Hs.191095ESTs 1.17 1.95
427356AW023482Hs.97849ESTs 7.31 41.00
427376AA401533Hs.19440ESTs 1.00 57.00
427383NM_005411Hs.177582surfactant, pulmonary-associated0.42 1.32
protein
427427AF077345Hs.177936lectin, superfamily1.00 20.00
member 1 (cartilage-
10427441AA412605Hs.343879SPANX family, member1.00 1.00
C
427445X80818Hs.178078glutamate receptor,0.97 1.03
metabotropic 4
427505AA361562Hs.17876126S proteasome-associated4.60 4.04
padl homolog
427510247542Hs.179312small nuclear RNA 22.00 45.00
acfivafing complex,
po
427528AU077143Hs.179565minichromosome maintenance97.45 92.00
deficient (S.
15427546AA188763Hs.36793hypothefical protein1.50 3.24
FLJ23188
427562856424Hs.26534ESTs 6.81 40.00
427585D31152Ns.179729collagen, type X, 69.91 62.00
alpha 1 (Schmid
metaph
427660AI741320Hs.114121Homo Sapiens cDNA: 2.70 49.00
FLJ23228 fis, clone
C
427666AI791495Ns.180142calmodulin-like 1.37 1.88
skin protein
427668AA298760Hs.180191hypothetical protein29.55 67.00
FLJ14904
427677NM Hs.180296FGFRi oncogene partner3.52 2.63
007045
427701AA411101Hs.243886nuclear autoantigenic7.41 34.00
sperm protein (his
427711M31659Hs.180408solute carrier family15.84 70.00
25 (milochondrial
427719AI393122Hs.134726ESTs 7.03 4.52
25427722AK000123Hs.180479hypothetical protein2.92 1.74
FLJ20116
427747AW411425Hs.180655serinelthreonine 1.76 1.26
kinase 12
427912AL022310Hs.181097tumor necrosis factor9.63 59.00
(ligand) superfami
427961AW293165Hs.143134ESTs 41.97 118.00
428004AA449563Hs.151393glutamate-cysteine 23.82 1.00
ligase, catalytic
sub
30428023AL038843 Homo Sapiens cDNA: 1.40 1.33
FLJ23602 fis, clone
L
428046AW812795Hs.337534ESTs, Moderately 96.28 167.00
similar to 138022
hypot
428093AW594506Hs.104830ESTs 1.25 1.29
428098AU077258Hs.182429protein disulfide 1.86 1.60
isomerase-related
prot
428129AI244311Hs.26912ESTs 1.00 42.00
35428169A1928984Hs.182793golgi phosphoprotein2.76 2.11
2
428182BE386042Hs.293317ESTs, Weakly similar1.00 1.00
to GGC1 HUMAN G
ANT
428227AA3216d9Hs.2248small inducible 85.59 181.00
cytokine subfamily
B (Cy
428242H55709Hs.2250leukemia inhibitory6.57 21.64
factor (cholinergic
428330L22524Hs.2256matrix metalloproteinase7.77 15.90
7 (matrilysin,
428434AI909935Hs.65551Homo Sapiens, Similar0.58 1.43
to DNA segment,
Ch
428450NN(...014791Hs.184339KIAA0175 gene product237.53 204.00
428471X57348Hs.184510stratifin 6.00 4.60
428479Y00272Hs.334562cell division cycle56.54 16.00
2, G1 to S and
G2 to
428464AF104D32Hs.184601solute carrier family3.53 2.15
7 (cationic amino
45428505AL035461Hs.2281chromogranin B (secretogranin1.00 1.00
1)
428532AF157326Hs.184786TBP-interacfing 1.00 58.00
protein
428645AA431400Hs.98729ESTs, Weakly similar1.00 16.00
to 2017205A dihydro
428664AK001666Hs.189095similar to SALL1 1.00 1,00
(sat (Drosophila)-like
428698AA852773Hs.334838KIAA1866 protein 187.37 255.00
50428728NM_016625Hs.191381hypothefical protein47.24 80.00
428748AW593206Hs.98785Ksp37 protein 1.00 87.00
428758AA433988Hs.98502hypofhe0calprotein 1.06 1.13
FLJ14303
428771AB028992Hs.193143KIAA1069 protein 1.98 92.00
428801AW277121Hs.254881ESTs 1.67 6.15
55428610AF068236Hs.193788nitric oxide synthase1.03 1.27
2A (inducible,
hep
428839AI767756Hs.82302Homo Sapiens cDNA 124.17 43.00
FLJ14814 fis, clone
NT
428845AL157579Hs.153610KIAA0751 gene product1.00 1.00
428959AF100779Hs.194680WNT1 inducible signaling15.16 27.00
pathway protein
428969AF120274Hs.19dfi89artemin 1.36 1.24
60429038AL023513Hs.194766seizure related 0.97 3.31
gene 6 (mouse)-like
429065AI753247Hs.29643Homo Sapiens cDNA 6.82 16.47
FLJ13103 fis, clone
NT
429164AI688663Hs.116586ESTs 19.08 67.00
429170NM Hs.2359dual specificity 16.18 105.00
001394 phosphatase 4
429183A8014604Hs.197955KIAA0704 protein 79.72 104.00
65429201X03178Hs.198246group-specific component1.00 1.00
(vitamin D bind
429211AF052693Hs.198249gap junction protein,1.33 1.09
beta 5 (connexin
3
429220AW207206 ESTs 1.00 7.00
429228A1553633Hs.32fi447ESTs 39.47 29.25
429259AA420450Hs.292911ESTs, Highly similar2.01 1.18
to S60712 band-6-pr
70429263AA019004Hs.198396ATP-binding cassette,1.07 1.00
sub-family A (ABC1
429276AF05fi085Hs.198612G protein-coupled 3.70 142.00
receptor 51
429359W00482Hs.2399matrix metailoproteinase1.30 1.94
14 (membrane-in
429412NM_006235Hs.2401POU domain, class 94.09 86.00
2, associating
factor
429413NM_014058Hs.201877DESC1 protein 41.91 10.00
75429486AF155827Hs.2D3963hypotheficalprotein12.19 1.00
FLJ10339
429504X99133Hs.204238lipocalin 2 (oncogene1.61 1.08
24p3)
429538BE182592Hs.11261small proline-rich 4.43 2.90
protein 2A
429547AA401369Hs.190721ESTs 1.06 17.00
429551AW450624Hs.220931ESTs 2.89 65.00
80429563BE619413Hs.2437eukaryofic translafion1.49 1.37
inifiafion factor
429597NM_003816Hs.2442a disiniegrfn and 61.86 100.00
metalloproteinase
doma
429610AB024937Hs.211092LUNX protein; PLUNC1.59 1.69
(palate lung and
nas
429612AF062649Hs.252587pituitary tumor-Transforming2.78 1.74
1
429616AI982722Hs.120845ESTs 1.00 1.00
429656X05608Hs.211584neurofilament, light1.00 4.00
polypepfide (68kD)
160
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
429663M6887dHs.211587phospholipase A2, 69.95104.00
group IVA (cytosolic,
429736AF125304Hs.212680tumornecrosisfactorreceptorsuperfami1.25 1.21
429782NM Hs.220689Ras-GTPase-activating1.00 7.00
005754 protein SH3-domain
429903AL134197Hs.93597cyclin-dependent kinase11.801.00
5, regulatory su
429918AW873986Hs.1i9383ESTs 1.00 78.00
429978AA249027 ribosomal protein 1.98 3.09
S6
429986AF092047Hs.227277sine oculis homeobox 1.00 48.00
(Drosophila) homolo
430044AA464510Hs.152812ESTs 69.2759.00
430114AA847744Hs.99640ESTs 1.00 1.00
1 430134BE380149Hs.105223ESTs, Weakly similar 1.00 51.00
~ to T33188 hypotheti
430147860704Hs.234434hairylenhancer-of-split1.10 2.22
related with YRP
430287AW182459Hs.125759ESTs, Weakly similar 1.00 127.00
to LEU5_HUMAN LEUKE
430294AI538226Hs.32976guanine nucleotide 3.80 1.47
binding protein 4
430300U60805Hs.238648oncostatin M receptor1.00 35.00
15430315NM Hs.239147guanine deaminase 92.3128.00
004293
430337M36707Hs.239600calmodulin-like 3 1.18 1.08
430378229572Hs.2556tumor necrosisfactorreceptorsuperfami5.28 66.00
430388AA356923Hs.240770nuclear cap binding 16.7638.00
protein subunit 2,
2
430393BE185030Ns.241305estrogen-responsive 1.63 1.50
B box protein
430439AL133561 DKFZP434B061 protein 1.00 1.00
430451AA836472Hs.297939cathepsin B 1.64 2.12
430454AW469011Hs.105635ESTs 63.3544.00
430466AF052573Hs.241517polymerase (DNA directed),2.47 1.91
theta
430481AA479678Hs.203269ESTs, Moderately similar1.00 31.00
to ALUS HUMAN A
25430486BE062109Hs.241551chloride channel, 12.2841.00
calcium activated,
fam
430508A1015435Hs.104637ESTs 4.75 7.27
430533AA480895Hs.57749ESTs, Weakly similar 1.00 1.00
to T17288 hypotheti
430563AF146074Hs.108660ATP-binding cassette,1.00 1.59
sub-family C (CFTR
430677226317Hs.94560desmoglein 2 1.72 1.30
3 430678AA401369Hs.190721ESTs 0.90 17.00
0
430686NM Hs.2633desmoglein 1 1.00 1.00
001942
430788AI742925Hs.7179ESTs, Weakly similar 1.62 1.84
l0 2004399A chromos
430890X54232Hs.2699glypican 1 1.58 1.40
430935AW072916 zinc finger protein 90.28132.00
131 (clone pHZ-10)
3 430985AA490232Hs.27323ESTs, Weakly similar 0.94 1.28
70178885 serinelth
431009BE149762Hs.48956gap junction protein,60.2528.00
beta 6 (connexin
3
431089BE041395 ESTs, Weakly similar 23.32941.00
to unknown protein
431092AI332764Hs.125757ESTs 13.4663.00
431124AF284221Hs.59506doublesex and mob-3relatedtranscriptio49.4362.00
431164AA493650Hs.94367Homo Sapiens cDNA: 0.44 2,20
FLJ23494 fis, clone
L
431211M86849Hs.323733gap junction protein,182.26101.00
beta 2, 26kD (coon
431221AW207837Hs.286145SRB7 (suppressor of 4.15 13.97
RNA polymerase B,
ye
431277AA501806Hs.345824ESTs 1.00 86.00
431322AW970622 gb:EST382704 MAGE 40.55200.00
resequences, MAGK
Homo
45431342AW971018Hs.2i659ESTs 1.00 53.00
431364BE158000Hs.285026gb:MR2-HT0377-150200-202-e030.94 1.14
HT0377 Homo
431462AW583672Hs.256311granin-like neuroendocrine1.30 1.25
peptide precu
431494AA991355Hs.298312hypotheticalprotein 3.90 26.00
DKFZp434A1315
431515NM Hs.258583endothelial differentiation,1.41 1.87
012152 lysophospha
431548AI834273Hs.9711novel protein 5.66 15.00
431630NM Hs.265829integrin, alpha 3 0.99 1.44
002204 (antigen CD49C, alpha
431745AW972448Hs.163425ESTs 0.99 3.51
431770BE221880Hs.2685555'-3' exoribonuclease67.1291.00
2
431830Y16645Hs.271387small inducible cytokine3.36 4.71
subfamily A (Cy
SS4318468E019924Hs.271580uroplakin 1B 4.49 2.51
431890X17033Hs.271986integrin, alpha 2 2.20 3.32
(CD49B, alpha 2 subuni
431934A8031481Hs.272214STG protein 1.01 1.04
431958X63629Hs.2B77cadherin 3, type 1, 51.1746.35
P-cadherin (placenta
432006AL137382Hs.272320Homo sapiens mRNA; 0.94 1.65
cDNA DKFZp434L1226
(f
60432023843020Hs.236223EST 0.94 47.00
432201AI538613Hs.298241Transmembrane protease,1.10 2.24
serine 3
432210AI567421Hs.273330Homo Sapiens, clone 1.42 1.45
IMAGE:3544662, mRNA,
432226AW182766Hs.273558phosphate cytidylyltransferase1.00 1.00
1, cholin
432239X81334Hs.2936matrix metalloproteinase18.671.00
13 (collagenase
65432265BE382679Hs.285753SCG10-like-protein 1.09 1.21
432281AK001239Hs.274263hypotheticalprotein 40.9858.00
FLJ10377
432365AK001106Hs.274419hypothelicalprotein 1.00 214.00
FLJ10244
432374W68815Hs.301885Homo Sapiens cDNA 157.3437.00
FLJ11346 fis, clone
PL
432375BE536069Hs.2962S100 calcium-binding 1.65 1.06
protein P
432407AA221036 gb:zr03f12.rt Stratagene73.7175.00
NT2 neuronal pr
432441AW292425Hs.163484ESTs 56.3572.00
432489AI804855Hs.207530ESTs 1.00 24.00
432543AA552690Hs.152423Homo Sapiens cDNA: 137.7298.00
FLJ21274 fis, clone
C
432552AI537170Hs.173725ESTs, Weakly similar 1.00 31.00
to ALUB HUMAN ALU
S
75432583AW023624Hs.162282potassium channel 0.27 35.18
TASK-4; potassium
chan
432606NM-002104Hs.3066granzyme K (serine 2.87 6.22
protease, granzyme
3;
432625AI243596Hs.94830ESTs, Moderately similar26.6356.00
to T03094 A-kin
432653N62096Hs.293185ESTs, Weakly similar 1.92 5.29
to JC7328 amino aci
432677NM-004462Hs.278611UDP-N-acetyl-alpha-D-galactosamine:polyp1.00 48.00
432715AA247152Hs.200483ESTs, Weakly similar 45.1331.00
to KIAA1074 protein
432753NM Hs.336938Homo Sapiens PR00593 1.00 68.00
014075 mRNA, complete cds
432788AA521091Hs.178499Homo Sapiens cDNA: 2.69 3.67
FLJ23117 fis, clone
L
432842AW674093Hs.334822hypotheticalprotein 1.22 1.34
MGC4485
432867AW016936Hs.233364ESTs 1.00 1.00
85432917NM_014125Hs.241517PR00327 protein 10.256.62
161
CA 02444691 2003-10-17
WO 43 PCT/US02/12476
02/0864
432920037689Hs.3128polymerase (RNA) 1.44 1.30
II (DNA directed)
polyp
433001AF217513Hs.279905clone H00310 PR00310p1154.79 85.64
433023AW864793Hs.87409thrombospondin 1 20.96 100.00
433042AW193534Hs.281895Homo Sapiens cDNA 1.00 10.00
FLJ11660 fis, clone
HE
433091Y12642Hs.3185lymphocyte antigen 1.20 1.09
6 complex, locus
D
433159A8035898Hs.150587kinesin-like protein13.82 39.00
2
433183AF231338Hs.222024transcription factor1.00 69.00
BMAL2
433258AA622788Hs.203613ESTs, Weakly similar1.00 1.25
to ALUB-HUMAN !!!!
433409AI278802Hs.25661ESTs 44.81 117.00
1 433437020536Hs.3280caspase 6, apoptosis-related70.39 105.00
~ cysteine pr
433485AI493076Hs.201967aldo-keto reductase11.55 2.00
family 1, member
C2
433537A1733692Hs.112488ESTs 8.66 55.00
433547W04978Hs.303023beta tubulin 1, 25.16 83.00
class VI
433556W56321Hs.111460calciumicalmodulin-dependent1.00 19.00
prote!n kin
15433647AA603367Hs.222294ESTs 20.30 49.00
433658L03678Hs.156110immunoglobulin kappa5.92 10.03
constant
433800A1094221Hs.135150lung typeI cell 2.29 2.22 ,
membrane-associated
gly
433819AW511097Hs.112765ESTs 3.71 8.00
433862D86960Hs.3610KIAA0205 gene product62.08 104.00
2~433980AA137152Hs.286049phosphoserine aminotransferase108.91 47.00
434088AF116677Hs.249270hypothetical protein1.00 1.00
PR01966
43409dAA305599Hs.238205hypothetical protein121.27 87.00
PR02013
434105AW952124Hs.13094presenilins associated1.22 1.23
rhomboid-like pro
434217AW014795Hs.23349ESTs 14.11 57.00
25434340AI193043Hs.128685ESTs, Weakly sim!lar2.10 2.56
to T17226 hypotheti
434360AA401369Hs.190721ESTs 40.98 17.00
434414A1798376 gbar34b07.x1 NCI_CGAP1.48 1.56
Ov23 Homo sap!ens
43d42dAI811202Hs.325335Homo sapiens cDNA: 1.00 64.00
FLJ23523 fis, clone
L
434467BE552368Hs.231853Homo Sapiens cDNA 54.91 85.00
FLJ13d45 fls, clone
PL
434551BE387162Hs.280858ESTs, Highly similar2.46 2.00
to A35661 DNA excis
434627AI221894Hs.39311ESTs 1.00 1.00
434699AA643687Hs.149425Homo Sapiens cDNA 1.00 23.00
FLJ11980 fis, clone
HE
434769AA648884Hs.134278Homo Sapiens cDNA 7.08 56.00
FLJ12676 fis, clone
NT
434792AA649253Hs.132458ESTs 8.52 44.00
35434808AF155108Hs.256150Homo Sapiens, Similar11.33 1.00
to RIKEN cDNA 2810
434828D90070Hs.96phorbol-12-myristate-13-acetate-induced1.00 1.00
434876AF160477Hs.61460Ig superfamilyreceptorLNIR1.25 1.29
434891AA814309Hs.123583ESTs 1.00 6.00
434928AW015595Hs.4267Homo Sapiens clones1.00 1.00
24714 and 24715
mRNA
435013H91923Hs.110024Target CAT 1.26 1.10
435066BE261750Ns.4747dyskeratos!s congen!ta1.69 1.37
1, dyskerin
435087AW975241Hs.23567ESTs 1.00 1.00
435099AC004770Hs.4756flap structure-specific2.90 1.93
endonuclease 1
435159AA668879Hs.116649ESTs 1.00 1.00
45435205X54136Hs.181125!mmunoglobulin lambda1.02 1.46
locus
435232NM_001262Hs.4854cyclin-dependent 2.04 2.70
kinase inhibitor
2C (pi
435304H10709Hs.269524ESTs 27.58 139.00
d35313AI769400Hs.189729ESTs 1.00 14.00
435505AF200492Hs.211238interleuk!n-1 homolog1.00 38.00
1
435509AI458679Hs.181915ESTs 1.00 1.00
435525AI831297Hs.123310ESTs 1.00 56.00
435532AW291488Hs.117305Homo Sapiens, clone1.00 2.00
IMAGE:3682908,
mRNA
435550AI224456Hs.324507H.sap!ens polyA 3.42 3.92
site DNA
435602AF217515Hs.283532uncharacterised 3.95 1.80
bone marrow protein
BM03
55435766811673Hs.186498ESTs 1.00 28.00
435793A8037734Hs.4993KIAA1313 protein 23.68 42.00
436069A1056879Hs.263209ESTs 1.00 58.00
436170AW450381Hs.14529ESTs 1.00 18.00
436211AK001581Hs.334828hypothetical protein5.84 22.00
FLJ107i9; KIAA1794
6~436213RA325512Hs.71472hypothetical protein1.42 1.27
FLJ10774; KIAA1709
436217T53925Hs.107fibrinogen-like 57.97 31.00
1
436238AK002163Hs.301724hypothetical protein2.51 1.71
FLJ11301
436251BE515065Hs.296585nucleolar prote!n 2.33 1.64
(KKEID repeat)
436291BE568452Hs.344037protein regulator 108.99 52.00
of cytokinesis
1
65436302AL355841Hs.99330hypothetical protein0.75 2.81
FLJ23588
436396AW992292Hs.152213wingless-type MMN 60.01 1.00
integration s!te
fami
436414BE264633Hs.143638WD repeat domain 2.50 2.19
4
436419AI948626Hs.171356ESTs 0.95 1.33
436443AW138211Hs.128746ESTs 1.12 9.26
436474AJ270693Hs.199887ESTs 1.00 1.00
436481AA379597Hs.5199HSPC150 protein 3.28 1.56
similar to ubiquitin-con
436486AA742221Hs.120633ESTs 1.00 19.00
436511AA721252Hs.291502ESTs 16.76 14.00
436553X57809Hs.181125immunoglobulin lambda1.08 1.74
locus
75436557W15573Hs.5027ESTs, Weakly similar19.20 9.75
to A47582 B-cell
g;
436608AA628980 down syndrome criflcal33.92 25.00
region protein
DS
436667AW025183Hs.127680ESTs 0.89 1.19
436771AW975687Hs.292979ESTs 1.00 10.00
436839AA401369Hs.190721ESTs 1.00 17.00
436887AW953157Hs.193235hypothetical protein1.06 1.15
DKFZp547D155
436944AW268614Hs.5840ESTs 1.00 1.00
436961AW375974Ns.156704ESTs 25.13 25.00
436972AA284679Hs.25640claudin 3 1.59 1.46
437016AU076916Hs.5398guan!ne monphosphate2.35 1.76
synthetase
85437044AL035864Hs.69517cDNA for differenflally1.34 1.13
expressed C016
g
162
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
437181AI306615Hs.125343ESTs, Weakly similar1.00 17.00
to KIAA075B protein
437204AL110216Hs.22826ESTs, Weakly similar40.55 82.00
to 155214 salivary
437205AL110232Hs.279243Homo sapiens mRNA; 1.00 112.00
cDNA DKFZp564D2071
(f
437259AI377755Hs.120695ESTs 1.00 205.00
437270818087Hs.323769cispia8n resistance 1.56 1.54
related protein
CRR
437271AL137445Hs.28846Homo Sapiens mRNA; t 13.25125.00
cDNA DKFZp5660134
(Fr
437370AL359567Hs.161962Homo Sapiens mRNA; 1.82 4.57
cDNA DKFZp547D023
(fr
437390AI125859Hs.112607ESTs 1.35 1.75
437412BE069288Hs.34744Homo Sapiens mRNA; 3.58 3.20
cDNA DKFZp547Ct36
(fr
1 437435AI306152Hs.27027hypotheticalprotein 3.03 1,08
~ DKFZp762H1311
437444H46008Hs.31518ESTs 1.00 39.00
437568AI954795Hs.156135ESTs 1.00 19.00
437623063880Hs.5719chromosome condensation-related1.95 1.57
SMGasso
437789AI581344Hs.127812ESTs, Weakly similar1.00 3.00
to T17330 hypotheti
15 437814Ai088192Hs.135474ESTs, Weakly similar1.00 45.00
to DDX9_HUMAN ATP-D
437840AA884836Hs.292014ESTs 1.07 1.76
437852BE001836Hs.256897ESTs, Weakly similar1.68 3.26
to 4J365012.1 [H.sa
437879BE262082Hs.5894hypothetical protein1.87 2.52
FLJ10305
437915AI637993Hs.202312Homo Sapiens clone 74.05 35.00
N11 NTera2D1 teratoca
437916BE566249Hs.20999hypotheticalprotein 23.15 89.00
FLJ23142
437937A1917222Hs.121655ESTs 1.00 1.00
437942A1888256Hs.307526ESTs 12.28 31.00
438091AW373062 nuclear receptor 1.53 10.85
subfamily 1, group
I, m
438113AI467908Hs.8882ESTs 1,80 2.39
25 438119AW963217Hs.203961ESTs, Moderately 22.67 36.90
similar to AF116721
89
438274AI918906Hs.55080ESTs 1.00 1.00
438378AW970529Hs.86434hypothetical protein38.92 38.00
FLJ21816
438403AA806607Hs.292206ESTs 1.00 1.00
438494AA908678Hs.130183ESTs 2.05 80.00
3~ 438546AW297204Hs.125811ESTs 1.00 131.00
438552AJ245820Hs.6314type I transmembrane1.43 1.45
receptor (seizure-r
438702AI879064Hs.54618ESTs 1.00 34.00
438724AW612553Hs.114670Human DNA sequence 1.33 1.10
from clone RP11-16L21
438746AI885815Hs.184727Human melanoma-associated2.42 1.59
antigen p97 (m
35 438779NM_003787Hs.6414nucleolar protein 1.00 18.00
4
438621AA826425Hs.i92375ESTs 2.03 2.57
438885A1886558Hs.184987ESTs 6.42 88.00
438898AA401369Hs.190721ESTs 22.41 17.00
438915AA280174Hs.285681Williams-Beuren syndrome1.00 1.00
chromosome regi
438956W00847Hs.135056Human DNA sequence 2.20 1.88
from clone RP5-850E9
439000AW979121 gb:EST391231 MAGE 2.78 4.81
resequences, MAGP
Homo
439023AA745978Hs.28273ESTs 1.17 1.31
439024896696Hs.35598ESTs 1.00 28.00
439128A1949371Hs.153089ESTs 1.00 67.00
45 439146AW138909Hs.156110immunoglobulinkappaconstant1.38 1.41
439223AW238299Hs.250618UL16 binding protein1.93 1.64
2
439285AL133916 hypothetical protein46.23 139.00
FLJ20093
439318AW837046Hs.6527G protein-coupled 2.00 2.2D
receptor 56
439343AF086161Hs.114611hypotheticaiprotein 6.10 7.37
FLJ11808
439394AA401369Hs.190721ESTs 3.39 17.00
439410AA632012Hs.188746ESTs 1.83 3.07
439451AF086270Hs.278554heterochromatin-like23.28 52.00
protein 1
439452AA918317Hs.579B7B.cell CLLllymphoma 18.76 122.00
11 B (zinc finger
pro
4394538E264974Hs.6566thyroid hormone recepfor2.78 1.58
interactor 13
439477W69813Hs.58042ESTs, Moderately 1.22 1.44
5 similar to GFR3_HUMAN
G
439492AF086310Hs.103159ESTs 7.46 39.00
439523W72348Hs.185029ESTs 1.00 1.19
439592AF086413Hs.58399ESTs 1.00 1.00
439606W79123Hs.5856iG protein-coupled 33.61 1.00
receptor 87
439670AF088076Hs.59507ESTs, Weakly similar1.00 1.00
to AC004858 3 Ut
sm
439702AW085525Hs.134182ESTs 4.30 10.00
439706AW872527Hs.59761ESTs, Weakly similar86.55 11.00
to DAPt HUMAN DEATH
439738BE246502Hs.9598sema domain, immunoglobulin2.36 1.88
domain (1g),
439750AL359053Hs.57664Homo sapiens mRNA 2.02 6.08
full length insert
cDN
65 439759AL359055Hs.67709Homo Sapiens mRNA 1.00 21.00
full length insert
cDN
439780AL109688 gb:Homo Sapiens mRNA7.27 25.00
full length insert
439840AW449211Hs.105445GDNF family receptor1.00 1.00
alpha 1
439926AWOi4875Hs.137007ESTs 32.58 71.00
439963AW247529Hs.6793platelet-activating 21.28 9.55
factor acetylhydrola
439979AW600291Hs.6823hypothetical protein68.83 61.00
FLJ10430
440006AK000517Hs.6844hypothetical protein1.83 4.02
FLJ20510
440028AW473675Hs.125843ESTs, Weakly similar1.42 2.54
to T17227 hypotheti
440106AA864968Hs.127699KIAA1603 protein 1.00 54.00
440138AB033023Hs.318127hypothetical protein24.18 52.00
FLJ 10201
75 440273AI805392Hs.325335Homo sapiens cDNA: 3.21 4.72
FLJ23523 gs, clone
L
440289AW450991Hs.192071ESTs 38.63 113.00
440325NM-003812Hs.7164a distntegrin and 62.88 147.00
metalloproteinase
doma
440492839127Hs.21433hypothetical protein2.35 3.62
DKFZp547J036
440527AV657117Hs.184164ESTs, Moderately 10.84 57.00
similar to S65657
alpha
440659AF134160Hs.7327claudin 1 3.18 2.37
440704M69241Hs.i62insulin-like growth 2.89 2.09
factor binding prole
440943AW082298Hs.146161hypothetical protein2.02 1,41
MGC2408
440994AI160011Hs.272068ESTs 1.29 1.14
441020AA401369Hs.190721ESTs 142.9917.00
g5 441031A1110684Hs.7645fibrinogen, B beta 1.41 99.00
' polypeplide
163
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
441128AA570256 ESTs, Weakly similar4.13 3.50
to T23273 hypotheti
441290W27501Hs.89605cholinergic receptor,1.00 1.00
nicotinic, alpha
p
441362BE614410Hs.23044RAD51 (S. cerevisiae)130.2343.00
homolog (E toll
Re
441377BE218239Hs,202656ESTs 22.03 i.OD
441390AI692560Hs.131175ESTs 3.65 7.70
441497851064Hs.23172ESTs 1,00 1.00
441525AW241867Hs.127728ESTs 1.53 1.42 '
441553AA281219Hs.121296ESTs 1.89 1.57
441607NM Hs.7912neuronal cell adhesion1.47 2.11
005010 molecule
1 441633- Hs.112242normal mucosa of 216.22363.00
~ AW958544 esophagus specific
1
441636AA081846Hs.7921Homo Sapiens mRNA; 2.31 2.05
cDNA DKFZp566Ei
83 (fr
441737X79449Hs.7957adenosine deaminase,1.30 1.49
RNA-specific
441790AA401369Hs.190721ESTs 44.15 17.00
441801AW2d2799Hs.86366ESTs 1.00 1.00
1 441919A1553802Hs.128121ESTs 1.00 122.00
~J
441937841782Hs.22279ESTs 0.86 1.37
441954AI744935Hs.8047Fanconi anemia, complementation1.48 1.39
group G
442025AW887434Hs.11810CDA11 protein 1.00 46.00
442029AW956698Hs.1d456neural precursor 9.92 45.00
cell expressed,
develop
442072A1740832Hs.12311Homo Sapiens clone 25.05 77.00
23570 mRNA sequence
442108AW452649Hs.16631dESTs 3.61 3.14
442117AW664964Hs.128899ESTs 3.00 5.49
442137AA977235Hs.128830ESTs, Weakly similar1.00 1.00
to 1192-HUMAN ZINC
442159AW163390Hs.278554heterochromafin-like1.92 1.66
protein 1
25 442179AA983842Hs.333555chromosome 2 open 27.22 50.00
reading frame 2
442328AI952430Hs.150614ESTs, Weakly similar5.00 3.42
to ALU4-HUMAN ALU
S
442432BE093589Hs.38178hypothetical protein181.5976.00
FLJ23d68
442530AI580830Hs.176508Homo Sapiens cDNA 10.59 144,00
FLJ14712 fis, clone
NT
442547AA306997Hs.217484ESTs, Weakly similar109.2398.00
to ALU1 HUMAN ALU
S
442556AL137761Hs.8379Homo Sapiens mRNA; 1.00 53.00
cDNA DKFZp586L2d2d
(f
442619AAd47492Hs.20183ESTs, Weakly similar29.02 50.00
to AF1fi47931 prote
442710A1015631Hs.23210ESTs 1.00 19.00
442717888362Hs.180591ESTs, Weakly similar1.00 5.00
to T23976 hypothefi
442875BE623003Hs.23625Homo Sapiens clone 22.85 50.00
TCCCTA00142 mRNA
sequ
35 442914AW188551Hs.99519hypothetical protein25.33 82.D0
FLJ14007
442932AA457211Hs.8858bromodomain adjacent3.18 4.41
to zinc finger doma
442942AW167087Hs.131562ESTs 8.45 64.00
443068A1188710 ESTs 1.00 27.00
443204AW205878Hs.29643Homo Sapiens cDNA 1.00 24.0D
FLJ13103 fis, clone
NT
4~ 443211AI128388Hs.1d3655ESTs 12.42 2.00
443247BE614387Hs.333893c-Myc target JP01 128.8496.00
443324844013Hs.164225ESTs 0.02 4.59
443383AI792453Hs.166507ESTs 1.00 47.00
443400828424Hs.250648ESTs 18.52 61.00
45 443426AF098158Hs.9329chromosome 20 open 4.02 1.75
reading frame 1
443572AA025610Hs.9605cleavage and polyadenylation2.98 2.57
specific fa
443575A1078022Hs.269636ESTs, Weakly similar1.00 29.00
to ALUt HUMAN ALU
S
443614AV655386Hs.7645fibrinogen, B beta 1.00 16.00
polypeptide
443633AL031290Hs.9654similar to pregnancy-associated1.00 39.00
plasma p
443648A1085377Hs.143610ESTs 39.81 70.00
443715A1583187Hs.9700cyclin E1 48.74 7.00
443723AI144442Hs.157144syntaxin 6 1.29 1.30
443802AW504924Hs.9805KIAA1291 protein 1.75 1.61
443859NM_013409Hs,9914follistatin 1.35 1.13
55 443892AA4D1369Hs.190721ESTs 1.00 17.00
443947W24187 gb:zb47f09.ri Soares_fetal_lung_NbHLI9W1.33 1.64
443991NAd.-002250Hs.10082potassium intermediatelsmall5.71 6.87
conductance
444006BE395085Hs.10086type I transmembrane1.47 1.92
protein Fn14
444009A1380792Hs.135104ESTs 1.90 77.00
444017U04840Hs.214neuro-ontologicalventralantigen1.00 1.00
1
444127N63620Hs.13281ESTs 1.00 29.00 ,
444129AW294292Hs.256212ESTs 1.00 1.00
444279U62432Hs.89605cholinergic receptor,0.60 7.80
nicotinic, alpha
p
444371BE540274Hs.239forkhead box M1 2.91 1.14
65 444378841339Hs.12569ESTs 1.00 1.00
444381BE387335Hs.283713ESTs, Weakly similar469.0055fi.D0
to S64054 hypotheti
444461853734Hs.25978ESTs, Weakly similar12.88 105.00
to 2109260A B cell
444471A8020684Hs.11217KIAA0877 protein 24.91 90.00
444489AI151010Hs.157774ESTs 1.00 111.00
70 444619BE538082Hs.8172ESTs, Moderately 1.00 70.00
similar to A46010
X-tin
444665BE613126Hs.47763B aggressive lymphoma30.56 139.00
gene
444707AI188613Hs.41690desmocollin 3 1.00 1.00
444735BE019923Hs.243122hypothetical protein77.02 90.00
FLJ13057 similaric
444781NM_014400Hs.11950GPI-anchored metastasis-associated1.57 1.31
prote
75 444783AK00146fiHs.62160anillin (Drosophila 77.55 2.00
Scraps homology,
act
445236AK001676Hs.12457hypothetical protein1.00 27.00
FLJ10814
445258AI635931Hs.147613ESTs 1.00 73.00
445413AA151342Hs.12677CGl-147 protein 28,14 50.00
445417AK001058Hs.12680Homo Sapiens cDNA 1.81 2.62
FLJ1019fi fis, clone
HE
445443AV653838Hs.322971ESTs 1.00 1.00
445462AA378776Hs.288649hypotheficalprotein 2.09 1.70
MGC3077
445517AF208855Hs.12830hypotheficalprotein 1.87 70.00
445537AJ245671Hs.12844EGF-like-domain, 1.71 2.72
mulfiple 6
445580AF167572Hs.12912skbl (S.pombe) homolog1.52 1.34
85 445654X91247Hs.13046thioredoxin reductase1.51 1.52
1
164
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
445669AI570830Hs.174870ESTs 10.95 11.45
4458188E045321Hs.136017ESTs 1.00 1.00
445873AA250970Hs.251946poly(Aj-binding protein,49.42 54.00
cytoplasmic 1-I
445885AI734009Hs.127699KIAA1603 protein 1.00 132.00
445898AF070623Hs.13423Homo sapiens clone 1.00 1.00
24468 mRNA sequence
445903AI347487Hs.132781classlcytokine receptor1.00 36.00
445932BE046441Hs.333555Homo Sapiens clone 2.41 2.88
24859 mRNA sequence
445962BE410233Hs.13501peccadillo (zebrafish)1.60 1.35
homolog 1, contai
446078AI339982Hs.156061ESTs 1.00 42.00
1~446102AW168067Hs.317694ESTs 1.00 1.00
446157BE270828Hs.131740Homo Sapiens cDNA: 1.70 1.53
FLJ22562 fis, clone
H
446269AW263155Hs.14559hypothetical protein73.01 48.00
FLJ10540
446292AF081497Hs.279682Rh type C glycoprotein1.55 1.26
446293AI420213Hs.149722ESTs 1.00 2.00
1 446423AW139655Hs.150i20ESTs 1.10 4.19
446428AW082270Hs.12496ESTs, Weakly similar0.53 3.26
to ALU4_HUMAN ALU
S
446432AI377320Hs.150058ESTs 1.00 5,00
446528AU076640Hs.15243nucleolar protein 1.36 1.31
1 (120kDj
446574AI310135Hs.335933ESTs 3.89 72.00
446619AU076643Hs.313secreted phosphoprotein32.03 20.23
1 (osteopontin,
446636AC002563Hs.15767citron (rho-interacting,4.19 5.07
serinelthreonin
446783AW138343Hs.141867ESTs 2.82 9.47
446839BE091926Hs.16244mitotic spindle coifed-coil110.2828.00
related prot
446849AU076617Hs.16251cleavage and polyadenylation3.26 2.94
specific fa
25446856AI814373Hs.164175ESTs 6.38 11.30
446872X97058Hs.16362pyrimidinergic receptor1.98 2.03
P2Y, G-protein c
446880AI8118D7Hs.108646Homo Sapiens cDNA 94.90 113.00
FLJ14934 Tic, clone
PL
446921AB012113Hs.16530small inducible cylokine1.67 3.90
subfamily A (Cy
446989AK001898Hs.16740hypothetical protein2.82 3.12
FLJ11036
447022AW291223Hs.157573ESTs 1.00 170.00
447033AI357412Hs.157601ESTs 7.15 107.00
447076AW885727Hs.9914ESTs 47.24 24.00
447061Y13896Hs.17287potassium inwardly-rectifying0.12 17.88
channel, s
447131NM Hs.17466retinoic acid receptor0.97 1.48
004585 responder (tazaro
3 447149BE299857Hs.326TAR (HIV) RNA-binding1.24 1.26
5 protein 2
447153AA8D5202Hs.315562ESTs 1.00 54.00
447164AF026941Hs.17518Homo Sapiens cig5 1.00 67.00
mRNA, partial sequence
447178AW594641Hs.192417ESTs 3.42 50.00
447250AI878909Hs.178B3protein phosphatase 1.60 1.52
1 G (formerly 2C),
ma
447289AW247017Hs.36978melanoma antigen, 1.00 1.00
family A, 3
447342AI199268Hs.19322Homo Sapiens, Similar28.63 1.00
to RIKEN cDNA 2010
447343AA256641Hs.236894ESTs, Highly similar146.6251.00
to S02392 alpha-2-m
447350A1375572Hs.172634ESTs 1.00 12.00
447377N27687Hs.334334transcription factor2.55 63.00
AP-2 alpha (acifvat
45447415AW937335Hs.28149ESTs, Weakly similar0.91 1.13
to KF3B HUMAN KINES
447425A1963747Hs.18573acylphosphatase 1, 1.00 35.00
erythrocyte (common)
447519U46258Hs.339665ESTs 59.89 49.00
447532AK000614Hs.1B791hypothelicalprotein 1.23 1.63
FLJ20607
447534AA401369Hs.190721ESTs 1.00 17.00
447636Y10043 high-mobility group 1.41 1.11
(nonhistone chromoso
447688N87079Hs.19236Target CAT 1.00 39.00
447733AF157482Hs.19400MAD2 (mitotic arrest1.17 1.12
deficient, yeast,
h
447769AW873704Hs.320S31Homo sapiens cDNA 6.47 5.95
FLJ14597 Tic, clone
NT
447802AW593432Hs.161455ESTs 0.73 2.34
5 447850AB018298Hs.19822SEC24 (S. cerevisiae)86.45 116.00
5 related gene Tamil
447924AI817226Hs.313413ESTs, Weakly similar1.00 1.00
to T23110 hypotheti
447973AB011169Hs.20141similar to S. cerevisiae3.50 4.27
SSM4
448030N30714Hs.325960membrane-spanning 4.13 142.00
4-domains, subfamily
A
448105A1538613Hs.298241Transmembrane protease,1.15 2.24
serine 3
6~448243AW369771Hs.52620integrin, beta 8 15.84 1.00
448278W07369Hs.11782ESTs 0.97 1.90
448290AK0021D7Ns.20843Homo Sapiens cDNA 1.00 1.00
FLJ11245 Tic, clone
PL
448296BE622756Hs.10949Homo Sapiens cDNA 2.42 2.17
FLJ14162 Tic, clone
NT
448357BE274396Hs.108923RA838, member RAS 1.44 1.08
oncogene family
65448390AL035414Hs.21068hypothetical protein1.00 43.00
448469AW504732Hs.21275hypothetical protein2.63 2.49
FLJ11011
448569BE382657Hs.21486signal transducer 1.84 2.53
and activator of
franc
448663BE614599Hs.106823hypothetical protein3.29 46.00
MGC14797
448672AI95551iHs.225106ESTs 1.00 21.00
448733NM-005629Hs.187958solute carrier family1.82 1.08
6 (neurotransmitte
448741BE614567Hs.19574hypothetical protein2.48 1.92
MGC5469
448757AI366784Hs.d8820TATA box binding 23.53 20.00
protein (TBP)-associate
448775AB025237Hs.388nudix (nucleoside 2.34 1.97
diphosphate linked
mot
448826AI580252Hs.2932d6ESTs, Weakly similar74.07 62.67
to putative p150
[H
75448830AL031658Hs.22181hypothetical protein1.37 1.31
4J310013.3
448644AI581519Hs.177164ESTs 1.00 31.00
448988Y09763Hs.22785gamma-aminobutyric 1.84 1.95
acid (GABA) A recepto
448993AI471630 KIAA0144 gene product1.63 1.49
449003X76342Hs.389alcohol dehydrogenase1.00 1.00
7 (class IV), mu
o
449029N28989Ns.22891solute comer family 1.91 2.26
7 (cationic amino
449040AF040704Hs.149443putativetumorsuppressor0.97 1.56
449048245051Hs.22920similar to 568401 27.13 90.00
(cattle) glucose
induc
449053AI625777Hs.344766ESTs 8.33 44.00
449054AF148848Hs.22934myoneurin 73.85 104.00
g5449101AA205847Hs.23016G protein-coupled 2.58 27.00
receptor
165
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
449167705095Hs.19597KIAA1694 protein 1.61 2.36
449207AL044222Hs.23255nucleoporin 155k0 2.36 1.56
449228AJ403107Hs.148590protein related with1.15 1.15
psoriasis
449230BE613348Hs.211579melanoma cell adhesion206.65151.00
molecule
449305AI638293 gbat09b07.x1 NCI-CGAP_GC617.28 45.00
Homo Sapiens
449318AW236021Hs.78531Homo sapiens, Similar26.39 35.00
to RIKEN cDNA 5730
449448060730Hs.57471ESTs 1.00 1.00
449467AW205006Hs.197042ESTs 1.00 1.00
449523NM Hs.54443chemokine (GC motif)56.80 216.86
000579 receptor 5
1 449722BE280074Hs.23960cyclin Bt 150.031.00
~
449976H06350Hs.135D56Human DNA sequence 2.16 2.85
from clone RP5-850E9
450001NM_001044Hs.406solute carrier family1.17 1.46
6 (neurotransmitte
450098W27249Hs.8109hypothetical protein1.79 2.38
FLJ21080
450101AV649989Hs.24385Human hbc647 mRNA i.00 69.00
sequence
15 450149AW969781Hs.132863Zic family member 1.00 1.00
2 (odd-paired Drosophi
450193AI916071Hs.15607Homo sapiens Fanconi29.85 34.00
anemia complementat
450221AA326102Hs.24641cytoskeleton associated1.00 1.00
protein 2
450372BE218107Hs.202436ESTs 1.00 1.00
450375AA009647Hs.8850a disintegrin and 51.26 93.00
metalloproteinase
doma
20 450447AF212223Hs.25010hypothetical protein123.20181.00
P15-2
450568AL050078Hs.25159Homo Sapiens cDNA 1.00 19.00
FLJ 10784 fis, clone
NT
450589AI701505Hs.202526ESTs t.00 23.00
450684AA872605Hs.25333interleukin 1 receptor,1.00 100.00
type II
450701H39960Hs.288467Homo Sapiens cDNA 1.89 1.55
FLJ12280 fis, clone
MA
2$ 450705U9D304Hs.25351Iroquois homeobox 1.00 45.00
protein 2A (IRX-2A)
(
450832AA401369Hs.190721ESTs 25.17 17.00
450937849131Hs.26267ATP-dependantinterferonresponse90.92 90.00
protei
450983AA3D5384Hs.25740ER01 (S. cerevisiaej-tike3.33 1.70
451105AI761324 gb:wi60b11.x1 NCI_CGAP_Col615.02 124.00
Homo Sapiens
451110AI955040Hs.265398ESTs, Weakly similar1.00 143.00
to transformation-r
451253H48299Hs.26126claudin 10 3.02 2.29
451291839286Hs.6702ESTs 1.00 1.00
451320AW498974 diacylglycerol kinase,2.92 18.00
zeta (104k0)
451380H09280Hs.13234ESTs 6.90 6.67
35 451386AB029006Hs.26334spasifc paraplegia 35.75 72.00
4 (autosomal dominant
451437H24143Hs.31945hypothetical protein1.00 69.00
FLJ11071
451462AK000367Hs.26434hypotheGcalprotein 1.83 2,10
FLJ20360
451524AK001466Hs.26516hypothetical protein1.13 1.07
FLJ1060d
451541BE279383Hs.26557plakophilin 3 1.88 1.33
451592A1805416Hs.213897ESTs 1.00 1.00
451635AA018899Hs.127179cryptic gene 1.52 1.92
451743AA401369Hs.190721ESTs 4.95 17.00
451806NM_003729Hs.27076RNA 3'-terminal phosphate13.55 31.00
cyclase
451807W52854 hypothetical protein1.55 35.00
FLJ23293 similar
to
45 451871AI821005Hs.118599ESTs 1.81 2.53
451952AL120173Hs.301663ESTs 1.00 22.00
452012AA307703Hs.279766kinesin family member3.43 2.26
4A
452046ABD18345Hs.27657KIAA0802 protein 56.59 19.00
452194AI694413Hs.332649olfactory receptor, 1.67 4.09
family 2, subfamily
452206AW340281Hs.33074Homo Sapiens, clone 9.31 53.00
IMAGE:3606519, mRNA,
452240AA401369Hs.190721ESTs 13.42 17.00
452256AK000933Hs.28661Homo Sapiens cDNA 39.03 94.00
FLJ10071 fis, clone
HE
452281793500Hs.28792Homo Sapiens cDNA 153.01340.00
FLJ11041 tis, clone
PL
452291AF015592Hs.28853CDC7 (cell division 1.95 23.00
cycle 7, S. cerevisi
452295BE379936Hs.28866programmed cell death42.33 61.00
S 10
452304AA025386Hs.61311ESTs, Weakly similar1.17 2.14
to S10590 cysteine
452340NM Hs.505ISL1 transcription 1.00 13.00
002202 factor, LIMlhomeedoma
452349A8028944Hs.29189ATPase, Gass VI, 1.09 1.42
type 11A
452367U71207Hs.29279eyes absent (Drosophila)54.49 53.00
homolog 2
452401NM_007115Hs.29352tumor necrosis factor,1,00 32.00
alpha-induced pro
452410AL133619 Homo Sapiens mRNA; 1.26 1.99
cDNA DKFZp434E2321
(f
452461N78223Hs.108106transcription factor24.47 35.00
452571W31518Hs.34665ESTs 54.61 102.00
452613AA461599Hs.23459ESTs 1.39 1.32
65 452699AW29539DHs.213062ESTs 1.00 26.00
452705H49805Hs.246005ESTs 1.00 1.00
452747AF160477Hs.61460i0 superfamilyreceptor112.871.29 .
LNIR
452787AW294022Hs.222707KIAA1718 protein 1.00 1.00
452795AW392555Hs.18878hypothetical protein1.00 1.00
FLJ21620
452823A8012124Hs.30696transcription factor-like7.91 75.00
5 (basic helix
452833BE55968iHs.30736KIAA0124 protein 3.16 1.92
452838U65011Hs.30743preferentially expressed174.351.00
antigen in mela
452862AA401369Hs.190721ESTs 98.26 17.00 '
452865AW173720Hs.345805ESTs, Weakly similar1.55 1.00
to A47582 B-cell
0r
75 452934AA581322Hs.4213hypothetical protein1.73 1.19
MGC16207
452946X95425Hs.31092EphA5 1.00 1,00
452976844214Ns.101189ESTs 1.58 1.98
453028AB006532Hs.31442RecO protein-like 1.80 1.60
4
453095AW295660Hs.252756ESTs 0.77 1.50
$~ 453102NM_007197Hs.31664frizzled (Drosophilaj1.00 1.00
homolog 10
453103AI301052Hs.153444ESTs 1.00 1.00
453120AA292891Hs.31773pregnancy-induced 1.23 1.20
growth inhibitor
453153N53893Hs.24360ESTs 1.00 83.00
453160A12633D7Hs.239884H2B histone family, 1.00 30.00
member L
$ 453197AI916269Hs.109057ESTs, Weakly similar1.00 134.00
5 fo ALU5_HUMAN ALU
S
166
CA 02444691 2003-10-17
WO 43 PCT/US02/12476
02/0864
453210AL13316iHs.32360hypothetical protein1,69 1.93
FLJ10867
453240Ai969564Hs,166254hypotheticaiprotein 1.00 1.00
DKFZp5661133
453317NM_002277Hs.41896keraUn, hair, acidic,11.19 1.27
453323AF034102Hs.3295isolute carrier family4.90 4.11
29 (nucleoside tra
453331AI240665Hs.8850ESTs 199.42340.00
453392023752Hs.32964SRY (sex determiningt.00 16.00
region Y)-box 11
453431AF094754Hs.32973glycine receptor, 1.00 1,00
beta
453439AI572438Hs.32976guanine nucleo5de 3.44 5.17
binding protein
4
453459BE047032Hs.257789ESTs 2.84 5.58
1 453563AW608906.comp Hs.i 81163 hypothetical
~ protein
MGC5629
4.58
90.00
453633AA357001Hs.34045hypothetical protein1.74 1.60
FLJ20764
453775NM-002916Hs.35120replication factor 19.49 1.00
C (activator 1)
4 (37
453830AA534296Hs.20953ESTs 24.92 25.00
453857AL080235Hs,35861DKFZP586E7621 protein167.5966.00
1 453867A1929383Hs.33032hypotheticalprotein 1.00 39.00
DKFZp434N185
453883A1638516Hs.3d7524cofactor required 1.97 1.58
for Sp1 transcriptions
453884AA355925Hs.36232KIAA0186 gene product63.89 20.00
453900AW003582Hs.226414ESTs, Weakly similar20,41 16.00
to ALUB_HUMAN ALU
S
453922AF053306Hs,36708budding uninhibited 7.D9 22.00
by banzimidazoles
1
453941039817Hs.36820Bloom syndrome , 29.75 19.00
453964AI961486Hs.12744ESTs 1,00 1.00
453968AA8d7843Hs.62711Homo Sapiens, clone 2.06 1.81
IMAGE;3351295, mRNA
453976BE463830Hs.163714ESTs 3.02 131.00
454024AA993527Hs.293907hypothetical protein1.00 131.00
FLJ23403
25454034NM_000691Hs.575aidehyde dehydrogenase1.23 1.02
3 family, member
454042719228Hs.172572hypothetical protein30.63 171.00
FLJ20093
454059NM_00315dHs.37048staiherin 1.00 1.00
454066X00356Hs.37058calcitoninlcalcitonin-related1.01 1.45
polypeptid
454098W27953Hs.292911ESTs, Highly similar1.26 1.11
to S60712 band-6-pr
3d454241BE144666 gb:CM2-HT0176-041099-017-cD26.33 5.04
HT0176 Nomo
454417AI244459Hs.110826trinucleotiderepeatcontaining94.30 7.82
454439AW819152Hs.154320DKFZP56601646 protein1.00 1.00
455175AW993247 gb:RC2-BN0033-180200-014-h0913.75 103.00
BN0033 Homo
455601A1368680Hs.816SRY (sex determining206.111.00
rogion Y)-box 2
35456237AA203682 gb:zx52e07.r1 Soares1.00 1.00
fetai_liver_spleen_
456321NM Hs.87225cancerltestis antigen1.14 1.10
001327
456475NM_000144Hs.95998Friedreich ataxia 1.00 48.00
456508AA502764Hs.i23469ESTs,WeaklysimilartoAF2088551BM-Ot162.25189.00
456534X91195Hs,100623phospholipase C, 2.12 1.80
beta 3, neighbor
pseudo
456736AW248217Hs.1619achaete-scute complex1.15 1.94
(Drosophila) homoi
456759BE259150Hs.127792delta (Drosophila)-like1.00 1.00
3
456990NM Hs.171545HIV-1 Rev binding 16.42 84,00
004504 protein
457200033749Hs.197764thyroid transcription0.57 1.76
factor 1
457234AW968360Hs.14355Homo Sapiens cDNA 2.71 4.15
FLJ13207 fls, clone
NT
45457465AW301344Hs.122908DNA replication factor46.37 47.00
457489AI693815Hs.127179cryptic gene 1.12 1.35
457646AA725650Hs.112948ESTs 1.55 2,51
457733AW974812Hs.291971ESTs 1.00 55.00
457819AA057484Hs.35406ESTs, Highly similar4.36 3.18
to unnamed protein
458092BE545684Hs.343566KIAAD251 protein 1.00 1.32
4580988E550224 metalloihionein 1 1.00 22,00
E (functional)
458207728472Hs.7655U2 small nuclear 2.06 1.88
ribonucleoprotein
auxil
458242BE299588Hs.28465Homo Sapiens cDNA: 1,00 1.0D
FLJ21869 Bs, clone
H
458247814439Hs.209194ESTs 7.00 9.85
55458679AW975460HS.142913ESTs 1.00 3,00
458778AW451034Hs.326525arylsulfatase D 1.31 2.01
458933AI638429Hs,24763RAN binding protein 1,98 1.71
t
459352AW810383Hs.206828ESTs 12.60 63,00
459670FD1020Hs,172004titin 1.00 1.00
459702AI204995 gb:an03c03.x1 Siralagene1.00 237.00
schizo brain S1
TABLE 9B
65 Pkey: Unique Eos probeset identifier number
CAT number. Gene cluster number
Accession: Genbank accession numbers
Pkey CAT Accession
Number
40774610i25_1AK001962 869415 BE464605 AA418699 AA053293 AA149075
AA058396 AW338226 AW272659 AA454607 AI139535 AW469852
AI275461
AW271982 AA730033 AA576507 AA991217 AA782067 A1985851
AA805864 AA505598 AW469857 869546 AA988279 AW001647
N63320
D62661727343 AA306950 AA360989 858778
408D701036688_1AW148852 BE350895
4D8660107294_1AA525775 AA056342 A1538978 AW975281 AA664986
75409522113735 AA075382 AA075431
1
4098661156522_1AW502152 H41202 H29772
4100321170435_1BE065985 BE065944 BE066008 BE066083 BE066093
411089123172_1AA456454 AA713730 AA091294 AA584921 N86077 AW836781
AA601031 AA579876 AA551106 AA633188 AW905577 A1955808
A1679386
AI679895 AA514764 AA454562 A1082382 AA595822 AA551351
AA586369 AA666384 AA188934 AA666398 AA551297 AA565188
4111521234028-1BE069199 AW936012 AW877466 AW819782 AW935798 AW835546
AW936042 BE069121 AW835625 AW877536 AW935885 BE0692D2
AW820019 AW935937 BE160180 AW9359d6 BE069101 BE069125
AW877521 BE160316 BE160398 AW935794 AW835701 AW935784
4125371304_1 AL031778 X59711 NM_002505 M59079 AI870439 Ai494259
AW664010 AA405063 AA436132 BE174516 AA412691 AI400314
AA436024
729403 BE079412 BE079428 N90322 AI631202 AI141758
A1016793 AI167566 AI862075 AI375230 A1208445 AW235763
AL044113 AA382556
AW953918 AA927051 AA889823 BE003094 AW390155 AW360805
AW360823 AW360810 AA425472 AI694282 AL044114 AI684577
AI809865
167
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
AI478773 AI160d45 AI674630 N69088 AW665529 N49278
AI129239 AI457890 AI621264 AW297152 AI268215 AA907787
AI286170 A1017982
AI963541 AI469807 AI969353 BE552356 N66509 AA736741
AA382555 AW075811 AW29202fi
412811 132943-1 H06382 AW957730 AA352014 813591 AA121201 D60420 BE263253
BE047862 241952 AI424991 AI693507 AI863108 AA599060
A1091148
AA598689 839887 AA8i34B2 AW016452 H063B3 841807 Ai364268
AA620528 AI2419d0 AW089149 AW090733 AW08BB75 238240
AA121202 817734
413690 1383256_1BE157489 BE157560
414883 15024_1 AA926960 AA926959 W76521 W24270 W21526 AA037172 BE267636
H83186AA469909 N86396 AA001348 BE535736 AA0817458E566245
AA082436 H72525 H77575 N49786 W80565 H78746 BE569085
W04339 898127155938 BE279271 AW960304129812 AA476873
BE297387
AA292753 AA177048 NM 001826 X54941 BE314366 AA908783
AI719075 BE270172 BE269819 AA889955 AI204630 W25243
AI935150
1 o AAB72039 W72395199630 AI422691 H98460 N31428 BE255916
H03265 AI857576 AA776920 AA910644 AA459522 AA293140
AW514667
875953 AW662396 AA662522 AI865147 AI423153 AW262230
AA584410 AA583187 AW024595 AW069734 AI828996 AA282997
AA876046
AW613002 AA527373 AW972459 AI831360 AA621337 AA100926
AA772418 AA594628 A1033892 W95096 A1034317 AA398727
A1085031
N95210 AI459432 A1041437 AA932124 AA627684 AA935829
A1004827 AI423513 A1094597 H42079 854703 AI630359
AA617681 AA978045
AA643280 W44561 Ai9919B8 AI531692 A1090262 AA740817
AI312104 AI911822 AA416871 AI185409 AA129784 AA701623
A1075239
15 AI139549 AA633648 AI339996 AI336880 AA399239 A1078708
A1085351 AI362835 AI346618 AI146955 AI9893B0 AI348243
N92892 AA765850
AI494230 AI278887 AA962596 AI492600 W80435 AA001979
897424 AI129015 N24127 AA157451 AA235549 AA459292
AA037114 AA129785
AI494211 AW059601 AW886710 892790 N59755 AI361128
AW589407 H47725 H97534 H48076 H48450199631 AW300758
H03431876789
AA954344 H77576 896823 A1457100 N92845 Nd9682 H42038
BE220698 BE220715 H99552 AA701624 N74173 854704
H79520 H72923
H03266 BE261919 AA769633 AA480310 AA507454 AA910586
AI203723 AW104725 W25611 W25071 188980 H03513177589
899156
W95095 897470 AA702275177551 AA911952 H82956 N83673
AA283672
415989 156454-1 AI267700 AI720344 AA191424 A1023543 AI469633 AA172056
AW958465 AA172236 AW953397 AA3550B6
417324 166714-1 AW265494 AA455904 AA195677 AW265432 AW991605 AA456370
418574 17690_1 N28754 N28747 AI568146 AI979339 AA322671 AA322672
AW955043 AI990326 AA776406 A1016250 AA843678 AW45i
882 N23137 N23129
W70051 A1038748 AA831327 AI925B45 AW945895
418712 1784125 242183 131621 197478
1
419443 184788 D62703AA242966 D79798
1
419502 18535_1 AU076704174854174860172098173265 173873
T69180174658158786160385173410168781167845167593173952
167864 160630
168367 Tfi8d01153959172360172099160377158961171712172821164738
T7dfi45172037168688 172063173258172826164242
1682201746731718001683551612271627381693171538501646921737681739621733821689141
70975173400160631173277
173203170498161409158925 NM 000508
M64982168301173729169445160424167922167736168716167755174765
173819158719
1747561604771748631611091683291588501718571734251537361686071588981643091720311
72079164305171908168107
1719161737871560351644251718701604761613761678201718951410061694411681701746171
71958169440161875
806796
H48353171914153939164121 AA693996172525167779168078
AA011465 AA345378 AV65d847 AV654272 AV656001 A1064740182897
N33594 AA344542 AW805054 AI207457161743 AA026737
H94389 AA382695 AA918409168044 582092139959 A1017721
AA312395
3 5 AA312919140156 H66239 AV652989 H38728 898521 AV655200
895790 W03250 W00913 AA344136 AV660126 897923 AA343596
AW470774 AV651256 N54417 AA812862 AW182929 AI111192
H61463 H72060 AA344503 H38639 AI277511 AV661108
AI207625 Td7810
AA235252127853147778 895746 H70620 AA701463 AW827166
898475 C20925 AV657287171959171313173920173333161618169293
169283173931172178172456 AV645639
AV653476172957172300158906171457170494172956170495168267174407185778
AA344726127854174485174101173868171518172304 AA343B53173909168070172065
H72149173493173495 AV645993 802293
170475164751 AA344441 AA343657 AA345732 AA344328
AI110639 AA344603 AF063513 T6d696168516172223160507167633
829500
172517 802292160599169206170452174677 829366161277174914160352
829675174843 AV645792 AA344408169197172057
169368 769358168258 AV650429173341161702 174598140095
K02272140106 AA343045 AA341908 AA341907 AA342807
AA341964
153747172042162764 A1064B99
AA343060167832172440171770168091169108172449169167171289168251
AV654844164375
AA345234167598 AA011414168036 H48262 AI207557168219
W86031169081164232 893196162136 AV650539 H67459172978
45 AA344583160362 H58121195711172803168055171715
829036172793169122164595162888169139168291164652
167971146862
AA693592 AI248502 829454164764157001173052171429151176158866
AV655414 H90426 AA342489173666167848172512153835
167837 173317 174273 T69d20168245174380167862 174474156068
419936 189181_1 AI79278BBE142230AA252019
421582 2041 AI910275 X00474 X52003 X05030 NM 003225 AA314326
1 AA308400 AA506787 AA314825 AI571948 AA507595 AA614579
AA587613 883818
_ AA568312 AA614409 AA307578 AI925552 AW950155 AI910083
M 12075 BE074052 AWOQ4668 AA578674 AA582084 BE074053
8E074126
BE074140 AA514776 AA5B8034 BE074051 BE07d068 AW009769
AW050690 AA858276 855389 A1001051 AW050700 AW750216
AA614539
BE074045 AI307407 AW602303 BE073575 AI202532 AA524242
AI970839 AI909751 BE076078 AI909749 855292
d22128 211994_1 AW881145 AA490718 M85637 AA304575106067 AA331991
423034 22d122 AL119930 AA320696 AW752565
1
_ AL031985 AL137241 AI7923B6 AI733664 AI857654 A1049911
55 d23816 23234-1
424200 236595 AA337221 AA336756 AW966196
1
424999 245835 AW953120 856325 AA349562
1
426966 273896 A1493134 A1498691 AW771508 A1498457 A1768408 A1783624
1 A1383985 A15B0267 D79813 AA393768
426991 27415 AK001536 AA191092 AW510354 AI554256 AL353968 AA134266
1
427260 276598 AA663848 AA400100 AA401424
1
428023 28589-2 AL038B43 AA161338 BE268213 AA425597 N87306 AA092969
BE566038 AA247451 N47392 A1928802 AW182584 AW027872
A1819831
AI936994 W56258 AI653448 AI278611 AI283557 AI824306
AW338658 AW150899 AA6B7514 N47393 N29885 AA973469
A1038904 AI292064
A1034339 AW674593 N72156 A1079733 A1038683 AI291616
AA491599 AA993675 AA837380 BE00655d BE006473 A1087090133044
AA652043 AI203503 AA583959 W35283 AI129926 241844
AW020925 AW575848 AI6B4603 AA493297 Ai 140689 AI277175
AA425444
65 AI932767 W02632 BE396786 837261
429220 301384 AW207206 AW341473 AA4d8195 A1951341
1
429978 31150_1 AA249027 AL038984 AK001993 ALOB0066 AV652725 BE566226
AA345557 AA315222 AA090585 AA375688 AA301092 AA298454
W05762
AW607939 H51658 D83880 N84323 BE296821 AW947007 D61461
AW079261 AA329482 AW901780 AI354442 AA772275 831663
AI354441
AI767525 H92d31 AI916735 H93575 AI394255 AW014741
AI573090 CO6i95 AW612857 AW265195 AI339558 AI377532
AI30B821 AI919424
70 AI589705 AW055215 AI336532 AI338051 AA806547 C75509
C00618 AW071172 AW769904 AA630381 AI678018 A1863985
D79662 8E221049
AW265018 AI589700 AW196655 N76573 AI370908 BE042393
N75017 AI698870 AW9601 1 5
430439 31808_1 AL133561 AL041090 AL117481 AL122069 AW439292 AI96B826
430935 325772-1 AW072916 AI184913 AA489195 AW466994 AW4690d4 N59350
AI819642 AI280239 AI220572 AA789302 AI473611 AW841126
D60937
d31089 3278251 BE041395AA491826AAfi21946AA7i5980AAfi6fi102
75 431322 331543_1AW970622 AA503009 AA502998 AA502989 AA502805 192188
432407 34624-1 AA221036 887170 BE537068 BE544757 Ci 8935 AW812058192565
AA227415 AA233942 AA223237 AA668403 AA601627 AW869639
BE061833 BE000620 AW961170 AW847519 AA308542 AW821833
AW945688 C04699 AA205504 AA377241 AW821667 AA055720
AW817981 AW856468 AA155719 AA179928103007 AW754298
AA227407 AA113928 AA307904 C16859
d34414 38585
AI798376S46400AW8116i7AW8ii616W005578E142245AW858232AW861851AW858362AA23235iAA2
i8567AA055556AW858231
1
_ AW857541 AW814172 H6621d AW814398 AF134164 AA243093
8~ AA173345 AA199942 AA2233B4 AA227092 AA227080112379
AA092174
161139 AA149776 AAfi99829 AW879188 AW813567 AW813538
AI267168 AA157718 AA157719 AA100472 AA100774 AA130756
AA157705
AA157730 AA157715 AA053524 AW849581 AW854566 C05254
AW882836192637 AW812621 AA206583 AA209204 BE156909
AA226824
AI829309 AW991957 N66951 AA527374 H66215 AA045564
AI694265 H60808 AA149726 AW195620 BE081333 BE073424
AW817662
AW817705 AW817703 AW817659 BE081531 H59570
85 436608 423613AA628980AI1266038E504035
168
CA 02444691 2003-10-17
WO 02/0864 43 PCT/US02/12476
438091 44964 AW373062 T55662 AI299190 BE174210 AW579001 H01811
1 W40186 867100 AI923886 AW952164 AA628440 AW898607
AW898616
_ AA709126 AW898628 AW898544 AA947932 AW898625 AW898622
AI276125 AI185720 AW510698 AA987230 T52522 BE467708
AW243d00
AW043642 A1288245 AI186932 D52654 D55017 D52715 D52477
D53933 D54679 AI298739 AI146984 AI922204 N98343 BE174213
AA845571
AI813854 AI214518 AI635262 AI139455 AI707807 AI698085
AW884528 A1024768 A1004723 AW087420 AI5fi5133 N94964
AI268939
AW513280 A10fi1126 AI435818 AI859106 AI360506 A1024767
AA513019 AA757598 X56196 AA902959 AI334784 AI860794
AA010207
AW890091 AW513771 AI951391 AI337671 T52499 AA890205
AI640908 H759fi6 AA463487 AA358688 AI961767 AI866295
AA780994
AI985913 BE174196 AA029094 AW592159 T55581 N79072
AI611201 AA910812 AI220713 AW149306 AI758412 AA045713
879750 N76096
439000 467716 AW979121 AA847986 AA829098
1
439285 47065-1AL133916 N79113 AF086101 N76721 AW950826 AA364013
AW955684 A1346341 A1867454 N54784 A1655270 A1421279
AW014882
1 ~ AA775552 N62351 N59253 AA626243 AI3d1407 BE175639
AAd56968 AI358918 AA457077
439780 47673-fAL109688 823665 826578
441128 51021_2AA570256 AW014761 AA573721 A1473237 A1022165 AA554071
AA127551 N90525 AW973623 AA447991 AA243852 BE328850
A11d8171
AI359627 A1005068 AI356567 AA232991 AW016855 AA906902
AA233101 AA127550 BE512923
443068 558874-1AI188710 A1032142 AW078833 N30308 AW675632 AI219028
AI341201 N22181 H95390
1 5 443947 W24187 W24194 817789
586160_1
447636 7301_1 Y10043 NM_005342 L05085 AL034450 BE614226 AW749053
AA379173 AA248230 BE51463d AA334622 870656 AA367593
AA214649
AA369318 AW957081 805760 AA039903 AI886597 AW630122
AA906264 AA041527 801145 A1088688 BE463637 AA398795
AI35d883
AI768938 AI569996 AI452952 AI168582 AI189869 A1086670
AW262560 AW613854 AA862839 AA435840 AA670197 A1024032
AI990659
AI990089 N81095 AA847919 AW960150 AA211075 AA044704
AA367594 AW582587 AW858854 AW818630 AW818281 AW818433
AW582595
AA096002 N83992
448993 79225-1AI471630 8E540637 BE265481 AW407710 BE513882 BE546739
AA053597 BE140503 BE218514 AW956702 AI656234 AI636283
AI567265
AW340858 BE207794 AA053085 869173 AA292343 AA454908
AA293504 AI659741 AI927478 AA399460 AI760441 AA346416
BE047245
AA730380 AA394063 AA454833 AI982791 AI567270 AI813332
AI767858 AA427705 D20284 AI221458 BE048537 A1263048
AA346417
AA911497 BE537702
449305 804424_1A1638293 AW813561
451105 859083 A1761324 AW880941 AW880937
1
451320 86576_1AW118072 AI631982 T15734 AA224195 AI701458 W20198
F26326 AA890570 N90552 AW071907 AI671352 AI375892
T03517 888265
AI124088 AA224388 A1084316 AI354686 T33652 AI1d0719
AI720211 T03490 AI372637 T15415 AW205836 AA630384
T03515 T33230
AA017131 AA443303 T33623 AI222556 T33511 T33785 AI419606
D55612
451807 8865_1 W52854 AL117600 BE2081 1 6 BE20B432 BE206239 BE082291
AW953423 AA351 619 BE180648 BE140560 W60080 AA865478
N90291
AW450652 AW449519 AA993634 AI806539 AA351618 AW449522
A1827626 AA90d788 AA380381 AA886045 AA774409 BE003229
241756
452410 9163_1 AL133619 AA468118 AA383064 AI476447 T09430 AI673758
AA524895 AI581345 AI300820 AW498812 AA256162 A1559724
AI685732
AA602400 AA905453 AI204595 AW166541 AA157456 AA15fi269
AA383652 AA431072 AW592707 AI435410 AW272464 AI215594
AA622747
874039 N35031 AI804128 AW513621 AA868351 A1026826
AI493388 AA614641 W81604 AI567080 AI214351 AA7301d0
AI125754 AI200813
3 5 AI269603 AI5fi5082 AI807095 AI476629 AA505909 AI368449
AI686077 AI582930 AW085038 AA757863 AA730154 AI767072
AA468316
A1734130 AI734138 AA426284 AA433997 AI741241 AW043563
AI732741 AI732734 AA437369 AA425820 AA6fi4048 874130
454241 1067807-1BE144666 BE184942 AW238414 BE184946
455175 1257335AW993247 AW861464
1
456237 168730 AA203682 811958
1
4~ 458098 47395_1BE550224 AA832519 N45402 AW885857 N29245 BE465409
W07677 AW970089 A1299731 AA482971 BE503548 H18151
W79223 AF086393
AA461301 W74510 834182 A1090689 N46003 BE071550 828075
AW134982 AI240204 AI138906 AW026179 AI572316 BE466182
AI206395
AI27fii54 AI273269 AI422817 AI371014 AI421274 AI188525
AA939164 BE549810 AW137865 AI694996 BE503841 AA459718
BE327407
BE467534 BE218421 BE467767 AA989054 BE467063 AI797130
BE327781
TABLE 9C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham I. et al." refers to the publication enUlled
'The DNA
sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-095.
Strand: Indicates DNA strand from which exons were predicted.
Nt_position: Indicates nucleoUde positions of predicted exons.
Pkey Ref StrandNt_position
4005129796593Minus1439-1615
4005179796686Minus49996-50346
4005609843598Plus94182-94323,97056-97243,101095-101236,102824-103005
4006648118496Plus13558-13721,13942-14090,14554-14679
4006658118496Plus16879-17023
4006668118496Plus17982-18115,20297-20456
4007497331445Minus9162-9293
4007638131616Minus35537-35784
4010277230983Minus70407-70554,71060-71160
4010938516137Minus22335-23166
4012039743387Minus172961-173056,173868-173928
4012129858408Plus87839-88028
4014117799787Minus144144-144329
4014358217934Minus54508-55233
4014646662291Minus170688-170834
401714(1715702Plus96484-96681
4017479789672Minus118596-118816,119119-119244,119609-119761,120422-
120990,130161-130381,130468-130593,131097-131258,131866-
131932,132451-132575,133580-134011
4017609929699Plus83126-83250,85320-85540,94719-95287
4017807249190Minus28397-28617,28920-29045,29135-29296,29411-29567,29705-
29787,30224-30573
4017817249190Minus83215-83435,83531-63656,83740-83901,84237-84393,84955-
85037,86290-86814
4017857249190Minus165776-165996,166189-166314,166408-166569,167112-
167268,167387-167469,168634-168942
4017976730720Plus6973-7118
4019614581193Minus124054-124209
4019852580474Plus61542-61750
4019944153858Minus42904-43124,43211-43336,44607-44763,45199-45261,46337-46732
4020758117407Plus121907-122035,122804-122921,124019-124161,124455-
124610,125672-126076
4022603399665Minus113765-113910,115653-115765,116808-116940
4022653287673Plus21059-21168
4022976598824Plus35279-35405,35573-35659
g5 4024089796239Minus110326-110491
169
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
4024209796339 129750-129919
Plus
4026748077106 39290-39502
Minus
4028023287156 53242-53432
Minus
4029942996643 4727-4969
Minus
4031379211494 92349-92572,92958-93084,93579-93712,93949-94072,94591-
94748,95214-95337
Minus
4033068099945 127100-127251
Plus
4033298516120 96450-96598
Pias
4033819438267 26009-26178
Minus
4034789958258 116458-116564
Plus
I d034859966528 2888-3001,3198-3532,3655-4117
~ Pius
4036278569879 23868-24342
Minus
4037157239669 85128-85292
Plus
4040449558573 225757-225939
Minus
4040769931752 3848-3967
Minus
1 d041018076925 125742-125997
Minus
4041409843520 37761-38147
Plus
4041659926489 69025-69128
Minus
4041854572584 129171-129327
Minus
4042105006246 169926-170121
Plus
Zo 4042539367202 55675-56055
Minus
4042872326514 53134-53281
Plus
4042989944263 73591-73723
Minus
4043479838195 74493-74829
Plus
4044407528051 80430-81581
Plus
25 4047219856648 17376&174294
Minus
4047944826439 101619-101898
Pius
4048547143420 14260-14537
Plus
4048771519284 1095-2107
Plus
4049277342002 68690-69563
Plus
4049968007890 37999-38145,38652-38998,39727-39872,40557-40674,42351-42450
Plus
4054497622497 42236-42570
Plus
4055686006906 35912-36065
Plus
4055723800891 85230-85938
Pius
4056464914350 741-969
Plus
3 4056764557087 73195-73917
5 Plus
4057702735037 61057-62075
Plus
4059327767812 123525-123713
Minus
4061379166422 30487-31058
Minus
d063609256107 7513-7673
Minus
4063999256288 63448-63554
Minus
4064679795551 182212-182958
Plus
TABLE agnostic and PrognosticNon-malignant Lung Disease
10A: targets for Therapy
Potential of Lung Cancer and
Therapeutic,
Di
45 Table
2A
shows
about
307
genes
up-regulated
in
non-malignant
lung
disease
relative
to
lung
tumors
and
normal
body
tissues
andlor
down-regulated
in
lung
tumors
relaUve
to
normal on the EoslAffymetrix Hu03
lung Genechip array.
and
non-malignant
lung
disease.
These
genes
were
selected
from
about
59680
probesets
Table
108
show
the
accession
numbers
for
those
Pkey's
lacking
UnigeneiD's
for
table
10A.
For
each
probaset
we
have
listed
the
gene
cluster
number
from
which
the
oligonucleotides ESTs and mRNAs. These
sequences
were were clustered based on
designed. sequence
Gene
clusters
were
compiled
using
sequences
derived
from
Genbank
similarity
using
Clustering
and
Alignment
Tools
(DoubieTwist,
Oakland
California).
The
Genbank
accession
numbers
for
sequences
comprising
each
cluster
are
listed
in
the
"Accession"
column.
Table0 show the in table 10A. For each
genomic predicted exon, we have
positioning listed the genomic
for those
Pkey's
lacking
Unigene
ID's and
accession
numbers
sequence Nucleotide locations
souroe of each predicted exon
used are also listed.
far
prediction.
55
Pkey:Unique Eos t identifier number
t probese
ExAccn:Exemplar number, Genbank accession
Accession number
UnigenelD: Unigene
number
UnigeneTitle: Unigene
gene title
R1; Average
of lung
tumors
(including
squamous
cell carcinomas,
adenocarcinomas,
small cell
carcinomas,
granulomatous
and carcinoid
tumors)
divided
by the
average
of normal
lung samples
R2: Average
of non-malignant
lung disease
samples
(including
bronchitis,
emphysema,
fibrosis,
ateleciasis,
asthma)
divided
by the
average
of normal
lung samples
65 PkeyExAccn UnigenelDUnigeneTitle Rt R2
404394 ENSP00000241075;TRRAP 3.10
PROTEIN. 0.79
404916 Target Exon 1.00 159.00
405257 Target Exon 1.00 422.00
407228M25079 Hs.155376hemoglobin, beta 0,47 2.33
70 407568AA740964 ESTs 1.00 123.00
Hs.62699
408562A1436323 Homo Sapiens mRNA for 230.00
Hs.31141 KIAA1568 protein, 1.00
409031AA376836 ESTs 1.00 128.00
Hs.76728
410434AF051152 Poll-like receptor 2 149.00
Hs.63668 39.65
410467AF102546 dachshund (Drosophilaj 109.00
Hs.63931 homolog 1.00
7$ d10808T4D326 Hs.167793ESTs 1.14 93.14
412351AL13596D T-cell acute lymphocytic2.27
Hs.73828 leukemia 1 0.37
412372865998 Hs.265243hypothetical protein 173.00
FLJ22029 1.0D
413795AL040178 ESTs 0.10 11.90
Hs.142003
414154AW205314 ESTs 0.62 2.09
Hs.323060
414214049958 Hs.75819giycoprotein M6A 0.03 4.55
414998NM_002543 oxidised low density 2.91
Hs.77729 lipoprotein (lectin
0.64
415122060708 Hs.22245ESTs 0.07 8.97
415765NM_005424 tyrosine kinase with 1.65
Hs.78824 immunoglobulin and
0.6T
415775H00747 Hs.29792ESTs, Weakly similar 2.64
to 138022 hypotheti
0.29
$5 415910020350 Hs.78913chemokine (GX3-C)receptort145.00
1.00
170
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
416319AI815601Hs.79197CD83 antigen (activated15.32237.00
B lymphocytes,
i
416402NM_D00715Hs.1012complement component0.64 4.00
4-binding protein,
417355013168Hs.82002endothelin receptor0.01 3.90
type B
417421AL138201Hs.82t20nuclear receptor 36.30357.00
subfamily 4, group
A, m
417511AL049176Hs.82223chordin-like 1.00 179.00
418489U76421Hs.85302adenosine deaminase,0.02 6.00
RNA-specific, B1
(h
418726BE241812Hs,87860protein tyrosine 1.00 113.00
phosphatase, non-recept
418741H83265Hs.8881ESTs, Weakly similar0.44 1.90
to S41044 chromosom
418883BE387036Hs.1211acid phosphatase 0.96 2.04
5, tartrate resistant
1 419086NM-000216Hs.89591Kallmann syndrome 0.62 2.74
~ 1 sequence
419150T29618Hs.89640TEK tyrosine kinase,0.03 6.90
endothelial (venous
419235AW47D411Hs,288433neurolrimin 1.48 5.13
419407AW410377Hs.41502hypothetical protein37.55336.00
FLJ21276
420556AA278300Hs.124292Homo Sapiens cDNA: 0.80 3.65
FLJ23123 fis, clone
L
1 420656AA279098H5.187636ESTs 1.65 8.07
420729AW964897Hs.290825ESTs 2.99 25.82
421177AW074211Hs.102415Homo sapiens mRNA; 0.46 1.95
cDNA DKFZp586N0121
(f
422060820893Hs.325823ESTs, Moderately 1.00 156.00
similar to ALU5_HUMAN
A
422426W79117Hs.58559ESTs 0.03 7.4d
d22652AW967969Hs.118958syntaxin 11 0.14 3.62
d23099NM-002837Hs.123641protein tyrosine 0.01 3.16
phosphatase, receptor
t
424433H04607Hs.9218ESTs 0.75 141.75
424585AA464840Hs.131987ESTs 1.00 167.00
424711NM_005795Hs.152175calcitonin receptor-like0.43 3.01
25 424973X92521Hs.154057matrix metalloproleinase0.37 19.45
19
425023AW956889Hs.154210endothelial differentiation,0.14 3.35
sphingolipi
425664AJ006276Hs,159003transient receptor 1.00 94.00
potential channel
6
425998AU076629Hs.165950fibroblast growth 0.68 1.42
factor receptor
4
426657NM Hs.171731solute carrier family0.03 3.74
015865 14 (urea transport
426753T89832Hs.170278ESTs 1.00 141.00
427558049493Hs.2171growth differentiation1.00 117.00
factor 10
d27983M17706Hs.2233colony stimulating 0.75 2.20
factor 3 (granulocyte
428467AK002121Hs.184465hypothetical protein0.76 2.25
FLJ11259
428927AA441837Hs.90250ESTs 0.01 3.62
35 429496AA453800Hs.192793ESTs 1.00 136.00
430468NM_004673Hs.241519angiopoietin-like 1.00 132.00
1
431385BE178536Hs.11090membrane-spanning 1.00 157.00
4-domains, subfamily
A
431728NM_007351Hs.268107multimerin 1.00 157.00
431848AI378857Hs.126758ESTs, Highly similar0.34 2.24
to AF1752831 zinc
432128AA127221Hs.117037ESTs 0.00 1.15
432519AI221311Hs.130704ESTs, Weakly similar0.01 2.06
to BCHUIA S-100
pro
43300.3W57554Hs.125019lymphoid nuclear 1.00 267.00
protein (tAF-4)
mRNA
433803AI823593Hs.27688ESTs 1.00 105.00
434730AA644669Hs.193042ESTs 1.05 3.15
45 435472AW972330Hs.283022triggering receptor0.83 1.94
expressed on myeloid
436532AA721522 gb:nv54h12.r1 NCI-CGAP_Ewt1.00 218.00
Homo Sapiens
437119AI379921Hs.177043ESTs 1.00 133.00
437140AA312799Hs.283689activator of CREM 0.67 122.67
in testis
437211AA382207Hs.5509ecotropic viral 1.00 142.00
integration site
2B
437960A1669586Hs.222194ESTs 1.00 147.00
438202AW169287Hs.22588ESTs 1.00 141.00
438873A13D2471Hs.124292Homo Sapiens cDNA: 0.71 3.66
FLJ23123 fis, clone
L
438875AA827640Hs.189059ESTs 23.32370.00
441048AA913488Hs.192102ESTs 0.77 8.50
55 441188AW292830Hs.2556D9ESTs 3.43 16.36
441499AW298235Hs.101689ESTs 1.00 167.00
444513AL120214Hs,7117glutamate receptor,1.00 151.00
ionotropic, AMPA
1
444527NM-005408Hs.11383small inducible 46.47153.00
cytokine subfamily
A (Cy
444561004469Hs.11392c-fos induced growth0.01 3.08
NM factor (vascular
en
445279_ Hs.22245ESTs 0.60 141.00
841900
446017N98238Hs.55185ESTs 0.18 2.39
446984AB020722Hs.16714Rho guanine exchange0.10 2.16
factor (GEF) 15
446998N99013Hs.16762Homo Sapiens mRNA; 0.01 2.53
cDNA DKFZp564B2062
(f
447357AI375922Hs.159367ESTs 0.46 2.6d
65 448106A1800470Hs.171941ESTs 18.05296.00
448253H25899Hs.201591ESTs 1.00 141.00
449275AW450848Hs.205457periaxin 0.56 1.38
450400A1694722Hs.2797A4ESTs 0.88 4.33
450696A1654223Hs.16026hypothetical protein0.52 2.08
FLJ23191
450726AW204600Hs.250505retinoic acid receptor,0,79 2.01
alpha
451497H83294Hs.284122Wnt inhibitory factor-10.35 2.03
451533NM Hs.26530serum deprivation 0.13 2.25
004657 response (phosphatidyl
453636867837Hs.169872ESTs 1.00 116.00
458332A1000341Hs.220491ESTs 1.00 192.00
75 459580AA022888Hs.176065ESTs 0.20 2.98
400269 Eos Control 0.40 2.40
403421 NM 016369":Homo 0.53 1.77
Sapiens claudin
18 (CLDN
407570219002Hs.37096zinc finger protein0.01 3.18
145 (Kruppel-like,
a
412295AW088826Hs.117176poly(A)-binding 0.56 1.74
protein, nuclear
1
414517M24461Hs.76305surfactant, pulmonary-associated0.64 1.50
protein
417204N81037Hs.1074surfactant, pulmonary-associated0.33 1.16
protein
418307U70867Hs,83974salute camer family0.53 1.55
21 (prostaglandin
418935T28499Hs.89485carbonic anhydraselV0.20 1.28
421502AF111856Hs.105039solute carrier family0.78 1.90
34 (sodium phospha
g5 421798N74880Hs.29877N-acylsphingosine 0.59 1.54
amidohydrolase
(acid c
171
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
423354AB011130Hs.127436calcium channel, 0.59 1.55
voltage-dependent,
alph
423738AB002134Hs.132195airway trypsin-like10.1451.00
protease
425211M18667Hs.1867progastricsin (pepsinogen0.35 1.62
C)
425438T62216Hs.270840ESTs 0.23 9.45
426828NM_000020Hs.172670activin A receptor 0.03 1.71 '
type II-like 1
427019AA001732Hs.173233hypothetical protein0.01 1.49
FLJ10970
428043T92248Hs.2240uteroglobin 0.42 1.26
430280AA361258Hs.237868tnterleukin 7 receptor0.46 2.43
431433X65018Hs.253495surfactant, pulmonary-associated0.57 1.59
protein
1 431723AW058350Hs.16762Homo sapiens mRNA; 0.29 1.80
~ cDNA DKFZp56482062
(f
432985T92363Hs.178703ESTs 0.32 2.27
441835AB036432Hs.184advanced glycosylation0.31 1.51
end product-specs
442275AW449467Hs.54795ESTs 0.55 1.78
443709A1082692Hs.134662ESTs 0.00 3.02
15 444325AW152618Hs.16757ESTs 0.32 2.49
450954AI90d740Hs.25691receptor (calcitonin)0.46 1.74
activity modifying
451558NM_001089Hs.26630ATP-binding cassette,0.52 1.87
sub-family A (A801
453310X70697Hs.553solute carrier family0.00 3.30
6 (neurotransmitte
456855AF035528Hs.153863MAD (mothers against0.01 2.31
decapentaplegic,
Dr
2~ 444342NM Hs.10887similar to lysosome-associated0.66 2.20
014398 membrane
400754 Target Exon 1.00 297.00
401045 011001883*:gi~6753278~ref~NP1.00 109.00
033938.1~c
401083 NM_0165ti2*:Homo 0.89 1.39
sapiens peptide
transpor
402474 NM_004079:Homo sapiens1.45 4.d7
cathepstn S (CTSS
25 402808 ENSP00000235229:SEMB.1.00 1.87
403021 021000030:gi~9955960pefINP_063957.1~AT1.00 149.00
403438 NM-031419*:Homo 1.06 2.96
sapiens molecule
possess
403687 NM_007037*:Homo 0.04 4.89
saptens a disintegrin-li
403764 NM-005463:Homo sapiens1.00 225.00
heterogeneous nuc
404277 NM-019111*:Homo 0.97 1.93
sapiens major htstocompa
404288 NM_002944*:Homo 1.00 68.00
sapiens v-ros avian
UR2
404518AI815601 CD83 antigen (activated0.02 1.83
B lymphocytes,
1
405106 C1f001637*:gi(50322d1~ref~NP-005732.1~z1.00 235.00
405381 Target Exon 1.00 93.00
35 406387 TargetExon 1.37 6.02
406646M33600 major histocompatibility0.86 2.46
complex, class
406714AI219304Hs.266959hemoglobin, gamma 0.01 3.19
G
406753AA505665Hs.217493annexin A2 1.00 147.00
406973M34996Hs.198253major histocompatibility1.03 2.04
complex, class
407248082275Hs.94498leukocyte immunoglobulin-like1.00 64.00
receptor,
407510096191 gb:Human trophoblast1.00 90.00
hypoxia-regulated
f
407731NM-000066Hs.38069complement component1.00 67.00
8, beta polypeptide
407830NM_001086Hs.587arylacetamide deacetylase1.00 102.00
(esterase)
408045AW138959Hs.245123ESTs 1.00 70.00
45 408074820723 ESTs 1.00 112.00
408374AW025430Hs.155591forkhead box F1 0.07 10.17
409064AA062954Hs.141883ESTs 0.39 2.31
409083AF050083Hs.673inlerleukin 12A 1,00 95.00
(natural killer
cell sti
409153W03754Hs.50813hypothetical protein0.01 4.55
FLJ20022
409203AA780473Hs.687cytochrome P450, 0.01 3.72
subfamily IVB,
polypept
409238ALD49990Hs.51515Homo sapiens mRNA; 1.00 79.00
cDNA DKFZp564G112
(fr
409389A8007979Hs.301281Homo Sapiens mRNA, 0.14 27.35
chromosome 1 specific
409718D86640Hs.56045src homology three 1.00 113.00
(SH3) and cysteine
r1
410798BE178622Hs.16291gb:PM3-HT0605-270200-001-a020.64 2.47
HT0605 Homo
S 411020NM Hs.67726macrophage receptor0.55 2.40
006770 with collagenous
slr
411667BE160198 gb:QV1-HT0413-010200-059-h031.00 111.00
HT0413 Homo
412000AW576555Hs.15780ATP-binding cassette,1.00 95.00
sub-family A (A801
412358BE047490Hs.24172ESTs 1.00 87.00
412420AL035668Hs.73853bone morphogenetic 1.43 8.07
protein 2
60 412564X83703Hs.31432cardiac ankyrin 0.02 3.07
repeat protein
412869AA290712Hs.82407CXC chemokine ligand0.93 1.72
16
412870N22788Hs.82407CXC chemokine ligand0.97 1.51
16
413529011874Hs.846interleukin 8 receptor,0.02 2.42
beta
413533BE146973 gb:OVd-HT0222-011199-019-e050.65 1.50
HT0222 Homo
65 413689BE157286Hs.2063izinc finger protein,20.87232.00
subfamily 1A, 5
(Pe
413724AA131466Hs.23767hypothetical protein1.00 80.00
FLJ12666
413800AI129238Hs.192235ESTs 1.00 85.00
413802AW964490Hs.32241ESTs, Weakly similar1.00 213.00
to S65657 alpha-1
G
413829NM_001872Hs.75572carboxypeptidase 0.02 3.93
82 (plasma)
414376BE393856Hs.66915ESTs, Weakly similar1.110115.00
to 16.7K4 protein
[
414577A1056548H5.72116hypothetical protein0.49 1.94
FLJ20992 similar
to
414700H63202Hs.38163ESTs 0.03 3.75
415078AA311223Hs.283091found in inflammatory0.86 1.95
zone 3
415120N64464Hs.34950ESTs 1.00 120.00
75 415323BE269352Hs.949neutrophil cytosolic0.60 2.48
factor 2 (65kD,
chr
415335AA847758Hs.111030ESTs 1.00 95.00
415582W92445Hs.165195Homo Sapiens cDNP, 1.00 136.00
FLJ 14237 fis,
clone NT
416030H15261Hs.21948ESTs 0.02 8.07
416427BE244050Hs.79307RacICdc42 guanine 1.00 73.00
exchangefactor(GEF)
416464NM-000132Hs.79345coagulation factorVlll,procoagulantco0.70 3.36
416585X54162Hs.79386leiomodin 1 (smooth0.06 6.56
~ muscle)
416847L43821Hs.80261enhancer of filamentation0.70 3.66
1 (cas-like do
417148AA359896Hs.293885hypothetical protein1.00 114.00
FLJ14902
417370T28651Hs.82030tryptophanyl-IRNAsynthetase0.85 1.30
g5 417673T87281Hs.16355ESTs 0.15 15.54
172
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WO PCT/US02/12476
02/086443
418067AI127958Hs.83393cystafin EIM 0.81 1.74
418296C01566Hs.86671ESTs 1.00 99.00
418643J03798Hs.86948small nuclear ribonucleoprotein1,00 60.00
D1 polyp
418832X04011Hs.88974cytochrome b-245, 2.40 14.74
beta polypeptide
(chro
418945BE246762Hs.89499arachidonate 5-lipoxygenase0.67 ' 3.16
419261X07876Hs.89791wingless-type MMN 1.00 73.00
integration site
fami
419564008989Hs.91139solute carrier family1.00 192.00
1 (neuronallepithe
419574AK001989Hs.91165hypothetical protein1.00 94.00
419968X04430Hs.93913interleukin 6 (interferon,61.16500.00
beta 2)
1 420256084722Hs.762D6cadherin 5, type 0,52 1.70
~ 2, VE-cadherin
(vascula
420285AA258124Hs.293878ESTs, Moderately 1.00 172.00
similar to ZN91
HUMAN Z
420577AA278436Hs.186649ESTs 1.00 97.00
421262AA2867d6Hs.9343Homo Sapiens cDNA f.00 64.00
FLJid265 fis, clone
PL
421445AA913059Hs.104433Homo Sapiens, clone0.88 1.51
IMAGE:4054868,
mRNA
15 421470827496Hs.1378annexin A3 0.05 11.26
421478AI683243Hs.97258ESTs, Moderately 1.00 73.00
similar to 529539
dbos
421563NM Hs.105806granulysin 0.82 2.42
006433
d21566NM_000399Hs.1395early growth response5.50 31.57
2 (Krox-20 (Drosop
421855F06504Hs.27384ESTs, Moderately 1.00 129.00
similar to ALU4-HUMAN
A
421913AI934365Hs.109439osleoglycin (osteoinductive1.00 101.00
factor, mime
421952AA300900Hs.98849ESTs, Moderately 0.60 63.60
similar to AF161511
1 H
422232D43945Hs.113274iranscriptionfactor1.00 148.00
EC
422386AF105374Hs.115830heparan sulfate 1.40 3.98
(glucosamine) 3-0-sulfot
423168834385Hs.124940GTP-binding protein0.34 3.59
25 423196AK001866Hs.125139hypothetical protein0.55 2.00
FLJ11004
423387AJ012074 vasoactiveintesfinalpepfidereceptorl0,09 2.13
423424AF150241Hs.128433prostaglandin D2 1,00 141.00
synthase, hematopoietic
423456AL110151Hs.128797DKFZP586D0824 protein1.00 66.00
423696292546 Sushi domain (SCR 0,73 1.27
repeat) containing
3 424027AW337575Hs.201591ESTs 0.5d 2.58
~
424212NM-005814Hs.143131glycoprotein A33 0.77 2.47
(lransmembrane)
425087862424Hs.126059ESTs 1.00 74.00
425175AF020202Hs.155001UNC13 (C. elegans)-like0.85 1.96
425771BE561776Hs.159494Bruton agammaglobulinemia1.18 2.56
tyrosine kings
3 426486BE178285Hs.170056Homo Sapiens mRNA; 1.00 76.00
cDNA DKFZp586B0220
(f
427507AF240467Hs.179152toll-like receptor 1.00 63.00
7
427618NM-000760Hs.2175colony stimulafingfactor3receptor(gr0.60 2.19
427732NNLD02980Hs.2199secretin receptor 0.97 1.42
427952AA765368Hs.293941ESTs, Moderately 1.00 105.00
similar to A53959
throm
428709BE268717Hs,104916hypothetical protein1.00 80.00
FLJ21940
428769AW207175Hs.106771ESTs 0.09 2.55
428780AI478578Hs.50636ESTs 1.00 98.00
428833AI928355Hs.185805ESTs 1.00 113.00
429657D13626Hs.2465KIAA0001 gene product;1.00 52.00
putative G-protei
45 430212AA469153 gb:nc67f04.s1 NCI-CGAP_Pr11.00 132.00
Homo Sapiens
d30226BE245562Hs.2551adrenergic, beta-2-,0.11 15.60
receptor, surface
430376AW292053Hs.12532chromosome 1 open 1.00 103.00
reading frame 21
43041dAW365665Hs.120388ESTs 0.50 6.96
430656AA482900Hs.162080ESTs 1.00 70.00
430843AI734149Hs.119514ESTs 1.00 90.00
430998AF128847Hs.204038indolethylamine 0.29 1.84
N-methyltransferase
431217NM Hs.250830Rho GTPase activating1.00 79.00
013427 protein 6
431921N46466Hs.58879ESTs 0.91 1.67
432176AW09D386Hs.112278arrestin, beta 1 0.66 2.63
5 432203AA305746Hs.49macrophage scavenger1.00 76.00
5 receptor 1
432231AA339977Hs.274127CLST 11240 protein 0.46 1.46
432485N90866Hs.276770CDW52 antigen (CAMPATH-10.79 2.25
antigen)
432522D11466Hs.51phosphatidylinositol1.93 4.83
glycan, class A
(pa
432596AJ224741Hs.278461matrilin 3 0.04 5.79
6~ 432850X87723Hs.31f0angiotensin receptor21.00 167.00
433138A8029496Hs.59729semaphorin sem2 0.04 9.16
433563AI732637Hs.277901ESTs 1.00 91.00
433588A1056872Hs.133386ESTs f20.i6315.00
434445AI349306Hs.11782ESTs 0.60 1.84
65 435496AW840171Hs.265398ESTs, Weakly similar1.00 128.00
to transformation-r
435974029690Hs.37744Homo Sapiens beta-11.00 108.00
adrenergic receptor
436061AI248584Hs.190745Homo Sapiens cDNA: 1.00 91.00
FLJ21326 fis, clone
C
437157BE048860Hs.120655ESTs 1.00 87.00
437207T27503Hs.15929hypotheficalprotein1.00 105.00
FLJ12910
437311AA370041Hs.9456SWIISNF related, 1.00 71.00
matrix associated,
acti
437439H29796Hs.269622ESTs 1.00 115.00
438199AW016531Hs.122147ESTs 1.00 80.00
439551W72062Hs.i1112ESTs 0.30 3.10
440515AJ131245Hs.7239SEC24 (S. cerevisiae)1.00 77,00
related gene famil
75 440887AI799488Hs.135905ESTs 1.00 85.00
441025AA913880Hs.176379ESTs 1.00 82.00
441384AA4478d9Hs.288660Homo Sapiens cDNA: 0.79 1.89
FLJ22f 82 fis,
clone H
441735AI738675Hs.127346ESTs 1.00 75.00
442200AW590572Hs.235768ESTs 0.78 5.83
442832AW206560Hs.253569ESTs 0.03 10.88
442957A1949952Hs.49397ESTs 1.00 70.00
443282T47764Hs.132917ESTs 1.00 197.00
443547AW271273Hs.23767hypotheficalprotein1.00 253.00
FLJ12666
443951F13272Hs.111334femfin,lightpolypepfide0.55 2.09
444330A1597655Hs.49265ESTs 1.00 90.00
173
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444515AW204908Hs.169979ESTs 1.00 84.00
445769A17d1471Hs.23666ESTs 0.02 4.38
445908813580Hs.13436Homo Sapiens clone 1.00 97.00
24425 mRNA sequence
446291BE397753Hs.14623interferon, gamma-inducible0.93 1.69
protein 30
446917AI347863Hs.156672ESTs 1.00 106.00
447261NM Hs.17917extracellularlinkdomain-containing0.40 47.20
006691 1
447432AW958473Hs.301957nudix (nucleoside 1.00 100.00
diphosphate linked
moi
447482AB033059Hs.18705KIAA1233 protein 0.05 8.21
447997H00656Hs.29792ESTs, Weakly similar0.02 5.42
to 138022 hypoiheti
1 448299AA497044Hs.20887hypothetical protein1.00 79.00
~ FLJ10392
448782AL050295Hs.22039KIAA0758 protein 0.42 1.56
450575NM Hs.29117pudne-rich element 0.17 11.33
005859 binding protein
A
450584AA040403Hs.60371ESTs 1.00 94.00
450693AWd50461Hs.203965ESTs 1.00 91.00
15 450715A1266484Hs.31570ESTs, Weakly similar1.00 152.00
to KIAAi 324 protein
451103852804Hs.25956DKFZP564D206 protein1.00 86.00
451220AF124251Hs.26054novel SH2-containing0.60 1.30
protein 3
451668243948Hs.326444cartilage acidic 0.54 1.91
protein 1
452197AW023595Hs.232048ESTs 1.00 67.00
452331AA598509Hs.29117purine-rich element4.53 11.07
binding protein
A
452353C18825Hs.29191epithelial membrane0.72 2.24
protein 2
453049BE537217Hs.30343ESTs 1.00 68.00
453107NM_016113Hs.2797d6vanilloid receptor-like0.83 1.70
protein 1
453355AW295374Hs.31412Homo Sapiens cDNA 1.00 132.00
FLJ11422 fis, clone
HE
25 453390AA862496Hs.28482ESTs 1.00 72.00
453531AA417940 ESTs, Weakly similar1.0D 68.00
to JC5795 CDEP
prot
454741BE154396 gb:CM2-HT0342-091299-050-b050.57 2.89
HT0342 Homo
456579AA287827Hs.284205up-regulated by 1.00 82.00
BCG-CWS
456672AK002016Hs.114727Homo Sapiens, clone0.79 1.96
MGC:16327, mRNA,
com
457400AF032906Hs.2525d9calhepsin Z 1.03 3.25
457718F18572Hs.22978ESTs, Weakly similar1.00 113.00
to ALU4_HUMAN ALU
S
459696F03027 gb:HSC1KA072 normalized1.00 544.00
infant brain cDN
35 TABLE 10B
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
4~ Pkey CAT Accession
Number
408074103684_1820723 AA263003 AA333916 AA334725 AA334151 AW965490
AA310513 AI810530 031302 AWi34897 AA830127 AA046953
AI668930
C06094 AW104534
4116671253334BE160198 AW935898 T11520 AW935930 AW856073 AW861034
1
4135331375344BE146973 BE146972 BE147042 BE147018 BE146783 BE147020
1 BE146781 BE147019 BE146766 BE147021 BE146952 BEid6767
BE14704d
45 _ BE146797 BE146776 BE146985 BE146793 BE146768 BE1d6771
BE146954 BE146760 BE1d7048 BE1d7025 BE147030
42338722779 AJ012074 011087 L13288 X75299 L20295 AW630780 H1d880
1 T28037 A1872991 872136 AW449839 T81622 T79697 T29519
894105 T83923
_ 873300 AI797007 873390 AA961010 H74168 AI689932 BE045543
AI808418 A1608912 AI806573 AW88408d AW872978 AW872985
AA565655
A1022915 850647 873210 H45098 846451 AW166269 T71132
AI264547 852146 AI304920 873391 AW884059 AW884085
H73241 T60038
T79612 873145 850549 A1094551 AI66B793 872302 AI564366
W01956 AA418962 W32571 872840 H45d09 872065 846356
846756
AA508805 AA418798 T83751 894072 T16182 AA928785 AA903896
42369623112_1292546 AA330586 AI570568 AW341d87 AI827050 AW298668
AI792189 A1015693 AI733599 AI572251 AI672488 AW193262
AI244716
AI864375 AI206100 AA912444 AI269365 AI6d0254 AW772d66
AI867336 AA627604 H16914 AA358477 AA338009
430212314437_1AA469153 AI718503 AA469225
436532421802 AA721522 AW975443 T93070
1
S 45353197026_1AA417940 AA036735 T07025
4547411232559_1BE154396 AW817959 BE154393
C)O TABLE 10C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham I. et al." refers tc the publication entitled
'The DNA
sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495.
Strand: Indicates DNA strand from which exons were predicted.
65 N~posilion: Indicates nucleotide positions of predicted exons.
Pkey Ref StrandNt-position
4007547331445Plus 144559-144684
4010458117619Plus 90044-90184,91111-91345
4010833242744Plus 33192-33360
4024747547175Minus53526-53628,55755-55920,57530-57757
4028086456148Minus114964-115136,115461-115585,115931-116047,117666-
117771,118004-118102
4030217547270Plus 120799-120966
4034219665041Minus126609-126773,139986-140205
75 4034389719679Plus 90792-90938
4036877387384Plus 9009-9534
4037647717105Minus118692-118853
4042771834458Minus91665-91946
4042882769644Plus 3512-3691
4043943135305Minus37121-37205,37491-37762,41053-41140,41322-41593,41773-41919
4045188151988Plus 84494-84603
4049167341826Plus 91057-91188
4051068079395Minus80877-81418
4052577329310Plus 73121-73273
4053816006920Minus7636-8054
174
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406387 9256180 Plus ti6229-ii637i,ii75i2-1i765i
175
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TABLE 11A: Genes Distinguishing Adenocarcinoma from Other Lung Diseases and
Normal Lung
Table 11A shows about 84 genes upregulated in lung adenocarcinomas relative to
other lung tumors, non-malignant lung disease, and normal lung. These genes
were selected
from about 59680 probesets on the Eos/Affymetrix Hu03 Genechip array.
Table 11 B show the accession numbers for those Pkey's lacking UnigenelD's for
table 11A. For each probeset we have listed the gene cluster number from which
the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and AlignmentTools (DoubleTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
l 0 "Accession" column.
Table 11 C show the genomic positioning for those Pkey's lacking Unigene ID's
and accession numbers in table 11A. For each predicted exon, we have listed
the genomic
sequence source used for prediction. Nucleotide locations of each predicted
exon are also listed.
Pkey:Unique
Eos
probeset
identifier
number
15 FxAccn:Exemplar
Accession
number,
Genbank
accession
number
UnigenelD: e
Unigen number
Unigene
Title:
Unigene
gene
title
R1: Average
of
lung
tumors
(including
squamous
cell
carcinomas,
adenocarcinomas,
small
cell
carcinomas,
granulomatous
and
carcinoid
tumors)
divided
by
the
average
of
normal
lung
samples
R2: Average nant lung disease hysema,
of samples (including fibrosis,
non-malig bronchitis, emp atelectasis,
asthma)
divided
by
the
average
of
normal
lung
samples
Pkey ExAccnUnigenelDUnigeneTitle R1 R2
403329 Target Exon 1.00 61.00
406399 NN-003122':Homo 1.00 39.00
sapiens serine
protease
406690M29540Hs.220529carcinoembryonic 226.37350.00
antigen-related
cell ad
407869AI827976Hs.24391hypothetical protein0.77 1.18
FLJ13612
407881AW072003Hs.40968heparan sulfate 1.00 10.00
(glucosamine) 3-0-sulfot
408908BE296227Hs.250822serine/threonine 7.76 1.00
kinase 15
409103AF251237Hs.112208XAGE-1 protein 80.4440.00
409187AF154830Hs.50966carbamoyl-phosphate1.00 1.00
synihetase 1, mitoch
409269AA576953Hs.22972hypothetical protein1.00 1.00
FLJ13352
410076T05387Hs.7991ESTs 1.12 1.50
410102AW248508Hs.279727Homo Sapiens cDNA 9.89 1.00
FLJ14035 fis, clone
HE
4103998E068889 synuclein, gamma 0.92 1.06
(breast cancer-specific
35 411908L27943Hs.72924cytidinedeaminase 1.00 1.00
412612NM-000047Hs.74131arylsulfatase E 1.02 1.03
(chondrodysplasia
puncta
414075Ui Hs.75741amiloride binding 0.84 1.07
1862 protein 1 (amine
oxida
416208AW291168Hs.41295ESTs, Weakly similar3.67 1.00
to MUC2-HUMAN MUCIN
417542J04129Hs.82269progestagen-associated1.28 1.35
endometrial prote
419183U60669Hs.896fi3cytochrome P450, 1.00 1.00
subfamily XXtV
(vitamin
419502AU076704 fibrinogen, A alpha13.05115.00
polypeptide
419631AW188117Hs.303154popeye protein 3 1.00 13.00
420931AF044197Hs.100431small inducible 1.00 8.00
cytokine B subfamily
(Cy
421155H87879Hs.102267lysyl oxidase 1.00 15.00
45 421190U95031Hs.102482mucin 5, subtype 1.17 1.55
B, tracheobronchial
d21474U76362Hs.104637solute carrier family1.46 1.76
1 (glutamate traps
421515Y11339Hs.105352GaINAc alpha-2, 1.00 3.00
6-sialyltransferase
I, I
421582AI910275 trefoil factor 1 1.23 1.00
(breast cancer,
estroge
422026U80736Hs.110826trinucleotide repeat1.00 52.00
containing 9
50 422095AI868872Hs.282804hypothetical protein4.37 2.34
FLJ22704
422311AF073515Hs.114948cytokine receptor-like1.15 1.78
factor 1
422867L32137Hs.1584cartilage cligomeric1.69 3.17
matrix protein
(pse
423472AF041260Hs.129057breast carcinoma 48.1372.00
amplified sequence
1
423554M90516Hs.1674glutamine-iructose-6-phosphate1.00 50.00
transamin
55 424502AF242388Hs.149585lengsin 1.00 1.00
424544M88700Hs.150403dopa decarboxylase 1.00 59.00
(aromatic L-amino
aci
424905NA~002497Hs.153704NIMA (never in mitosis21.351.00
gene a)-related
k
424960BE245380Hs.1539525' nucleotidase 1.00 1.00
(CD73)
425523AB007948Hs.158244KIAA0479 protein 1.00 35.00
426230AA367019Hs,241395protease, serine,1 1.00 83.00
(trypsin 1)
427701AA411101Hs.243886nuclear autoaniigenic7.41 34.00
sperm protein (his
428585AB007863Hs.185140KIAA0403 protein 1.00 6.00
428758AA433988Hs.98502hypothetical protein1.06 1.13
FLJ14303
429170NM Hs.2359dual specificity 16.18105.00
001394 phosphatase 4
65 429263AA019004Hs.198396ATP-binding cassette,1.07 1.00
sub-family A (ABC1
429610AB024937Hs.211092LUNX protein; PLUNC1.59 1.69
(palate lung and
pas
430508A1015435Hs.104637ESTs 4.75 7.27
430985AA490232Hs.27323ESTs, Weakly similar0.94 1.28
to 178885 serinelth
431548AI834273Hs.9711novel protein 5.66 15.00
431566AF176012Hs.260720J domain containing49.7637.00
protein 1
431986AA536130Hs.149018Novel human gene 1.19 1.47
mapping to chomosome
20
432375BE536069Hs,2962S100 calcium-binding1.65 1.06
protein P
432677NM_004482Hs.278611UDP-N-acetyl-alpha-D-galactosamine:polyp1.00 48.00
433556W56321Hs.111460calciumlcalmodulin-dependent1.00 19.00
protein kin
75 433819AW511097Hs.112765ESTs 3.71 8.00
434001AW950905Hs.3697serine (or cysteine)29.3172.00
proteinase inhibito
434424AI811202Hs.325335Homo Sapiens cDNA: 1.00 64.00
FLJ23523 fls, clone
L
434792AA649253Hs.132458ESTs 8.52 44.00
436217T53925Hs.107fibrinogen-Pike 57.9731.00
1
436749AA584890Hs.5302lectin, galactoside-binding,1.10 1.41
soluble, 4
436972AA284679Hs.25640claudin 3 1.59 1.46
437866AA156781 metallothionein1E(functional)3.62 101.00
437935AW939591Hs.5940mucin 13, epithelial1.60 1.39
transmembrane
438915AA280174Hs.285681Williams-Beuren 1.00 1.0D
syndrome chromosome
regi
g5 439451AF086270Hs.278554heterochromatin-like23.2852.00
protein 1
176
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439759AL359055Hs.67709Homo sapiens mRNA 1.0D 21.00
full length insert
cDN
441031AI1106B4Hs.7645fibrinogen, 8 beta 1.41 99.00
polypeptide
441377BE218239Hs.202656ESTs 22.031.00
443614AV655386Hs.7645fibrinogen, B beta 1.00 16.00
polypeplide
443813AA876372Hs.93961Homo sapiens mRNA; 1.20 1.99
cDNA DKFZp667D095
(fr
443991NM Hs.10082potassium intermediatelsmall5.71 6.87
002250 conductance
444670H58373Hs.332938hypothetical protein1.9B 38.00
MGC5370
444931AV652066Hs.75113general transcription1.00 54.00
factor IIIA
446102AW168067Hs.317694ESTs 1.00 1.00
1 446163AA026880Hs.25252Homo sapiens cDNA 1.00 36.00
~ FLJ13603 fis, clone
PL
446469BE094848Hs.15113homogentisate 1,2-dioxygenase1.00 11.00
(homogenti
447388AW630534Hs.76277Homo sapiens, clone1,24 1.16
MGC:9381, mRNA,
comp
447532AK000614Hs.18791hypothetical protein1.23 1.63
FLJ20607
448243AW369771Hs.52620integrin, beta 8 15.841.00
1 448844A1581519Hs.177164ESTs 1.00 31.00
449444AW818436Hs.23590solute carrier family1.00 83.00
16 (monocarboxylic
451807W52854 hypoiheUcal protein1.55 35.00
FLJ23293 similar
to
452689F33868Hs.284176transferrin 1.54 1.44
453392023762Hs.32964SRY (sex determining1.00 16.00
region Yj-box 11
453464AI8B4911Hs.32989receptor (calcitonin)1.55 2.45
activity modifying
453735A1066629Hs.125073ESTs 1.01 1.30
TABLE 11 B
25 Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession. Genbank accession numbers
Pkey CAT Number Accession
410399 11995-1' BE068889 BE068882 AF04d311 AF017256 NM-003087 AF037207
AF010126 AA633976 AA872836 BE298825 BE299889 A1016464 AI684600
A1936527 AA804675 AA394097 A1139933 AA946606 BE171313 AA722407 AA293803
A1468480 AA056035 AA055968 AW796957 A1637713
AA410737 H49348 AA486472 AA411094 AA235594 AA402624 AA443638 AW452137 AA421708
AW26521 1 AI493266 AA365132 AW966044
4195D2 18535-1 AU076704174854174860
T720981732651738731691801746581587861603851734101687811678451675931739521678641
60630
168367168401153959172360172099160377158961171712172821 164738174645172037
168688172063 173258172826164242
3 J~ T6B22D 174673171800168355161227162738 769317153850164692173768173962
T733B2168914170975173400160631173277
17320317(1498161409158925 NM 000508
M64982168301173729169445160424167922167736168716167755174765173619 158719
174756160477174863161109168329158850171851173425153736168607
T5B898164309172031172079164305171908168107
1719161737871560351644251718701604761613761678201718951410061694411681701746171
71958169440161875 806796
H48353171914153939164121 AA693996172525167779 168078 AA011465 AA345378
AV654847 AV654272 AV656001 A1064740182897
4o N33594 AA344542 AW805054 AI207457161743 AA026737 H94389 AA382695 AA9184D9
168044 S82092139959 A1017721 AA312395
AA312919140156 H66239 AV652989 H3B72B 898521 AV655200 895790 W03250 W00913
AA344136 AV660126 897923 AA343596
AWd70774 AV651256 N54417 AA812862 AWi82929 Alt 11192 H61463 H72060 AA344503
H38639 AI277511 AV661108 AI207625147810
AA235252 127853147778 895746 H70620 AA701463 AW827166 898475 C20925
AV657287171959171313173920173333161618169293
169283173931172178172456 AV645639
AV653476172957172300158906171457170494172956170495168267174407185778
45 AA34d726127854 174485174101173868171518172304 AA343853173909168070172065
H72149173493173495 AV645993 802293
170475164751 AA344441 AA343657 AA345732 AA344328 AI110639 AA344603
AF063513164696168516172223160507167633 829500
172517 802292160599169206170452174677 829366161277174914160352 829675174843
AV645792 AA344408169197172057
169368 169358 168258 AV650429 173341161702174598140095 K02272140106 AA343045
AA34i 908 AA341907 AA342807 AA341964
153747172042162764 A1064899 AA343060167832172440171770168091169108172449
769167171289168251 AV654844164375
5 o AA345234167598 AA011414168036 H48262 At207557168219 W86031169081164232
893196162136 AVfi50539 H67459172978
AA344583160362 H58121195711172803168055171715
829036172793169122164595162888169139168291164652167971146862
AA693592 AI248502 829454164764157001773052171429151176158866 AV655414 H90426
AA342489173666 167848 172512153835
767837173317174273169420168245 774380167862 774474156068
421582 2041 1 AI910275 X00474 X52003 X05030 NM 003225 AA314326 AA308400
AA506787 AA314825 AI571948 AA507595 AA614579 AA587613 883818
55 AA56B312 AA614409 AA3D7578 AI925552 AW950155 AI910083 M12075 BE074052
AW004668 AA578674 AA582084 BE074053 BE074126
BE074140 AA514776 AA588034 BE074051 BE074068 AW009769 AW050690 AA85B276 855389
A1001051 AW050700 AW750216 AA614539
BE074045 AI307407 AW602303 BE073575 AI202532 AA524242 AI970839 AI909751
BE076078 AI909749 855292
437866 44433_2 AA156781 AW293839 052054 AA024963 AA778446 BE073977 AW444904
AW602574 BE164040 BE164012 BE163972 BE163974 BE163992
AA837481 AW468444 BE185091 AW468002 AA687333 AA811830 AA581806 AI866686
AI57212d AA043777 AA040926 D20160 AI536733
AA812489 AW874142 AI471883 W84421 AA156850
451807 8865 1 W52854 AL117600 BE208116 BE20B432 BE206239 BE082291 AW953423
AA351619 BE180648 BE140560 W60080 AAB65478 N90291
AW450652 AW449519 AA993634 AI806539 AA351618 AWd49522 AI827626 AA904788
AA380381 AA886045 AA774409 BE003229 241756
65 TABLE 11C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham I. et al." refers to the publication entitled
'The DNA
sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-095.
Strand: Indicates DNA strand from which axons were predicted.
Nt_position: Indicates nucleotide positions of predicted axons.
Pkey Ref Strand Nt_position
403329 8516120 Plus 96450-96598
7S 406399 9256288 Minus 63448-63554
177
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WO 02/086443 PCT/US02/12476
TABLE 12A: Genes Distinguishing Squamous Cell Carcinoma from Other Lung
Diseases and Normal Lung
Table 12A shows about 72 genes upregulated in squamous cell carcinomas of the
lung relafive to other lung tumors, non-malignant lung disease, and normal
lung. These genes
were selected from about 59680 probesets on the EosIAffymetrix Hu03 Genechip
array.
Table 128 show the accession numbers for those Pkey's lacking UnigenelD's for
table 12A. For each probeset we have listed the gene cluster number from which
the
oligonucleofides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Tools (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
Table 12C show the genomic positioning for those Pkey's lacking Unigene ID's
and accession numbers in table 12A. For each predicted exon, we have listed
the genomic
sequence source used for prediction. Nucleotide locations of each predicted
exon are also listed.
Pkey: Unique
Eos
probeset
identifier
number
ExAccn:Exemplar .
Accession
number,
Genbank
accession
number
UnigenelD:Unigenenumber
Unigenee: gene
Titl Unigenetitle
R1: Averageof
lung
tumors
(including
squamous
cell
carcinomas,
adenocarcinomas,
small
cell
carcinomas,
granulomatous
and
carcinoid
tumors)
divided
by
the
averageof samples
normal
lung
R2: Averageof
non-malignant
lung
disease
samples
(including
bronchitis,
emphysema,
fibrosis,
atelectasis,
asthma)
divided
by
the
average
of
normal
lung
samples
Pkey ExAccnUnigenelDUnigeneTifie R1 R2
400289X07820Hs.2258matrix metalloproteinase132.454.00
10 (stromelysin
400666 NM 002425:Homo Sapiens3.26 3.22
matrix metallopro
401780 NM_00555T:Homo Sapiens26.47 10.50
keratin 16 (foca
401781 Target Exon 10.33 4.61
401785 NM_002275':Homo 4.13 2.70
Sapiens keratin
15 (KRT1
401994 TargetExon 61.84 47.00
402075 ENSP00000251056':Plasma1.00 1.00
membrane calcium
404996 Target Exon 1.00 1.00
407839AA045144Hs.161566ESTs 173.91108.00
408000L11690Hs.620bullous pemphigoid 151.178.00
antigen 1 (2301240kD)
408522AI541214Hs.46320Small praline-rich 1.98 1.24
protein SPRK [human,
410561BE540255Hs.6994Homo Sapiens cDNA: 10.04 1.00
FLJ22044 fis, clone
H
415091AL044872Hs.779103-hydroxy-3-methylglutaryl-CoenzymeAsy1.00 30.00
415817U88967Hs.78867protein tyrosine 24.30 1.00
phosphatase, receptor-t
416658U03272Hs.79432fibrillin 2 (congenital53.29 51.00
contractural ara
417034NM Hs.80962neurotensin 1.00 1.00
006183
417366BE185289Hs.1076small praline-rich 8.97 3.27
protein 1B (comifin)
418663AK001100Hs.41690desmocollin 3 112.1719.00
418678NM-001327Hs.87225cancerltesfis antigen1.18 1.10
419121AA374372Hs.89626parathyroid hormone-like1.00 1.00
hormone
420783AI659838Hs.99923lectin, galactoside-binding,3.04 1.25
soluble, 7
421773W69233Hs.112457ESTs 1.12 1.14
421948L42583Hs.334309keratin 6A , 51.83 20.25
421978AJ243662Hs.110196NICE-1 protein 1.01 0.91
422158L10343Hs.112341protease inhibitor 2.37 1.10
3, skin-derived
(SKAL
422440NM Hs.116724atria-keto reductase47.53 32.00
004812 family 1, member
810
423634AW959908Hs.1690heparin-binding 76.02 1.00
growth factor binding
pr
423725AJ403108Hs.132127hypothetical protein4.20 1.00 ,
LOC57822
423738AB002i34Hs.132195airway lrypsin-like10.14 51.00
protease
424012AW368377Hs.i37569tumor protein 63 233.4268.00
kDa with strong
homolog
424046AF027866Hs.138202serine (orcysteine)1.00 1.00
proteinase inhibito
424098AF077374Hs.139322small praline-rich 137.8254.00
protein 3
424834AK001432Hs.153408Homo Sapiens cDNA 56.19 12.00
FLJ 10570 fis,
clone NT
425650NM_001944Hs.1925desmoglein 3 (pemphigus33.45 1.00
vulgaris antigen
427099AB032953Hs.173560odd Ozlten-m homolog4.24 17.00
2 (Drosophila,
mous
427335AA448542Hs.251677G antigen 7B 51.83 4.00
428182BE386042Hs.293317ESTs, Weakly similar1.00 1.00
to GGC1 IiUMAN
G ANT
428645AA431400Hs.98729ESTs, Weakly similar1.00 16.00
to 2017205A dihydro
428748AW593206Hs.98785Ksp37 protein 1.00 87.00
429259AA420450Hs.292911ESTs, Highly similar2.01 1.18
to S60712 band-6-pr
429538BE182592Hs.11261small praline-rich 4.43 2.90
protein 2A
429903AL134197Hs.93597cyclin-dependentkinase11.80 1.00
5,regulatory su
430486BE062109Hs.241551chloride channel, 12.28 41.00
calcium activated,
fam
430890X54232Hs.2699glypican 1 1.58 1.40
431009BE149762Hs.48956gap junction protein,60.25 28.00
beta 6 (connexin
3
431846BE019924Hs.271580uroplakin 1B 4.49 2.51
433091Y12642Hs.3185lymphocyte antigen 1.20 1.09
6 complex, locus
D
434360AW015415Hs.127780ESTs 40.98 27.00
434880U02388Hs.101cytochrome P450, 1.00 1.00
subfamily IVF,
polypept
435505AF200492Hs.211238inlerleukin-1 homolog1.00 38.00
1
435793AB037734Hs.4993KIAA1313 protein 23.68 42.00
436511AA721252Hs.291502ESTs 16.76 14.00
438403AA806607Hs.292206ESTs 1.00 1.00
439285AL133916 hypotheticalprotein46.23 139.00
FLJ20093
439606W79123Hs.58561G protein-coupled 33.61 1.00
receptor 87
439670AF088076Hs.59507ESTs, Weakly similar1.00 1.00
to AC004858 3 U1
sm
439706AW872527Hs.59761ESTs, Weakly similar86.55 11.00
to DAP1 HUMAN DEATH
440325NM Hs.7164a disintegrin and 62.88 147.00
003812 metalloproteinase
doma
441525AW241867Hs.127728ESTs 1.53 1.42
443162T49951Hs.9029DKFZP434G032 protein31.11 38.00
444378841339Hs.12569ESTs 1.00 1.00
178
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446292 AF081497Hs.279682Rh type C glycoprotein1,55 1.26
447078 AW885727Hs.991dESTs 47.24 24.00
447342 AI199268Hs.19322Homo Sapiens, Similar28.63 1.00
to RIIfEN cDNA
2010
449003 X76342Hs.389alcohol dehydrogenase1.00 1.00
7 (class IV),
mu o
S 449101AA205847Hs.23016G protein-coupled 2.58 27.00
receptor
450832 AW970602Hs.105421ESTs 25.17 36.00
452240 A1591i47Hs.61232ESTs 13.42 1.00
453317 NM-002277Hs.41696keratin, hair, 1.19 1.27
aoidic,1
453830 AA534296Hs.20953ESTs 24.92 25.00
1 ~ 454098W27953Hs.292911ESTs, Highly similar1.26 1.11
to S60712 band-6-pr
455601 AI368680Hs.816SRY (sex determining206.111.00
region Y)-box
2
TABLE 128
1 S Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT Number Accession
2~ 43928547065_1 AL133916 N79113 AF086101 N76721 AW950828 AA364013
AW955684 AI346341 AI867454 N54784 AI655270 AI421279
AW014882
AA775552 N62351 N59253 AA626243 AI341407 BE175639 AA456968
AI358918 AA457077
TABLE
12C
ZS ,
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column
are Genbank Identifier (GI) numbers. "Dunham I. et
al." refers to the publication entitled 'The DNA
sequence of human chromosome 22." Dunham I. et al" Nature
(1999) 402:489-495.
SUand:Indicates DNA strand from which exons were predicted.
N>_position:Indicates nucleotide positions of predicted exons.
Pkey Ref Strand Nt_position
4006668118496 Plus 17982-18115,20297-20456
4017807249190 Minus 28397-28617,28920-29045,29135-29296,29di1-29567,29705-
29787,30224-3D573
3S 4017817249190 Minus 83215-83435,83531-83656,83740-83901,84237-84393,84955-
85037,86290-86814
4017857249190 Minus 165776-165996,166189-166314,166408-166569,167112-
167268,167387-167469,16663-0-168942
4019944153858 Minus 42904-43124,43211-43336,44607-44763,45199-45281,46337-
46732
4020758117407 Plus 121907-122035,122804-122921,124019-124161,124455-
124610,125672-126076
4049966007890 Plus 37999-38145,38652-38998,39727-39872,40557-40674,42351-42450
40
179
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TABLE 13A: Genes Distinguishing Non-Malignant Lung Disease from Lung Tumors
and Normal lung
Table 13A shows about 23 genes upregulated in non-malignant lung disease
relative to lung tumors and normal lung. These genes were selected from about
59680 probesets on
the EosIAffymetrix Hu03 Genechip array.
Table 138 show the accession numbers for those Pkey's lacking UnigenelD's for
table 13A. For each probeset we have listed the gene cluster number from which
the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Tools (DoubleTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
1 O "Accession" column.
Table 13C show the genomic positioning for those Pkey's lacking Unigene ID's
and accession numbers in table 13A. For each predicted exon, we have listed
the genomic
sequence source used for prediction. Nucleofide locations of each predicted
exon are also listed.
15Pkey:Unique Eos probeset identifier
number
ExAccn:Exemplar Accession number,
Genbank accession number
UnigenelD: Unigene number
Unigene
Title:
Unigene
gene
title
R1. Average of lung tumors (including
squamous cell carcinomas,
adenocaroinomas, small cell
carcinomas, granulomatous
and carcinoid tumors) divided
by the
2o average of normal lung samples
R2: Average of non-malignant lungphysema,atelectasis, asthma) divided
disease samples (including fibrosis,by the average of normal
bronchitis, em lung samples
Pkey ExAccn UnigenelD UnigeneTitleRt R2
408562AI436323 Hs.31141 Homo sapiens1.00 230.00
mRNA for KIAA1568 protein,
409031AA376836 Hs.76728 ESTs 1.00 128.00
412372865998 Hs.285243 hypothetical1.00 173.00
protein FLJ22029
415910020350 Hs.78913 chemokine 1.00 145.00
(GX3-C) receptor 1
417511AL049176 Hs.82223 chordin-like1.00 179.00
418819AA228776 Hs.191721 ESTs 1.00 140.00
422060820893 Hs.325823 ESTs, Moderately1.00 156.00
similar to ALU5_HUMAN A
424585AA464840 Hs.131987 ESTs 1.00 167.00
426753T89832 Hs.170278 ESTs 1.00 141.00
429496AA453800 Hs.192793 ESTs 1.00 138.00
430719AA488988 Hs.293796 ESTs 1.00 133.00
3 431089BE041395 ESTs, Weakly similar23.32 941.00
to unknown protein
431385BE178536 Hs.11090 membrane-spanning1.00 157.00
4-domains, subfamily A
431728NM_007351 Hs.268107 multimerin1.00 157.00
436532AA721522 gb:nv54h12.r1 NCI_CGAP_Ew11.00 218.00
Homosapiens
437960AI669586 Hs.222194 ESTs 1.00 147.00
438202AW169287 Hs.22588 ESTs 1.00 141.00
441499AW298235 Hs.101689 ESTs 1.00 167.00
444513AL120214 Hs.7117 glutamate 1.00 151.D0
receptor, ionotropic, AMPA
1
448253H25899 Hs.201591 ESTs 1.00 141.00
453636867837 Hs.169872 ESTs 1.00 1 l 6.00
45458332A1000341 Hs.220491 ESTs 1.00 192.00
459587AA031956 gb:zk15e04.s1 Soares~regnant_uterus-NbH1.00 154.00
TABLE 13B
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT Number Accession
5 5 431089 327825_1 BE041395 AA491826 AA621946 AA715980 AA666102
436532 421802_1 AA721522 AW975443 T93070
6o TABLE 13C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Idenfifier (GI) numbers. "Dunham I. et al."refers to the publication entitled
"fhe DNA
sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495.
Strand: Indicates DNA strand from which exons were predicted.
65 NLposition: Indicates nucleofide posifions of predicted exons.
Pkey Ref Strand Nt-position
,70 402075 8117407 Plus 121907-122035,122804-122921,124019-124161,124455-
124610,125672-126076
Ig
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
TABLE 14A: Preferred Utility and Subcellular Localization for Potenfial Lung
Disease Targets
Table 14A shows the subcellular localization and preferred utility for the
genes appearing in Tables 9A and 10A. mAb symbolizes monoclonal antibody, diag
symbolizes
diagnostic, s.m. symbolizes small molecule, and CTL symbolizes cytotoxic
lymphocytic ligand. These genes were selected from 59680 probesets on the
EoslAffymetrix Hu03
Genechip array.
Table 14B show the accession numbers for those Pkey's lacking UnigenelD's for
table 14A. For each probeset we have listed the gene cluster number from which
the '
otigonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESls and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and Alignment Toots (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
1 ~ "Accession" column.
Table 14C show the genomic positioning for those Pkey's lacking Unigene ID's
and accession numbers in table 14A, For each predicted exon, we have listed
the genomic
sequence source used for prediction. Nucleotide locafions of each predicted
exon are also listed.
15
Pkey:Unique
Eos
probeset
identifier
number
ExAccn:Exemplar
Accession
number,
Genbank
accession
number
UnigenelD:
Unigene
number
Unigene
Title:
Unigene
gene
title
Pref.Utility:
Preferred
Utility
Pred.Loc:Predicted
subcellular
localization
Pkey ExAccnUnigenelDUnigene Title Pref UtilityPred.
Loc
400289X07820Hs.2258matrix metalloproteinasemAb & extracellular
10 (stromelysin diag
& s.m.
400303AA242758Hs.79136LIV-1 protein, mAb plasma
estrogen regulated membrane
402075 ENSP00000251056':Plasma secreted
membrane calcium
mAb & diag
407811AW190902Hs.40098cysteine knot diag secreted
superfamily 1,
BMP antagon
408243Y00787Hs.624interleukin 8 diag secreted
408790AW580227Hs.47860neurotrophic tyrosinemAb & plasma
kinase, receptor,s.m. membrane
408908BE296227Hs.250822serinelthreonine s.m. cytoplasm
kinase 15
409041A8033025Hs.50081Hypothetical protein,CTL & secreted
XP 051860 (KIAA119diag
409103AF251237Hs.112208RAGE-1 protein CTL nuclear
409420215008Hs.54451laminin, gamma diag secreted
2 (nicein (100kD),
kalini
409632W74001Hs.55279serine (or cysteine)diag secreted
proteinase inhibito
35409757NM Hs.123114cystatin SN diag extracellular
001898
409893AW247090Hs.57101minichromosome CTL nuclear
maintenance deficient
(S.
409956AW103364Hs.727inhibin, beta diag extracellular
A (activin A,
aclivin AB a
410001A8041036Hs.57771kallikrein 11 diag extracellular
410407X66839Hs.63287carbonic anhydrasemAb & plasma
IX s.m. membrane
410418D31382Hs.63325transmembrane mAb & plasma
protease, sertne diag membrane
4 & s.m.
412140AA219691Hs.73625R4B6 interacting,s.m.
kinesin-like
(rabkines
412719AW016610Hs.816ESTs s.m. nuclear
414774X02419Hs.77274plasminogen activator,diag extracellular
urokinase
414883AA926960 CDC28 protein s.m.
kinase 1
45415138C18356Hs.295944tissue factor CTL & extracellular
pathway inhibitordiag
2
415669NM Hs.78589serine (or cysteine)mAb & secreted
005025 proteinase inhibitodiag
& s.m.
415817088967Hs.78867protein tyrosine mAb & plasma
phosphatase, s.m. membrane
receptor-t
416658003272Hs.79432fibriilin 2 (congenitaldiag extracellular
contractural
ara
417034NM Hs.80962neurotensin diag extracellular
006183
50417079065590Hs.81134interleukin 1 diag extracellular
receptor antagonist
417308H60720Hs.81892KIAA0101 gene s.m. mitochondrial
product
417389BE260964Hs.82045midkine (neurite mAb & secreted
growth-promoting diag
factor
417433BE270266Hs.821285T4 oncofetal mAb plasma
trophoblast glycoprotein membrane
417933X02308Hs.82962thymidylate synthetases.m. endoplasmic
reticulum
55418478038945Hs.1174cyclin-dependent s.m. cytoplasm
kinase inhibitor
2A (me
418506AA084248Hs.85339G protein-coupledmAb & plasma
receptor 39 s.m. membrane
418678NM Hs.167379cancerltestis CTL cytopiasmic
001327 antigen (NY-ESO-1)
419121AA374372Hs.89626parathyroid hormone-likediag secreted
hormone
419171NM Hs.89655protein tyrosine mAb & plasma
002846 phosphatase, s.m. membrane
receptor t
419183060669Hs.89663cytochrome P450, CTL & mitochondrial
subfamily XXIV s.m.
(vitamin
419216AU07671Hs.164021small inducible diag secreted
B cytokine subfamily
B (Cy
419235AW470411Hs.288433neurotdmin mAb & plasma
diag membrane
419452033635Hs.90572PTKl protein tyrosinemAb & plasma
kinase 7 s.m. membrane
419556029615Hs.91093chitinase 1 (chilotriosidase)mAb & extracellular'
diag
65420610AI683183Hs.99348distal-less homeoCTL nuclear
box 5
421110AJ250717Hs.1355calhepsin E sm & diagextracellular
421379Y15221Hs.103982small inducible diag secreted
cyfokine subfamily
B (Cy
421474076362Hs.104637solute carrier mAb & plasma
family 1 (glutamates.m. membrane
traps
421552AF026692Hs.105700secreted frizzled-relateddiag secreted
protein 4
70421753BE314828Hs.107911ATP-binding cassette,mAb & plasma
sub-family B s.m. membrane
(MDW
421817AF146074Hs.108660ATP-binding cassette,mAb & plasma
sub-family C s.m. membrane
(CFTR
422109S73265Hs.1473gastrin-releasingdiag secreted
peptide
422158L10343Hs.112341protease inhibitordiag secreted
3, skin-derived
(SKAL
422262AF019225Hs.114309apolipoprolein diag secreted
L
75422283AW411307Hs.114311CDC45 (cell divisions.m. nuclear
cycle 45, S.cerevis
422424AI186431Hs.296638prostate differentiationdiag extracellular
factor
422765AW409701Hs.1578baculoviral IAP s.m. cytoplasm
repeat-containing
5 (sur
422809AK001379Hs.121028hypothetical proteins.m. nuclear
FLJ10549
422867L32137Hs.1584cartilage oligomertcdiag extracellular
matrix protein
(pse
8~422956BE545072Hs.122579ECT2 protein (EpithelialCTL &
cell transforms s.m.
423634AW959908Hs.1690hepaitn-binding ding
growth factor
binding pr
423673BE003054Hs.1695matrtx metalloproteinasemAb & secreted
12 (macrophage diag
& s.m.
423961D13666Hs.136348periosfin (OSF-2os)mAb & exfracelluiar
diag
424046AF027866Hs.138202sertne (or cysleine)diag secreted
proteinase inhibito
g5424381AA285249Hs.146329protein kinase s.m. nuclear
Chk2
181
CA 02444691 2003-10-17
WO PCT/US02/12476
02/086443
424502AF242388Hs.149585lengsin s.m. cytoplasmic
424503NM Hs.149609integrin, alpha mAb plasma membrane
002205 5 (fibronectin & s.m.
receptor,
424687J05070Hs.151738matrix metalloproteinasediag extracellular
9 (gelatinase
B
425247NM Hs.155324matrix metalloproteinasemAb secreted
005940 11 (stromelysin & diag
& s.m.
425322U63630Hs.155637protein kinase, s.m. cytoplasmic
DNA-activated,
catalytic
425650NM Hs.1925desmoglein 3 (pemphigusmAb plasma membrane
001944 vulgads antigen
425734AF056209Hs.159396peptidylglycine s.m.
alpha-amidating
monooxyg
425776U25128Hs.159499parathyroid hormonemAb plasma membrane
receptor 2 & diag
425852AK001504Hs.159651death receptor mAb plasma membrane
6, TNF superfamily& s.m.
member
1 426215AW963419Hs.155223sianniocalcin 2 mAb secreted
~ & diag
426427M86699Hs.169840TTK protein kinaseCTL nuclear
& s.m.
426514BE616633Hs.170195bone morphogeneticmAb secreted
protein 7 (osteogenic& diag
427335AA448542Hs.251677G antigen 78 CTL cytoplasmic
427747AW411425Hs.180655serinelthreonine s.m. cytoplasmic
kinase 12
15428242H55709Hs.2250leukemia inhibitorydiag
factor (cholinergic
428330L22524Hs.2256matrix metalloproteinasemAb extracellular
7 (matrilysin, & diag
& s.m.
428450NM Hs.184339KIAA0175 gene products.m. nuclear
014791
428479Y00272Hs.334562cell division cycles.m. nuclear
2, G1 to S and
G2 to
428484AF104032Hs.184601solute carrier mAb plasma membrane
family 7 (cationic& s.m.
amino
2~428664AK001666Hs.189095similar to SALL1 CTL nuclear
(sat (Drosophila)-like& s.m.
428698AA852773Hs.334838KIAA1866 protein mAb
428748AW593206Hs.98785Ksp37 protein diag extracellular
428758AA433988Hs.98502CA125 antigen; ding mitochodria* -
mucin 16
428969AF120274Hs.194689artemin diag extracellular
25429211AF052693Hs.198249gap junction protein,mAb plasma membrane
beta 5 (connexin & s.m.
3
429263AA019004Hs.198396ATP-binding cassette,mAb plasma membrane
sub-family A (ABC1& s.m.
429547AW009166Hs.99376ESTs diag secreted
429610AB024937Hs.211092LUNX protein; PLUNCmAb secreted
(palate lung and & diag
nas
429903AL134197Hs.93597cyclin-dependent s.m.
kinase 5, regulatory
su
430486BE062109Hs.241551chloride channel, mAb plasma membrane
calcium activated,& s.m.
fam
431462AW583672Hs.256311granin-like neuroendocrinediag extracellular
peptide precu
431515NM Hs.258583endothelial differentiation,mAb plasma membrane
012152 lysophospha & s.m.
431846BE019924Hs.271580uroplakin 1 B mAb plasma membrane
& diag
431958X63629Hs.2877cadherin 3, type mAb plasma membrane
t, P-cadherin & diag
(placenta
3 432201AI538613Hs.298241Transmembrane protease,mAb plasma membrane
serine 3 & diag
& s.m.
433001AF217513Hs.279905clone H00310 PR00310p1s.m. nuclear
435505AF200492Hs.211238interleukin-1 homologdiag secreted
1
436481AA379597Hs.5199HSPC150 protein s.m.
similar to ubiquitin-con
437016AU076916Hs.5398guanine monphosphates.m. cytoplasm
synthetase
437044AL035864Hs.69517differentially CTL ER
expressed in Fanconi's
an
437789AI581344Hs.127812ESTs, Weakly similarCTL nuclear
to T17330 hypotheti
437852BE001836Hs.256897ESTs, Weakly similarmAb plasma membrane
to dJ365012.1 & s.m.
[H.sa
439223AW238299Hs.250618UL16 binding proteinmAb plasma membrane
2
439477W69813Hs.58042ESTs, Moderately mAb
similar to GFR3_HUMAN& s.m.
G
45439606W79123Hs.58561G protein-coupled mAb plasma membrane
receptor 87 & s.m.
439738BE246502Hs.9598sema domain, immunoglobulinmAb plasma membrane
domain (1g), & s.m.
440006AK000517Hs.6844NALP2 protein; s.m. nuclear
PYRIN-Containing
APAF1-li
441362BE614410Hs.23044RAD51 (S. cerevisiae)s.m.
homolog (E colt
Re
442117AW664964Hs.i ESTs; hypotheticalmAb plasma membrane
28899 protein for IMAGE:447& s.m.
443247BE614387Hs.333893c-Myc target JP01 CTL extracellular'
443426AF098158Hs.9329chromosome 20 openCTL
reading frame
1
443859NM-013409Hs.9914follistalin diag extracellular
444006BE395085Hs.10086type I transmembranemAb plasma membrane
protein Fnl4
444371BE540274Hs.239forkhead box Mi s.m. nuclear
55444381BE387335Hs.283713ESTs, Weakly similardiag secreted
to S64054 hypothe6
d4478tNM-014400Hs.11950GPI-anchored metastasis-associatedmAb plasma
membrane
prote & diag
445537AJ245671Hs.1284dEGF-like-domain, mAb secreted
multiple 6 & diag
446619AU076643Hs.313secreted phosphoproteindiag secreted
1 (osteopontin,
446921AB012113Hs.16530small inducible diag extracellular
cytokine subfamily
A (Cy
447033AI357412Hs.157601ESTs CTL secreted
& diag
447342A1199268Hs.19322Homo sapiens, SimilarCTL
to RIKEN cDNA
2010
448243AW369771Hs.52620integrin, beta mAb plasma membrane
8 & s.m.
-
448844AI581519Hs.177164ESTs mAb
& s.m.
449048245051Hs.22920similar to S68401 mAb plasma membrane
(cattle) glucose
induc
65449722BE280074Hs.23960cyclin Bi s.m. cytoplasm
450001NM_001044Hs.406solute carrier mAb plasma membrane
family 6 (neurotransmitte& s.m.
450375AA009647 a disintegrin and mAb plasma membrane
metalloproteinase & diag
doma & s.m.
450701H39960Hs.288467hypothetical proteinmAb plasma membrane
XP 098151 (leucine-& diag
450983AA305384Hs.25740ER01 (S. cerevisiae)-likediag secreted
451668143948Hs.326444cartilage acidic mAb plasma membrane
protein 1 & diag
452281T93500Hs.28792Homo sapiens cDNA diag
FLJ11041 fis,
clone PL
452401NM-007115Hs.29352tumor necrosis diag extracellular
factor, alpha-induced
pro
452747BE153855Hs.61460Ig superfamily mAb plasma membrane
receptor LNIR
452838U65011Hs.30743preferentially CTL nuclear
expressed antigenin
mela
75453968AA847843Hs.62711High mobility groupCTL nuclear
(nonhistone chromoso& s.m.
457489AI693815Hs.127179cryptic gene diag secreted
TABLE 148
8~ Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT Number Accession
182
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
414883 15024-1 AA926960 AA926959 W76521 W24270 W21526 AA037172 BE267636 H83186
AA469909 N86396 AA001348 BE535736 AA081745 BE566245
AA082436 H72525 H77575 N49786 W80565 H78746 BE569085 W04339 898127 T55938
BE279271 AW960304 T29812 AA476873 BE297387
AA292753 AA177048 NM_001826 X54941 BE314366 AA908783 AI719075 BE270172
BE269819 AA889955 A1204630 W25243 AI935150
AA872039 W72395 T99630 AI422691 H98460 N31428 BE255916 H03265 AI857576
AA776920 AA910644 AA459522 AA29314D AW514667
875953 AW662396 AA662522 AI865147 AI423153 AW262230 AA584410 AA583187 AW024595
AW069734 AI828996 AA282997 AA876046
AW613002 AA527373 AW972459 AI831360 AA621337 AA100926 AA772418 AA594628
A1033892 W95096 A1034317 AA398727 A1085031
N95210 AI459432 A1041437 AA932124 AA627684 AA935829 A1004827 AI423513 A1094597
H42079 854703 AI630359 AA617681 AA978045
AA643280 W44561 AI991988 AI537692 A1090262 AA740817 AI312104 AI911822 AA416871
AI185409 AA129784 AA701623 A1075239
AI139549 AA633648 AI339996 AI336880 AA399239 A1078708 A1085351 AI362835
AI346618 AI146955 AI989380 AI348243 N92892 AA765850
1 ~ AI494230 AI278887 AA962596 AI492600 W80435 AA001979 897424 AI129015 N24127
AA157451 AA235549 AA459292 AA037114 AA129785
AI494211 AW059601 AW886710 892790 N59755 AI361128 AW589407 H47725 H97534
H48076 H48450 T99631 AW300758 H03431876789
AA954344 H77576 896823 AI457100 N92845 N49682 H42038 BE220698 BE220715 H99552
AA701624 N74173 854704 H79520 H72923
H03266 BE261919 AA769633 AA480310 AA507454 AA910586 AI203723 AW104725 W25611
W25071 T88980 H03513 T77589 899156
W95095 897470 AA702275 T77551 AA911952 H82956 N83673 AA283672
15 450375 83327-1 AA009647 AA131254 AA374293 AW954405 H04410 AW606284 AA151166
BE157467 BE157601 H04384 W46291 AW663674 H04021 H01532
AA190993 H03231 H59605 H01642 AA852876 AA113758 AA626915 AA746952 AI161014
AA099554 869067
2o TABLE 14C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank
Identifier (GI) numbers. "Dunham I. et al." refers to the publication entitled
"The DNA
sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402.489-495.
Strand: Indicates DNA strand from which axons were predicted.
25 Nt_position: Indicates nucleotide positions of predicted axons.
Pkey Ref Strand Nt-position
30 402075 8117407 Plus 121907-122035,122804-122921,124019-124161,124455-
124610,125672-126076
183
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WO 02/086443 PCT/US02/12476
TABLE 15A: Information for all sequences in Table 16
Table 15A shows the Seq ID No, Pkey, ExAccn, UnigenelD, and Unigene Title for
all of the sequences in Table 16.
Table 158 show the accession numbers for those Pkey's lacking UnigenelD's for
table 15A. For each probeset we have listed the gene cluster number from which
the
oligonucleotides were designed. Gene clusters were compiled using sequences
derived from Genbank ESTs and mRNAs. These sequences were clustered based on
sequence
similarity using Clustering and AlignmentTcols (DoubIeTwist, Oakland
California). The Genbank accession numbers for sequences comprising each
cluster are listed in the
"Accession" column.
1 o Table 15C show the genomic positioning for those Pkey's lacking Unigene
ID's and accession numbers in table 15A. For each predicted exon, we have
listed the genomic
sequence souroe used for prediction. Nucleotide locations of each predicted
exon are also listed.
Seq ID
No; Sequence
ID number
15 Pkey: Unique
Eos probeset
identifier
number
ExAccn:
ExempIarAccession
number,
Genbank
accession
number
UnigenelD:
Unigene
number
Unigene
Title:
Unigene
gene title
Seq ID PkeyExAccn UnigenelDUnigene Title
No:
Seq ID 410407X66839 Hs.63287carbonic anhydrase
No:1 & IX
2
Seq ID 412719AW016610Hs.816 ESTs
No: 3
& 4
Seq ID 417034NM 006183Hs.80962neurotensin
No: 5
& 6
ZS Seq ID 430486BE062109Hs.241551chloride channel,
No: 7 calcium activated,
& 8 fam
Seq ID d07788BE514982Hs.38991S100 calcium-binding
No: 9 protein A2
& 10
Seq ID 407788BE514982Hs.38991S100 calcium-binding
No:11 protein A2
& 12
Seq ID 407788BE514982Hs.38991S100 calcium-binding
No:13 protein A2
& 14
Seq ID 407788BE514982Hs.38991S100 calcium-binding
No:15 protein A2
& 16
Seq ID 439285AL133916 hypothetical protein
No:17 FLJ20093
& 18
Seq ID 413753U17760 Hs.75517laminin, beta
No:19 3 (nicein (125kD),
& 20 kalinin
Seq ID 120486AW368377Hs.137569tumor protein
No: 21 63 kDa with strong
& 22 homolog
Seq ID 425650NM_001944Hs.1925desmoglein 3 (pemphigus
No: 23 ! vulgaris antigen
& 24
Seq ID 412140AA219691Hs.73625RAB6 interacting,
No: 25 kinesin-like
& 26 (rabkines
35 Seq ID 423673BE003054Hs.1695matrix metalloproteinase
No: 27 12 (macrophage
& 28
Seq ID 452838U65011 Hs.30743preferentially
No: 29 expressed antigen
& 30 in mela
Seq ID 418663AK001100Hs.41690desmocollin 3
No: 31
& 32
Seq ID 418663AK001100Hs.41690desmocollin 3
No: 33
& 34
Seq ID 409632W74001 Hs.55279serine (or cysteine)
No: 35 proteinase inhibito
& 36
4~ Seq ID 429610AB024937Hs.211092LUNX protein;
No: 37 PLUNC (palate
& 38 lung and nas
Seq ID 406690M29540 Hs.220529carcinoembryonic
No: 39 antigen-related
& 40 cell ad
Seq ID 431846BE019924Hs.271580uroplakin 18
No: 41
& 42
Seq ID 4188308E513731Hs.88959hypothetical protein
No: 43 MGC4816
& 44
Seq ID 424098AF077374Hs.139322small proline-rich
No: 45 protein 3
& 46
45 Seq ID 443648A1085377Hs.143610ESTs
No: d7
& 48
Seq ID 311034BE567130Hs.311389ESTs, Highly similar
No. 49 to NKGD HUMAN
NKG2-
Seq ID 408522AI541214Hs.46320Small proline-rich
No: 50 protein SPRK
& 51 [human,
Seq ID 422158L10343 Hs.112341protease inhibitor
No: 52 3, skin-derived
& 53 (SKAL
Seq ID 435505AF200492Hs.211238interleukin-1
No: 54 homolog 1
& 55
50 Seq ID 417366BE185289Hs.1076small proline-rich
No: 56 protein 1B (cornifin)
& 57
Seq ID 431958X63629 Hs.2877cadherin 3, type
No: 58 1, P-cadherin
& 59 (placenta
Seq ID 441020W79283 Hs.35962ESTs
No: 60
& 61
Seq ID 423217NM 000094Hs.1640collagen, type
No: 62 VII, alpha 1
& 63 (epidermolys
Seq ID 429538BE182592Hs.11261small proline-rich
No: 64 protein 2A
& 65
Seq ID 448733NM_005629Hs.187958solute carrier
5 No: 66 family 6 (neurotransmitte
& 67
Seq ID 444371BE540274Hs.239 forkhead box M1
No: 68
& 69
Seq ID 444371BE540274Hs.239 forkhead box Mi
No: 70
& 71
Seq ID 444371BE540274Hs.239 forkhead box M1
No. 72
& 73
Seq ID 422168AA586894Hs.1124085100 calcium-binding
No; 74 protein A7 (psorias
& 75
Seq ID 422168AA586894Hs.112408S100 calcium-binding
No: 76 protein A7 (psorias
& 77
Seq ID 429259AA420450Hs.292911Plakophilin
No: 78
& 79
Seq ID 426440BE382756Hs.169902solute carrier
No: 80 family 2 (facilitated
& 81 glu
Seq ID 437044AL035864Hs.69517differentially
No: 82 expressed in
& 83 Fanconi's an
Seq ID 423662AK001035Hs.130881B-cell CLUlymphoma
No: 84 11A (zinc finger
& 85 pro
65 Seq ID 428484AF104032Hs.184601solute carrier
No: 86 family 7 (cationic
& 87 amino
Seq ID 429211AF052693Hs.198249gapjuncUon protein,
No: 88 beta 5 (connexin
& 89 3
Seq ID 417389BE260964Hs.82045midkine (neurite
No: 90 growth-promoting
& 91 factor
Seq ID 423634AW959908Hs.1690heparin-binding
No: 92 growth factor
& 93 binding pr
Seq ID 417515L24203 Hs.82237ataxia-telangiectasia
No: 94 group D-associated
& 95
Seq ID 441362BE614410Hs.23044RAD51 (S. cerevisiae)
No: 96 homolog (E colt
& 97 Re
Seq ID 425322U63630 Hs.155637protein kinase,
No: 98 DNA-activated,
& 99 catalytic
Seq ID 449003X76342 Hs.389 alcohol dehydrogenase
No:100 7 (class IV),
& 101 mu o
Seq ID 431009BE149762Hs.48956gap junction protein,
No:102 beta 6 (connexin
& 103 3
Seq ID 409103AF251237Hs.112208XAGE-1 protein
No:104
& 105
75 Seq ID 417542J04129 Hs.82269progestagen-associated
No:106 endometrial prote
& 107
Seq ID 428471X57348 Hs.184510stratifin
No.108
& 109
Seq ID 418004U37519 Hs.87539aldehyde dehydrogenase
No:110 3 family, member
& 111
Seq ID 414761AU077228Hs.77256enhancer of zeste
No:112 (Drosophila)
& 113 homolog 2
Seq ID 418203X54942 Hs.83758CDC28 protein
No: t kinase 2
14 & 115
8~ Seq ID 447343AA256641Hs.236894ESTs, Highly similar
No:116 to S02392 alpha-2-m
Seq ID 437016AU076916Hs.5398guanine monphosphate
No:117 synthetase
& 118
Seq ID 449230BE613348Hs.211579melanoma cell
No.119 adhesion molecule
& 120
Seq ID 446989AK001898Hs.16740hypothetical protein
No:121 FLJ11036
& 122
Seq ID 457819AA057484Hs.35406ESTs, Highly similario
No:123 unnamed protein
& 124
85 Seq ID 424687J05070 Hs.151738matrix metalloproteinase
No:125 9 (gelatinase
& 126 B
184
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Seq ID 414430AI346201Hs.76118ubiquitin carboxyl-terminal esterase
No:127 L1
& 128
Seq ID 418462BE001596Hs.85266integdn, beta 4
No:129
& 130
Seq ID 100668L05424Hs.169610CD44 anfigen (homing function and
No:131 Indian
& 132
Seq ID 458933AI638429Hs.24763RAN binding protein 1
No:133
& 134
Seq ID 418478038945Hs.1174cyclin-dependent kinase inhibitor
No:135 2A (me
& 136
Seq ID 418478038945Hs.1174cyclin-dependent kinase inhibitor
No:137 2A (me
& 138
Seq ID 418478038945Hs.1174cyclin-dependent kinase inhibitor
No:139 2A (me
& 140
Seq ID 418478038945Hs.1174cyclin-dependent kinase inhibitor
No:141 2A (me
& 142
Seq ID 446269AW263i55Hs.14559hypothefical protein FLJ10540
No:143
& 144
1 Seq ID 422765AW409701Hs.1578baculoviral IAP n?peat-containing
~ No: i45 5 (sur
& 146
Seq ID 436481AA379597Hs.5199HSPC150 protein similar to ubiquilin-con
No:147
& 148
Seq ID 440325NM_003812Hs.7164a disintegrin and metalloproteinase
No:149 doma
& 150
Seq ID 439606W79123Hs.58561G protein-coupled receptor 87
No:151
& 152
Seq ID 453884AA355925Hs.36232KIAA0186 gene product
No:153
& 154
15Seq ID 453884AA355925Hs.36232KIAA0186 gene product
No:155
& 156
Seq ID 453884AA355925Hs.36232KIAA0186 gene product
No:157
& 158
Seq ID 453884AA355925Hs.36232KIAA0186 gene product
No:159
& 160
Seq ID 404877 NM 005365:Homo Sapiens melanoma
No:161 antigen,
& 162
Seq ID 413129AF292100Hs.104613RP42 homolog
No:163
& 164
Seq ID 413281AA861271Hs.222024transcription factor BMAL2
No:165
& 166
Seq ID 444781NM_014400Hs.11950GPI-anchored metastasis-associated
No: 167 prote
& 168
Seq ID 416819077735Hs.80205pim-2 oncogene
No:169
& 170
Seq ID 451320AW118072 diacylglycerol kinase, zeta (104k0)
No:171
& 172
Seq ID 418543NM Hs.85962hyaluronan synthase 3
No:173 005329
& 174
Seq ID 454034NM Hs.575aldehyde dehydrogenase 3 family,
No:175 000691 member
& 176
Seq ID 425397J04088Hs.156346topoisomerase (DNA) II alpha (170k0)
Nc:177
& 178
Seq ID 415817088967Hs.78867protein tyrosine phosphatase, receptor-t
No:179
& 180
Seq ID 415817088967Hs.78867protein tyrosine phosphatase, receptor-t
No:181
& 182
Seq ID 415817088967Hs.78867protein tyrosine phosphatase, receptor-t
No:183
& 184
Seq ID 415817088967Hs.78867protein tyrosine phosphatase, receptor-t
No:185
& 186
Seq ID 415817088967Hs.78867protein tyrosine phosphatase, receptor-t
No:187
& 188
Seq ID 419121AA374372Hs.89626parathyroid hormone-like hormone
No:189
& 190
Seq ID 448993AI471630Hs.8127KIAA0144 gene product
No:191
& 192
Seq ID 421817AF146074Hs.108660ATP-binding cassette, sub-family
No:193 C (CFTR
& 194
35Seq ID 430393BE185030Hs.241305estrogen-responsive B box protein
No.195
& 196
Seq ID 425057AA826434Hs.1619achaete-scute complex (Drosophila)
No:197 homol
& 198
Seq ID 420462AF050147Hs.97932chondromodulin I precursor
No:199
& 200
Seq ID 102963X02404Hs.274534calcitonin-related polypeptide,
No. 201 beta
& 202
Seq ID 100576X00356Hs.37058calcitoninicalcitonin-related polypeptid
No: 203
& 204
40Seq ID 101175082671Hs.36980melanoma anfigen, family A, 2
No: 205
& 206
Seq ID 429038AL023513Hs.194766seizure related gene 6 (mouse)-like
No: 207
& 208
Seq ID 418678NM Hs.167379cancerltestis antigen (NY-ESO-1)
No: 209 001327
& 210
Seq ID 418678NM Hs.167379cancedleslis antigen (NY-ESO-1)
No: 211 001327
& 212
Seq ID 131927AJ003112Hs.34780doublecortex; lissencephaly, X-linked
No: 213 (d
& 214
45Seq ID 428182BE386042Hs.293317ESTs, Weakly similar to GGC1 HUMAN
No: 215 G ANT
& 216
Seq ID 427335AA448542Hs.251677G antigen 78
No: 217
& 218
Seq ID 409420. 215008Hs.54451laminin, gamma 2 (nicein (100k0),
No: 219 kalini
& 220
Seq ID 114346AL137256Hs.130489ATPase, aminophospholipid transporter-li
No: 221
& 222
Seq ID 438956W00847Hs.135056Human DNA sequence from clone RP5-850E9
No: 223
& 224
5oSeqlD No: 404440 NM_021048:Homo Sapiens melanoma
225 & antigen,
226
Seq ID 415669NM_005025Hs.78589serine (or cysteine) proleinase
No: 227 inhibito
& 228
Seq ID 103312Y12642Hs.3185lysosomal
No: 229
& 230
Seq ID 320843BE069288Hs.34744Homo Sapiens mRNA; cDNA DKFZp547C136
No: 231 (fr
& 232
Seq ID 429065Ai753247Hs.29643Homo sapiens cDNA FLJ13103 fis,
No. 233 clone NT
55Seq ID 446102AW168067Hs.317694ESTs
No: 234
& 235
Seq ID 330495047924Hs.71642guanine nucleotide binding protein
No: 236 (G pr
& 237
Seq ID 413573AI733859Hs.149089ESTs
No: 238
Seq ID 428479Y00272Hs.334562cell division cycle 2, G1 to S and
No: 239 G2 to
& 240
Seq ID 428479Y00272Hs.334562cell division cycle 2, G1 to S and
No: 241 G2 to
& 242
60Seq ID 332180AF134160Hs.7327claudin 1
No. 243
& 244
Seq ID 437915AI637993Hs.202312Homo Sapiens clone N11 NTera2D1
No: 245 teratoca
Seq ID 441553AA281219Hs.121296ESTs
No: 246
& 247
Seq ID 331692AI683487Hs.152213wingless-type MMTV integration site
No: 248 fami
& 249
Seq ID 429413NM Hs.201877DESCi protein
No: 250 014058
& 251
65Seq ID 422283AW411307Hs.114311CDC45 (cell division cycle 45, S.cerevis
No: 252
& 253
Seq ID 448357N20169Hs.108923RAB38, member RAS oncogene family
No: 254
& 255
Seq ID 446292AF081497Hs.279682Rh type C glycoprotein
No: 256
& 257
Seq ID 416209AA236776Hs.79078MAD2 (mitofic arrest deficient,
No. 258 yeast, h
& 259
Seq ID 453922AF053306Hs.36708budding uninhibited by benzimidazoles
No: 260 1
& 261
Seq ID 424046AF027866Hs.138202serine (or cysteine) proteinase
No: 262 inhibito
& 263
Seq ID 439223AW238299Hs.250618UL16 binding protein 2
No: 264
& 265
Seq ID 429228AI553633Hs.326447ESTs
No: 266
& 267
Seq ID 409757NM Hs.123114cystatin SN
No: 266 001898
& 269
Seq ID 411089AA456454Hs.214291cell division cycle 2-like 1 (PITSLRE
No: 270 pr
& 271
75Seq ID 436511AA721252Hs.291502ESTs
No: 272
& 273
Seq ID 428969AF120274Hs.194689artemin
No: 274
& 275
Seq ID 428969AF120274Hs.194689artemin
No: 276
& 277
Seq ID 428969AF120274Hs.194689artemin
No: 278
& 279
Seq ID 428969AF120274Hs.194689artemin
No: 280
& 281
8~Seq ID 407137T97307 gb:ye53h05.s1 Soares fetal liver
No: 282 spleen
Seq ID 412723AA648459Hs.335951hypothetical protein AF301222
No: 283
& 284
Seq ID 450701H39960Hs.288467hypothefical protein XP 098151 (leucine-
No: 285
& 286
Seq ID 405770 NM_002362:Homo sapiens melanoma
No. 287 anfigen,
& 288
Seq ID 439453BE264974Hs.6566thyroid hormone receptor interactor
No: 289 13
& 290
85Seq ID 414774X02419Hs.77274plasminogen acfivator, urokinase
No: 291
& 292
185
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Seq ID 424629M90656Hs.151393glutamate-cysteine ligase, catalytic
No: 293 sub
& 294
Seq ID 437789AI581344Hs.127812ESTs, Weakly similar to T17330 hypotheti
No: 295
& 296
Seq ID 437789AI581344Hs.127812ESTs, Weakly similar to T17330 hypotheti
No: 297
& 298
Seq ID 437789AI581344Hs.127812ESTs, Weakly similar to T17330 hypotheG
No: 299
& 300
Seq ID 437789AI581344Hs.127812ESTs, Weakly similar to T17330 hypotheti
No: 301
& 302
Seq ID 437789AI581344Hs.127812ESTs, Weakly similar to T17330 hypotheti
No: 303
& 304
Seq ID 453968AA847843Hs.62711High mobility group (nonhistone
No: 305 chromoso
& 306
5eq ID 403478 NM-022342:Homo sapiens kinesin protein
No: 307 9
& 308
Seq ID 441525AW241867Hs.127728ESTs
No: 309
1 Seq ID 434105AW952124Hs.13094presenilins associated rhomboid-like
~ No: 310 pro
& 311
Seq ID 428810AF068236Hs.193788nitric oxide synthase 2A (inducible,
No: 312 hep
& 313
Seq ID 413691AB023173Hs.75478ATPase, Class Vi, type 11 B
No: 314
& 315
Seq ID 423934089995Hs.159234forkhead box E1 (thyroid transcription
No: 316 f
& 317
Seq ID 409228816611Hs.22010ESTs, Weakly similar to 2109260A
No: 318 B cell
& 319
15Seq ID 425734AF056209Hs.159396peptidylglycine alpha-amidating
No: 320 monooxyg
& 321
Seq ID 413582AW295647Hs.71331hypothetical protein MGC5350
No: 322
& 323
Seq ID 438403AA806607Hs.292206ESTs
No: 324
& 325
Seq ID 403329 unnamed protein product (Homo sapiens]
No: 326
& 327
Seq ID 409893AW247090Hs.57101minichromosome maintenance deficient
No: 328 (S.
& 329
Seq ID 119073BE245360Hs.279477v-ets erylhroblastosis virus E26
No: 330 oncogen
& 331
Seq ID 113195H83265Hs.8881ESTs, Weakly similar to S41044 chromosom
No: 332
& 333
Seq ID 102283AW161552Hs.83381guanine nucleotide binding protein
No: 334 11
& 335
Seq ID 101345NM_005795Hs.152175calcitonin receptor-like
No: 336
& 337
Seq ID 103280084722Hs.76206cadherin 5, type 2, VE-cadherin
No. 338 (vascula
& 339
25Seq ID 102012BE259035Hs.118400singed (Drosophila)-like (sea urchin
No: 340 fas
& 341
Seq ID 105729H46612Hs.293815Homo sapiens HSPC285 mRNA, partial
No: 342 cds
& 343
Seq ID 134299AW580939Hs.97199complement component C1q receptor
No: 344
& 345
Seq ID 412719AW016610Hs.816ESTs
No: 346
& 347
Seq ID 422158L10343Hs.112341protease inhibitor 3, skin-derived
No: 348 (SKAL
& 349
30Seq ID 128924BE279383Hs.26557plakophilin 3
No: 350
& 351
Seq ID 100486T19006Hs.10842RAN, member RAS oncogene family
No: 352
& 353
Seq ID 419121AA374372Hs.89626parathyroid hormone-like hormone
No: 354
& 355
Seq ID 409459D86407Hs.54481low density lipoprotein receptor-related
No: 356
& 357
Seq ID 330493M27826 endogenous retroviral protease
No: 358
& 359
35Seq 1D 417866AW067903Hs.82772collagen, type XI, alpha 1
No: 360
& 361
Seq ID 418113AI272141Hs.83484SRY (sex determining region Y)-box
No: 362 4
& 363
Seq ID 437016AU076916Hs.5398guanine monphosphate synthetase
No: 364
& 365
Seq ID 429612AF062649Hs.252587pituitary tumor-transforming 1
No: 366
& 367
Seq ID 440704M69241Hs.162insulin-like growth factor binding
No: 368 prote
& 369
40Seq ID 431221AA449015Hs.286145SRB7 (suppressor of RNA polymerase
No: 370 B, ye
& 371
Seq ID 431565AF161470Hs.260622butyrate-induced transcript 1
No: 372
& 373
Seq ID 431565AF161470Hs.260622butyrate-induced transcript 1
No: 374
& 375
Seq ID 132354BE185289Hs.1076small proline-rich protein 18 (cornitin)
No: 376
& 377
Seq ID 424441X14850Hs.147097H2A histone family, member X
No. 378
& 379
45Seq ID 103768AF086009Hs.296398gb:Homo sapiens full length insert
No: 380 cDNA
& 381
Seq ID 417512X76534Hs.82226glycoprotein (transmembrane) nmb
No: 382
& 383
Seq ID 425266J00077Hs.155421alpha-fetoprotein
No: 384
& 385
Seq ID 424503NM-002205Hs.149609inlegrin, alpha 5 (fibronectin receptor,
No: 386
& 387
Seq ID 400289X07820Hs.2258matrix metalloproteinase 10 (stromelysin
No: 388
& 389
50Seq ID 418007M13509Hs.83169matrix metalloproteinase 1 (interstitial
No: 390
& 391
Seq ID 418007M13509Hs.83169matrix metalloproteinase 1 (interstitial
No: 392 ~
& 393
Seq ID 418738AW388633Hs.6682solute carrier family 7, (cationic
No: 394 amino
& 395
Seq ID 415138C18356Hs.295944tissue factor pathway inhibitor
No: 396 2
& 397
Seq ID 418506AA084248Hs.85339G protein-coupled receptor 39
No: 398
& 399
5$Seq ID 423961D13666Hs.136348periostin (OSF-2os)
No: 400
& 401
Seq ID 414812X72755Hs.77367monokine induced by gamma interferon
No. 402
& 403
Seq ID 417433BE270266Hs.821285T4 oncofetal trophoblast glycoprotein
No: 404
& 405
Seq ID 417433BE270266Hs.821285T4 oncofelal trophoblast glycoprotein
No: 406
& 407
Seq ID 422867L32137Hs.1584cartilage oligomeric matrix protein
No: 408 (pse
& 409
Seq ID 428227AA321649Hs.2248small inducible cytokine subfamily
No: 410 B (Cy
& 411
Seq ID 444381BE387335Hs.283713ESTs, Weakly similar to S64054 hypotheti
No: 412
& 413
Seq ID 400303AA242758Hs.79136LIV-1 protein, estrogen regulated
No: 414
& 415
Seq ID 411789AF245505Hs.72157Adlican
No: 416
& 417
Seq ID 428698AA852773Hs.334838KIAA1866 protein
No: 418
& 419
65Seq ID 450098W27249Hs.8109hypothetical protein FLJ21080
No: 420
& 421
Seq ID 421552AF026692Hs.105700secreted frizzled-related protein
No: 422 4
& 423
Seq ID 452747BE153855Hs.61460Ig superfamily receptor LNIR
No: 424
& 425
Seq ID 450375AA009647 a disinlegrin and melalloproteinase
No: 426 dome
& 427
Seq ID 426215AW963419Hs.155223stanniocalcin 2
No: 428
& 429
Seq ID 425247NM_005940Hs.155324matrix metalloprotelnase 11 (stromelysin
No. 430
& 431
Seq ID 432201AI538613Hs.298241Transmembrane protease, serine 3
No: 432
& 433
Seq ID 427585D31152Hs.179729collagen, type X, alpha 1 (Schmid
No: 434 metaph
& 435
Seq ID 442117AW664964Hs.128899ESTs; hypothetical protein for IMAGE:447
No: 436
& 437
Seq ID 431211M86849Hs.323733gap junction protein, beta 2, 26kD
No: 438 (coon
& 439
75Seq ID 447033AI357412Hs.157601ESTs
No: 440
& 441
Seq ID 447033AI357412Hs.151601ESTs
No: 442
& 443
Seq ID 447033AI357412Hs.157601ESTs
No: 444
& 445
Seq ID 115522BE614387Hs.333893c-Myc targetJP01
No: 446
& 447
Seq ID 410418D31382Hs.63325transmembrane protease, serine 4
No: 448
& 449
8 Seq ID 409041AB033025Hs.50081Hypothetical protein, XP_051860
~ No: 450 (KIAA119
& 451
Seq ID 409041AB033025Hs.50081Hypothetical protein, XP 051860
No: 452 (KIAA119
& 453
Seq ID 452461N78223Hs.108106transcription factor
No: 454
& 455
Seq ID 412420AL035668Hs.73853bone morphogeneiic protein 2
No: 456
& 457
Seq ID 416658003272Hs.79432fibdllin 2 (congenital contractural
No: 458 era
& 459
85Seq ID 407811AW190902Hs.40098cysteine knot superfamily 1, 8MP
No: 460 antagon
& 461
186
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Seq ID 437852BE001836Hs.256897ESTs, Weakly similar to dJ365012.1
No: 462 [H.sa
& 463
Seq ID 402075 ENSP00000251056':Plasma membrane
No: 464 calcium
& 465
Seq ID 421110AJ250717Hs.1355cathepsin E
No: 466
& 467
Seq ID 451668243948 Hs.326444cartilage acidic protein 1
No: 468
& 469
Seq ID 451668243948 Hs.326444cartilage acidic protein 1
No: 470
& 471
Seq ID 451668243948 Hs.326444cartilage acidic protein 1
No: 472
& 473
Seq ID 422282AF019225Hs.114309apolipoprotein L
No: 474
& 475
Seq ID 425852AK001504Hs.159651death receptor 6, TNF superfamily
No: 476 member
& 477
Seq ID 439738BE246502Hs.9598sema domain, immunoglobulin domain
No: 478 (1g),
& 479
1 Seq ID 427747AW411425Hs.180655serinellhreonine kinase 12
~ No: 480
& 481
Seq ID 420281AI623693Hs.323494Predicted canon efflux pump
No: 482
& 483
Seq ID 405932 015000305:gi~3806122~gb~AAC69198.1~
No: 484 (AFO
& 485
Seq ID 405932 015000305:gi~3806122~gb~AAC69198.1~
No: 486 (AFO
& 487
Seq ID 444342NM_014398Hs.10887similar to lysosome-associated membrane
No: 488
& 489
15 SeqlD No: 421379Y15221 Hs.103982small inducible cytokine subfamily
490 & B (0y
491
Seq ID 417079065590 Hs.81134interleukin 1 receptor antagonist
No: 492
& 493
Seq ID 430890X54232 Hs.2699glypican 1
No: 494
& 495
Seq ID 419721NM-001650Hs.288650aquaporin 4
No: 496
& 497
Seq ID 444471A8020684Hs.11217KIAA0877 protein
No: 498
& 499
Seq ID 413063AL035737Hs.75184chitinase 3-like 1 (cartilage glycoprote
No: 500
& 501
Seq ID 433800A1034361Hs.135150lung type-I cell membrane-associated
No: 502 gly
& 503
Seq ID 452401NM_007115Hs.29352tumor necrosis factor, alpha-induced
No; 504 pro
& 505
Seq ID 452401NM-007115Hs.29352tumor necrosis factor, alpha-induced
No: 506 pro
& 507
Seq ID 450001NM-001044Hs.406solute carrier family 6 (neurotransmitle
No: 508
& 509
25 Seq ID 410407X66839 Hs.63287carbonic anhydrase IX
No: 510
& 511
Seq ID 309931AW341683 gb:hd13d01.x1 Soares-NFL_T_GBC_S1
No: 512 Homo s
& 513
Seq ID 412719AW016610Hs.816ESTs
No. 514
& 515
Seq ID 417034NM-006183Hs.80962neurotensin
No: 516
& 517
Seq ID 430486BE062109Hs.241551chloride channel, calcium acfivated,
No: 518 fam
& 519
Seq 1D 413753017760 Hs.75517laminin, beta 3 (nicein (125kD),
No: 520 kalinin
& 521
Seq ID 425650NM-001944Hs.1925desmoglein 3 (pemphigus vulgaris
No: 522 antigen
& 523
Seq ID 423673BE003054Hs.1695matrix metalloproteinase 12 (macrophage
No: 524
& 525
Seq ID 418663AK001100Hs.41690desmocollin 3
No: 526
& 527
Seq ID 418663AK001100Hs.41690desmocollin 3
No: 528
& 529
3 Seq ID 429610AB02d937Hs.211092LUNX protein; PLUNC (palate lung
No: 530 and nas
& 531
Seq ID 406690M29540 Hs.220529carcinoembryonic antigen-related
No: 532 cell ad
& 533
Seq ID 431846BE019924Hs.271580uroplakin 1 B
No: 534
& 535
Seq ID 422158L10343 Hs.112341protease inhibitor 3, skin-derived
No: 536 (SKAL
& 537
Seq ID 431958X63629 Hs.2877cadherin 3, type 1, P-cadherin (placenta
No: 538
& 539
Seq ID 437044AL035864Hs,69517differentially expressed in Fanconi's
No: 540 an
& 541
Seq ID 428484AF104032Hs.184601solute carrier family 7 (cationic
No: 542 amino
& 543
Seq ID 429211AF052693Hs.198249gap junction protein, beta 5 (connexin
No. 544 3
& 545
5eq ID 417389BE260964Hs.82045midkine (neurite growth-promofing
No: 546 factor
& 547
Seq ID 431009BE149762Hs.48956gap junction protein, beta 6 (connexin
No: 548 3
& 549
45 Seq ID 417542J04129 Hs.82269progestagen-associated endometrial
No: 550 prote
& 551
Seq ID 449230BE613348Hs.211579melanoma cell adhesion molecule
No: 552
& 553
Seq ID 410555092649 Hs.64311a disintegrin and metalloproteinase
No: 554 doma
& 555
5eq ID 410555092649 Hs.64311a disintegrin and metalloproteinase
No. 556 doma
& 557
Seq ID 424687J05070 Hs.151738matrix metalloproteinase 9 (gelafinase
No: 558 B
& 559
Seq ID 4184628E001596Hs.85266integrin, beta 4
No: 560
& 561
Seq ID 410274AA381807Hs.61762hypoxia-inducible protein 2
No: 562
& 563
Seq ID 439606W79123 Hs.5B561G protein-coupled receptor 87
No: 564
& 565
Seq ID 404877 NM-005365:Homo sapiens melanoma
No: 566 antigen,
& 567
Seq ID 444781NM_014400Hs.11950GPI-anchored metastasis-associated
No. 568 prole
& 569
5 Seq ID 418543NM-005329Hs.85962hyaluronan synlhase 3
5 No: 570
& 571
Seq ID 415817088967 Hs.78B67protein tyrosine phosphatase, receptor-t
No: 572
& 573
Seq ID 415817088967 Hs.78867protein tyrosine phosphatase, receptor-t
No: 574
& 575
Seq ID 415817088967 Hs.78867protein tyrosine phosphatase, receptor-t
No: 576
& 577
Seq ID 415817088967 Hs.78867protein tyrosine phosphatase, receptor-t
No: 578
& 579
5eq ID 415817088967 Hs.78867protein tyrosine phosphatase, receptor-t
No: 580
& 581
Seq ID 415817088967 Hs.78867protein tyrosine phosphatase, receptor-t
No: 582
& 583
5eq ID 421817AF146074Hs.108660ATP-binding cassette, sub-family
No: 58d C (CFTR
& 585
Seq ID 418678NM_001327Hs.167379cancerltestis antigen (NY-ESO-1)
No: 586
& 587
Seq ID 418678NM-001327Hs.167379cancerltesfis antigen (NY-ESO-1)
No: 588
& 589
65 Seq ID 409420215008 Hs.5d451laminin, gamma 2 (nicein (100kD),
No: 590 kalini
& 591
Seq ID 332180AF134160Hs.7327claudin 1
No: 592 '
& 593
Seq ID 408790AW580227Hs.47860neurotrophic tyrosine kinase, receptor,
No: 594
& 595
Seq ID 408790AW580227Hs.47860neurotrophic tyrosine kinase, receptor,
No: 596
& 597
Seq ID 439223AW238299Hs.250618UL16 binding protein 2
No: 598
& 599
Seq ID 409757NM-001898Hs.123114cystatin SN
No: 600
& 601
Seq ID 428969AF120274Hs.194689arlemin
No: 602
& 603
Seq ID 428969AF120274Hs.194689artemin
No: 604
& 605
Seq ID 428969AF120274Hs.194689artemin
No: 606
& 607
Seq ID 428969AF120274Hs.194689artemin
No: 608
& 609
75 Seq ID 450701H39960 Hs.288467hypothefical protein XP 098151 (leucine-
No: 610
& 611
Seq ID 450701H39960 Hs.288467hypothefical protein XP 098151 (leucine-
No: 612
& 613
Seq ID 414774X02419 Hs.77274plasminogen acfivator, urokinase
No: 614
& 615
Seq ID 407944834008 Hs.239727desmocollin 2
No: 616
& 617
Seq ID 407944834008 Hs.239727desmocollin 2
No: 618
& 619
8~ Seq ID 457489AI693815Hs.127179cryptic gene
No: 620
& 621
Seq ID 429547AW009166Hs.99376ESTs
No: 622
& 623
Seq ID 407242M18728 gb:Human nonspecific crossreacting
No: 624 anfig
& 625
Seq ID 407242M18728 gb:Human nonspecific crossreacting
No: 626 antig
& 627
5eq ID 407242M18728 gb:Human nonspecific crossreacling
No: 628 antig
& 629
85 Seq ID 444006BE395085Hs.10086type I iransmembrane protein Fnl4
No: 630
& 631
187
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Seq ID 429597NM-003816Hs.2442a disiniegrin and metalloprofeinase
No: 632 doma
& 633
Seq ID 422109S73265Hs.1473gastrin-releasing pepfide
No: 634
& 635
Seq ID 419235AW470411Hs.288433neurotdmin
No: 636
& 637
Seq ID 449048245051Hs.22920similar to 568401 (cattle) glucose
No: 638 induc
& 639
Seq ID 419216AU076718Hs.164021small inducible cytokine subfamily
No: 640 B (Cy
& 641
Seq ID 431462AW583672Hs.256311granin-like neuroendocrine peptide
No: 642 precu
& 643
Seq ID 448243AW369771Hs.52620integrin, beta 8
No: 644
& 645
Seq ID 426427M86699Hs.169840TTK protein kinase
No: 646
& 647
Seq ID 445537AJ245671Hs.12844EGF-like-domain, multiple 6
No: 648
& 649
1 Seq ID 422278AF072873Hs.114218frizzled (Drosophila) homolog 6
~ No: 650
& 651
Seq ID 428450NM Hs.184339KIAA0175 gene product
No: 652 014791
& 653
Seq ID 446619AU076643Hs.313secreted phosphoprotein 1 (osteopontin,
No: 654
& 655
Seq ID 453392023752Hs.32964SRY (sex determining region Y)-box
No: 656 11
& 657
Seq ID 426514BE616633Hs.170195bone morphogenetic protein 7 (osteogenic
No: 658
& 659
15Seq ID 42577602512 8 Hs.159499parathyroid hormone receptor 2
No: 660
& 661
Seq 1D 425776025128Hs.159499parathyroid hormone receptor 2
No: 662
& 663
Seq ID 431515NM Hs.258583endothelial differentiation, lysophospha
No: 664 012152
& 665
Seq ID 419452033635Hs.90572PTK7 protein tyrosine kinase 7
No: 666
& 667
Seq ID 432653N62096Hs.293185ESTs, Weakly similar to JC7328 amino
No: 668 aci
& 669
Seq ID 432653N62096Hs.293185ESTs, Weakly similar to JC7328 amino
No: 670 aci
& 671
Seq ID 432653N62096Hs.293185ESTs, Weakly similar to JC7328 amino
No: 672 aci
& 673
Seq ID 432653N62096Hs.293185ESTs, Weakly similar to JC7328 amino
No: 674 aci
& 675
Seq ID 410001AB041036Hs.57771kallikrein 11
No: 676
& 677
Seq ID 426501AW043782Hs.293616ESTs
No: 678
& 679
25Seq ID 408369838438Hs.182575solute carrier family 15 (H?7? transport
No: 680
& 681
Seq ID 445413AA151342Hs.12677CGI-147 protein
No: 682
& 683
5eq ID 422424AI186431Hs.296638prostate differentiation factor
No: 684
& 685
Seq ID 428330L22524Hs.2256matrix melalloproteinase 7 (matrilysin,
No: 686
& 687
Seq ID 420610AI683183Hs.99348distal-less homeo box 5
No: 688
& 689
3
o
TABLE 158
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
35 Accession: Genbank accession numbers
Pkey CAT Number Accession
309931AW341683
33049333264-5 M27826 878416 AA307645 AW957879 AW957800 AA633529
H03662
43928547065_1 AL133916 N79113 AF086101 N76721 AW950828 AA364013
AW955684 AI346341 AI867454 N54784 AI655270 AI421279 AW014882
AA775552 N62351 N59253 AA626243 AI341407 BE175639 AA456968
AI358918 AA457077
45037583327_1 AA009647 AA13i254 AA374293 AW954405 H04410 AW606284
AA151166 BE157467 BE157601 H04384 Wd6291 AW66367d H04021
H01532
AA190993 H03231 H59605 H01642 AA852876 AA113758 AA626915
AA746952 AI161014 AA099554 869067
45132086576_1 AW118072 A1631982 T15734 AA224195 A1701458 W20198
F26326 AA890570 N90552 AW071907 A1671352 A1375892 T03517
888265
4S AI124088 AA224388 A1084316 AI354686 T33652 AI140719 AI720211
T03490 AI372637 T15415 AW205836 AA630384 T03515 T33230
AA017131 AA443303 T33623 AI222556 T33511 T33785 AI419606
D5561 Z
TABLE
15C
SO ,
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are
Genbank Idenfifier (GI) numbers. "Dunham I. et al." refers
to the publication entitled 'The DNA
sequence of human chromosome 22." Dunham I. et al., Nature
(1999) 402:489-495.
Strand:Indicates DNA strand from which axons were predicted.
55Nt_position:Indicates nucleotide posifions of predicted axons.
Pkey Ref Strand Nt_position
4020758117407 Plus 121907-122035,122804-122921,124019-124161,124455-
124610,125672-126076
4033298516120 Plus 96450-96598
4034789958258 Plus 116458-116564
4044407528051 Plus 80430-81581
4048771519284 Plus 1095-2107
4057702735037 Plus 61057-62075
4059327767812 Minus 123525-123713
65
188
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Table 16
Seq Ib 1 DNA
NO: sequence
Nucleic 0012 16
Aci d Accession
#:
NM
S _
Coding
sequence:
43..1422
1 11 21 31 41 51
I
I I I I I CCTGTGCCCC60
GCCCGTACACACCGTGTGCTGGGACACCCCACAGTCAGCCGCATGGCTCC
I AGCCCCTGGCTCCCTCTGTTGATCCCGGCCCCTGCTCCAGGCCTCACTGTGCAACTGCTG120
O
CTGTCACTGCTGCTTCTGATGCCTGTCCATCCCCAGAGGTTGCCCCGGATGCAGGAGGAT180
TCCCCCTTGGGAGGAGGCTCTTCTGGGGAAGATGACCCACTGGGCGAGGAGGATCTGCCC240
AGTGAAGAGGATTCACCCAGAGAGGAGGATCCACCCGGAGAGGAGGATCTACCTGGAGAG300
GAGGATCTACCTGGAGAGGAGGATCTACCTGAAGTTAAGCCTAAATCAGAAGAAGAGGGC360
I TCCCTGAAGTTAGAGGATCTACCTACTGTTGAGGCTCCTGGAGATCCTCAAGAACCCCAG420
S
AATAATGCCCACAGGGACAAAGAAGGGGATGACCAGAGTCATTGGCGCTATGGAGGCGAC480
CCGCCCTGGCCCCGGGTGTCCCCAGCCTGCGCGGGCCGCTTCCAGTCCCCGGTGGATATC540
CGCCCCCAGCTCGCCGCCTTCTGCCCGGCCCTGCGCCCCCTGGAACTCCTGGGCTTCCAG600
CTCCCGCCGCTCCCAGAACTGCGCCTGCGCAACAATGGCCACAGTGTGCAACTGACCCTG660
ZOCCTCCTGGGCTAGAGATGGCTCTGGGTCCCGGGCGGGAGTACCGGGCTCTGCAGCTGCAT720
CTGCACTGGGGGGCTGCAGGTCGTCCGGGCTCGGAGCACACTGTGGAAGGCCACCGTTTC780
CCTGCCGAGATCCACGTGGTTCACCTCAGCACCGCCTTTGCCAGAGTTGACGAGGCCTTG840
GGGCGCCCGGGAGGCCTGGCCGTGTTGGCCGCCTTTCTGGAGGAGGGCCCGGAAGAAAAC900
AGTGCCTATGAGCAGTTGCTGTCTCGCTTGGAAGAAATCGCTGAGGAAGGCTCAGAGACT960
~SCAGGTCCCAGGACTGGACATATCTGCACTCCTGCCCTCTGACTTCAGCCGCTACTTCCAA1020
TATGAGGGGTCTCTGACTACACCGCCCTGTGCCCAGGGTGTCATCTGGACTGTGTTTAAC1080
CAGACAGTGATGCTGAGTGCTAAGCAGCTCCACACCCTCTCTGACACCCTGTGGGGACCT1140
GGTGACTCTCGGCTACAGCTGAACTTCCGAGCGACGCAGCCTTTGAATGGGCGAGTGATT1200
GAGGCCTCCTTCCCTGCTGGAGTGGACAGCAGTCCTCGGGCTGCTGAGCCAGTCCAGCTG1260
3 AATTCCTGCCTGGCTGCTGGTGACATCCTAGCCCTGGTTTTTGGCCTCCTTTTTGCTGTC1320
O
ACCAGCGTCGCGTTCCTTGTGCAGATGAGAAGGCAGCACAGAAGGGGAACCAAAGGGGGT1380
GTGAGCTACCGCCCAGCAGAGGTAGCCGAGACTGGAGCCTAGAGGCTGGATCTTGGAGAA1440
TGTGAGAAGCCAGCCAGAGGCATCTGAGGGGGAGCCGGTAACTGTCCTGTCCTGCTCATT1500
ATGCCACTTCCTTTTAACTGCCAAGAAATTTTTTAAAATAAATATTTATAAT
S
Seq ID 2 Protein
N0: sequence:
Protein
Accession
#: NP
001207
1 11 21 31 41 51
A I I I 1 1 I
O
~t
MAPLCPSPWLPLLIPAPAPGLTVQLLLSLLLLMPVHPQRLPRMQEDSPLGGGSSGEDDPL60
GEEDLPSEEDSPREEDPPGEEDLPGEEDLPGEEDLPEVKPKSEEEGSLKLEDLPTVEAPG120
DPQEPQNNAHRDKEGDDQSHWRYGGDPPWPRVSPACAGRFQSPVDIRPQLAAFCPALRPL180
ELLGFQLPPLPELRLRNNGHSVQLTLPPGLEMALGPGREYRALQLHLHWGAAGRPGSEHT240
~ VEGHRFPAEIHVVHLSTAFARVDEALGRPGGLAVLAAFLEEGPEENSAYEQLLSRLEEIA300
'-FS
EEGSETQVPGLDISALLPSDFSRYFQYEGSLTTPPCAQGVIWTVFNQTVMLSAKQLHTLS360
DTLWGPGDSRLQLNFRATQPLNGRVIEASFPAGVDSSPRAAEPVQLNSCLAAGDILALVF420
GLLFAVTSVAFLVQMRRQHRRGTKGGVSYRPAEVAETGA
SOSeq ID 3 DNA
NO: sequence
Nucleic
Acid
Accession
#: BC013923
Coding
sequence:
438-1391
1 11 21 31 41 51
SSI I I I I I
AGCGGGGTTGTCTATTAACTTGTTCAAAAAGTATCAGGAGTTGTCAAGGCAGAGAAGAGA60
GTGTTTGCAAAAGGGGGAAAGTAGTTTGCTGCCTCTTTAAGACTAGGACTGAGAGAAAGA120
AGAGGAGAGAGAAAGAAAGGGAGAGAAGTTTGAGCCCCAGGCTTAAGCCTTTCCAAAAAA180
TAATAATAACAATCATCGGCGGCGGCAGGATCGGCCAGAGGAGGAGGGAAGCGCTTTTTT240
6OTGATCCTGATTCCAGTTTGCCTCTCTCTTTTTTTCCCCCAAATTATTCTTCGCCTGATTT300
TCCTCGCGGAGCCCTGCGCTCCCGACACCCCCGCCCGCCTCCCCTCCTCCTCTCCCCCCG360
CCCGCGGGCCCCCCAAAGTCCCGGCCGGGCCGAGGGTCGGCGGCCGCCGGCGGGCCGGGC420
CCGCGCACAGCGCCCGCATGTACAACATGATGGAGACGGAGCTGAAGCCGCCGGGCCCGC480
AGCAAACTTCGGGGGGCGGCGGCGGCAACTCCACCGCGGCGGCGGCCGGCGGCAACCAGA540
G AAAACAGCCCGGACCGCGTCAAGCGGCCCATGAATGCCTTCATGGTGTGGTCCCGCGGGC600
VS
AGCGGCGCAAGATGGCCCAGGAGAACCCCAAGATGCACAACTCGGAGATCAGCAAGCGCC660
TGGGCGCCGAGTGGAAACTTTTGTCGGAGACGGAGAAGCGGCCGTTCATCGACGAGGCTA720
AGCGGCTGCGAGCGCTGCACATGAAGGAGCACCCGGATTATAAATACCGGCCCCGGCGGA780
AAACCAAGACGCTCATGAAGAAGGATAAGTACACGCTGCCCGGCGGGCTGCTGGCCCCCG840
7OGCGGCAATAGCATGGCGAGCGGGGTCGGGGTGGGCGCCGGCCTGGGCGCGGGCGTGAACC900
AGCGCATGGACAGTTACGCGCACATGAACGGCTGGAGCAACGGCAGCTACAGCATGATGC960
AGGACCAGCTGGGCTACCCGCAGCACCCGGGCCTCAATGCGCACGGCGCAGCGCAGATGC1020
AGCCCATGCACCGCTACGACGTGAGCGCCCTGCAGTACAACTCCATGACCAGCTCGCAGA1080
CCTACATGAACGGCTCGCCCACCTACAGCATGTCCTACTCGCAGCAGGGCACCCCTGGCA1140
7STGGCTCTTGGCTCCATGGGTTCGGTGGTCAAGTCCGAGGCCAGCTCCAGCCCCCCTGTGG1200
TTACCTCTTCCTCCCACTCCAGGGCGCCCTGCCAGGCCGGGGACCTCCGGGACATGATCA1260
GCATGTATCTCCCCGGCGCCGAGGTGCCGGAACCCGCCGCCCCCAGCAGACTTCACATGT1320
CCCAGCACTACCAGAGCGGCCCGGTGCCCGGCACGGCCATTAACGGCACACTGCCCCTCT1380
CACACATGTGAGGGCCGGACAGCGAACTGGAGGGGGGAGAAATTTTCAAAGAAAAACGAG1440
8 GGAAATGGGAGGGGTGCAAAAGAGGAGAGTAAGAAACAGCATGGAGAAAACCCGGTACGC1500
O
TCAAAAAAAA~ AAAATCCCATCACCCACAGCAAATGACAGCTGCAAAAGAG1560
AACACCAATCCCATCCACACTCACGCAAAAACCGCGATGCCGACAAGAAAACTTTTATGA1620
GAGAGATCCTGGACTTCTTTTKGGGGGACTATTTTTGTACAGAGAAAACCTGGGGAGGGT1680
GGGGAGGGCGGGGGAATGGACCTTGTATAGATCTGGAGGAAAGAAAGCTACGAAAAACTT1740
8 TTTAAAAGTTCTAGTGGTACGGTAGGAGCTTTGCAGGAAGTTTGCAAAAGTCTTTACCAA1800
S
TAATATTTAGAGCTAGTCTCCAAGCGACGAAAAAAATGTTTTAATATTTGCAAGCAACTT1860
TTGTACAGTATTTATCGAGATAAACATGGCAATCAAAATGTCCATTGTTTATAAGCTGAG1920
189
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
AATTTGCCAA TATTTTTCAACTTGCTGAATTTTGATTCTGCAGCTGAAAT1980
GGAGAGGCTT
TTAGGACAGT TGCAAACGTGAATTATTCAAATTTGGACATTTTAATTGTT2040
AAAAGAAGAA
TAAAAATTGT ACAAAAGGAATAAGTACTGGCGAACCATCTCTGTGGTCTT2100
AAAATTAGAA
GTTTAAAAAG GGCAAAAGTTCTAAATTTTATAACTTACTGTTAAAAGCAA2160
TTAGACTGTA
S AAATGGCCAT GCAGGTTGACATTTATAATAGCTTTTGTTCGATCCCAACT2220
ACCGTTGGTA
TTCCATTTTG TTCAGATAAAAAATTACTGTGTTTGAAATATTTTCTTATG2280
AAAAACCATG
GTTTGTAATA TTTCTGTAAATATTTTAAGGTTTTCCCCCCTTTATTTTCC2340
TTTATTGTGA
GTAGTTGTAT TTTAAAAGATATTATTTGAATCAGTCTGCCGAGAATCCAT2400
TCGGCTCTGT
GTATATATTT GAACTAATATACAGGTACATTTTCAACTTAAGTTTTTACT2460
CATCCTTATA
1 CCATTATGCA CAGTTTGAGATTTGAAATATGGACACTGAAAAAAAAAAAA2520
O TAAATAAATT
AAAAAAACAA AACAAAAAAAAAACAGAAAAAACAAAAAAAAAAACAAAAC2580
CAAAAAACAA
CACAACACAA AAACAAAAAAAACAAACACACAACACAACACAACACAAAA2640
AAAAAAAAGA
CCACAACACA AACAACAACA
CACAGAGGG
1 Seq ID N0: 4 Protein
S sequence:
Protein Accession
#:CAA83435.1
1 11 21 31 41 51
GO MYNMMETELK PPGPQQTSGGGGNQKNSPDRVKRPMNAFMVWSRGQRRKMA60
GGGNSTAAAA
QENPKMHNSE ISKRLGAEWKIDEAKRLRALHMKEHPDYKYRPRRKTKTLM120
LLSETEKRPF
KKDKYTLPGG LLAPGGNSMAAGVNQRMDSYAHMNGWSNGSYSMMQDQLGY180
SGVGVGAGLG
PQHPGLNAHG AAQMQPMHRYTSSQTYMNGSPTYSMSYSQQGTPGMALGSM240
DVSALQYNSM
GSWKSEASS SPPWTSSSH RDMISMYLPGAEVPEPAAPSRLHMSQHYQS300
SRAPCQAGDL
.~ GPVPGTAING TLPLSHM
GS
Seq ID N0: 5 DNA sequence
Nucleic Acid Accession
#: U91618
Coding sequence: 29-541
1 11 21 31 41 51
I i
I I I I ATGAAAATCCAGCTTGTATG60
CGGACTTGGC TTGTTAGAAGGATGGCAGGA
GCTGAAAGAT
CATGCTACTC CTGGCTTTCATCTGTGCTCAGATTCAGAAGAGGAAATGAA120
GCTCCTGGAG
3 AGCATTAGAA GCAGATTTCTGCATACATCAAAGATTAGTAAAGCACATGT180
S TGACCAATAT
TCCCTCTTGG AAGATGACTCTTGCAGTCTTGTAAATAATTTGAACAGCCC240
TGCTAAATGT
AGCTGAGGAA ACAGGAGAAGGGAGCTTGTTGCAAGAAGGAAACTTCCTAC300
TTCATGAAGA
TGCTTTAGAT GGCTTTAGCTGTTGACAATATACCAGCTCCACAAAATCTG360
TGGAAGCAAT
TCACAGCAGG GCTTTTCAACAATCCAGGAAGATATTCTTGATACTGGAAA420
ACTGGGAGTT
~ TGACAAAAAT GGAAAGGAAGGAGAAAAATTCCTTATATTCTGAAACGGCA480
'tOAAGTCATAAA
GCTGTATGAG AATAAACCCACATACTCAAAAGAGATTCTTACTATTACTG540
GAAGACCCTA
AGAGAATAAA TCATTTATTTGTGATTCATCATCCCTTAATTAAATATCAA600
ACATGTGATT
ATTATATTTG TGTGAAAATGACTTATCTGTCTCTTCTACAATTGTGGTTT660
TGACAAACAC
ATTGAATGTG TTTTTCTGCATTAGACTAAGTGTTTTCAAATAAATCTAAA720
CTAATAGAAA
~ TCTTCAAAAA AAAAAAAAAAGCAATT
4S AAATGGGGCC
Seq ID NO: 6 Protein
sequence:
SO Protein Accession
#: AAS50564
1 11 21 31 41 51
I I
I I I I MHTSKISKAHVPSWKMTLLN60
MMAGMKIQLV CMLLLAFSSWKALEADFLTN
SLCSDSEEEM
S VCSLVNNLNS PAEETGEVHETALDGFSLEAMLTIYQLHKICHSRAFQHWE120
S EELVARRKLP
LIQEDILDTG NDKNGKEEVIQLYENKPRRPYILKRDSYYY
KRKIPYILKR
Seq ID N0: 7 DNA sequence
006536.2
Nucleic Acid Accession
#: NM
60 -
Coding sequence: 109-2940
1 11 21 31 41 51
I I
I I I I CATATTGAAAACCTGACACA60
ACCTAAAACC TTGCAAGTTCCATCTGCATC
AGGAAGAAAC
6S ATGTATGCAG CAGGCTCAGTTGGAGGCTTCTCTACAACATGACCCAAAGG120
GTGAGTGAAC
AGCATTGCAG GTCCTATTTGTTTGTGACTCTCCTGGTTGCCTTAAGTTCA180
CAACCTGAAG
GAACTCCCAT TCCTGGGAGCCTTCAAGACAATGGGTATAATGGATTGCTC240
TGGAGTACAG
ATTGCAATTA ATCCTCAGGTCAGAACCTCATCTCAAACATTAAGGAAATG300
ACCTGAGAAT
ATAACTGAAG CTTCATTTTAGCTACCAAGAGAAGAGTATTTTTCAGAAAT360
CCTATTTAAT
7O ATAAAGATTT TAATACCTGCGCTAATAATAACAGCAAAATAAAACAAGAA420
CACATGGAAA
TCATATGAAA AGGCAAATGTGACTGGTATGGGGCACATGGAGATGATCCA480
CATAGTGACT
TACACCCTAC AATACAGAGGGAGGGAAAATACATTCATTTCACACCTAAT540
GTGTGGAAA,T1
TTCCTACTGA ATGATAACTTTACGGATCACGAGGCCGAGTGTTTGTCCAT600
AACAGCTGGC
GAATGGGCCC ACCTCCGTTGGATGAGTATAACAATGACAAACCTTTCTAC660
GGGTGTGTTC
~7 ATAAATGGGC AAAATCAAATAGGTGTTCATCTGACATCACAGGCATTTTT720
/S TAAAGTGACA
GTGTGTGAAA AAGGTCCTTGAACTGTATTATTAGTAAGCTTTTTAAAGAA780
CCCCCAAGAA
GGATGCACCT TTATCTACAAAATGCAACTGCATCAATAATGTTCATGCAA840
TAGCACCCAA
AGTTTATCTT CTGTGGTTGAGCAAGTACCCACAACCAAGAAGCACCAAAC900
ATTTTGTAAT
CTACAGAACC AGATGTGCAGGCATGGGATGTAATCACAGACTCTGCTGAC960
CCTCAGAAGT
p TTTCACCACA GCTTTCCCATGAGCTTCCACCTCCTCCCACATTCTCGCTT1020
OO GAATGGGACT
GTACAGGCTG GTGACAAAGTGTGCTGGATGTGTCCAGCAAGATGGCAGAG1080
GGTCTGTTTA
GCTGACAGAC TCCTTCAACTGCAGAATTTTATTTGATGCAGATTGTTGAA1140
ACAACAAGCC
ATTCATACCT TCGTGGGCATGACAGCAAAGGAGAGATCAGAGCCCAGCTA1200
TGCCAGTTTC
CACCAAATTA ACAGCAATGATTGCTGGTTTCATATCTGCCCACCACTGTA1260
TGATCGAAAG
S TCAGCTAAAA CAGACATCAGGGGCTTAAGAAAGGATTTGAGGTGGTTGAA1320
S CATTTGTTCA
AAACTGAATG GAAAAGCTTAATGATATTAGTGACCAGCGGAGATGATAAG1380
TGGCTCTGTG
CTTCTTGGCA ATTGCTTACCAGCAGTGGTTCAACAATTCACTCCATTGCC1440
CACTGTGCTC
190
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
CTGGGTTCAT CTGCAGCCCCGAATTATCACGTCTTACAGGAGGTTTAAAG1500
AAATCTGGAG
TTCTTTGTTC CAGATATATCAGCATGATTGATGCTTTCAGTAGAATTTCC1560
AAACTCCAAT
TCTGGAACTG GAGACATTTTATTCAGCTTGAAAGTACAGGTGAAAATGTC1620
CCAGCAACAT
AAACCTCACC ATCAATTGAAACTGTGGATAATACTGTGGGCAACGACACT1680
AAACACAGTG
S ATGTTTCTAG TTACGTGGCACCTCCTGAGATTATATTATTTGATCCTGAT1740
GGCCAGTGGT
GGACGAAAAT ACTACACAAAACCAATCTAACTTTTCGGACAGCTAGTCTT1800
TAATTTTATC
TGGATTCCAG GAACAGCTAATGGACTTACACCCTGAACAATACCCATCAT1860
GCCTGGGCAC
TCTCTGCAAG CCCTGAAAGTTCTCGCGCCTCCAACTCAGCTGTGCCCCCA1920
GACAGTGACC
GCCACTGTGG AAGCCTTTGTAGCCTCCATTTTCCTCATCCTGTGATGATT1980
GGAAAGAGAC
1 TATGCCAATG TGAAACAGGGATTCTTAATGCCACTGTCACTGCCACAGTT2040
O ATTTTATCCC
GAGCCAGAGA CTGGAGATCCAGACTCCTTGATGATGGAGCAGGTGCTGAT2100
TGTTACGCTG
GTTATAAAAA ATGATGGAATTATTTTTTCTCCTTTGCTGCAAATGGTAGA2160
TTACTCGAGG
TATAGCTTGA AAGTGCATGTCCCAGCATAAGCACCCCAACCCACTCTATT2220
CAATCACTCT
CCAGGGAGTC ATGCTATGTATACACAGCAAACGGTAATATTCAGATGAAT2280
TGTACCAGGT
ISGCTCCAAGGA AATCAGTAGGGAGGAGCGAAAGTGGGGCTTTAGCCGAGTC2340
CAGAAATGAG
AGCTCAGGAG GCTCCTTTTCGTTCCAGCTGGCCCCCACCCTGATGTGTTT2400
AGTGCTGGGA
CCACCATGCA AAATTATTGAGTAAAAGTAGAAGAGGAATTGACCCTATCT2460
CCTGGAAGCT
TGGACAGCAC CTGGAGAAGAGGCCAGGCTACAAGCTATGAAATAAGAATG2520
CTTTGATCAG
AGTAAAAGTC TACAGAATATTTTAACAATGCTATTTTAGTAAATACATCA2580
CCAAGATGAC
ZOAAGCGAAATC CTCAGCAAGCGAGATATTTACGTTCTCACCCCAGATTTCC2640
TGGCATCAGG
ACGAATGGAC CTGAACATCAGAAACACATGAAAGCCACAGAATTTATGTT2700
GCCAAATGGA
GCAATACGAG CAATGGATAGCAGTCTGCTGTATCTAACATTGCCCAGGCG2760
GAACTCCTTA
CCTCTGTTTA TTCCCCCCAAGTACCTGCCAGAGATTATCTTATATTGAAA2820
TTCTGATCCT
TTTTAA CAGCAATGGG ATCATTTGCCTTATTATAGTTGTGACACAT2880
TTTGATAGGA
GGAG
ZS, AAGAAAGAGAATGGAACAAAATTATTATAA2940
CATACTTTAA GCAGGAAAAA
GAGAGCAGAC
ATAAATATCC AAAGTGTCTTTATAAGACCCATGGCCTTCGACTACAAAAA3000
CCTTCTTAGA
CATACTAACA AAGTCAAATTCTGTATTAAAATGCATTGAGTTTTTGTACA3060
AACATCAAAA
ATACAGATAA GATTTTTACAACAATTCTTTTTGGGGGTAGATTAGAAAAC3120
TGGTAGATCA
CCTTACACTT TGGCTATGAAAAATTATTCTTTAAAGTAATGTCTTTAAAG3180
CAAATAATAA
3 GCAAAGGGAA GGGTAAAGTCCAAGGAAAGTTTGTTTTATTGAGGTGGAAA3240
O GGACCAGTGT
AATAGCCCCA AGCAGAGAAAGTCTGCATTATAACTGTCTGTGTGAAGCAA3300
AGGAGGGTAG
TCATTTAGTT ACTTTGATTATCTCCTTATCTGTGCAGTACAGGTTGCTTG3360
ATTTTTCTTT
TTTACATGAA GATCATGCTAATGTAGCCCCTAATGCAAAGCTCTTTACCT3420
TATTTTATAT
CTTGCTATTT TGTTATATATACATCTCCCTGCTAATGCTCAGAGATCTTT3480
ATTTCAGATG
3 TTTCACTGTA AGAGGTAACCTGGGTATTACCTTTGTCTCTTCATACCGGT3540
S TTTAACAATA
TTTATGACAA AGGTCTATTGTNTGTAAGTTTCTACTCCCATCAAAGCAGC3600
AATTTATTTG
TTTCTAAGTT TATTGCCTTGGAATGATAGTTATAGCCCCNTATAATGCCT3660
GGTTATTATG
TACCTAGGAA A
4O Seq ID N0: 8 Protein sequence:
Protein Accession #: NP 006527.1
1 11 21 31 41 51
'tSMTQRSIAGPICNLKFVTLLVALSSELPFLGAGVQLQDNGYNGLLIAINPQVPENQNLISN60
IKEMITEASFYLFNATKRRVFFRNIKILIPATWKANNNSKIKQESYEKANVIVTDWYGAH120
GDDPYTLQYRGCGKEGKYIHFTPNFLLNDNLTAGYGSRGRVFVHEWAHLRWGVFDEYNND180
KPFYINGQNQIKVTRCSSDITGIFVCEKGPCPQENCIISKLFKEGCTFIYNSTQNATASI240
MFMQSLSSWEFCNASTHNQEAPNLQNQMCSLRSAWDVITDSADFHHSFPMNGTELPPPP300
S TFSLVQAGDKWCLVLDVSSKMAEADRLLQLQQAAEFYLMQIVEIHTFVGIASFDSKGEI360
O
RAQLHQINSNDDRKLLVSYLPTTVSAKTDISICSGLKKGFEWEKLNGKAYGSVMILVTS420
GDDKLLGNCLPTVLSSGSTIHSIALGSSAAPNLEELSRLTGGLKFFVPDISNSNSMIDAF480
SRISSGTGDIFQQHIQLESTGENVKPHHQLKNTVTVDNTVGNDTMFLVTWQASGPPEIIL540
FDPDGRKYYTNNFITNLTFRTASLWIPGTAKPGHWTYTLNNTHHSLQALKVTVTSRASNS600
S AVPPATVEAFVERDSLHFPHPVMIYANVKQGFYPILNATVTATVEPETGDPVTLRLLDDG660
S
AGADVIKNDGIYSRYFFSFAANGRYSLKVHVNHSPSISTPAHSIPGSHAMYVPGYTANGN720
IQMNAPRKSVGRNEEERKWGFSRVSSGGSFSVLGVPAGPHPDVFPPCKIIDLEAVKVEEE780
LTLSWTAPGEDFDQGQATSYEIRMSKSLQNIQDDFNNAILVNTSKRNPQQAGIREIFTFS840
PQISTNGPEHQPNGETHESHRIYVAIRAMDRNSLQSAVSNIAQAPLFIPPNSDPVPARDY900
6OLILKGVLTAMGLIGIICLIIWTHHTLSRKKRADKKENGTXLL
Seq ID N0: 9 DNA sequence
G Nucleic Acid Accession #: Eos sequence
VS Coding sequence: 336-632
Z 11 21 31 41 51
CTCCCCTCACCCCGGTCCAGGATGCCCAGTCCCCACGACACCTCCCACTTCCCACTGTGG
60
~7CCTGGGTGGGCTCAGGGGCTGCCCTTGACCTGGCCTAGAGCCCTCCCCCAGCTGGTGGTG
/O 120
GAGCTGGCACTCTCTGGGAGGGAGGGGGCTGGGAGGGAATGAGTGGGAATGGCAAGAGGC
180
CAGGGTTTGGTGGGATCAGGTTGAGGCAGGTTTGGTTTCCTTAAAATGCCAAGTTGGGGG
240
CCAGTGGGGCCCACATATAAATCCTCACCCTGGGAGCCTGGCTGCCTTGCTCTCCTTCCT
300
GGGTCTGTCTCTGCCACCTGGTCTGCCACAGATCCATGATGTGCAGTTCTCTGGAGCAGG
360
~7CGCTGGCTGTGCTGGTCACTACCTTCCACAAGTACTCCTGCCAAGAGGGCGACAAGTTCA
/S 420
AGCTGAGTAAGGGGGAAATGAAGGAACTTCTGCACAAGGAGCTGCCCAGCTTTGTGGGGG
480
AGAAAGTGGATGAGGAGGGGCTGAAGAAGCTGATGGGCAGCCTGGATGAGAACAGTGACC
540
AGCAGGTGGACTTCCAGGAGTATGCTGTTTTCCTGGCACTCATCACTGTCATGTGCAATG
600
ACTTCTTCCAGGGCTGCCCAGACCGACCCTGAAGCAGAACTCTTGACTTCCTGCCATGGA
660
S TCTCTTGGGCCCAGGACTGTTGATGCCTTTGAGTTTTGTATTCAATAAACTTTTTTTGTC
O 720
TGTTGATAATATTTTAATTGCTCAGTGATGTTCCATAACCCGGCTGGCTCAGCTGGAGTG
780
CTGGGAGATGAGGGCCTCCTGGATCCTGCTCCCTTCTGGGCTCTGACTCTCCTGGAAATC
840
TCTCCAAGGCCAGAGCTATGCTTTAGGTCTCAATTTTGGAATTTCAAACACCAGCAAAAA
900
ATTGGAAATCGAGATAGGTTGCTGACTTTTATTTTGTCAAATAAAGATATTAAAAAAGGC
960
S AAATACCA
S
Seq ID N0: 10 Protein sequence:
191
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Protein
Accession
#: NP
005969.1
1 11 21 31 41 51
S MMCSSLEQALAVLVTTFHKYSCQEGDKFKLSKGEMKELLHKELPSFVGEKVDEEGLKKLM60
GSLDENSDQQVDFQEYAVFLALITVMCNDFFQGCPDRP
Seq ID 11
NO: DNA
sequence
1 Nucleic
O Acid
Accession
#: Eos
sequence
Coding
sequence:
336-626
1 11 21 31 41 51
I CTCCCCTCACCCCGGTCCAGGATGCCCAGTCCCCACGACACCTCCCACTTCCCACTGTGG60
S
CCTGGGTGGGCTCAGGGGCTGCCCTTGACCTGGCCTAGAGCCCTCCCCCAGCTGGTGGTG120
GAGCTGGCACTCTCTGGGAGGGAGGGGGCTGGGAGGGAATGAGTGGGAATGGCAAGAGGC180
CAGGGTTTGGTGGGATCAGGTTGAGGCAGGTTTGGTTTCCTTAAAATGCCAAGTTGGGGG240
CCAGTGGGGCCCACATATAAATCCTCACCCTGGGAGCCTGGCTGCCTTGCTCTCCTTCCT300
2OGGGTCTGTCTCTGCCACCTGGTCTGCCACAGATCCATGATGTGCAGTTCTCTGGAGCAGG360
CGCTGGCTGTGCTGGTCACTACCTTCCACAAGTACTCCTGCCAAGAGGGCGACAAGTTCA420
AGCTGAGTAAGGGGGAAATGAAGGAACTTCTGCACAAGGAGCTGCCCAGCTTTGTGGGGC480
ATTCCAGAGAACCATGTGCTGTGAGGGCCTTCCGAGTCCATCTGTTTAATCCTGTCATTG540
GAGACTTGAGAAACCAGAGCCCAGAAGGGAAAAGTGATTGTCCCAAGATCACACAGCACT600
2SGGAGAAAGTGGATGAGGAGGGGCTGAAGAAGCTGATGGGCAGCCTGGATGAGAACAGTGA660
CCAGCAGGTGGACTTCCAGGAGTATGCTGTTTTCCTGGCACTCATCACTGTCATGTGCAA720
TGACTTCTTCCAGGGCTGCCCAGACCGACCCTGAAGCAGAACTCTTGACTTCCTGCCATG780
GATCTCTTGGGCCCAGGACTGTTGATGCCTTTGAGTTTTGTATTCAATAAACTTTTTTTG840
TCTGTTGATAATATTTTAATTGCTCAGTGATGTTCCATAACCCGGCTGGCTCAGCTGGAG900
3 TGCTGGGAGATGAGGGCCTCCTGGATCCTGCTCCCTTCTGGGCTCTGACTCTCCTGGAAA960
O
TCTCTCCAAGGCCAGAGCTATGCTTTAGGTCTCAATTTTGGAATTTCAAACACCAGCAAA1020
AAATTGGAAATCGAGATAGGTTGCTGACTTTTATTTTGTCAAATAAAGATATTAAAAAAG1080
GCAAATACCA
3 Seq ID 12 sequence:
S N0: Protein
Protein
Accession
#: Eos
sequence
1 11 21 31 41 51
'tOMMCSSLEQALAVLVTTFHKYSCQEGDKFKLSKGEMKELLHKELPSFVGHSREPCAVRAFR60
VHLFNPVIGDLRNQSPEGKSDCPKITQHWRKWMRRG
Seq ID 13 ence
N0: DNA
sequ
4SNucleic
Acid
Accession
#: Eos
sequence
Coding
sequence:
58-354
1 11 21 31 41 51
S GTGAGCTCACCATGTGGGGGTGAGGCTGAGAGAAAACAAGTACACAGCCACAGATCCATG60
O
ATGTGCAGTTCTCTGGAGCAGGCGCTGGCTGTGCTGGTCACTACCTTCCACAAGTACTCC120
TGCCAAGAGGGCGACAAGTTCAAGCTGAGTAAGGGGGAAATGAAGGAACTTCTGCACAAG180
GAGCTGCCCAGCTTTGTGGGGGAGAAAGTGGATGAGGAGGGGCTGAAGAAGCTGATGGGC240
AGCCTGGATGAGAACAGTGACCAGCAGGTGGACTTCCAGGAGTATGCTGTTTTCCTGGCA300
S CTCATCACTGTCATGTGCAATGACTTCTTCCAGGGCTGCCCAGACCGACCCTGAAGCAGA360
S
ACTCTTGACTTCCTGCCATGGATCTCTTGGGCCCAGGACTGTTGATGCCTTTGAGTTTTG420
TATTCAATAAACTTTTTTTGTCTGTTGATAATATTTTAATTGCTCAGTGATGTTCCATAA480
CCCGGCTGGCTCAGCTGGAGTGCTGGGAGATGAGGGCCTCCTGGATCCTGCTCCCTTCTG540
GGCTCTGACTCTCCTGGAAATCTCTCCAAGGCCAGAGCTATGCTTTAGGTCTCAATTTTG600
6OGAATTTCAAACACCAGCAAAAAATTGGAAATCGAGATAGGTTGCTGACTTTTATTTTGTC660
AAATAAAGATATTAAAAAAGGCAAATACCA
Seq ID 14 sequence:
N0: Protein
005969.1
Protein
Accession
#: NP
6S1 11 _ 31 41 51
21 I
I I I I 1 VDEEGLKKLM60
MMCSSLEQALAVLVTTFHKYSCQEGDKFKLSKGEMKELLHKELPSFVGEK
GSLDENSDQQVDFQEYAVFLALITVMCNDFFQGCPDRP
7O
Seq ID NO: 15 DNA sequence
Nucleic Acid Accession #: Eos sequence
Coding sequence: 62-358
7SZ 11 21 31 41 51
I I
I I I I TGGAACCTCGGCCACAGATC
GGAGGGTGTGCCGCTGAGTC ACTGCCTGGG 60
CATCTGGGCC
CATGATGTGCAGTTCTCTGG AGCAGGCGCTGTCACTACCTTCCACAAGTA
GGCTGTGCTG 120
CTCCTGCCAAGAGGGCGACA AGTTCAAGCTGAAATGAAGGAACTTCTGCA
GAGTAAGGGG 180
CAAGGAGCTGCCCAGCTTTG TGGGGGAGAAGAGGGGCTGAAGAAGCTGAT
AGTGGATGAG 240
GGGCAGCCTGGATGAGAACA GTGACCAGCACAGGAGTATGCTGTTTTCCT
GGTGGACTTC 300
GGCACTCATCACTGTCATGT GCAATGACTTTGCCCAGACCGACCCTGAAG
CTTCCAGGGC 360
CAGAACTCTTGACTTCCTGC CATGGATCTCGACTGTTGATGCCTTTGAGT
TTGGGCCCAG 420
TTTGTATTCAATAAACTTTT TTTGTCTGTTTAATTGCTCAGTGATGTTCC
GATAATATTT 480
B ATAACCCGGCTGGCTCAGCT GGAGTGCTGGCCTCCTGGATCCTGCTCCCT
S GAGATGAGGG 540
TCTGGGCTCTGACTCTCCTG GAAATCTCTCGCTATGCTTTAGGTCTCAAT
CAAGGCCAGA 600
TTTGGAATTTCAAACACCAG CAAAAAATTGTAGGTTGCTGACTTTTATTT
GAAATCGAGA 660
192
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
TGTCAAATAA AGATATTAAA AAAGGCAAAT ACCA
Seq ID N0: 16 Protein sequence:
S Protein Accession #: NP 005969.1
1 11 21 31 41 51
MMCSSLEQAL AVLVTTFHKY SCQEGDKFKL SKGEMKELLH KELPSFVGEK VDEEGLKKLM 60
1 O GSLDENSDQQ VDFQEYAVFL ALITVMCNDF FQGCPDRP
Seq ID N0: 17 DNA sequence
Nucleic Acid Accession #: Eos sequence
1 S Coding sequence: 939-2372
1 11 21 31 41 51
AAGACGGATTCTCAGACAAGGCTTGCAAATGCCCCGCAGCCATCATTTAACTGCACCCGC60
~1AGAATAGTTACGGTTTGTCACCCGACCCTCCCGGATCGCCTAATTTGTCCCTAGTGAGAC120
GO
CCCGAGGCTCTGCCCGCGCCTGGCTTCTTCGTAGCTGGATGCATATCGTGCTCCGGGCAG180
CGCGGGCGCAGGGCACGCGTTCGCGCACACCCTAGCACACATGAACACGCGCAAGAGCTG240
AACCAAGCACGGTTTCCATTTCAAAAAGGGAGACAGCCTCTACCGCGATTGTAGAAGAGA300
CTGTGGTGTGAATTAGGGACCGGGAGGCGTCGAACGGAGGAACGGTTCATCTTAGAGACT360
~1AATTTTCTGGAGTTTCTGCCCCTGCTCTGCGTCAGCCCTCACGTCACTTCGCCAGCAGTA420
GS
GCAGAGGCGGCGGCGGCGGCTCCCGGAATTGGGTTGGAGCAGGAGCCTCGCTGGCTGCTT480
CGCTCGCGCTCTACGCGCTCAGTCCCCGGCGGTAGCAGGAGCCTGGACCCAGGCGCCGCC540
GGCGGGCGTGAGGCGCCGGAGCCCGGCCTCGAGGTGCATACCGGACCCCCATTCGCATCT600
AACAAGGAATCTGCGCCCCAGAGAGTCCCGGGAGCGCCGCCGGTCGGTGCCCGGCGCGCC660
3 GGGCCATGCAGCGACGGCCGCCGCGGAGCTCCGAGCAGCGGTAGCGCCCCCCTGTAAAGC720
O
GGTTCGCTATGCCGGGGCCACTGTGAACCCTGCCGCCTGCCGGAACACTCTTCGCTCCGG780
ACCAGCTCAGCCTCTGATAAGCTGGACTCGGCACGCCCGCAACAAGCACCGAGGAGTTAA840
GAGAGCCGCAAGCGCAGGGAAGGCCTCCCCGCACGGGTGGGGGAAAGCGGCCGGTGCAGC900
GCGGGGACAGGCACTCGGGCTGGCACTGGCTGCTAGGGATGTCGTCCTGGATAAGGTGGC960
3 ATGGACCCGCCATGGCGCGGCTCTGGGGCTTCTGCTGGCTGGTTGTGGGCTTCTGGAGGG1020
S
CCGCTTTCGCCTGTCCCACGTCCTGCAAATGCAGTGCCTCTCGGATCTGGTGCAGCGACC1080
CTTCTCCTGGCATCGTGGCATTTCCGAGATTGGAGCCTAACAGTGTAGATCCTGAGAACA1140
TCACCGAAATTTTCATCGCAAACCAGAAAAGGTTAGAAATCATCAACGAAGATGATGTTG1200
AAGCTTATGTGGGACTGAGAAATCTGACAATTGTGGATTCTGGATTAAAATTTGTGGCTC1260
~ ATAAAGCATTTCTGAAAAACAGCAACCTGCAGCACATCAATTTTACCCGAAACAAACTGA1320
'tO
CGAGTTTGTCTAGGAAACATTTCCGTCACCTTGACTTGTCTGAACTGATCCTGGTGGGCA1380
ATCCATTTACATGCTCCTGTGACATTATGTGGATCAAGACTCTCCAAGAGGCTAAATCCA1440
GTCCAGACACTCAGGATTTGTACTGCCTGAATGAAAGCAGCAAGAATATTCCCCTGGCAA1500
ACCTGCAGATACCCAATTGTGGTTTGCCATCTGCAAATCTGGCCGCACCTAACCTCACTG1560
~ TGGAGGAAGGAAAGTCTATCACATTATCCTGTAGTGTGGCAGGTGATCCGGTTCCTAATA1620
'h8
TGTATTGGGATGTTGGTAACCTGGTTTCCAAACATATGAATGAAACAAGCCACACACAGG1680
GCTCCTTAAGGATAACTAACATTTCATCCGATGACAGTGGGAAGCAGATCTCTTGTGTGG1740
CGGAAAATCTTGTAGGAGAAGATCAAGATTCTGTCAACCTCACTGTGCATTTTGCACCAA1800
CTATCACATTTCTCGAATCTCCAACCTCAGACCACCACTGGTGCATTCCATTCACTGTGA1860
S AAGGCAACCCCAAACCAGCGCTTCAGTGGTTCTATAACGGGGCAATATTGAATGAGTCCA1920
O
AATACATCTGTACTAAAATACATGTTACCAATCACACGGAGTACCACGGCTGCCTCCAGC1980
TGGATAATCCCACTCACATGAACAATGGGGACTACACTCTAATAGCCAAGAATGAGTATG2040
GGAAGGATGAGAAACAGATTTCTGCTCACTTCATGGGCTGGCCTGGAATTGACGATGGTG2100
CAAACCCAAATTATCCTGATGTAATTTATGAAGATTATGGAACTGCAGCGAATGACATCG2160
S GGGACACCACGAACAGAAGTAATGAAATCCCTTCCACAGACGTCACTGATAAAACCGGTC2220
S
GGGAACATCTCTCGGTCTATGCTGTGGTGGTGATTGCGTCTGTGGTGGGATTTTGCCTTT2280
TGGTAATGCTGTTTCTGCTTAAGTTGGCAAGACACTCCAAGTTTGGCATGAAAGGTTTTG2340
TTTTGTTTCATAAGATCCCACTGGATGGGTAGCTGAAATAAAGGAAAAGACAGAGAAAGG2400
GGCTGTGGTGCTTGTTGGTTGATGCTGCCATGTAAGCTGGACTCCTGGGACTGCTGTTGG2460
G CTTATCCCGGGAAGTGCTGCTTATCTGGGGTTTTCTGGTAGATGTGGGCGGTGTTTGGAG2520
VO
GCTGTACTATATGAAGCCTGCATATACTGTGAGCTGTGATTGGGGAACACCAATGCAGAG2580
GTAACTCTCAGGCAGCTAAGCAGCACCTCAAGAAAACATGTTAAATTAATGCTTCTCTTC2640
TTACAGTAGTTCAAATACAAAACTGAAATGAAATCCCATTGGATTGTACTTCTCTTCTGA2700
AAAGTGTGCTTTTTGACCCTACTGGACATTTATTGACTTAATTGCTTCTGTTTATTAAAA2760
G TTGACCTGCAAAGTTAAAAAAAAATTAAAGTTGAGAACAGGTATAAGTGCACACTGAATA2820
VS
GTCTAATCTACATGTAACACATATTTTAGTGTGATTTTCTATACTCTAATCAGCACTGAA2880
TTCAGAGGGTTTGACTTTTTCATCTATAACACAGTGACTAAAAGAGTTAAGGGTATATAT2940
ACCATCACTTTGGGACTTGGTAGTATTATTAAAAGGTTATTTCCTTCACTGTCAATAAAA3000
GTCCAAATGTTTAGCTTAGGTCTGAGAGTCAAACAATGTTAAGGATTGTCTTAAAGTTCC3060
~7TTAGCCAGCAAAACAAAACAAAACAAAACAAACAAATGAAAAACGTTTAAAAAGAAGAAG3120
/O
AAGAAAAAAAACAAGAACAAGCAGCAACAGCTGTTTTGTTGGGGCTATAGATTTAAGTTA3180
GGCATAGTCAATTTCAGAATAACTAAGAGTGGAATATATGCATATGGTGAAATTATAACC3240
TTGCCCTTTTTTATTTGCCCTCTGCGATCCACCTGCTTTTTAGAAGTCTGCCGAGTGAGA3300
AGGCCACAGTATCTCATGCTGTTTGCATTACAGAACTGCAGCTTTTCTACTCTGAAAAGG3360
7SCCTGGGAGCAGAATGGCTGGCCTGCTGTGAGCAGGAGAGGAGATTCTAAGAAGGATAGTC3420
CCCCCTACAACATACTGTCATACTGCTGGGTTTTCATGGGTAGGAAAGCTTGTCCTGACC3480
CCAGCAGCAAAGAGGTGGCAGGTCGCTAATGAATATATGCTTTATAATGTCCTTCTTCAT3540
TGCTGAGAGGGCAGCCTTAGAGCTGTGGATTTCTGCATCCCCCCTGAGTCTGACCCATGG3600
ACACCTGTTTCATTCACTTTAGCATCACAGTGACCTTTGTATGCTCTGTTCAGTCTGTGT3660
S CAGGCAGTATGCTTGTCCTGAAGAGAGGTTTGGCTATCCCCACCCCACCCCACCCCACCC3720
O
TGTTCCTTTTTTATCAGGAGGACTTCAGAGCCAGGCCTGCAGCATTTTGTTTGAAAACAC3780
AATCAGCTCTGACAGTTAGACATGCACACAGACGCCATAGCTGGATTGGAAACATTGATG3840
TTTTAAAAATTTATTTTTTTTGGAAATAGTTGCACAAATGCTGCAATTTAGCTTTAAGGT3900
TCTATAGATTTTTAACTAGTCCAACACAGTCAGAAACATTGTTTTGAATCCTCTGTAAAC3960
S CAAGGCATTAATCTTAATAAACCAGGATCCATTTAGGTACCACTTGATATAAAAAGGATA4020
S
TCCATAATGAATATTTTATACTGCATCCTTTACATTAGCCACTAAATACGTTATTGCTTG4080
ATGAAGACCTTTCACAGAATCCTATGGATTGCAGCATTTCACTTGGCTACTTCATACCCA4140
193
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
TGCCTTAAAG AGGGGCAGTTAGAAACATGCCGCCAGTTCT 4200
TCTCAAAAGC CAAGTTTTCC
TCCTAACTCC ATTTGAATGTGGCCCCCAATGTGGGGAGGT 4260
AAGGGCAGCT CCGAACATTT
TCTGAATTCC CATTTTCTTGAATGACAGTTTCTGTCATTA 4320
TTCGCGGCTA CTTAGATTCC
GATCTTTCCC AAAGGTGTTGAGGCCAGCTAATAGCAGAAA 4380
ATTTACAAAG TCATGACCCT
S GAAAGAGAGA TGAAATTCAAAGGCAGGAGCTCAGTATGGC 4440
GCTGTGAGCC AAAGGTTCTT
GAGAATCAGC CATTTGGTACTTTAAAGCTTTTATGTTATA 4500
AAAAAAGATT CCATGGAGCC
ATAGAAAGGC TATGGATTGTTTTTAAAGTGTTCCAGACCC 4560
TTAAGAACTA AAAAAGGAAA
AATAAAAAAA AAGGAATATTAGCTAGAAGGATTGCAAGGT 4620
TGTACCCAAC AGATTTTTGT
TTTAAAATGG AGAGAAGTGGCCATTTAATATATCAAAGAT 4680
ACAGATAAGG CAGTTGACAT
1 CTCCTAGGGA ATGATGAAAAT
O CAGCAGGCTA
Seq ID N0: 18 Protein sequence:
Protein Accession #: CAAS3571
1 1 11 21 31 41 51
S I I
MSSWIRWHGPI ~ I SRIWCSDPSPGIVAFPRLEP
AMARLWGFCWLWGFWRAAFACPTSCKCSA 60
NSVDPENITEIFIANQKRLEIINEDDVEAYVGLRNLTIVDSGLKFVAHKAFLKNSNLQHI
120
NFTRNKLTSLSRKHFRHLDLSELILVGNPFTCSCDIMWIKTLQEAKSSPDTQDLYCLNES
180
~1 SKNIPLANLQIPNCGLPSANLAAPNLTVEEGKSITLSCSVAGDPVPNMYWDVGNLVSKHM
GO 240
NETSHTQGSLRITNISSDDSGKQISCVAENLVGEDQDSVNLTVHFAPTITFLESPTSDHH
300
WCIPFTVKGNPKPALQWFYNGAILNESKYICTKIHVTNHTEYHGCLQLDNPTHMNNGDYT
360
LIAKNEYGKDEKQISAHFMGWPGIDDGANPNYPDVIYEDYGTAANDIGDTTNRSNEIPST
420
DVTDKTGREHLSVYAVWIASWGFCLLVMLFLLKLARHSKFGMKGFVLFHKIPLDG
~S
Seq ID 19
N0: DNA
sequence
Nucleic 28
Acid
Accession
#: NM_0002
Coding
sequence:
82-3600
3O 1 11 21 31 41 51
1 I
I I I I CAAGGAAAGGTCCTTTCTGG60
GCTTTCAGGCGATCTGGAGAAAGAACGGCAGAACACACAG
GGATCACCCCATTGGCTGAAGATGAGACCATTCTTCCTCTTGTGTTTTGCCCTGCCTGGC120
CTCCTGCATGCCCAACAAGCCTGCTCCCGTGGGGCCTGCTATCCACCTGTTGGGGACCTG180
3 CTTGTTGGGAGGACCCGGTTTCTCCGAGCTTCATCTACCTGTGGACTGACCAAGCCTGAG240
S
ACCTACTGCACCCAGTATGGCGAGTGGCAGATGAAATGCTGCAAGTGTGACTCCAGGCAG300
CCTCACAACTACTACAGTCACCGAGTAGAGAATGTGGCTTCATCCTCCGGCCCCATGCGC360
TGGTGGCAGTCCCAGAATGATGTGAACCCTGTCTCTCTGCAGCTGGACCTGGACAGGAGA420
TTCCAGCTTCAAGAAGTCATGATGGAGTTCCAGGGGCCCATGCCCGCCGGCATGCTGATT480
4O GAGCGCTCCTCAGACTTCGGTAAGACCTGGCGAGTGTACCAGTACCTGGCTGCCGACTGC540
ACCTCCACCTTCCCTCGGGTCCGCCAGGGTCGGCCTCAGAGCTGGCAGGATGTTCGGTGC600
CAGTCCCTGCCTCAGAGGCCTAATGCACGCCTAAATGGGGGGAAGGTCCAACTTAACCTT660
ATGGATTTAGTGTCTGGGATTCCAGCAACTCAAAGTCAAAAAATTCAAGAGGTGGGGGAG720
ATCACAAACTTGAGAGTCAATTTCACCAGGCTGGCCCCTGTGCCCCAAAGGGGCTACCAC780
4S CCTCCCAGCGCCTACTATGCTGTGTCCCAGCTCCGTCTGCAGGGGAGCTGCTTCTGTCAC840
GGCCATGCTGATCGCTGCGCACCCAAGCCTGGGGCCTCTGCAGGCCCCTCCACCGCTGTG900
CAGGTCCACGATGTCTGTGTCTGCCAGCACAACACTGCCGGCCCAA~TTGTGAGCGCTGT960
GCACCCTTCTACAACAACCGGCCCTGGAGACCGGCGGAGGGCCAGGACGCCCATGAATGC1020
CAAAGGTGCGACTGCAATGGGCACTCAGAGACATGTCACTTTGACCCCGCTGTGTTTGCC1080
SO GCCAGCCAGGGGGCATATGGAGGTGTGTGTGACAATTGCCGGGACCACACCGAAGGCAAG1140
AACTGTGAGCGGTGTCAGCTGCACTATTTCCGGAACCGGCGCCCGGGAGCTTCCATTCAG1200
GAGACCTGCATCTCCTGCGAGTGTGATCCGGATGGGGCAGTGCCAGGGGCTCCCTGTGAC1260
CCAGTGACCGGGCAGTGTGTGTGCAAGGAGCATGTGCAGGGAGAGCGCTGTGACCTATGC1320
AAGCCGGGCTTCACTGGACTCACCTACGCCAACCCGCAGGGCTGCCACCGCTGTGACTGC1380
S AACATCCTGGGGTCCCGGAGGGACATGCCGTGTGACGAGGAGAGTGGGCGCTGCCTTTGT1440
S
CTGCCCAACGTGGTGGGTCCCAAATGTGACCAGTGTGCTCCCTACCACTGGAAGCTGGCC1500
AGTGGCCAGGGCTGTGAACCGTGTGCCTGCGACCCGCACAACTCCCCTCAGCCCACAGTG1560
CAACCAGTTCACAGGGCAGTGCCCTGTCGGGAAGGCTTTGGTGGCCTGATGTGCAGCGCT1620
GCAGCCATCCGCCAGTGTCCAGACCGGACCTATGGAGACGTGGCCACAGGATGCCGAGCC1680
6O TGTGACTGTGATTTCCGGGGAACAGAGGGCCCGGGCTGCGACAAGGCATCAGGCCGCTGC1740
CTCTGCCGCCCTGGCTTGACCGGGCCCCGCTGTGACCAGTGCCAGCGAGGCTACTGCAAT1800
CGCTACCCGGTGTGCGTGGCCTGCCACCCTTGCTTCCAGACCTATGATGCGGACCTCCGG1860
GAGCAGGCCCTGCGCTTTGGTAGACTCCGCAATGCCACCGCCAGCCTGTGGTCAGGGCCT1920
GGGCTGGAGGACCGTGGCCTGGCCTCCCGGATCCTAGATGCAAAGAGTAAGATTGAGCAG1980
G ATCCGAGCAGTTCTCAGCAGCCCCGCAGTCACAGAGCAGGAGGTGGCTCAGGTGGCCAGT2040
VS
GCCATCCTCTCCCTCAGGCGAACTCTCCAGGGCCTGCAGCTGGATCTGCCCCTGGAGGAG2100
GAGACGTTGTCCCTTCCGAGAGACCTGGAGAGTCTTGACAGAAGCTTCAATGGTCTCCTT2160
ACTATGTATCAGAGGAAGAGGGAGCAGTTTGAAAAAATAAGCAGTGCTGATCCTTCAGGA2220
GCCTTCCGGATGCTGAGCACAGCCTACGAGCAGTCAGCCCAGGCTGCTCAGCAGGTCTCC2280
7O GACAGCTCGCGCCTTTTGGACCAGCTCAGGGACAGCCGGAGAGAGGCAGAGAGGCTGGTG2340
CGGCAGGCGGGAGGAGGAGGAGGCACCGGCAGCCCCAAGCTTGTGGCCCTGAGGCTGGAG2400
ATGTCTTCGTTGCCTGACCTGACACCCACCTTCAACAAGCTCTGTGGCAACTCCAGGCAG2460
ATGGCTTGCACCCCAATATCATGCCCTGGTGAGCTATGTCCCCAAGACAATGGCACAGCC2520
TGTGGCTCCCGCTGCAGGGGTGTCCTTCCCAGGGCCGGTGGGGCCTTCTTGATGGCGGGG2580
7S CAGGTGGCTGAGCAGCTGCGGGGCTTCAATGCCCAGCTCCAGCGGACCAGGCAGATGATT2640
AGGGCAGCCGAGGAATCTGCCTCACAGATTCAATCCAGTGCCCAGCGCTTGGAGACCCAG2700
GTGAGCGCCAGCCGCTCCCAGATGGAGGAAGATGTCAGACGCACACGGCTCCTAATCCAG2760
CAGGTCCGGGACTTCCTAACAGACCCCGACACTGATGCAGCCACTATCCAGGAGGTCAGC2820
'GAGGCCGTGCTGGCCCTGTGGCTGCCCACAGACTCAGCTACTGTTCTGCAGAAGATGAAT2880
SO GAGATCCAGGCCATTGCAGCCAGGCTCCCCAACGTGGACTTGGTGCTGTCCCAGACCAAG2940
CAGGACATTGCGCGTGCCCGCCGGTTGCAGGCTGAGGCTGAGGAAGCCAGGAGCCGAGCC3000
CATGCAGTGGAGGGCCAGGTGGAAGATGTGGTTGGGAACCTGCGGCAGGGGACAGTGGCA3060
CTGCAGGAAGCTCAGGACACCATGCAAGGCACCAGCCGCTCCCTTCGGCTTATCCAGGAC3120
AGGGTTGCTGAGGTTCAGCAGGTACTGCGGCCAGCAGAAAAGCTGGTGACAAGCATGACC3180
S AAGCAGCTGGGTGACTTCTGGACACGGATGGAGGAGCTCCGCCACCAAGCCCGGCAGCAG3240
S
GGGGCAGAGGCAGTCCAGGCCCAGCAGCTTGCGGAAGGTGCCAGCGAGCAGGCATTGAGT3300
GCCCAAGAGGGATTTGAGAGAATAAAACAAAAGTATGCTGAGTTGAAGGACCGGTTGGGT3360
194
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
CAGAGTTCCATGCTGGGTGAGCAGGGTGCCCGGATCCAGAGTGTGAAGACAGAGGCAGAG3420
GAGCTGTTTGGGGAGACCATGGAGATGATGGACAGGATGAAAGACATGGAGTTGGAGCTG3480
CTGCGGGGCAGCCAGGCCATCATGCTGCGCTCGGCGGACCTGACAGGACTGGAGAAGCGT3540
GTGGAGCAGATCCGTGACCACATCAATGGGCGCGTGCTCTACTATGCCACCTGCAAGTGA3600
S TGCTACAGCTTCCAGCCCGTTGCCCCACTCATCTGCCGCCTTTGCTTTTGGTTGGGGGCA3660
GATTGGGTTGGAATGCTTTCCATCTCCAGGAGACTTTCATGCAGCCTAAAGTACAGCCTG3720
GACCACCCCTGGTGTGTAGCTAGTAAGATTACCCTGAGCTGCAGCTGAGCCTGAGCCAAT3780
GGGACAGTTACACTTGACAGACAAAGATGGTGGAGATTGGCATGCCATTGAAACTAAGAG3840
CTCTCAAGTCAAGGAAGCTGGGCTGGGCAGTATCCCCCGCCTTTAGTTCTCCACTGGGGA3900
1 GGAATCCTGGACCAAGCACAAAAACTTAACAAAAGTGATGTAAAAATGAAAAGCCAAATA3960
O
AAAATCTTTGG
Seq ID 20 sequence:
N0: Protein
Protein
Accession
#: NP
000219
1 -
S
1 1l 21 31 41 51
MRPFFLLCFALPGLLHAQQACSRGACYPPVGDLLVGRTRFLRASSTCGLTKPETYCTQYG60
EWQMKCCKCDSRQPHNYYSHRVENVASSSGPMRWWQSQNDVNPVSLQLDLDRRFQLQEVM120
2OMEFQGPMPAGMLIERSSDFGKTWAVYQYLAADCTSTFPRVRQGRPQSWQDVRCQSLPQRP180
NARLNGGKVQLNLMDLVSGIPATQSQKIQEVGEITNLRVNFTRLAPVPQRGYHPPSAYYA240
VSQLRLQGSCFCHGHADRCAPKPGASAGPSTAVQVHDVCVCQHNTAGPNCERCAPFYNNR300
PWRPAEGQDAHECQRCDCNGHSETCHFDPAVFAASQGAYGGVCDNCRDHTEGKNCERCQL360
HYFRNRRPGASIQETCISCECDPDGAVPGAPCDPVTGQCVCKEHVQGERCDLCKPGFTGL420
~STYANPQGCHRCDCNILGSRRDMPCDEESGRCLCLPNWGPKCDQCAPYHWKLASGQGCEP480
CACDPHNSPQPTVQPVHRAVPCREGFGGLMCSAAAIRQCPDRTYGDVATGCRACDCDFRG540
TEGPGCDKASGRCLCRPGLTGPRCDQCQRGYCNRYPVCVACHPCFQTYDADLREQALRFG600
RLRNATASLWSGPGLEDRGLASRILDAKSKIEQIRAVLSSPAVTEQEVAQVASAILSLRR660
TLQGLQLDLPLEEETLSLPRDLESLDRSFNGLLTMYQRKREQFEKISSADPSGAFRMLST720
3 AYEQSAQAAQQVSDSSRLLDQLRDSRREAERLVRQAGGGGGTGSPKLVALRLEMSSLPDL780
O
TPTFNKLCGNSRQMACTPISCPGELCPQDNGTACGSRCRGVLPRAGGAFLMAGQVAEQLR840
GFNAQLQRTRQMIRAAEESASQIQSSAQRLETQVSASRSQMEEDVRRTRLLIQQVRDFLT900
DPDTDAATIQEVSEAVLALWLPTDSATVLQKMNEIQAIAARLPNVDLVLSQTKQDIARAR960
RLQAEAEEARSRAHAVEGQVEDWGNLRQGTVALQEAQDTMQGTSRSLRLIQDRVAEVQQ1020
3 VLRPAEKLVTSMTKQLGDFWTRMEELRHQARQQGAEAVQAQQLAEGASEQALSAQEGFER1080
S
IKQKYAELKDRLGQSSMLGEQGARIQSVKTEAEELFGETMEMMDRMKDMELELLRGSQAI1140
MLRSADLTGLEKRVEQIRDHINGRVLYYATCK
A Seq ID NO: 21 DNA sequence
4O Nucleic Acid Accession #: NM 003722
Coding sequence: 145-1491
1 11 21 31 41 51
4STCGTTGATATCAAAGACAGTTGAAGGAAATGAATTTTGAAACTTCACGGTGTGCCACCCT60
ACAGTACTGCCCTGACCCTTACATCCAGCGTTTCGTAGAAACCCAGCTCATTTCTCTTGG120
AAAGAAAGTTATTACCGATCCACCATGTCCCAGAGCACACAGACAAATGAATTCCTCAGT180
CCAGAGGTTTTCCAGCATATCTGGGATTTTCTGGAACAGCCTATATGTTCAGTTCAGCCC240
ATTGACTTGAACTTTGTGGATGAACCATCAGAAGATGGTGCGACAAACAAGATTGAGATT300
S AGCATGGACTGTATCCGCATGCAGGACTCGGACCTGAGTGACCCCATGTGGCCACAGTAC360
O
ACGAACCTGGGGCTCCTGAACAGCATGGACCAGCAGATTCAGAACGGCTCCTCGTCCACC420
AGTCCCTATAACACAGACCACGCGCAGAACAGCGTCACGGCGCCCTCGCCCTACGCACAG480
CCCAGCTCCACCTTCGATGCTCTCTCTCCATCACCCGCCATCCCCTCCAACACCGACTAC540
CCAGGCCCGCACAGTTTCGACGTGTCCTTCCAGCAGTCGAGCACCGCCAAGTCGGCCACC600
S TGGACGTATTCCACTGAACTGAAGAAACTCTACTGCCAAATTGCAAAGACATGCCCCATC660
S
CAGATCAAGGTGATGACCCCACCTCCTCAGGGAGCTGTTATCCGCGCCATGCCTGTCTAC720
AAAAAAGCTGAGCACGTCACGGAGGTGGTGAAGCGGTGCCCCAACCATGAGCTGAGCCGT780
GAATTCAACGAGGGACAGATTGCCCCTCCTAGTCATTTGATTCGAGTAGAGGGGAACAGC840
CATGCCCAGTATGTAGAAGATCCCATCACAGGAAGACAGAGTGTGCTGGTACCTTATGAG900
6OCCACCCCAGGTTGGCACTGAATTCACGACAGTCTTGTACAATTTCATGTGTAACAGCAGT960
TGTGTTGGAGGGATGAACCGCCGTCCAATTTTAATCATTGTTACTCTGGAAACCAGAGAT1020
GGGCAAGTCCTGGGCCGACGCTGCTTTGAGGCCCGGATCTGTGCTTGCCCAGGAAGAGAC1080
AGGAAGGCGGATGAAGATAGCATCAGAAAGCAGCAAGTTTCGGACAGTACAAAGAACGGT1140
GATGGTACGAAGCGCCCGTTTCGTCAGAACACACATGGTATCCAGATGACATCCATCAAG1200
6SAAACGAAGATCCCCAGATGATGAACTGTTATACTTACCAGTGAGGGGCCGTGAGACTTAT1260
GAAATGCTGTTGAAGATCAAAGAGTCCCTGGAACTCATGCAGTACCTTCCTCAGCACACA1320
ATTGAAACGTACAGGCAACAGCAACAGCAGCAGCACCAGCACTTACTTCAGAAACATCTC1380
CTTTCAGCCTGCTTCAGGAATGAGCTTGTGGAGCCCCGGAGAGAAACTCCAAAACAATCT1440
GACGTCTTCTTTAGACATTCCAAGCCCCCAAACCGATCAGTGTACCCATAGAGCCCTATC1500
7OTCTATATTTTAAGTGTGTGTGTTGTATTTCCATGTGTATATGTGAGTGTGTGTGTGTGTA1560
TGTGTGTGCGTGTGTATCTAGCCCTCATAAACAGGACTTGAAGACACTTTGGCTCAGAGA1620
CCCAACTGCTCAAAGGCACAAAGCCACTAGTGAGAGAATCTTTTGAAGGGACTCAAACCT1680
TTACAAGAAAGGATGTTTTCTGCAGATTTTGTATCCTTAGACCGGCCATTGGTGGGTGAG1740
GAACCACTGTGTTTGTCTGTGAGCTTTCTGTTGTTTCCTGGGAGGGAGGGGTCAGGTGGG1800
~7GAAAGGGGCATTAAGATGTTTATTGGAACCCTTTTCTGTCTTCTTCTGTTGTTTTTCTAA1860
/S
AATTCACAGGGAAGCTTTTGAGCAGGTCTCAAACTTAAGATGTCTTTTTAAGAAAAGGAG1920
AAAAAAGTTGTTATTGTCTGTGCATAAGTAAGTTGTAGGTGACTGAGAGACTCAGTCAGA1980
CCCTTTTAATGCTGGTCATGTAATAATATTGCAAGTAGTAAGAAACGAAGGTGTCAAGTG2040
TACTGCTGGGCAGCGAGGTGATCATTACCAAAAGTAATCAACTTTGTGGGTGGAGAGTTC2100
p TTTGTGAGAACTTGCATTATTTGTGTCCTCCCCTCATGTGTAGGTAGAACATTTCTTAAT2160
OO
GCTGTGTACCTGCCTCTGCCACTGTATGTTGGCATCTGTTATGCTAAAGTTTTTCTTGTA2220
CATGAAACCCTGGAAGACCTACTACAAAAAAACTGTTGTTTGGCCCCCATAGCAGGTGAA2280
CTCATTTTGTGCTTTTAATAGAAAGACAAATCCACCCCAGTAATATTGCCCTTACGTAGT2340
TGTTTACCATTATTCAAAGCTCAAAATAGAATTTGAAGCCCTCTCACAAAATCTGTGATT2400
S AATTTGCTTAATTAGAGCTTCTATCCCTCAAGCCTACCTACCATAAAACCAGCCATATTA2460
CTGATACTGTTCAGTGCATTTAGCCAGGAGACTTACGTTTTGAGTAAGTGAGATCCAAGC2520
AGACGTGTTAAAATCAGCACTCCTGGACTGGAAATTAAAGATTGAAAGGGTAGACTACTT2580
19S
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
TTCTTTTTTT TACTCAAAAG TTTAGAGAAT CTCTGTTTCT TTCCATTTTA AAAACATATT 2640
TTAAGATAAT AGCATAAAGA CTTTAAAAAT GTTCCTCCCC TCCATCTTCC CACACCCAGT 2700
CACCAGCACT GTATTTTCTG TCACCAAGAC AATGATTTCT TGTTATTGAG GCTGTTGCTT 2760
S TTGTGGATGT GTGATTTTAA TTTTCAATAA ACTTTTGCAT CTTGGTTTAA AAGAAA
Seq ID N0: 22 Protein sequence:
Protein Accession #: NP 003713
1 O 1 11 21 31 41 51
I I I I I I
MSQSTQTNEF LSPEVFQHIW DFLEQPICSV QPIDLNFVDE PSEDGATNKI EISNmCIRMQ 60
DSDLSDPMWP QYTNLGLLNS MDQQIQNGSS STSPYNTDHA QNSVTAPSPY AQPSSTFDAL 120
SPSPAIPSNT DYPGPHSFDV SFQQSSTAKS ATWTYSTELK KLYCQIAKTC PIQIKVMTPP 180
PQGAVIRAMP VYKKAEHVTE WKRCPNHEL SREFNEGQIA PPSHLIRVEG NSHAQWEDP 240
1 S ITGRQSVLVP YEPPQVGTEF TTVLYNFMCN SSCVGGMNRR PILIIVTLET RDGQVLGRRC 300
FEARICACPG RDRKADEDSI RKQQVSDSTK NGDGTKRPFR QNTHGIQMTS IKKRRSPDDE 360
LLYLPVRGRE TYEMLLKIKE SLELMQYLPQ HTIETYRQQQ QQQHQHLLQK HLLSACFRNE 420
LVEPRRETPK QSDVFFRHSK PPNRSVYP
2O
Seq ID N0: 23 DNA sequence
Nucleic Acid Accession #: NM_001944.1
Coding sequence: 84-3083
~S 1 11 21 31 41 51
I I
1 I i I GCAGCGGCTCACTTGGACTT60
TTTTCTTAGACATTAACTGCAGACGGCTGGCAGGATAGAA
TTTCACCAGGGAAATCAGAGACAATGATGGGGCTCTTCCCCAGAACTACAGGGGCTCTGG120
CCATCTTCGTGGTGGTCATATTGGTTCATGGAGAATTGCGAATAGAGACTAAAGGTCAAT180
3 ATGATGAAGAAGAGATGACTATGCAACAAGCTAAAAGAAGGCAAAAACGTGAATGGGTGA240
O
AATTTGCCAAACCCTGCAGAGAAGGAGAAGATAACTCAAAAAGAAACCCAATTGCCAAGA300
TTACTTCAGATTACCAAGCAACCCAGAAAATCACCTACCGAATCTCTGGAGTGGGAATCG360
ATCAGCCGCCTTTTGGAATCTTTGTTGTTGACAAAAACACTGGAGATATTAACATAACAG420
CTATAGTCGACCGGGAGGAAACTCCAAGCTTCCTGATCACATGTCGGGCTCTAAATGCCC480
3 AAGGACTAGATGTAGAGAAACCACTTATACTAACGGTTAAAATTTTGGATATTAATGATA540
S
ATCCTCCAGTATTTTCACAACAAATTTTCATGGGTGAAATTGAAGAAAATAGTGCCTCAA600
ACTCACTGGTGATGATACTAAATGCCACAGATGCAGATGAACCAAACCACTTGAATTCTA660
AAATTGCCTTCAAAATTGTCTCTCAGGAACCAGCAGGCACACCCATGTTCCTCCTAAGCA720
GAAACACTGGGGAAGTCCGTACTTTGACCAATTCTCTTGACCGAGAGCAAGCTAGCAGCT780
~f ATCGTCTGGTTGTGAGTGGTGCAGACAAAGATGGAGAAGGACTATCAACTCAATGTGAAT840
GTAATATTAAAGTGAAAGATGTCAACGATAACTTCCCAATGTTTAGAGACTCTCAGTATT900
CAGCACGTATTGAAGAAAATATTTTAAGTTCTGAATTACTTCGATTTCAAGTAACAGATT960
TGGATGAAGAGTACACAGATAATTGGCTTGCAGTATATTTCTTTACCTCTGGGAATGAAG1020
GAAATTGGTTTGAAATACAAACTGATCCTAGAACTAATGAAGGCATCCTGAAAGTGGTGA1080
~ AGGCTCTAGATTATGAACAACTACAAAGCGTGAAACTTAGTATTGCTGTCAAAAACAAAG1140
4S
CTGAATTTCACCAATCAGTTATCTCTCGATACCGAGTTCAGTCAACCCCAGTCACAATTC1200
AGGTAATAAATGTAAGAGAAGGAATTGCATTCCGTCCTGCTTCCAAGACATTTACTGTGC1260
AAAAAGGCATAAGTAGCAAAAAATTGGTGGATTATATCCTGGGAACATATCAAGCCATCG1320
ATGAGGACACTAACAAAGCTGCCTCAAATGTCAAATATGTCATGGGACGTAACGATGGTG1380
SO GATACCTAATGATTGATTCAAAAACTGCTGAAATCAAATTTGTCAAAAATATGAACCGAG1440
ATTCTACTTTCATAGTTAACAAAACAATCACAGCTGAGGTTCTGGCCATAGATGAATACA1500
CGGGTAAAACTTCTACAGGCACGGTATATGTTAGAGTACCCGATTTCAATGACAATTGTC1560
CAACAGCTGTCCTCGAAAAAGATGCAGTTTGCAGTTCTTCACCTTCCGTGGTTGTCTCCG1620
CTAGAACACTGAATAATAGATACACTGGCCCCTATACATTTGCACTGGAAGATCAACCTG1680
S TAAAGTTGCCTGCCGTATGGAGTATCACAACCCTCAATGCTACCTCGGCCCTCCTCAGAG1740
S
CCCAGGAACAGATACCTCCTGGAGTATACCACATCTCCCTGGTACTTACAGACAGTCAGA1800
ACAATCGGTGTGAGATGCCACGCAGCTTGACACTGGAAGTCTGTCAGTGTGACAACAGGG1860
GCATCTGTGGAACTTCTTACCCAACCACAAGCCCTGGGACCAGGTATGGCAGGCCGCACT1920
CAGGGAGGCTGGGGCCTGCCGCCATCGGCCTGCTGCTCCTTGGTCTCCTGCTGCTGCTGT1980
6O TGGCCCCCCTTCTGCTGTTGACCTGTGACTGTGGGGCAGGTTCTACTGGGGGAGTGACAG2040
GTGGTTTTATCCCAGTTCCTGATGGCTCAGAAGGAACAATTCATCAGTGGGGAATTGAAG2100
GAGCCCATCCTGAAGACAAGGAAATCACAAATATTTGTGTGCCTCCTGTAACAGCCAATG2160
GAGCCGATTTCATGGAAAGTTCTGAAGTTTGTACAAATACGTATGCCAGAGGCACAGCGG2220
TGGAAGGCACTTCAGGAATGGAAATGACCACTAAGCTTGGAGCAGCCACTGAATCTGGAG2280
6S GTGCTGCAGGCTTTGCAACAGGGACAGTGTCAGGAGCTGCTTCAGGATTCGGAGCAGCCA2340
CTGGAGTTGGCATCTGTTCCTCAGGGCAGTCTGGAACCATGAGAACAAGGCATTCCACTG2400
GAGGAACCAATAAGGACTACGCTGATGGGGCGATAAGCATGAATTTTCTGGACTCCTACT2460
TTTCTCAGAAAGCATTTGCCTGTGCGGAGGAAGACGATGGCCAGGAAGCAAATGACTGCT2520
TGTTGATCTATGATAATGAAGGCGCAGATGCCACTGGTTCTCCTGTGGGCTCCGTGGGTT2580
~7 GTTGCAGTTTTATTGCTGATGACCTGGATGACAGCTTCTTGGACTCACTTGGACCCAAAT2640
/O
TTAAAAAACTTGCAGAGATAAGCCTTGGTGTTGATGGTGAAGGCAAAGAAGTTCAGCCAC2700
CCTCTAAAGACAGCGGTTATGGGATTGAATCCTGTGGCCATCCCATAGAAGTCCAGCAGA2760
CAGGATTTGTTAAGTGCCAGACTTTGTCAGGAAGTCAAGGAGCTTCTGCTTTGTCCGCCT2820
CTGGGTCTGTCCAGCCAGCTGTTTCCATCCCTGACCCTCTGCAGCATGGTAACTATTTAG2880
~7 TAACGGAGACTTACTCGGCTTCTGGTTCCCTCGTGCAACCTTCCACTGCAGGCTTTGATC2940
/S
CACTTCTCACACAAAATGTGATAGTGACAGAAAGGGTGATCTGTCCCATTTCCAGTGTTC3000
CTGGCAACCTAGCTGGCCCAACGCAGCTACGAGGGTCACATACTATGCTCTGTACAGAGG3060
ATCCTTGCTCCCGTCTAATATGACCAGAATGAGCTGGAATACCACACTGACCAAATCTGG3120
ATCTTTGGACTAAAGTATTCAAAATAGCATAGCAAAGCTCACTGTATTGGGCTAATAATT3180
BO TGGCACTTATTAGCTTCTCTCATAAACTGATCACGATTATAAATTAAATGTTTGGGTTCA3240
TACCCCAAAAGCAATATGTTGTCACTCCTAATTCTCAAGTACTATTCAAATTGTAGTAAA3300
TCTTAAAGTTTTTCAAAACCCTAAAATCATATTCGC
Seq ID NO: 24 Protein sequence:
S Protein Accession #: NP 001935.1
11 21 31 41 51
196
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
~
I I 1 1 I I
MMGLFPRTTGALAIFWVILVHGELRIETK QQAKRRQKREWVKFAKPCRE60
GQYDEEEMTM
GEDNSKRNPIAKITSDYQATQKITYRISGV VVDKNTGDINITAIVDREET120
GIDQPPFGIF
PSFLITCRALNAQGLDVEKPLILTVKILDI IFMGEIEENSASNSLVMILN180 ,
NDNPPVFSQQ
S ATDADEPNHLNSKIAFKIVSQEPAGTPMFL LTNSLDREQASSYRLWSGA240
LSRNTGEVRT
DKDGEGLSTQCECNIKVKDVNDNFPMFRDS LSSELLRFQVTDLDEEYTDN300
QYSARIEENI
WLAVYFFTSGNEGNWFEIQTDPRTNEGILK QSVKLSIAVKNKAEFHQSVI360
WKALDYEQL
SRYRVQSTPVTIQVINVREGIAFRPASKTF LVDYILGTYQAIDEDTNKAA420
TVQKGISSKK
SNVKYVMGRNDGGYLMIDSKTAEIKFVKNM TITAEVLAIDEYTGKTSTGT480
NRDSTFIVNK
1 VYVRVPDFNDNCPTAVLEKDAVCSSSPSW TGPYTFALEDQPVKLPAWS540
O VSARTLNNRY
ITTLNATSALLRAQEQIPPGVYHISLVLTD SLTLEVCQCDNRGICGTSYP600
SQNNRCEMPR
TTSPGTRYGRPHSGRLGPAAIGLLLLGLLL CDCGAGSTGGVTGGFIPVPD660
LLLAPLLLLT
GSEGTIHQWGIEGAHPEDKEITNICVPPVT EVCTNTYARGTAVEGTSGME720
ANGADFMESS
MTTKLGAATESGGAAGFATGTVSGAASGFG GQSGTMRTRHSTGGTNKDYA780
AATGVGICSS
1 DGAISMNFLDSYFSQKAFACAEEDDGQEAN ADATGSPVGSVGCCSFIADD840
S DCLLIYDNEG
LDDSFLDSLGPKFKKLAEISLGVDGEGKEV IESCGHPIEVQQTGFVKCQT900
QPPSKDSGYG
LSGSQGASALSASGSVQPAVSIPDPLQHGN GSLVQPSTAGFDPLLTQNVI960
YLVTETYSAS
VTERVICPISSVPGNLAGPTQLRGSHTMLC
TEDPCSRLI
LO Seq ID N0: 25 DNA sequence
Nucleic Acid Accession #: Eos sequence
Coding sequence: 56-1642
1 11 21 31 41 51
2S I I I I I I
AGTATCCCAGGAGGAGCAAGTGGCACGTCTTCGGACCTAGGCTGCCCCTGCCGTCATGTC60
GCAAGGGATCCTTTCTCCGCCAGCGGGCTTGCTGTCCGATGACGATGTCGTAGTTTCTCC120
CATGTTTGAGTCCACAGCTGCAGATTTGGGGTCTGTGGTACGCAAGAACCTGCTATCAGA180
CTGCTCTGTCGTCTCTACCTCCCTAGAGGACAAGCAGCAGGTTCCATCTGAGGACAGTAT240
3 GGAGAAGGTGAAAGTATACTTGAGGGTTAGGCCCTTGTTACCTTCAGAGTTGGAACGACA300
O
GGAAGATCAGGGTTGTGTCCGTATTGAGAATGTGGAGACCCTTGTTCTACAAGCACCCAA360
GGACTCTTTTGCCCTGAAGAGCAATGAACGGGGAATTGGCCAAGCCACACACAGGTTCAC420
CTTTTCCCAGATCTTTGGGCCAGAAGTGGGACAGGCATCCTTCTTCAACCTAACTGTGAA480
GGAGATGGTAAAGGATGTACTCAAAGGGCAGAACTGGCTCATCTATACATATGGAGTCAC540
3 TAACTCAGGGAAAACCCACACGATTCAAGGTACCATCAAGGATGGAGGGATTCTCCCCCG600
S
GTCCCTGGCGCTGATCTTCAATAGCCTCCAAGGCCAACTTCATCCAACACCTGATCTGAA660
GCCCTTGCTCTCCAATGAGGTAATCTGGCTAGACAGCAAGCAGATCCGACAGGAGGAAAT720
GAAGAAGCTGTCCCTGCTAAATGGAGGCCTCCAAGAGGAGGAGCTGTCCACTTCCTTGAA780
GAGGAGTGTCTACATCGAAAGTCGGATAGGTACCAGCACCAGCTTCGACAGTGGCATTGC840
~ TGGGCTCTCTTCTATCAGTCAGTGTACCAGCAGTAGCCAGCTGGATGAAACAAGTCATCG900
4O
ATGGGCACAGCCAGACACTGCCCCACTACCTGTCCCGGCAAACATTCGCTTCTCCATCTG960
GATCTCATTCTTTGAGATCTACAACGAACTGCTTTATGACCTATTAGAACCGCCTAGCCA1020
ACAGCGCAAGAGGCAGACTTTGCGGCTATGCGAGGATCAAAATGGCAATCCCTATGTGAA1080
AGATCTCAACTGGATTCATGTGCAAGATGCTGAGGAGGCCTGGAAGCTCCTAAAAGTGGG1140
A TCGTAAGAACCAGAGCTTTGCCAGCACCCACCTCAACCAGAACTCCAGCCGCAGTCACAG1200
4S
CATCTTCTCAATCAGGATCCTACACCTTCAGGGGGAAGGAGATATAGTCCCCAAGATCAG1260
CGAGCTGTCACTCTGTGATCTGGCTGGCTCAGAGCGCTGCAAAGATCAGAAGAGTGGTGA1320
ACGGTTGAAGGAAGCAGGAAACATTAACACCTCTCTACACACCCTGGGCCGCTGTATTGC1380
TGCCCTTCGTCAAAACCAGCAGAACCGGTCAAAGCAGAACCTGGTTCCCTTCCGTGACAG1440
S CAAGTTGACTCGAGTGTTCCAAGGTTTCTTCACAGGCCGAGGCCGTTCCTGCATGATTGT1500
O
CAATGTGAATCCCTGTGCATCTACCTATGATGAAACTCTTCATGTGGCCAAGTTCTCAGC1560
CATTGCTAGCCAGGTGACTTGTGCATGCCCCACCTATGCAACTGGGATTCCCATCCCTGC1620
ACTCGTTCATCAAGGAACATAGTCTTCAGGTATCCCCCAGCTTAGAGAAAGGGGCTAAGG1680
CAGACACAGGCCTTGATGATGATATTGAAAATGAAGCTGACATCTCCATGTATGGCAAAG1740
S AGGAGCTCCTACAAGTTGTGGAAGCCATGAAGACACTGCTTTTGAAGGAACGACAGGAAA1800
S
AGCTACAGCTGGAGATGCATCTCCGAGATGAAATTTGCAATGAGATGGTAGAACAGATGC1860
AACAGCGGGAACAGTGGTGCAGTGAACATTTGGACACCCAAAAGGAACTATTGGAGGAAA1920
TGTATGAAGAAAAACTAAATATCCTCAAGGAGTCACTGACAAGTTTTTACCAAGAAGAGA1980
TTCAGGAGCGGGATGAAAAGATTGAAGAGCTAGAAGCTCTCTTGCAGGAAGCCAGACAAC2040
6O AGTCAGTGGCCCATCAGCAATCAGGGTCTGAATTGGCCCTACGGCGGTCACAAAGGTTGG2100
CAGCTTCTGCCTCCACCCAGCAGCTTCAGGAGGTTAAAGCTAAATTACAGCAGTGCAAAG2160
CAGAGCTAAACTCTACCACTGAAGAGTTGCATAAGTATCAGAAAATGTTAGAACCACCAC2220
CCTCAGCCAAGCCCTTCACCATTGATGTGGACAAGAAGTTAGAAGAGGGCCAGAAGAATA2280
TAAGGCTGTTGCGGACAGAGCTTCAGAAACTTGGTGAGTCTCTCCAATCAGCAGAGAGAG2340
6S CTTGTTGCCACAGCACTGGGGCAGGAAAACTTCGTCAAGCCTTGACCACTTGTGATGACA2400
TCTTAATCAAACAGGACCAGACTCTGGCTGAACTGCAGAACAACATGGTGCTAGTGAAAC2460
TGGACCTTCGGAAGAAGGCAGCATGTATTGCTGAGCAGTATCATACTGTGTTGAAACTCC2520
AAGGCCAGGTTTCTGCCAAAAAGCGCCTTGGTACCAACCAGGAAAATCAGCAACCAAACC2580
AACAACCACCAGGGAAGAAACCATTCCTTCGAAATTTACTTCCCCGAACACCAACCTGCC2640
7O AAAGCTCAACAGACTGCAGCCCTTATGCCCGGATCCTACGCTCACGGCGTTCCCCTTTAC2700
TCAAATCTGGGCCTTTTGGCAAAAAGTACTAAGGCTGTGGGGAAAGAGAAGAGCAGTCAT2760
GGCCCTGAGGTGGGTCAGCTACTCTCCTGAAGAAATAGGTCTCTTTTATGCTTTACCATA2820
TATCAGGAATTATATCCAGGATGCAATACTCAGACACTAGCTTTTTTCTCACTTTTGTAT2880
TATAACCACCTATGTAATCTCATGTTGTTGTTTTTTTTTATTTACTTATATGATTTCTAT2940
7S GCACACAAAAACAGTTATATTAAAGATATTATTGTTCACATTTTTTATTGAATTCCAAAT3000
GTAGCAAAATCATTAAAACAAATTATAAAAGGGACAGAAAAA
Seq ID N0: 26 Protein sequence:
o O Protein Accession #: Eos sequence
0 1 11 21 31 41 51
1 I I I I I
MSQGILSPPA GLLSDDDVW SPMFESTAAD LGSWRKNLL SDCSWSTSL EDKQQVPSED 60
SMEKVKVYLR VRPLLPSELE RQEDQGCVRI ENVETLVLQA PKDSFALKSN ERGIGQATHR 120
H S FTFSQIFGPE VGQASFFNLT VKEMVKDVLK GQNWLIYTYG VTNSGKTHTI QGTIKDGGIL 7.80
PRSLALIFNS LQGQLHPTPD LKPLLSNEVI WLDSKQIRQE EMKKLSLLNG GLQEEELSTS 240
LKRSVYIESR IGTSTSFDSG IAGLSSISQC TSSSQLDETS HRWAQPDTAP LPVPANIRFS 300
197
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
IWISFFEIYNELLYDLLEPPSQQRKRQTLRLCEDQNGNPYVKDLNWIHVQDAEEAWKLLK360
VGRKNQSFASTHLNQNSSRSHSIFSIRILHLQGEGDIVPKISELSLCDLAGSERCKDQKS420
GERLKEAGNINTSLHTLGRCIAALRQNQQNRSKQNLVPFRDSKLTRVFQGFFTGRGRSCM480
IVNVNPCASTYDETLHVAKFSAIASQVTCACPTYATGIPIPALVHQGT
S
Seq 27
ID DNA
NO: sequence
Nucleic
Acid
Accession
#:
Eos
sequence
Coding ence:
sequ 13-1424
l 1 11 21 31 41 51
O
TAGAAGTTTACAATGAAGTTTCTTCTAATACTGCTCCTGCAGGCCACTGCTTCTGGAGCT60
CTTCCCCTGAACAGCTCTACAAGCCTGGAAAAAAATAATGTGCTATTTGGTGAAAGATAC120
TTAGAAAAATTTTATGGCCTTGAGATAAACAAACTTCCAGTGACAAAAATGAAATATAGT180
1 GGAAACTTAATGAAGGAAAAAATCCAAGAAATGCAGCACTTCTTGGGTCTGAAAGTGACC240
S
GGGCAACTGGACACATCTACCCTGGAGATGATGCACGCACCTCGATGTGGAGTCCCCGAT300
GTCCATCATTTCAGGGAAATGCCAGGGGGGCCCGTATGGAGGAAACATTATATCACCTAC360
AGAATCAATAATTACACACCTGACATGAACCGTGAGGATGTTGACTACGCAATCCGGAAA420
GCTTTCCAAGTATGGAGTAATGTTACCCCCTTGAAATTCAGCAAGATTAACACAGGCATG480
ZO GCTGACATTTTGGTGGTTTTTGCCCGTGGAGCTCATGGAGACTTCCATGCTTTTGATGGC540
AAAGGTGGAATCCTAGCCCATGCTTTTGGACCTGGATCTGGCATTGGAGGGGATGCACAT600
TTCGATGAGGACGAATTCTGGACTACACATTCAGGAGGCACAAACTTGTTCCTCACTGCT660
GTTCACGAGATTGGCCATTCCTTAGGTCTTGGCCATTCTAGTGATCCAAAGGCCGTAATG720
TTCCCCACCTACAAATATGTTGACATCAACACATTTCGCCTCTCTGCTGATGACATACGT780
~1 GGCATTCAGTCCCTGTATGGAGACCCAAAAGAGAACCRACGCTTGCCAAATCCTGACAAT840
GS
TCAGAACCAGCTCTCTGTGACCCCAATTTGAGTTTTGATGCTGTCACTACCGTGGGAAAT900
AAGATCTTTTTCTTCAAAGACAGGTTCTTCTGGCTGAAGGTTTCTGAGAGACCAAAGACC960
AGTGTTAATTTAATTTCTTCCTTATGGCCAACCTTGCCATCTGGCATTGAAGCTGCTTAT1020
GAAATTGAAGCCAGAAATCAAGTTTTTCTTTTTAAAGATGACAAATACTGGTTAATTAGC1080
3 AATTTAAGACCAGAGCCAAATTATCCCAAGAGCATACATTCTTTTGGTTTTCCTAACTTT1140
O
GTGAAAAAAATTGATGCAGCTGTTTTTAACCCACGTTTTTATAGGACCTACTTCTTTGTA1200
GATAACCAGTATTGGAGGTATGATGAAAGGAGACAGATGATGGACCCTGGTTATCCCAAA1260
CTGATTACCAAGAACTTCCAAGGAATCGGGCCTAAAATTGATGCAGTCTTCTACTCTAAA1320
AACAAATACTACTATTTCTTCCAAGGATCTAACCAATTTGAATATGACTTCCTACTCCAA1380
3 CGTATCACCAAAACACTGAAAAGCAATF1GCTGGTTTGGTTGTTGAAAATGGTGTAATTAA1440
S
TGGTTTTTGTTAGTTCACTTCAGCTTAATAAGTATTTATTGCATATTTGCTATGTCCTCA1500
GTGTACCACTACTTAGAGATATGTATCATAAAAATAAAATCTGTAAACCATAGGTAATGA1560
TTATATAAAATACATAATATTTTTCAATTTTGAAAACTCTAATTGTCCATTCTTGCTTGA1620
CTCTACTATTAAGTTTGAAAATAGTTACCTTCAAAGCAAGATAATTCTATTTGAAGCATG1680
~ CTCTGTAAGTTGCTTCCTAACATCCTTGGACTGAGAAATTATACTTACTTCTGGCATAAC1740
'tO
TAAAATTAAGTATATATATTTTGGCTCAAATAAAATTG
Seq 28 sequence:
ID Protein
NO:
Protein
Accession
#:
Eos
sequence
S
~-t
1 11 21 31 41 51
MKFLLILLLQATASGALPLNSSTSLEKNNVLFGERYLEKFYGLEINKLPVTKMKYSGNLM60
KEKIQEMQHFLGLKVTGQLDTSTLEMMHAPRCGVPDVHHFREMPGGPWRKHYITYRINN120
S YTPDMNREDVDYAIRKAFQVWSNVTPLKFSKINTGMADILWFARGAHGDFHAFDGKGGI180
O
LAHAFGPGSGIGGDAHFDEDEFWTTHSGGTNLFLTAVHEIGHSLGLGHSSDPKAVMFPTY240
KYVDINTFRLSADDIRGIQSLYGDPKENQRLPNPDNSEPALCDPNLSFDAVTTVGNKIFF300
FKDRFFWLKVSERPKTSVNLISSLWPTLPSGIEAAYEIEARNQVFLFKDDKYWLISNLRP360
EPNYPKSIHSFGFPNFVKKIDAAVFNPRFYRTYFFVDNQYWRYDERRQMMDPGYPKLITK420
S NFQGIGPKIDAVFYSKNKYYYFFQGSNQFEYDFLLQRITKTLKSNSWFGC
S
Seq 29
ID DNA
NO: sequence
Nucleic 15.1
Acid
Accession
#:
NM_0061
Coding
sequence:
236..1765
'O
V
1 11 21 31 41 51
GCTTCAGGGTACAGCTCCCCCGCAGCCAGAAGCCGGGCCTGCAGCCCCTCAGCACCGCTC60
CGGGACACCCCACCCGCTTCCCAGGCGTGACCTGTCAACAGCAACTTCGCGGTGTGGTGA120
G ACTCTCTGAGGAAAAACCATTTTGATTATTACTCTCAGACGTGCGTGGCAACAAGTGACT180
VS
GAGACCTAGAAATCCAAGCGTTGGAGGTCCTGAGGCCAGCCTAAGTCGCTTCAAAATGGA240
ACGAAGGCGTTTGTGGGGTTCCATTCAGAGCCGATACATCAGCATGAGTGTGTGGACAAG300
CCCACGGAGACTTGTGGAGCTGGCAGGGCAGAGCCTGCTGAAGGATGAGGCCCTGGCCAT360
TGCCGCCCTGGAGTTGCTGCCCAGGGAGCTCTTCCCGCCACTCTTCATGGCAGCCTTTGA420
~7 CGGGAGACACAGCCAGACCCTGAAGGCAATGGTGCAGGCCTGGCCCTTCACCTGCCTCCC480
/O
TCTGGGAGTGCTGATGAAGGGACAACATCTTCACCTGGAGACCTTCAAAGCTGTGCTTGA540
TGGACTTGATGTGCTCCTTGCCCAGGAGGTTCGCCCCAGGAGGTGGAAACTTCAAGTGCT600
GGATTTACGGAAGAACTCTCATCAGGACTTCTGGACTGTATGGTCTGGAAACAGGGCCAG660
TCTGTACTCATTTCCAGAGCCAGAAGCAGCTCAGCCCATGACAAAGAAGCGAAAAGTAGA720
~7 TGGTTTGAGCACAGAGGCAGAGCAGCCCTTCATTCCAGTAGAGGTGCTCGTAGACCTGTT780
S
CCTCAAGGAAGGTGCCTGTGATGAATTGTTCTCCTACCTCATTGAGAAAGTGAAGCGAAA840
GAAAAATGTACTACGCCTGTGCTGTAAGAAGCTGAAGATTTTTGCAATGCCCATGCAGGA900
TATCAAGATGATCCTGAAAATGGTGCAGCTGGACTCTATTGAAGATTTGGAAGTGACTTG960
TACCTGGAAGCTACCCACCTTGGCGAAATTTTCTCCTTACCTGGGCCAGATGATTAATCT1020
8 GCGTAGACTCCTCCTCTCCCACATCCATGCATCTTCCTACATTTCCCCGGAGAAGGAAGA1080
O
GCAGTATATCGCCCAGTTCACCTCTCAGTTCCTCAGTCTGCAGTGCCTGCAGGCTCTCTA1140
TGTGGACTCTTTATTTTTCCTTAGAGGCCGCCTGGATCAGTTGCTCAGGCACGTGATGAA1200
CCCCTTGGAAACCCTCTCAATAACTAACTGCCGGCTTTCGGAAGGGGATGTGATGCATCT1260
GTCCCAGAGTCCCAGCGTCAGTCAGCTAAGTGTCCTGAGTCTAAGTGGGGTCATGCTGAC1320
p CGATGTAAGTCCCGAGCCCCTCCAAGCTCTGCTGGAGAGAGCCTCTGCCACCCTCCAGGA1380
OS
CCTGGTCTTTGATGAGTGTGGGATCACGGATGATCAGCTCCTTGCCCTCCTGCCTTCCCT1440
GAGCCACTGCTCCCAGCTTACAACCTTAAGCTTCTACGGGAATTCCATCTCCATATCTGC1500
198
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
CTTGCAGAGTCTCCTGCAGCACCTCATCGGGCTGAGCAATCTGACCCACGTGCTGTATCC1560
TGTCCCCCTGGAGAGTTATGAGGACATCCATGGTACCCTCCACCTGGAGAGGCTTGCCTA1620
TCTGCATGCCAGGCTCAGGGAGTTGCTGTGTGAGTTGGGGCGGCCCAGCATGGTCTGGCT1680
TAGTGCCAACCCCTGTCCTCACTGTGGGGACAGAACCTTCTATGACCCGGAGCCCATCCT1740
S GTGCCCCTGTTTCATGCCTAACTAGCTGGGTGCACATATCAAATGCTTCATTCTGCATAC1800
TTGGACACTAAAGCCAGGATGTGCATGCATCTTGAAGCAACAAAGCAGCCACAGTTTCAG1860
ACAAATGTTCAGTGTGAGTGAGGAAAACATGTTCAGTGAGGAAAAAACATTCAGACAAAT1920
GTTCAGTGAGGAAAAAAAGGGGAAGTTGGGGATAGGCAGATGTTGACTTGAGGAGTTAAT1980
GTGATCTTTGGGGAGATACATCTTATAGAGTTAGAAATAGAATCTGAATTTCTAAAGGGA2040
I GATTCTGGCTTGGGAAGTACATGTAGGAGTTAATCCCTGTGTAGACTGTTGTAAAGAAAC2100
O
TGTTGAAAATAAAGAGAAGCAATGTGAAGCAAAAAAAAAAAAAAAAAA
Seq ID 30 sequence:
N0: Protein
Protein
Accession
#: NP
006106.1
S
1 11 21 31 41 51
GCTTCAGGGTACAGCTCCCCCGCAGCCAGAAGCCGGGCCTGCAGCGCCTCAGCACCGCTC60
CGGGACACCCCACCCGCTTCCCAGGCGTGACCTGTCAACAGCAACTTCGCGGTGTGGTGA120
~1 ACTCTCTGAGGAAAAACCATTTTGATTATTACTCTCAGACGTGCGTGGCAACAAGTGACT180
GO
GAGACCTAGAAATCCAAGCGTTGGAGGTCCTGAGGCCAGCCTAAGTCGCTTCAAAATGGA240
ACGAAGGCGTTTGTGGGGTTCCATTCAGAGCCGATACATCAGCATGAGTGTGTGGACAAG300
CCCACGGAGACTTGTGGAGCTGGCAGGGCAGAGCCTGCTGAAGGATGAGGCCCTGGCCAT360
TGCCGCCCTGGAGTTGCTGCCCAGGGAGCTCTTCCCGCCACTCTTCATGGCAGCCTTTGA420'
2 CGGGAGACACAGCCAGACCCTGAAGGCAATGGTGCAGGCCTGGCCCTTCACCTGCCTCCC480
S
TCTGGGAGTGCTGATGAAGGGACAACATCTTCACCTGGAGACCTTCAAAGCTGTGCTTGA540
TGGACTTGATGTGCTCCTTGCCCAGGAGGTTCGCCCCAGGAGGTGGAAACTTCAAGTGCT600
GGATTTACGGAAGAACTCTCATCAGGACTTCTGGACTGTATGGTCTGGAAACAGGGCCAG660
TCTGTACTCATTTCCAGAGCCAGAAGCAGCTCAGCCCATGACAAAGAAGCGAAAAGTAGA720
3 TGGTTTGAGCACAGAGGCAGAGCAGCCCTTCATTCCAGTAGAGGTGCTCGTAGACCTGTT780
O
CCTCAAGGAAGGTGCCTGTGATGAATTGTTCTCCTACCTCATTGAGAAAGTGAAGCGAAA840
GAAAAATGTACTACGCCTGTGCTGTAAGAAGCTGAAGATTTTTGCAATGCCCATGCAGGA900
TATCAAGATGATCCTGAAAATGGTGCAGCTGGACTCTATTGAAGATTTGGAAGTGACTTG960
TACCTGGAAGCTACCCACCTTGGCGAAATTTTCTCCTTACCTGGGCCAGATGATTAATCT1020
3 GCGTAGACTCCTCCTCTCCCACATCCATGCATCTTCCTACATTTCCCCGGAGAAGGAAGA1080
S
GCAGTATATCGCCCAGTTCACCTCTCAGTTCCTCAGTCTGCAGTGCCTGCAGGCTCTCTA1140
TGTGGACTCTTTATTTTTCCTTAGAGGCCGCCTGGATCAGTTGCTCAGGCACGTGATGAA1200
CCCCTTGGAAACCCTCTCAATAACTAACTGCCGGCTTTCGGAAGGGGATGTGATGCATCT1260
GTCCCAGAGTCCCAGCGTCAGTCAGCTAAGTGTCCTGAGTCTAAGTGGGGTCATGCTGAC1320
4O CGATGTAAGTCCCGAGCCCCTCCAAGCTCTGCTGGAGAGAGCCTCTGCCACCCTCCAGGA1380
CCTGGTCTTTGATGAGTGTGGGATCACGGATGATCAGCTCCTTGCCCTCCTGCCTTCCCT1440
GAGCCACTGCTCCCAGCTTACAACCTTAAGCTTCTACGGGAATTCCATCTCCATATCTGC1500
CTTGCAGAGTCTCCTGCAGCACCTCATCGGGCTGAGCAATCTGACCCACGTGCTGTATCC1560
TGTCCCCCTGGAGAGTTATGAGGACATCCATGGTACCCTCCACCTGGAGAGGCTTGCCTA1620
A TCTGCATGCCAGGCTCAGGGAGTTGCTGTGTGAGTTGGGGCGGCCCAGCATGGTCTGGCT1680
4S
TAGTGCCAACCCCTGTCCTCACTGTGGGGACAGAACCTTCTATGACCCGGAGCCCATCCT1740
GTGCCCCTGTTTCATGCCTAACTAGCTGGGTGCACATATCAAATGCTTCATTCTGCATAC1800
TTGGACACTAAAGCCAGGATGTGCATGCATCTTGAAGCAACAAAGCAGCCACAGTTTCAG1860
ACAAATGTTCAGTGTGAGTGAGGAAAACATGTTCAGTGAGGAAAAAACATTCAGACAAAT1920
S GTTCAGTGAGGAAAAAAAGGGGAAGTTGGGGATAGGCAGATGTTGACTTGAGGAGTTAAT1980
O
GTGATCTTTGGGGAGATACATCTTATAGAGTTAGAAATAGAATCTGAATTTCTAAAGGGA2040
GATTCTGGCTTGGGAAGTACATGTAGGAGTTAATCCCTGTGTAGACTGTTGTAAAGAAAC2100
TGTTGAAAATAAAGAGAAGCAATGTGAAGCAAAAAAAAAAAAAAAAAA
SS
Seq ID N0: 31 DNA sequence
Nucleic Acid Accession #: Eos sequence
Coding sequence: 64-2754
VO 1 11 21 31 41 51
GGCAGGTCTCGCTCTCGGCACCCTCCCGGCGCCCGCGTTCTCCTGGCCCTGCCCGGCATC60
CCGATGGCCGCCGCTGGGCCCCGGCGCTCCGTGCGCGGAGCCGTCTGCCTGCATCTGCTG120
CTGACCCTCGTGATCTTCAGTCGTGATGGTGAAGCCTGCAAAAAGGTGATACTTAATGTA180
6S CCTTCTAAACTAGAGGCAGACAAAATAATTGGCAGAGTTAATTTGGAAGAGTGCTTCAGG240
TCTGCAGACCTCATCCGGTCAAGTGATCCTGATTTCAGAGTTCTAAATGATGGGTCAGTG300
TACACAGCCAGGGCTGTTGCGCTGTCTGATAAGAAAAGATCATTTACCATATGGCTTTCT360
GACAAAAGGAAACAGACACAGAAAGAGGTTACTGTGCTGCTAGAACATCAGAAGAAGGTA420
TCGAAGACAAGACACACTAGAGAAACTGTTCTCAGGCGTGCCAAGAGGAGATGGGCACCT480
7O ATTCCTTGCTCTATGCAAGAGAATTCCTTGGGCCCTTTCCCATTGTTTCTTCAACAAGTT540
GAATCTGATGCAGCACAGAACTATACTGTCTTCTACTCAATAAGTGGACGTGGAGTTGAT600
AAAGAACCTTTAAATTTGTTTTATATAGAAAGAGACACTGGAAATCTATTTTGCACTCGG660
CCTGTGGATCGTGAAGAATATGATGTTTTTGATTTGATTGCTTATGCGTCAACTGCAGAT720
GGATATTCAGCAGATCTGCCCCTCCCACTACCCATCAGGGTAGAGGATGAAAATGACAAC780
~7 CACCCTGTTTTCACAGAAGCAATTTATAATTTTGAAGTTTTGGAAAGTAGTAGACCTGGT840
/S
ACTACAGTGGGGGTGGTTTGTGCCACAGACAGAGATGAACCGGACACAATGCATACGCGC900
CTGAAATACAGCATTTTGCAGCAGACACCAAGGTCACCTGGGCTCTTTTCTGTGCATCCC960
AGCACAGGCGTAATCACCACAGTCTCTCATTATTTGGACAGAGAGGTTGTAGACAAGTAC1020
TCATTGATAATGAAAGTACAAGACATGGATGGCCAGTTTTTTGGATTGATAGGCACATCA1080
S ACTTGTATCATAACAGTAACAGATTCAAATGATAATGCACCCACTTTCAGACAAAATGCT1140
O
TATGAAGCATTTGTAGAGGAAAATGCATTCAATGTGGAAATCTTACGAATACCTATAGAA1200
GATAAGGATTTAATTAACACTGCCAATTGGAGAGTCAATTTTACCATTTTAAAGGGAAAT1260
GAAAATGGACATTTCAAAATCAGCACAGACAAAGAAACTAATGAAGGTGTTCTTTCTGTT1320
GTAAAGCCACTGAATTATGAAGAAAACCGTCAAGTGAACCTGGAAATTGGAGTAAACAAT1380
H GAAGCGCCATTTGCTAGAGATATTCCCAGAGTGACAGCCTTGAACAGAGCCTTGGTTACA1440
S
GTTCATGTGAGGGATCTGGATGAGGGGCCTGAATGCACTCCTGCAGCCCAATATGTGCGG1500
ATTAAAGAAAACTTAGCAGTGGGGTCAAAGATCAACGGCTATAAGGCATATGACCCCGAA1560
199
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
AATAGAAATGGCAATGGTTTAAGGTACAAAAAATTGCATGATCCTAAAGGTTGGATCACC1620
ATTGATGAAATTTCAGGGTCAATCATAACTTCCAAAATCCTGGATAGGGAGGTTGAAACT1680
CCCAAAAATGAGTTGTATAATATTACAGTCCTGGCAATAGACAAAGATGATAGATCATGT1740
ACTGGAACACTTGCTGTGAACATTGAAGATGTAAATGATAATCCACCAGAAATACTTCAA1800
S GAATATGTAGTCATTTGCAAACCAAAAATGGGGTATACCGACATTTTAGCTGTTGATCCT1860
GATGAACCTGTCCATGGAGCTCCATTTTATTTCAGTTTGCCCAATACTTCTCCAGAAATC1920
AGTAGACTGTGGAGCCTCACCAAAGTTAATGATACAGCTGCCCGTCTTTCATATCAGAAA1980
AATGCTGGATTTCAAGAATATACCATTCCTATTACTGTAAAAGACAGGGCCGGCCAAGCT2040
GCAACAAAATTATTGAGAGTTAATCTGTGTGAATGTACTCATCCAACTCAGTGTCGTGCG2100
I ACTTCAAGGAGTACAGGAGTAATACTTGGAAAATGGGCAATCCTTGCAATATTACTGGGT2160
O
ATAGCACTGCTCTTTTCTGTATTGCTAACTTTAGTATGTGGAGTTTTTGGTGCAACTAAA2220
GGGAAACGTTTTCCTGAAGATTTAGCACAGCAAAACTTAATTATATCAAACACAGAAGCA2280
CCTGGAGACGATAGAGTGTGCTCTGCCAATGGATTTATGACCCAAACTACCAACAACTCT2340
AGCCAAGGTTTTTGTGGTACTATGGGATCAGGAATGAAAAATGGAGGGCAGGAAACCATT2400
I GAAATGATGAAAGGAGGAAACCAGACCTTGGAATCCTGCCGGGGGGCTGGGCATCATCAT2460
S
ACCCTGGACTCCTGCAGGGGAGGACACACGGAGGTGGACAACTGCAGATACACTTACTCG2520
GAGTGGCACAGTTTTACTCAACCCCGTCTCGGTGAAAAATTGCATCGATGTAATCAGAAT2580
GAAGACCGCATGCCATCCCAAGATTATGTCCTCACTTATAACTATGAGGGAAGAGGATCT2640
CCAGCTGGTTCTGTGGGCTGCTGCAGTGAAAAGCAGGAAGAAGATGGCCTTGACTTTTTA2700
2O AATAATTTGGAACCCAAATTTATTACATTAGCAGAAGCATGCACAAAGAGATAATGTCAC2760
AGTGCTACAATTAGGTCTTTGTCAGACATTCTGGAGGTTTCCAAAAATAATATTGTAAAG2820
TTCAATTTCAACATGTATGTATATGATGATTTTTTTCTCAATTTTGAATTATGCTACTCA2880
CCAATTTATATTTTTAAAGCCAGTTGTTGCTTATCTTTTCCAAAAAGTGAAAAATGTTAA2940
AACAGACAACTGGTAAATCTCAAACTCCAGCACTGGAATTAAGGTCTCTAAAGCATCTGC3000
2S TCTTTTTTTTTTTTACGGATATTTTAGTAATAAATATGCTGGATAAATATTAGTCCAACA3060
ATAGCTAAGTTATGCTAATATCACATTATTATGTATTCACTTTAAGTGATAGTTTAAAAA3120
ATAAACAAGAAATATTGAGTATCACTATGTGAAGAAAGTTTTGGAAAAGAAACAATGAAG3180
ACTGAATTAAATTAAAAATGTTGCAGCTCATAAAGAATTGGGACTCACCCCTACTGCACT3240
ACCAAATTCATTTGACTTTGGAGGCAAAATGTGTTGAAGTGCCCTATGAAGTAGCAATTT3300
3 TCTATAGGAATATAGTTGGAAATAAATGTGTGTGTGTATATTATTATTAATCAATGCAAT3360
O
ATTTAAAATGAAATGAGAACAAAGAGGAAAATGGTAAAAACTTGAAATGAGGCTGGGGTA3420
TAGTTTGTCCTACAATAGAAAAAAGAGAGAGCTTCCTAGGCCTGGGCTCTTAAATGCTGC3480
ATTATAACTGAGTCTATGAGGAAATAGTTCCTGTCCAATTTGTGTAATTTGTTTAAAATT3540
GTAAATAAATTAAACTTTTCTGGTTTCTGTGGGAAGGAAATAGGGAATCCAATGGAACAG3600
3 TAGCTTTGCTTTGCAGTCTGTTTCAAGATTTCTGCATCCACAAGTTAGTAGCAAACTGGG3660
S
GAATACTCGCTGCAGCTGGGGTTCCCTGCTTTTTGGTAGCAAGGGTCCAGAGATGAGGTG3720
TTTTTTTCGGGGAGCTAATAACAAAAACATTTTAAAACTTACCTTTACTGAAGTTAAATC3780
CTCTATTGCTGTTTCTATTCTCTCTTATAGTGACCAACATCTTTTTAATTTAGATCCAAA3840
TAACCATGTCCTCCTAGAGTTTAGAGGCTAGAGGGAGCTGAGGGGAGGATCTTACTGAAA3900
A GCACCCTGGGGAGATTGATTGTCCTTAAACCTAAGCCCCACAAACTTGACACCTGATCAG3960
4O
GTCTGGGAGCTACAAAATTTCATTTTTCTCCTCACTGCCCTTCTTCTGAGTGGCATTGGC4020
CTGAATCAAGGAAAGCCAGGCCTTGTGGGCCCCCTTCTTTCGGCTTTCTGCTAAAGCAAC4080
ACCTCCAGCAGAGATTCCCTTAAGTGACTCCAGGTTTTCCACCATCCTTCAGCGTGAATT4140
AATTTTTAATCAGTTTGCTTTCTCCAGAGAAATTTTAAAATAATAGAAGAAATAGAAATT4200
~ TTGAATGTATAAAAGAAAAAGATCAAGTTGTCATTTTAGAACAGAGGGAACTTTGGGAGA4260
'tS
AAGCAGCCCAAGTAGGTTATTTGTACAGTCAGAGGGCAACAGGAAGATGCAGGCCTTCAA4320
GGGCAAGGAGAGGCCACAAGGAATATGGGTGGGAGTAAAAGCAACATCGTCTGCTTCATA4380
CTTTTTCCTAGGCTTGGCACTGCCTTTTCCTTTCTCAGGCCAATGGCAACTGCCATTTGA4440
GTCCGGTGAGGGATCAGCCAACCTCTTCTCTATGGCTCACCTTATTTGGAGTGAGAAATC4500
S AAGGAGACAGAGCTGACTGCATGATGAGTCTGAAGGCATTTGCAGGATGAGCCTGAACTG4560
O
GTTGTGCAGAACAAACAAGGCATTCATGGGAATTGTTGTATTCCTTCTGCAGCCCTCCTT4620
CTGGGCACTAAGAAGGTCTATGAATTAAATGCCTATCTAAAATTCTGATTTATTCCTACA4680
TTTTCTGTTTTCTAATTTGACCCTAAAATCTATGTGTTTTAGACTTAGACTTTTTATTGC4740 .
CCCCCCCCCCTTTTTTTTTGAGACGGAGTCTCGCTCTGACGCACAGGCTGGAGTGCAGTG4800
S GCTCCGATCTCTGCTCACTGAAAGCTCCGCCTCCCGGGTTCATGCCATTCTCCTGCCTCA4860
S
GCCTCCTGAGTAGCTGGGACTACAGGCGCCCACCACCACGCCCGGCTAATTTTTTGTATT4920
TTTAATAGAGACGGGGTTTCACTGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTCGTG4980
ATCCGCCTGCCTCGGCCTCCCAAAGTGCTGGGATTACAGGCATGACCCACCGCTCCCGGC5040
CTTGTTTTCCGTTTAAAGTCGTCTTCTTTTAATGTAATCATTTTGAACATGTGTGAAAGT5100
6O TGATCATACGAATTGGATCAATCTTGAAATACTCAACCAAAAGACAGTCGAGAAGCCAGG5160
GGGAGAAAGAACTCAGGGCACAAAATATTGGTCTGAGAATGGAATTCTCTGTAAGCCTAG5220
TTGCTGAAATTTCCTGCTGTAACCAGAAGCCAGTTTTATCTAACGGCTACTGAAACACCC5280
ACTGTGTTTTGCTCACTCCCTCACTCACCGATCAAAACCTGCTACCTCCCCAAGACTTTA5340
CTAGTGCCGATAAACTTTCTCAAAGAGCAACCAGTATCACTTCCCTGTTTATAAAACCTC5400
6S TAACCATCTCTTTGTTCTTTGAACATGCTGAAAACCACCTGGTCTGCATGTATGCCCGAA5460
TTTGTAATTCTTTTCTCTCAAATGAAAATTTAATTTTAGGGATTCATTTCTATATTTTCA5520
CATATGTAGTATTATTATTTCCTTATATGTGTAAGGTGAAATTTATGGTATTTGAGTGTG5580
CAAGAAAATATATTTTTAAAGCTTTCATTTTTCCCCCAGTGAATGATTTAGAATTTTTTA5640
TGTAAATATACAGAATGTTTTTTCTTACTTTTATAAGGAAGCAGCTGTCTAAAATGCAGT5700
7O GGGGTTTGTTTTGCAATGTTTTAAACAGAGTTTTAGTATTGCTATTAAAAGAAGTTACTT5760
TGCTTTTAAAGAAACTTGGCTGCTTAAAATAAGCAAAAATTGGATGCATAAAGTAATATT5820
TACAGATGTGGGGAGATGTAATAAAACAATATTAACTTGGTTTCTTGTTTTTGCTGTATT5880
TAGAGATTAAATAATTCTAAGATGATCACTTTGCAAAATTATGCTTATGGCTGGCATGGA5940
AATAGAAATACTCAATTATGTCTTTGTTGTATTAATGGGGAATATTTTGGACAATGTTTC6000
~7 ATTATCAAATTGTCGACATCATTAATATATATTGTAATGTTGGGAAGAGATCACTATTTT6060
/S
GAAGCACAGCTTTACAGATGAGTATCTATGATACATATGTATAATAAATTTTGATCGGGT6120
ATTAAAAGTATTAGAAGGTGGTTATAATTGCAGAGTATTCCATGAATAGTACACTGACAC6180
AGGGGTTTTACTTTGAGGACCAGTGTAGTCAAGGGAAAACATGAGTTAAAAAGAAAAGCA6240
GGCAATATTGCAGTCTTGATTCTGCCACTTACAGGATAGATAATGCCTGAACTTTAATGA6300
SO CAAGATGATCCAACCATAAAGGTGCTCTGTGCTTCACAGTGAATCTTTTCCCCATGCAGG6360
AGTGTGCTCCCCTACAAACGTTAAGACTGATCATTTCAAAAATCTATTAGCTATATCAAA6420
AGCCTTACATTTTAATATAGGTTGAACCAAAATTTCAATTCCAGTAACTTCTATTGTAAC6480
CATTATTTTTGTGTATGTCTTCAAGAATGTTCATTGGATTTTTGTTTGTAATAGTAAAAT6540
ACCGGATACATTTCACGTGTCCTTCAGTATTGATTTGGTTGAATATTGGGTCATAATGGT6600
S TGAGAAGCATGGACACTAGAGCCAGAATGCTTGGATATGAATCCTGGATCTGTCACTTAC6660
S
TTCTGTGTGACCTTTGAAAGGCTACTTATTTCCTCTCTTAGCTTTCTCATTAAAATCAAT6720
GAACAATGCCAGCCTCATGGGGTTGTTGAATGATTAAATTAGTTAATATACCTAAAGTAC6780
200
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
ATAGAACACT GCCTGCACAT AGTAAAAGAA TTATAAGTGT GAGGTAGTTG GTAAAATTAT 6840
GTAGTTGGAT ATACTACCGA ACAATATCTA ATCTCTTTTT AGGGAAATAA AGTTTGTGCA 6900
TATATATAAT CCCGAAACAT G
S Seq ID N0: 32 Protein sequence:
Protein Accession #: NP 001932.1
1 11 21 31 41 51
I MAAAGPRRSVRGAVCLHLLLTLVIFSRDGE ACKKVILNVPRVNLEECFRS60
O SKLEADKIIG
ADLIRSSDPDFRVLNDGSVYTARAVALSDK KRSFTIWLSDVLLEHQKKVS120
KRKQTQKEVT
KTRHTRETVLRRAKRRWAPIPCSMQENSLG PFPLFLQQVEYSISGRGVDK180
SDAAQNYTVF
EPLNLFYIERDTGNLFCTRPWREEYDVFD LIAYASTADGIRVEDENDNH240
YSADLPLPLP
PVFTEAIYNFEVLESSRPGTTVGWCATDR DEPDTMHTRLSPGLFSVHPS300
KYSILQQTPR
I TGVITTVSHYLDREVVDKYSLIMKVQDMDG QFFGLIGTSTNAPTFRQNAY360
S CIITVTDSND
EAFVEENAFNVEILRIPIEDKDLINTANWR VNFTILKGNEETNEGVLSW420
NGHFKISTDK
KPLNYEENRQVNLEIGVNNEAPFARDIPRV TALNRALVTVCTPAAQWRI480
HVRDLDEGPE
KENLAVGSKINGYKAYDPENRNGNGLRYKK LHDPKGWITIKILDREVETP540
DEISGSIITS
KNELYNITVLAIDKDDRSCTGTLAVNIEDV NDNPPEILQEYTDILAWPD600
YWICKPKMG
~1 EPVHGAPFYFSLPNTSPEISRLWSLTKVND TAARLSYQKNTVKDRAGQAA660
GO AGFQEYTIPI
TKLLRVNLCECTHPTQCRATSRSTGVILGK WAILAILLGIVCGVFGATKG720
ALLFSVLLTL
KRFPEDLAQQNLIISNTEAPGDDRVCSANG FMTQTTNNSSMKNGGQETIE780
QGFCGTMGSG
MMKGGNQTLESCRGAGHHHTLDSCRGGHTE VDNCRYTYSEEKLHRCNQNE840
WHSFTQPRLG
DRMPSQDYVLTYNYEGRGSPAGSVGCCSEK QEEDGLDFLNEACTKR
NLEPKFITLA
S
Seq ID 33 DNA sequence
N0:
Nucleic
Acid
Accession
#: Eos
sequence
Coding
sequence:
64-2583
1 11 21 31 41 51
GGCAGGTCTCGCTCTCGGCA GCCCGCGTTCTCCTGGCCCTGCCCGGCATC60
CCCTCCCGGC
CCGATGGCCGCCGCTGGGCC GTGCGCGGAGCCGTCTGCCTGCATCTGCTG120
CCGGCGCTCC
3 CTGACCCTCGTGATCTTCAG GAAGCCTGCAAAAAGGTGATACTTAATGTA180
S TCGTGATGGT
CCTTCTAAACTAGAGGCAGA GGCAGAGTTAATTTGGAAGAGTGCTTCAGG240
CAAAATAATT
TCTGCAGACCTCATCCGGTC GATTTCAGAGTTCTAAATGATGGGTCAGTG300
AAGTGATCCT
TACACAGCCAGGGCTGTTGC AAGAAAAGATCATTTACCATATGGCTTTCT360
GCTGTCTGAT
GACAAAAGGAAACAGACACA ACTGTGCTGCTAGAACATCAGAAGAAGGTA420
GAAAGAGGTT
~ TCGAAGACAAGACACACTAG CTCAGGCGTGCCAAGAGGAGATGGGCACCT480
4O AGAAACTGTT
ATTCCTTGCTCTATGCAAGA GGCCCTTTCCCATTGTTTCTTCAACAAGTT540
GAATTCCTTG
GAATCTGATGCAGCACAGAA TTCTACTCAATAAGTGGACGTGGAGTTGAT600
CTATACTGTC
AAAGAACCTTTAAATTTGTT AGAGACACTGGAAATCTATTTTGCACTCGG660
TTATATAGAA
CCTGTGGATCGTGAAGAATA GATTTGATTGCTTATGCGTCAACTGCAGAT720
TGATGTTTTT
A GGATATTCAGCAGATCTGCC CCCATCAGGGTAGAGGATGAAAATGACAAC780
'tS CCTCCCACTA
CACCCTGTTTTCACAGAAGC TTTGAAGTTTTGGAAAGTAGTAGACCTGGT840
AATTTATAAT
ACTACAGTGGGGGTGGTTTG AGAGATGAACCGGACACAATGCATACGCGC900
TGCCACAGAC
CTGAAATACAGCATTTTGCA AGGTCACCTGGGCTCTTTTCTGTGCATCCC960
GCAGACACCA
AGCACAGGCGTAATCACCAC TATTTGGACAGAGAGGTTGTAGACAAGTAC1020
AGTCTCTCAT
S TCATTGATAATGAAAGTACA GGCCAGTTTTTTGGATTGATAGGCACATCA1080
O AGACATGGAT
ACTTGTATCATAACAGTAAC GATAATGCACCCACTTTCAGACAAAATGCT1140
AGATTCAAAT
TATGAAGCATTTGTAGAGGA AATGTGGAAATCTTACGAATACCTATAGAA1200
AAATGCATTC
GATAAGGATTTAATTAACAC AGAGTCAATTTTACCATTTTAAAGGGAAAT1260
TGCCAATTGG
GAAAATGGACATTTCAAAAT AAAGAAACTAATGAAGGTGTTCTTTCTGTT1320
CAGCACAGAC
S GTAAAGCCACTGAATTATGA CAAGTGAACCTGGAAATTGGAGTAAACAAT1380
S AGAAAACCGT
GAAGCGCCATTTGCTAGAGA GTGACAGCCTTGAACAGAGCCTTGGTTACA1440
TATTCCCAGA
GTTCATGTGAGGGATCTGGA GAATGCACTCCTGCAGCCCAATATGTGCGG1500
TGAGGGGCCT
ATTAAAGAAAACTTAGCAGT ATCAACGGCTATAAGGCATATGACCCCGAA1560
GGGGTCAAAG
AATAGAAATGGCAATGGTTT AAATTGCATGATCCTAAAGGTTGGATCACC1620
AAGGTACAAA
6O ATTGATGAAATTTCAGGGTC TCCAAAATCCTGGATAGGGAGGTTGAAACT1680
AATCATAACT
CCCAAAAATGAGTTGTATAA CTGGCAATAGACAAAGATGATAGATCATGT1740
TATTACAGTC
ACTGGAACACTTGCTGTGAA GTAAATGATAATCCACCAGAAATACTTCAA1800
CATTGAAGAT
GAATATGTAGTCATTTGCAA GGGTATACCGACATTTTAGCTGTTGATCCT1860
ACCAAAAATG
GATGAACCTGTCCATGGAGC TTCAGTTTGCCCAATACTTCTCCAGAAATC1920
TCCATTTTAT
6S AGTAGACTGTGGAGCCTCAC GATACAGCTGCCCGTCTTTCATATCAGAAA1980
CAAAGTTAAT
AATGCTGGATTTCAAGAATA ATTACTGTAAAAGACAGGGCCGGCCAAGCT2040
TACCATTCCT
GCAACAAAATTATTGAGAGT GAATGTACTCATCCAACTCAGTGTCGTGCG2100
TAATCTGTGT
ACTTCAAGGAGTACAGGAGT AAATGGGCAATCCTTGCAATATTACTGGGT2160
AATACTTGGA
ATAGCACTGCTCTTTTCTGT TTAGTATGTGGAGTTTTTGGTGCAACTAAA2220
ATTGCTAACT
7O GGGAAACGTTTTCCTGAAGA CAAAACTTAATTATATCAAACACAGAAGCA2280
TTTAGCACAG
CCTGGAGACGATAGAGTGTG GGATTTATGACCCAAACTACCAACAACTCT2340
CTCTGCCAAT
AGCCAAGGTTTTTGTGGTAC GGAATGAAAAATGGAGGGCAGGAAACCATT2400
TATGGGATCA
GAAATGATGAAAGGAGGAAA GAATCCTGCCGGGGGGCTGGGCATCATCAT2460
CCAGACCTTG
ACCCTGGACTCCTGCAGGGG GAGGTGGACAACTGCAGATACACTTACTCG2520
AGGACACACG
.7 GAGTGGCACAGTTTTACTCA GGTGAAGAATCCATTAGAGGACACACTGGT2580
/S ACCCCGTCTC
TAAAAATTAAACATAAAAGA ATGTAATCAGAATGAAGACCGCATGCCATC2640
AATTGCATCG
CCAAGATTATGTCCTCACTT GGGAAGAGGATCTCCAGCTGGTTCTGTGGG2700
ATAACTATGA
CTGCTGCAGTGAAAAGCAGG CCTTGACTTTTTAAATAATTTGGAACCCAA2760
AAGAAGATGG
ATTTATTACATTAGCAGAAG GAGATAATGTCACAGTGCTACAATTAGGTC2820
CATGCACAAA
SO TTTGTCAGACATTCTGGAGG TAATATTGTAAAGTTCAATTTCAACATGTA2880
TTTCCAAAAA
TGTATATGATGATTTTTTTC ATTATGCTACTCACCAATTTATATTTTTAA2940
TCAATTTTGA
AGCCAGTTGTTGCTTATCTT TGAAAAATGTTAAAACAGACAACTGGTAAA3000
TTCCAAAAAG
TCTCAAACTCCAGCACTGGA CTAAAGCATCTGCTCTTTTTTTTTTTTACG3060
ATTAAGGTCT
GATATTTTAGTAATAAATAT TATTAGTCCAACAATAGCTAAGTTATGCTA3120
GCTGGATAAA
S ATATCACATTATTATGTATT GATAGTTTAAAAAATAAACAAGAAATATTG3180
CACTTTAAGT
AGTATCACTATGTGAAGAAA AGAAACAATGAAGACTGAATTAAATTAAAA3240
GTTTTGGAAA
ATGTTGCAGCTCATAAAGAA CCCCTACTGCACTACCAAATTCATTTGACT3300
TTGGGACTCA
201
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
TTGGAGGCAAAATGTGTTGAAGTGCCCTATGAAGTAGCAA GAATATAGTT3360
TTTTCTATAG
GGAAATAAATGTGTGTGTGTATATTATTATTAATCAATGC ATGAAATGAG3420
AATATTTAAA
AACAAAGAGGAAAATGGTAAAAACTTGAAATGAGGCTGGG TCCTACAATA3480
GTATAGTTTG
GAAAAAAGAGAGAGCTTCCTAGGCCTGGGCTCTTAAATGC CTGAGTCTAT3540
TGCATTATAA
S GAGGAAATAGTTCCTGTCCAATTTGTGTAATTTGTTTAAA AATTAAACTT3600
ATTGTAAATA
TTCTGGTTTCTGTGGGAAGGAAATAGGGAATCCAATGGAA GCTTTGCAGT3660
CAGTAGCTTT
CTGTTTCAAGATTTCTGCATCCACAAGTTAGTAGCAAACT CGCTGCAGCT3720
GGGGAATACT
GGGGTTCCCTGCTTTTTGGTAGCAAGGGTCCAGAGATGAG CGGGGAGCTA3780
GTGTTTTTTT
ATAACAAAAACATTTTAAAACTTACCTTTACTGAAGTTAA GCTGTTTCTA3840
ATCCTCTATT
I TTCTCTCTTATAGTGACCAACATCTTTTTAATTTAGATCC GTCCTCCTAG3900 .
O AAATAACCAT
AGTTTAGAGGCTAGAGGGAGCTGAGGGGAGGATCTTACTG GGGGAGATTG3960
AAAGCACCCT
ATTGTCCTTAAACCTAAGCCCCACAAACTTGACACCTGAT AGCTACAAAA4020
CAGGTCTGGG
TTTCATTTTTCTCCTCACTGCCCTTCTTCTGAGTGGCATT AAGGAAAGCC4080
GGCCTGAATC
AGGCCTTGTGGGCCCCCTTCTTTCGGCTTTCTGCTAAAGC GCAGAGATTC4140
AACACCTCCA
I CCTTAAGTGACTCCAGGTTTTCCACCATCCTTCAGCGTGA AATCAGTTTG4200
S ATTAATTTTT
CTTTCTCCAGAGAAATTTTAAAATAATAGAAGAAATAGAA TATAAAAGAA4260
ATTTTGAATG
AAAGATCAAGTTGTCATTTTAGAACAGAGGGAACTTTGGG CCAAGTAGGT4320
AGAAAGCAGC
TATTTGTACAGTCAGAGGGCAACAGGAAGATGCAGGCCTT GAGAGGCCAC4380
CAAGGGCAAG
AAGGAATATGGGTGGGAGTAAAAGCAACATCGTCTGCTTC CTAGGCTTGG4440
ATACTTTTTC
2OCACTGCCTTTTCCTTTCTCAGGCCAATGGCAACTGCCATT GAGGGATCAG4500
TGAGTCCGGT
CCAACCTCTTCTCTATGGCTCACCTTATTTGGAGTGAGAA CAGAGCTGAC4560
ATCAAGGAGA
TGCATGATGAGTCTGAAGGCATTTGCAGGATGAGCCTGAA AGAACAAACA4620
CTGGTTGTGC
AGGCATTCATGGGAATTGTTGTATTCCTTCTGCAGCCCTC CTAAGAAGGT4680
CTTCTGGGCA
CTATGAATTAAATGCCTATCTAAAATTCTGATTTATTCCT TTTTCTAATT4740
ACATTTTCTG
2STGACCCTAAAATCTATGTGTTTTAGACTTAGACTTTTTAT CCCTTTTTTT4800
TGCCCCCCCC
TTGAGACGGAGTCTCGCTCTGACGCACAGGCTGGAGTGCA TCTCTGCTCA4860
GTGGCTCCGA
CTGAAAGCTCCGCCTCCCGGGTTCATGCCATTCTCCTGCC GAGTAGCTGG4920
TCAGCCTCCT
GACTACAGGCGCCCACCACCACGCCCGGCTAATTTTTTGT GAGACGGGGT4980
ATTTTTAATA
TTCACTGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTC TGCCTCGGCC5040
GTGATCCGCC
3 TCCCAAAGTGCTGGGATTACAGGCATGACCCACCGCTCCC TCCGTTTAAA5100
O GGCCTTGTTT
GTCGTCTTCTTTTAATGTAATCATTTTGAACATGTGTGAA ACGAATTGGA5160
AGTTGATCAT
TCAATCTTGAAATACTCAACCAAAAGACAGTCGAGAAGCC AGAACTCAGG5220
AGGGGGAGAA
GCACAAAATATTGGTCTGAGAATGGAATTCTCTGTAAGCC AATTTCCTGC5280
TAGTTGCTGA
TGTAACCAGAAGCCAGTTTTATCTAACGGCTACTGAAACA TTTGCTCACT5340
CCCACTGTGT
3 CCCACTCACCGATCAAAACCTGCTACCTCCCCAAGACTTT ATAAACTTTC5400
S ACTAGTGCCG
TCAAAGAGCAACCAGTATCACTTCCCTGTTTATAAAACCT CTTTGTTCTT5460
CTAACCATCT
TGAACATGCTGAAAACCACCTGGTCTGCATGTATGCCCGA CTTTTCTCTC5520
ATTTGTAATT
AAATGAAAATTTAATTTTAGGGATTCATTTCTATATTTTC TATTATTATT5580
ACATATGTAG
TCCTTATATGTGTAAGGTGAAATTTATGGTATTTGAGTGT ATATTTTTAA5640
GCAAGAAAAT
4OAGCTTTCATTTTTCCCCCAGTGAATGATTTAGAATTTTTT ACAGAATGTT5700
ATGTAAATAT
TTTTCTTACTTTTATAAGGAAGCAGCTGTCTAAAATGCAG TTTGCAATGT5760
TGGGGTTTGT
TTTAAACAGAGTTTTAGTATTGCTATTAAAAGAAGTTACT AGAAACTTGG5820
TTGCTTTTAA
CTGCTTAAAATAAGCAAAAATTGGATGCATAAAGTAATAT GGGGAGATGT5880
TTACAGATGT
AATAAAACAATATTAACTTGGCTGCTTAAAATAAGCAAAA TAAAGTAATA5940
ATTGGATGCA
~ TTTACAGATGTGGGGAGATGTAATAAAACAATATTAACTT TTTTGCTGTA6000
4S GGTTTCTTGT
TTTAGAGATTAAATAATTCTAAGATGATCACTTTGCAAAA GGCTGGCATG6060
TTATGCTTAT
GAAATAGAAATACTCAATTATGTCTTTGTTGTATTAATGG GGACAATGTT6120
GGAATATTTT
TCATTATCAAATTGTCGACATCATTAATATATATTGTAAT GATCACTATT6180
GTTGGGAAGA
TTGAAGCACAGCTTTACAGATGAGTATCTATGATACATAT TTTTGATCGG6240
GTATAATAAA
S GTATTAAAAGTATTAGAAGGTGGTTATAATTGCAGAGTAT GTACACTGAC6300
O TCCATGAATA
ACAGGGGTTTTACTTTGAGGACCAGTGTAGTCAAGGGAAA AAAAGAAAAG6360
ACATGAGTTA
CAGGCAATATTGCAGTCTTGATTCTGCCACTTACAGGATA GAACTTTAAT6420
GATAATGCCT
GACAAGATGATCCAACCATAAAGGTGCTCTGTGCTTCACA TCCCCATGCA6480
GTGAATCTTT
GGAGTGTGCTCCCCTACAAACGTTAAGACTGATCATTTCA AGCTATATCA6540
AAAATCTATT
S AAAGCCTTACATTTTAATATAGGTTGAACCAAAATTTCAA TTCTATTGTA6600
S TTCCAGTAAC
ACCATTATTTTTGTGTATGTCTTCAAGAATGTTCATTGGA TAATAGTAAA6660
TTTTTGTTTG
ATACCGGATACATTTCACGTGTCCTTCAGTATTGATTTGG GGTCATAATG6720
TTGAATATTG
GTTGAGAAGCATGGACACTAGAGCCAGAATGCTTGGATAT TCTGTCACTT6780
GAATCCTGGA
ACTTCTGTGTGACCTTTGAAAGGCTACTTATTTCCTCTCT ATTAAAATCA6840
TAGCTTTCTC
6OATGAACAATGCCAGCCTCATGGGGTTGTTGAATGATTAAA TACCTAAAGT6900
TTAGTTAATA
ACATAGAACACTGCCTGCACATAGTAAAAGAATTATAAGT TGGTAAAATT6960
GTGAGGTAGT
ATGTAGTTGGATATACTACCGAACAATATCTAATCTCTTT AAAGTTTGTG7020
TTAGGGAAAT
CATATATATAATCCCGAAACATG
6S Seq ID N0: 34 Protein sequence:
Protein Accession #: NP 077741.1
1 11 21 31 41 51
7OMAAAGPRRSVRGAVCLHLLLTLVIFSRDGE ACKKVILNVPRVNLEECFRS60
SKLEADKIIG
ADLIRSSDPDFRVLNDGSVYTARAVALSDK KRSFTIWLSDVLLEHQKKVS120
KRKQTQKEVT
KTRHTRETVLRRAKRRWAPIPCSMQENSLG PFPLFLQQVEYSISGRGVDK180
SDAAQNYTVF
EPLNLFYIERDTGNLFCTRPVDREEYDVFD LIAYASTADGIRVEDENDNH240
YSADLPLPLP
PVFTEAIYNFEVLESSRPGTTVGWCATDR DEPDTMHTRLSPGLFSVHPS300
KYSILQQTPR
~7TGVITTVSHYLDREWDKYSLIMKVQDMDG QFFGLTGTSTNAPTFRQNAY360
/S CIITVTDSND
EAFVEENAFNVEILRIPIEDKDLINTANWR VNFTILKGNEETNEGVLSW420
NGHFKISTDK
KPLNYEENRQVNLEIGVNNEAPFARDIPRV TALNRALVTVCTPAAQYVRI480
HVRDLDEGPE
KENLAVGSKINGYKAYDPENRNGNGLRYKK LHDPKGWITIKILDREVETP540
DEISGSIITS
KNELYNITVLAIDKDDRSCTGTLAVNIEDV NDNPPEILQEYTDILAVDPD600
YWICKPKMG
SOEPVHGAPFYFSLPNTSPEISRLWSLTKVND TAARLSYQKNTVKDRAGQAA660
AGFQEYTIPI
TKLLRVNLCECTHPTQCRATSRSTGVILGK WAILAILLGIVCGVFGATKG720
ALLFSVLLTL
KRFPEDLAQQNLIISNTEAPGDDRVCSANG FMTQTTNNSSMKNGGQETIE780
QGFCGTMGSG
MMKGGNQTLESCRGAGHHHTLDSCRGGHTE VDNCRYTYSEEESIRGHTG
WHSFTQPRLG
S Seg ID NO: 35 DNA sequence
Nucleic Acid Accession #: Eos sequence
Coding sequence: 146-1273
202
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
1 11 21 31 41 51
I I
I ~ I I AGACACGGTC60
GGGAGTGGGCGTGGCGGTGCTGCCCAGGTGAGCCACCGCT
GCTTCTGCCC
S GCCTCCACATCCAGGTCTTTGTGCTCCTCGCTTGCCTGTT GCATTTTCCA120
CCTTTTCCAC
GGATAACTGTGACTCCAGGCCCGCAATGGATGCCCTGCAA CGGCTTTTGC180
CTAGCAAATT
CGTTGATCTGTTCAAACAACTATGTGAAAAGGAGCCACTG TCTTCTCTCC240
GGCAATGTCC
AATCTGTCTCTCCACCTCTCTGTCACTTGCTCAAGTGGGT ACACTGCAAA300
GCTAAAGGTG
TGAAATTGGACAGGTTCTTCATTTTGAAAATGTCAAAGAT GATTTCAAAC360
ATACCCTTTG
1 AGTAACATCGGATGTAAACAAACTTAGTTCCTTTTACTCA TCAAGCGGCT420
O CTGAAACTAA
CTACGTAGACAAATCTCTGAATCTTTCTACAGAGTTCATC AGAGACCCTA480
AGCTCTACGA
TGCAAAGGAATTGGAAACTGTTGACTTCAAAGATAAATTG AAGGTCAGAT540
GAAGAAACGA
CAACAACTCAATTAAGGATCTCACAGATGGCCACTTTGAG CTGACAACAG600
AACATTTTAG
TGTGAACGACCAGACCAAAATCCTTGTGGTTAATGCTGCC GCAAGTGGAT660
TACTTTGTTG
I GAAGAAATTTCCTGAATCAGAAACAAAAGAATGTCCTTTC AGACAGACAC720
S AGACTCAACA
CAAACCAGTGCAGATGATGAACATGGAGGCCACGTTCTGT TTGACAGTAT780
ATGGGAAACA
CAATTGTAAGATCATAGAGCTTCCTTTTCAAAATAAGCAT TCATCCTACT840
CTCAGCATGT
ACCCAAGGATGTGGAGGATGAGTCCACAGGCTTGGAGAAG AACTCAACTC900
ATTGAAAAAC
AGAGTCACTGTCACAGTGGACTAATCCCAGCACCATGGCC TCAAACTCTC960
AATGCCAAGG
2OCATTCCAAAATTTAAGGTGGAAAAGATGATTGATCCCAAG AAAATCTAGG7.020
GCTTGTCTGG
GCTGAAACATATCTTCAGTGAAGACACATCTGATTTCTCT AGACCAAGGG1080
GGAATGTCAG
AGTGGCCCTATCAAATGTTATCCACAAAGTGTGCTTAGAA ATGGTGGGGA1140
ATAACTGAAG
TTCCATAGAGGTGCCAGGAGCACGGATCCTGCAGCACAAG ATGCTGACCA1200
GATGAATTGA
TCCCTTTATTTACATCATCAGGCACAACAAAACTCGAAAC TTGGCAAATT1260
ATCATTTTCT
2SCTGTTCTCCTTAAGTGGCATAGCCCATGTTAAGTCCTCCC GTGGATGCCG1320
TGACTTTTCT
ATTTCTGTAAACTCTGCATCCAGAGATTCATTTTCTAGAT GCTAATGTTG1380
ACAATAAATT
CTGGATCAGGAAGCCGCCAGTACTTGTCATATGTAGCCTT GACCTTTTTT1440
CACACAGATA
TTTTTCCAATTCTATCTTTTGTTTCCTTTTTTCCCATAAG ACGCTTTTAA1500
ACAATGACAT
TGAAAAGGAATCACGTTAGAGGAAAAATATTTATTCATTA TGTCCGGGGT1560
TTTGTCAAAT
3 AGTTGGCAGAAATACAGTCTTCCACAAAGAAAATTCCTAT TGGAAGCTCT1620
O AAGGAAGATT
TCTTCCCAGCACTATGCTTTCCTTCTTTGGGATAGAGAAT TTCTCGCTTC1680
GTTCCAGACA
CCTGAAAGACTGAAGAAAGTGTAGTGCATGGGACCCACGA GCTCCAGTGA1740
AACTGCCCTG
AACTTGGGCACATGCTCAGGCTACTATAGGTCCAGAAGTC GCCCTGGCAG1800
CTTATGTTAA
GCAGGTGTTTATTAAAATTCTGAATTTTGGGGATTTTCAA TTTACATACA1860
AAGATAATAT
3 CTGTATGTTATAGAACTTCATGGATCAGATCTGGGGCAGC TCAACACCTT1920
S AACCTATAAA
AATATGCTGCAACAAAATGTAGAATATTCAGACAAAATGG ACTAAGTAGC1980
ATACATAAAG
CCATAAGGGGTCAAAATTTGCTGCCAAATGCGTATGCCAC AAACACTTCG2040
CAACTTACAA
TTCGCAGAGCTTTTCAGATTGTGGAATGTTGGATAAGGAA CTAGTAGCTG2100
TTATAGACCT
AAATGCAAGACCCCAAGAGGAAGTTCAGATCTTAATATAA ATTTTTGATA2160
ATTCACTTTC
A GCTGTCCCATCTGGTCATGTGGTTGGCACTAGACTGGTGG TAGCTGACTC2220
4O CAGGGGCTTC
GCACAGGGATTCTCACAATAGCCGATATCAGAATTTGTGT TGTCTCTTCA2280
TGAAGGAACT
TCTAATATGATAGCGGGAAAAGGAGAGGAAACTACTGCCT TAAGTAAAGT2340
TTAGAAAATA
GATTAAAGTGCTCACGTTACCTTGACACATAGTTTTTCAG TAGTTACTTT2400
TCTATGGGTT
AGATGGCAAGCATGTAACTTATATTAATAGTAATTTGTAA ATAAGCTATC2460
AGTTGGGTGG
A CCTGTTGCCGGTTCATGGATTACTTCTCTATAAAAAATAT AAAAATTTTG2520
4S ATATTTACCA
TGACATTCCTTCTCCCATCTCTTCCTTGACATGCATTGTA TCTTGTTCTG2580
AATAGGTTCT
AGATTCAATATTGAATTTCTCCTATGCTATTGACAATAAA ACTACC
ATATTATTGA
Seq ID N0: 36 Protein sequence:
SO Protein Accession #: NP 002630.1
1 11 21 31 41 51
I
I I I I I 60
MDALQLANSAFAVDLFKQLC SPICLSTSLSLAQVGAKGDT
EKEPLGNVLF ANEIGQVLHF
S ENVKDIPFGFQTVTSDVNKL RLYVDKSLNLSTEFISSTKR 120
S SSFYSLKLIK PYAKELETVD
FKDKLEETKGQINNSIKDLT NSVNDQTKILVVNAAYFVGK 180
DGHFENILAD WMKKFPESET
KECPFRLNKTDTKPVQMMNM SINCKIIELPFQNKHLSMFI 240
EATFCMGNID LLPKDVEDES
TGLEKIEKQLNSESLSQWTN LSIPKFKVEKMIDPKACLEN 300
PSTMANAKVK LGLKHIFSED
TSDFSGMSETKGVALSNVIH GDSIEVPGARILQHKDELNA 360
KVCLEITEDG DHPFIYIIRH
6ONKTRNIIFFGKFCSP
Seq ID N0: 37 DNA sequence
Nucleic Acid Accession #: NM_0168583
6S Coding sequence: 72-842
1 11 21 31 41 S1
I I
I I i I CCTCTAAGAA 60
GGAGTGGGGGAGAGAGAGGAGACCAGGACAGCTGCTGAGAGTCCAGATAC
7OTAAGAGCAAAGATGTTTCAAACTGGGGGCCTCATTGTCTTCTACGGGCTG 120
TTAGCCCAGA
CCATGGCCCAGTTTGGAGGCCTGCCCGTGCCCCTGGACCAGACCCTGCCC 180
TTGAATGTGA
ATCCAGCCCTGCCCTTGAGTCCCACAGGTCTTGCAGGAAGCTTGACAAAT 240
GCCCTCAGCA
ATGGCCTGCTGTCTGGGGGCCTGTTGGGCATTCTGGAAAACCTTCCGCTC 300
CTGGACATCC
TGAAGCCTGGAGGAGGTACTTCTGGTGGCCTCCTTGGGGGACTGCTTGGA 360
AAAGTGACGT
~1CAGTGATTCCTGGCCTGAACAACATCATTGACATAAAGGTCACTGACCCC 420
/S CAGCTGCTGG
AACTTGGCCTTGTGCAGAGCCCTGATGGCCACCGTCTCTATGTCACCATC 480
CCTCTCGGCA
TAAAGCTCCAAGTGAATACGCCCCTGGTCGGTGCAAGTCTGTTGAGGCTG 540
GCTGTGAAGC
TGGACATCACTGCAGAAATCTTAGCTGTGAGAGATAAGCAGGAGAGGATC 600
CACCTGGTCC
TTGGTGACTGCACCCATTCCCCTGGAAGCCTGCAAATTTCTCTGCTTGAT 660
GGACTTGGCC
o CCCTCCCCATTCAAGGTCTTCTGGACAGCCTCACAGGGATCTTGAATAAA 720
OO GTCCTGCCTG
AGTTGGTTCAGGGCAACGTGTGCCCTCTGGTCAATGAGGTTCTCAGAGGC 780
TTGGACATCA
CCCTGGTGCATGACATTGTTAACATGCTGATCCACGGACTACAGTTTGTC 840
ATCAAGGTCT
AAGCCTTCCAGGAAGGGGCTGGCCTCTGCTGAGCTGCTTCCCAGTGCTCA 900
CAGATGGCTG
GCCCATGTGCTGGAAGATGACACAGTTGCCTTCTCTCCGAGGAACCTGCC 960
CCCTCTCCTT
SSTCCCACCAGGCGTGTGTAACATCCCATGTGCCTCACCTAATAAAATGGCT 1020
AAAAAAAAAAAAAAAAAAAAAAAAAAAAA CTTCTTCTGC
203
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Seq ID N0: 38 Protein sequence:
Protein Accession #: NP 057667
S 1 11 21 31 41 51
MFQTGGLIVF YGLLAQTMAQ FGGLPVPLDQ TLPLNVNPAL PLSPTGLAGS LTNALSNGLL 60
SGGLLGILEN LPLLDILKPG GGTSGGLLGG LLGKVTSVIP GLNNIIDIKV TDPQLLELGL 120
VQSPDGHRLY VTIPLGIKLQ VNTPLVGASL LRLAVKLDIT AEILAVRDKQ ERIHLVLGDC 180
THSPGSLQIS LLDGLGPLPI QGLLDSLTGI LNKVLPELVQ GNVCPLVNEV LRGLDITLVH 240
1 O DIVNMLIHGL QFVIKV
Seq ID N0: 39 DNA sequence
Nucleic Acid Accession #: NM_004363.1
1 S Coding sequence: 115-2223
1 11 21 31 41 51
CTCAGGGCAG GACAGCAGACCAGACAGTCACAGCAGCCTTGACAAAACGT60
AGGGAGGAAG
2OTCCTGGAACT TCCACAGAGGAGGACAGAGCAGACAGCAGAGACCATGGAG120
CAAGCTCTTC
TCTCCCTCGG CAGATGGTGCATCCCCTGGCAGAGGCTCCTGCTCACAGCC180
CCCCTCCCCA
TCACTTCTAA CCCGCCCACCACTGCCAAGCTCACTATTGAATCCACGCCG240
CCTTCTGGAA
TTCAATGTCG GGAGGTGCTTCTACTTGTCCACAATCTGCCCCAGCATCTT300
CAGAGGGGAA
TTTGGCTACA AGGTGAAAGAGTGGATGGCAACCGTCAAATTATAGGATAT360
GCTGGTACAA
2 GTAATAGGAA TACCCCAGGGCCCGCATACAGTGGTCGAGAGATAATATAC420
S CTCAACAAGC
CCCAATGCAT CCAGAACATCATCCAGAATGACACAGGATTCTACACCCTA480
CCCTGCTGAT
CACGTCATAA TGTGAATGAAGAAGCAACTGGCCAGTTCCGGGTATACCCG540
AGTCAGATCT
GAGCTGCCCA CTCCAGCAACAACTCCAAACCCGTGGAGGACAAGGATGCT600
AGCCCTCCAT
GTGGCCTTCA TGAGACTCAGGACGCAACCTACCTGTGGTGGGTAAACAAT660
CCTGTGAACC
3 CAGAGCCTCC CAGGCTGCAGCTGTCCAATGGCAACAGGACCCTCACTCTA720
O CGGTCAGTCC
TTCAATGTCA CACAGCAAGCTACAAATGTGAAACCCAGAACCCAGTGAGT780
CAAGAAATGA
GCCAGGCGCA CATCCTGAATGTCCTCTATGGCCCGGATGCCCCCACCATT840
GTGATTCAGT
TCCCCTCTAA CAGATCAGGGGAAAATCTGAACCTCTCCTGCCACGCAGCC900
ACACATCTTA
TCTAACCCAC CTCTTGGTTTGTCAATGGGACTTTCCAGCAATCCACCCAA960
CTGCACAGTA
3 GAGCTCTTTA CACTGTGAATAATAGTGGATCCTATACGTGCCAAGCCCAT1020
S TCCCCAACAT
AACTCAGACA TAGGACCACAGTCACGACGATCACAGTCTATGCAGAGCCA1080
CTGGCCTCAA
CCCAAACCCT CAACAACTCCAACCCCGTGGAGGATGAGGATGCTGTAGCC1140
TCATCACCAG
TTAACCTGTG TCAGAACACAACCTACCTGTGGTGGGTAAATAATCAGAGC1200
AACCTGAGAT
CTCCCGGTCA GCAGCTGTCCAATGACAACAGGACCCTCACTCTACTCAGT1260
GTCCCAGGCT
4OGTCACAAGGA ACCCTATGAGTGTGGAATCCAGAACGAATTAAGTGTTGAC1320
ATGATGTAGG
CACAGCGACC GAATGTCCTCTATGGCCCAGACGACCCCACCATTTCCCCC1380
CAGTCATCCT
TCATACACCT AGGGGTGAACCTCAGCCTCTCCTGCCATGCAGCCTCTAAC1440
ATTACCGTCC
CCACCTGCAC GCTGATTGATGGGAACATCCAGCAACACACACAAGAGCTC1500
AGTATTCTTG
TTTATCTCCA GAAGAACAGCGGACTCTATACCTGCCAGGCCAATAACTCA1560
ACATCACTGA
4SGCCAGTGGCC TACAGTCAAGACAATCACAGTCTCTGCGGAGCTGCCCAAG1620
ACAGCAGGAC
CCCTCCATCT CTCCAAACCCGTGGAGGACAAGGATGCTGTGGCCTTCACC1680
CCAGCAACAA
TGTGAACCTG CACAACCTACCTGTGGTGGGTAAATGGTCAGAGCCTCCCA1740
AGGCTCAGAA
GTCAGTCCCA GTCCAATGGCAACAGGACCCTCACTCTATTCAATGTCACA1800
GGCTGCAGCT
AGAAATGACG TGTATGTGGAATCCAGAACTCAGTGAGTGCAAACCGCAGT1860
CAAGAGCCTA
S GACCCAGTCA CCTCTATGGGCCGGACACCCCCATCATTTCCCCCCCAGAC1920
O CCCTGGATGT
TCGTCTTACC GAACCTCAACCTCTCCTGCCACTCGGCCTCTAACCCATCC1980
TTTCGGGAGC
CCGCAGTATT CAATGGGATACCGCAGCAACACACACAAGTTCTCTTTATC2040
CTTGGCGTAT
GCCAAAATCA TAACGGGACCTATGCCTGTTTTGTCTCTAACTTGGCTACT2100
CGCCAAATAA
GGCCGCAATA CAAGAGCATCACAGTCTCTGCATCTGGAACTTCTCCTGGT2160
ATTCCATAGT
S CTCTCAGCTG CGGCATCATGATTGGAGTGCTGGTTGGGGTTGCTCTGATA2220
S GGGCCACTGT
TAGCAGCCCT CTTCATTTCAGGAAGACTGACAGTTGTTTTGCTTCTTCCT2280
GGTGTAGTTT
TAAAGCATTT CAGTCTAAAATTGCTTCTTTACCAAGGATATTTACAGAAA2340
GCAACAGCTA
AGACTCTGAC GACCATCCTAGCCAACATCGTGAAACCCCATCTCTACTAA2400
CAGAGATCGA
AAATACAAAA CTTGGTGGCGCGCACCTGTAGTCCCAGTTACTCGGGAGGC2460
ATGAGCTGGG
6OTGAGGCAGGA AACCCGGGAGGTGGAGATTGCAGTGAGCCCAGATCGCACC2520
GAATCGCTTG
ACTGCACTCC CAGAGCAAGACTCCATCTCAAAAAGAAAAGAAAAGAAGAC2580
AGTCTGGCAA
TCTGACCTGT ACAAGTTTCTGATACCACTGCACTGTCTGAGAATTTCCAA2640
ACTCTTGAAT
AACTTTAATG CAGCTTCATGAAACTGTCCACCAAGATCAAGCAGAGAAAA2700
AACTAACTGA
TAATTAATTT AATGAACTAATGAGGATTGCTGATTCTTTAAATGTCTTGT2760
CATGGGACTA
6STTCCCAGATT TTTTTTCTTTTAAGCTATCCACTCTTACAGCAATTTGATA2820
TCAGGAAACT
AAATATACTT AAATTGAGACATTTACATTTTCTCCCTATGTGGTCGCTCC2880
TTGTGAACAA
AGACTTGGGA GAATATTTATATTGTATGGTAATATAGTTATTGCACAAGT2940
AACTATTCAT
TCAATAAAAA GTATAACAGAAAAA
TCTGCTCTTT
/0 Seq ID N0: 40 Protein sequence:
Protein Accession #: NP 004354.1
1 11 21 31 41 51
/SMESPSAPPHRWCIPWQRLLLTASLLTFWNPPTTAKLTIESTPFNVAEGKE 60
VLLLVHNLPQ
HLFGYSWYKGERVDGNRQIIGYVIGTQQATPGPAYSGREIIYPNASLLIQ 120
NIIQNDTGFY
TLHVIKSDLVNEEATGQFRVYPELPKPSISSNNSKPVEDKDAVAFTCEPE 180
TQDATYLWWV
NNQSLPVSPRLQLSNGNRTLTLFNVTRNDTASYKCETQNPVSARRSDSVI 240
LNVLYGPDAP
TISPLNTSYRSGENLNLSCHAASNPPAQYSWFVNGTFQQSTQELFIPNIT 300
VNNSGSYTCQ
SOAHNSDTGLNRTTVTTITVYAEPPKPFITSNNSNPVEDEDAVALTCEPEIQ 360
NTTYLWWVNN
QSLPVSPRLQLSNDNRTLTLLSVTRNDVGPYECGIQNELSVDHSDPVILN 420
VLYGPDDPTI
SPSYTYYRPGVNLSLSCHAASNPPAQYSWLIDGNIQQHTQELFISNITEK 480
NSGLYTCQAN
NSASGHSRTTVKTITVSAELPKPSISSNNSKPVEDKDAVAFTCEPEAQNT 540
TYLWWVNGQS
LPVSPRLQLSNGNRTLTLFNVTRNDARAYVCGIQNSVSANRSDPVTLDVL 600
YGPDTPIISP
S PDSSYLSGANLNLSCHSASNPSPQYSWRINGIPQQHTQVLFIAKITPNNN 660
S GTYACFVSNL
ATGRNNSIVKSITVSASGTSPGLSAGATVGIMIGVLVGVALI
204
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
Seq ID N0:
41 DNA sequence
Nucleic Acid
Accession
#: NM_006952.1
Coding sequence:
11-793
S
1 11 21 31 41 51
,
I I I I
AATCCCGACA ACAACTCAACTGTTCGTTGCTTCCAGGGCCTGCTGATTTT60
ATGGCGAAAG
TGGAAATGTG GTTGCGGCATTGCCCTGACTGCGGAGTGCATCTTCTTTGT120
ATTATTGGTT
I ATCTGACCAA ACCCACTGCTTGAAGCCACCGACAACGATGACATCTATGG180
O CACAGCCTCT
GGCTGCCTGG TTGTGGGCATCTGCCTCTTCTGCCTGTCTGTTCTAGGCAT240
ATCGGCATAT
TGTAGGCATC GCAGGAAAATTCTTCTGGCGTATTTCATTCTGATGTTTAT300
ATGAAGTCCA
AGTATATGCC CATCTTGTATCACAGCAGCAACACAACGAGACTTTTTCAC360
TTTGAAGTGG
ACCCAACCTC AGATGCTAGAGAGGTACCAAAACAACAGCCCTCCAAACAA420
TTCCTGAAGC
I TGATGACCAG ATGGAGTCACCAAAACCTGGGACAGGCTCATGCTCCAGGA480
S TGGAAAAACA
CAATTGCTGT GTCCATCAGACTGGCAAAAATACACATCTGCCTTCCGGAC540
GGCGTAAATG
TGAGAATAAT ATCCCTGGCCTCGTCAATGCTGTGTTATGAACAATCTTAA600
GATGCTGACT
AGAACCTCTC CTTGTAAACTAGGCGTGCCTGGTTTTTATCACAATCAGGG660
AACCTGGAGG
CTGCTATGAA GTCCAATGAACCGACACGCCTGGGGGGTTGCCTGGTTTGG720
CTGATCTCTG
2OATTTGCCATT CTTTTTGGGTTCTCCTGGGTACCATGTTCTACTGGAGCAG780
CTCTGCTGGA
AATTGAATAT
TAAGAA
Seq ID N0: sequence:
42 Protein
Protein Accession
#: NP 008883.1
2J
1 11 21 31 41 51
I
I ~ I ~ ~
MAKDNSTVRC IIGCCGIALTAECIFFVSDQHSLYPLLEAT DNDDIYGAAW
FQGLLIFGNV 60
IGIFVGICLF MKSSRKILLAYFILMFIVYAFEVASCITAA TQRDFFTPNL
CLSVLGIVGI 120
3 FLKQMLERYQ WKNNGVTKTWDRLMLQDNCCGVNGPSDWQK YTSAFRTENN
O NNSPPNNDDQ 180
DADYPWPRQC NLEACKLGVPGFYHNQGCYELISGPMNRHA WGVAWFGFAI
CVMNNLKEPL 240
LCWTFWVLLG
TMFYWSRIEY
3 S Seq ID NO: 43 DNA sequence
Nucleic Acid Accession #: Eos sequence
Coding sequence: 83-2605
1 11 21 31 41 51
A I I I I i I
O
~-t
GCCGGACAGA TCCTGGAGCCGGCCCAGTTGTGAACTAGGAGAGCTTTGGG60
TCTGCGCGTA
ACCTCTGTCC AGATGAATGGAGAGTATAGAGGCAGAGGATTTGGACGAGG120
CAAGCAAGAG
AAGATTTCAA GGGGAAGAGGTGGTGGGAACTTCTCAGGAAAATGGAGAGA180
AGCTGGAAAA
AAGAGAACAC TGAGTAAAACCACAGGAAAACGTACTTCTGAACAAACCCC240
AGACCTGATC
4SACAGTTTTTG AGACCCCACAGTCAATGCAGTCAACATTGGATCGATTCAT300
CTTTCAACAA
ACCATATAAA TTTATTTCTCTGAAGTTTACAGCGATAGCTCTCCTTTGAT360
GGCTGGAAGC
TGAGAAGATT AAAAATTTTTCACAAGGCATATTGATTTGTATGACAAGGA420
CAAGCATTTG
TGAAATAGAA GTATTTTGGTAGATTTTAAAGAACTGACAGAAGGTGGTGA480
AGAAAGGGAA
AGTAACTAAC ATATAGCAACTGAACTAAGAGATGCACCTGAGAAAACCTT540
TTGATACCAG
S GGCTTGCATG TACATCAGGTGTTAACTAAGGACCTTGAAAGGCATGCAGC600
O GGTTTGGCAA
TGAGTTACAA GATTGTCTAATGATGGAGAAACAATGGTAAATGTGCCACA660
GCCCAGGAAG
TAT'~CATGCA ACTATGAGCCTTTGACACAGCTCAAGAATGTCAGAGCAAA720
AGGGTGTACA
TTACTATGGA CTCTAAGAGGGACAGTGGTTCGTGTCAGTAATATAAAGCC780
AAATACATTG
TCTTTGCACC TTCTTTGTGCTGCATGTGGAGAAATTCAGAGCTTTCCTCT840
AAGATGGCTT
S TCCAGATGGA TTCCCACAAAGTGTCCTGTGCCTGTGTGTCGAGGCAGGTC900
S AAATACAGTC
ATTTACTGCT CTCCTCTCACAGTTACGATGGACTGGCAGTCAATCAAAAT960
CTCCGCAGCT
CCAGGAATTG ATCAGAGAGAAGCAGGTCGGATTCCACGAACAATAGAATG1020
ATGTCTGATG
TGAGCTTGTT TGGATAGCTGTGTCCCGGGAGACACAGTGACTATTACTGG1080
CATGATCTTG
AATTGTCAAA CGGAAGAAGGTTCTCGAAATAAGAATGACAAGTGTATGTT1140
GTCTCAAATG
6OCCTTTTGTAT ATTCTATTAGTAATAGCAAAGGACAGAAAACAAAGAGTTC1200
ATTGAAGCAA
TGAGGATGGG GAATGTTGATGGAGTTCTCACTTAAAGACCTTTATGCCAT1260
TGTAAGCATG
CCAAGAGATT AAAACCTGTTTAAACTCATTGTCAACTCGCTTTGCCCTGT1320
CAAGCTGAAG
CATTTTTGGT TTAAAGCAGGTTTGGCATTAGCACTCTTTGGAGGAAGCCA1380
CATGAACTTG
GAAATACGCA ACAGAATTCCAATTCGGGGAGACCCCCACATCCTTGTTGT1440
GATGACAAAA
G TGGAGATCCA AAAGTCAAATGCTACAGGCAGCGTGCAATGTTGCCCCACG1500
VSGGCCTAGGAA
TGGCGTGTAT ACACCACGACCACCTCTGGTCTGACGGTAACTCTTTCAAA1560
GTTTGTGGTA
AGATAGTTCC TTGCTTTGGAAGCTGGTGCCCTGGTACTTGGTGATCAAGG1620
TCTGGAGATT
TATTTGTGGA TTGATAAGATGGGGAATCAACATCAAGCCTTGTTGGAAGC1680
ATCGATGAAT
CATGGAGCAG GTCTTGCTAAGGCTGGTGTGGTTTGTAGCCTTCCTGCAAG1740
CAAAGTATTA
1 AACTTCCATT CAAATCCAGTTGGAGGACATTACAATAAAGCCAAAACAGT1800
O ATTGCTGCTG
TTCTGAGAAT GGAGTGCACTACTATCCAGATTTGATTTGGTCTTTATCCT1860
TTAAAAATGG
GTTAGATACT ATCATGATCACTTACTCTCTGAACATGTGATTGCAATAAG1920
CCAAATGAGC
AGCTGGAAAG TTAGCAGTGCCACAGTAGCTCGTATGAATAGTCAAGATTC1980
CAGAGAACCA
AAATACTTCC TAGTTTCTGAGAAGCCATTATCAGAAAGACTAAAGGTGGT2040
GTACTTGAAG
7STCCTGGAGAA CCATTCCCCACCAGCTATTGAGAAAGTACATTGGCTATGC2100
ACAATAGATC
TCGGCAGTAT GGCTATCCACAGAAGCTGCTCGAGTTCTTCAAGATTTTTA2160
GTGTACCCAA
CCTTGAGCTC GCCAGAGGTTAAATAGCTCACCAATCACTACCAGGCAGCT2220
CGGAAACAGA
GGAATCTTTG CAGAGGCACGAGCAAGGTTGGAATTGAGAGAGGAAGCAAC2280
ATTCGTCTGA
CAAAGAAGAC TAGTGGAAATTATGAAATATAGCATGCTAGGAACTTACTC2340
GCTGAGGATA
SOTGATGAATTT ATTTTGAGCGATCCCAGCATGGTTCTGGAATGAGCAACAG2400
GGGAACCTAG
GTCAACAGCG TTTCTGCTCTCAACAACGTTGCTGAAAGAACTTATAATAA2460
AAAAGATTTA
TATATTTCAA TTCGGCAGATTGCCAAAGAACTAAACATTCAGGTTGCTGA2520
TTTCATCAAC
TTTTGAAAAT CACTAAATGACCAGGGTTACCTCTTGAAAAAAGGCCCAAA2580
TTTATTGGAT
AGTTTACCAG TGTAAAAGGACTTCACCAAGTTAGGGCCTCCTGGGTTTAT2640
CTTCAAACTA
S TGCAGATTAA GTGAAGATATGCGTGCACGCACAGACAGACAGACACACAC2700
S AGCCATCTCA
ACACACACAC ACACACACACACACACAGTCAAATACTGTTCTCTGAAAAA2760
ACACACACAC
TGATGTCCCA AATAGGAAAAAAGCATTAAATATAATAAACTAATTTAAGA2820
AAAGTATTAT
20S
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
AGTGATAAAGTCTCCAGATGCAGTAGCTCACACTGTAATCACAGTGACTCAGGAGGCTGA2880
GGTGAGAGGATTCCTTGAGGCCAGGGTTCGAGACCAACCTTGGGCAACATAGCAAGACCC2940
CATTTCTTAAAAAAAAAAAAAAAAAATTTAAACTTAGCTGGGTATGGTGGCACATGCCTA3000
TAGTCTCAGCTACTTGTGAGGCTGAGGCAGGAGGATTCTTTGAGCCCAGGAGTTTGAGGT3060
S TACAGTGAGCCACAATCACACCAATCACTGCACTCCAGCCTGGGCAATAAAGTAACTCTT3120
GACTCAAAAAAATAAAAAAAATTGTAGTGGTAGCCATGTGTTAATTGTTAAATAAATTCT3180
CCAAAGGGCTAAAAGTAAATTACTTATAAATTTTTTATAGTTGTATTTTTGACCTGCCTT3240
TTATATGTATGAATATTTCATAGTTTTGCATATCAGATGTAGGCATACAGACAAATACAT3300
AAACCAATGAATATATTACATATTCTGTGTTCCAATAAAACTTTATTTATGGACACTAAA3360
ATTTGAATTTCATAAAATTTTCCCATGTCAAGAATACAAAATACTTGAGTTTTGTTTTTA3420
GCTATTTAATAATAGGTCTCATTTATTCCACAGGCTGTAGTTTGTAGTCTTGCTTGAAAC3480
AATAGAAACAGACTGATTAAGCAGGAGAAGTTTTTTGAAAGAATTTTGTTTGGCTCACGG3540
AATTATTAGAAGGCAGGTGAACCAGGAGGGTAAGCTTCCAGCAGCAATTTGTAAAACCAT3600
GCCTTAGAATTGGACTAAGGAAGAAGCTGCTGACACTCCACTGCCACACAGGGCACTGGA3660
I AGAAAGTGCTGCTGCCTCCCTGCCCCACCTTTGCCACTTCTGCAGCAGGAATAGGTAGAA3720
S
GAATGCCCCCACCCGCACCGGAACAGCAACAAAAGGATTCTGCATGAGATGCCTCCCTAA3780
ATTGCTGAATTCAAAAAAGAAGTTGCATACAAAGACATCTGATTGAAAAAGGGTATGTTA3840
TATGCCCCTTTCATAGGCTGCTAGGGAGTTTTCCTGGTTCTACTTTCAGGTGGTGGGATC3900
AATAAGACCAGAATTTCTCATATGTTGTGAGAGGATTCAAATGTTACAGGGTTGCCAGCC3960
2OAAACTATCAATCATGTATAAATCCAACAAACACTTTGTAACATACAAGAACTCAGGAAAT4020
GTGAACCATTGTTGGAGAATCTACTAAAATACGGCTTCCCGCAAACGAAGATGAATGGAA4080
AATGTAAATAAAAAGAACTGGCAGTGTATATCAGATGTTTAACTATAGGACCAGAACTAA4140
GATGTGGAGACTATTGCCATAGACCACAATGTAAATTTTTAAGTGAGGAAGGAAAAATCA4200
GGAATCAAAAGGGGCCAGGTGCAGTGGCTCACATCTATAATCCCAGAGCTTTGGGAGTTC4260
2SGAGGCAGGAGGATCACTTGAAGCCAGTTTTGAGACCAGCCTATGCAACACATTGAGACCC4320
TATCTCTACAAAAAATAGATTAGCTGGGCACGGTGGTGCATGCCTATTGTCCTACCTACT4380
GTGGAGGCTGAAGTAGGAAATCACTTGAGCCCGAGAGTTTGAGGTTACAGTGAGCTATGA4440
TTATACCACTGCACTCCAGCCTGGGCAAGAGAGCAAGACCTTGTCTCTT
3 Seq ID 44 sequence:
0 NO: Protein
Protein
Accession
#: CAH55276.2
1 11 21 31 41 51
3 MNGEYRGRGFGRGRFQSWKRGRGGGNFSGKWREREHRPDLSKTTGKRTSEQTPQFLLSTK60
S
TPQSMQSTLDRFIPYKGWKLYFSEVYSDSSPLIEKIQAFEKFFTRHIDLYDKDEIERKGS120
ILVDFKELTEGGEVTNLIPDIATELRDAPEKTLACMGLAIHQVLTKDLERHAAELQAQEG180
LSNDGETMVNVPHIHARVYNYEPLTQLKNVRANYYGKYIALRGTWRVSNIKPLCTKMAF240
LCAACGEIQSFPLPDGKYSLPTKCPVPVCRGRSFTALRSSPLTVTMDWQSIKIQELMSDD300
A QREAGRIPRTIECELVHDLVDSCVPGDTVTITGIVKVSNAEEGSRNKNDKCMFLLYIEAN360
'+O
SISNSKGQKTKSSEDGCKHGMLMEFSLKDLYAIQEIQAEENLFKLIVNSLCPVIFGHELV420
KAGLALALFGGSQKYADDKNRIPIRGDPHILWGDPGLGKSQMLQAACNVAPRGVWCGN480
TTTTSGLTVTLSKDSSSGDFALEAGALVLGDQGICGIDEFDKMGNQHQALLEAMEQQSIS540
LAKAGWCSLPARTSIIAAANPVGGHYNKAKTVSENLKMGSALLSRFDLVFILLDTPNEH600
,pHDHLLSEHVIAIRAGKQRTISSATVARMNSQDSNTSVLEVVSEKPLSERLKWPGETIDP660
'tS
IPHQLLRKYIGYARQYVYPRLSTEAARVLQDFYLELRKQSQRLNSSPITTRQLESLIRLT720
EARARLELREEATKEDAEDIVEIMKYSMLGTYSDEFGNLDFERSQHGSGMSNRSTAKRFI780
SALNNVAERTYNNIFQFHQLRQIAKELNIQVADFENFIGSLNDQGYLLKKGPKVYQLQTM
S0
Seq ID N0: 45 DNA sequence
Nucleic Acid Accession #: NM_005416.1
Coding sequence: 149..658
SS 1 11 21 31 41 51
ACCAGATCCCAGAGGCTGAACACCTCGACCTTCTCTGCACAGCAGATGATCCCTGAGCAG
60
CTGAAGACCAGAAAAGCCACTAAGACTTTCTGCTTAATTCAGGAGCTTAGAGGATTCTTC
120
AAAGAGTGTGTCCACGATCCTTTGAAGCATGAGTTCTTACCAGCAGAAGCAGACCTTTAC
180
6O CCCACCACCTCAGCTTCAACAGCAGCAGGTGAAACAACCCAGCCAGCCTCCACCTCAGGA
240
AATATTTGTTCCCACAACCAAGGAGCCATGCCACTCAAAGGTTCCACAACCTGGAAACAC
300
AAAGATTCCAGAGCCAGGCTGTACCAAGGTCCCTGAGCCAGGCTGTACCAAGGTCCCTGA
360
GCCAGGCTGTACCAAGGTCCCTGAGCCAGGTTGTACCAAGGTCCCTGAGCCAGGCTGTAC
420
CAAGGTCCCTGAGCCAGGTTGTACCAAGGTCCCTGAGCCAGGCTACACCAAGGTCCCTGA
480
6S ACCAGGCAGCATCAAGGTCCCTGACCAAGGCTTCATCAAGTTTCCTGAGCCAGGTGCCAT
540
CAAAGTTCCTGAGCAAGGATACACCAAAGTTCCTGTGCCAGGCTACACAAAGCTACCAGA
600
GCCATGTCCTTCAACGGTCACTCCAGGCCCAGCTCAGCAGAAGACCAAGCAGAAGTAAT~'
660
TGGTGCACAGACAAGCCCTTGAGAAGCCAACCACCAGATGCTGGACACCCTCTTCCCATC
720
TGTTTCTGTGTCTTAATTGTCTGTAGACCTTGTAATCAGCACATTGTCACCCCAAGCCAT
780
~7 AGTCTCTCTCTTATTTGTATCCTAAAAATACGTACTATAAAGCTTTTGTTCACACACACT
O 840
CTGAAGAATCCTGTAAGCCCCTGAATTAAGCAGAAAGTCTTCATGGCTTTTCTGGTCTTC
900
GGCTGCTCAGGGTTCATCTGAAGATTCGAATGAAAAGAAATGCATGTTTCCTGCTCTTCC
960
CTCATTAAATTGCTTTTAATTCCA
7S
Seq ID N0: 46 Protein sequence:
Protein Accession #: NP 005407.1
1 11 21 3I 41 51
MSSYQQKQTF TPPPQLQQQQ VKQPSQPPPQ EIFVPTTKEP CHSKVPQPGN TKIPEPGCTK 60
VPEPGCTKVP EPGCTKVPEP GCTKVPEPGC TKVPEPGCTK VPEPGYTKVP EPGSIKVPDQ 120
GFIKFPEPGA IKVPEQGYTK VPVPGYTKLP EPCPSTVTPG PAQQKTKQK
~S Seq ID NO: 47 DNA sequence
Nucleic Acid Accession #: Eos sequence
206
CA 02444691 2003-10-17
WO 02/086443 PCT/US02/12476
1 1l 21 31 41 51
GCGTCGTGTG CGGGCTGTGGATAATTAGACACGTTCTTCCCTCATTGCCC60
CAGGCGTCCC
AAGGCTCGTT CTAGAGCTGTATCATGTATTTTCTTTCAAATTAACTTTGC120
AGAATTCGCC
S TTGCAATTAA CCAGCAACAAAAGCAAACTTGGCCCGAGGTCGTTCACCGC180
GCTTAGGGAA
GAAAATGGAT TCTTCCCCGATTTAAGGGGAAAGATTCCTGCGGCCAGCGC240
TAGAGAAACT
TTTGGGGAAA CGCAGAGGCGACGACAGGGGAGCAGGAAGCTGCTCACGGT300
GTGCCCCGAC
AGTCGGCGTT GTGGCCTTCCTCATCTGGGCGATGTGGGCTCCTAGAAGAG360
GGCGGCAGCG
TAAGGATAAC TGACTTCTGTACGGTTTGAGCCCAACTGCACACTCATGAC420
ATCCTGGAAA
1 TTGGAGCTGC TACAGTTTACCAAACACATTCATGAACATAATCTCATTTA480
1 CCTGTGGAGT
O
CTAAAAACTT TTCTTTTACTAAAATTTTTTCTTATTACAAA
TGTGAGAATT
Seq ID N0: 48 DNA sequence:
1 S Nucleic Acid Accession #: CAT cluster
1 11 21 31 41 51
TTCCAAATTTTTTTTTTTGT AATTTTAGTA CTCACAAAGT
AATAAGAAAA AAAGAAAATT 60
2O TTTTAGTAAATGAGATTATG TGTTTGGTAA CACAGGGCAG
TTCATGAATG ACTGTAACTC 120
CTCCAAGTCATGAGTGTGCA AACCGTACAG CAGGATGTTA
GTTGGGCTCA AAGTCATTTC 180
TCCTTACTCTTCTCGGAGCC AGATGAGGAA GCCGCCAACG
CACATCGCCC GGCCACCGCT 240
CCGACTACCGTGAGCAGCTT TGTCGTCGCC GGGCACTTTC
CCTGCTCCCC TCTGCGGTCG 300
CCCAAAGCGCTGGCCGCAGG CTTAAATCGG TCTCTAATCC
AATCTTTCCC GGAAGAAGTT 360
2S ATTTTCGCGGTGAACGACCT TTGCTTTTGT CTAAGCTTAA
CGGGCCAAGT TGCTGGTTCC 420
TTGCAAGCAAAGTTAATTTG CATGATACAG AATTCTAACG
AAAGAAAATA CTCTAGGGCG 480
AGCCTTGGGCAATGAGGGAA AGTTATCCAC CGCCTGCACA
GAACGTGTCT AGCCCGGGGA 540
CGACGCT
3 O Seq ID NO: 49 DNA sequence
Nucleic Acid Accession #: CAT cluster
1 11 21 31 41 51
3 TCTTTCTTCTGCTGCTCGTT GTGCTCTTCTTCTTTCTTTCCCTCGCCGCT60
S TGTCTCTCCT
CCTGCCGACCTCTGTTGTCT GGCGGGGGGCGGGAGAAGCTGACCGGTGAG120
CTTCTCTGAT
ACCGTAGACCCGAAACCATT AGCCGGTCGCCGGCTTTTTTGGGAGAACCC180
GGGTGTCACA
GACACATGCAGACCAGTTTT CATGACCATGTTATTACTATGGGCCGCCTC240
CCTGGAACNG
CCCAACCAAAGTGTTTAAAA CACCCCCAAAATTTTTTTTTTTTTTTTTTT300
CTTTTTAGGG
A TTCATTTAAAAAACTCTAAT AATACAAAGATACCCAAACCCTTTATGCTT360
4O ATTTATATTA
CTTTCTCTGATCTGTGTCTT CAGCATCTCCATTTTTTTTCTGCTGCTTCA420
TTTTCTTTGA
TCGCTGTAGCCATGGGAATC TTATGGTAGCAATATGGAGTGCTGTATTCC480
CGTTTCATTA
TAAAGAAACTGACACAGGAG ACTTGGGAGGCAGAGTTTGCAGTGAGCCGA540
AATCACTTGA
GATTGAACCAGTGCACTCCA CGGAGCAAGATTCTGTCACAGTTCCTGAAG600
GCCTTGGCAG
A TGCTGGTATCGTCCTGCAGC GTTCCATTGCGCTGCCAGGCAGGGTGCTGG660
4S CCCATCCTCG
GACGTGGGGAGAGCTGGTCT GTGAAGCTCAGCTGTGGCACACCTTGGATG720
ATATATCCGG
CCGGGTCTCTCCTGGCCCCG ATTTTTGCCACGAGTGTACACCAAACAAAG780
GGGACCTAGT
GAGACAGCATCATTTATGAG CCACCCTACTGCTGTATCCAGTTTCCATTG840
CCTGCAGCAT
ACTG
S
O
Seq ID 50 DNA sequence
N0:
Nucleic
Acid
Accession
#: L05187
Coding
sequence:
1991..2260
SS1 11 21 31 41 51
CTGCAGGGAGGCAGGTAGAA GGTTTTCAGGTGGGGGGCAGTCTAGCCTGA60
AAGGCTTTTG
TCAGAAAGGAGGAAAAGGCC TCTGGGTGGAGTGAAGGGAAAAAGTGATCC120
AGGGCAGATG
CAGAAGAAGGATTAGCCCCT GAAGTAGGAGAAGGGTAAAGGTGTGGTTGG180
GAAAGTCCCT
6OTGAAGGAAAGCAGGTTTTCC ACCAGTCAGGGGGAGGAAGGTGAGAGTGGG240
CAGATTAGCA
AGAGTCATAAGTAAATTATT GTAGTTTAATGGAATTGGGAAAAAGATGGG300
CTGAATGTGT
GGAAATGGATGGAAGGTCTT ACAAGGGGTCTATAATCAGTCCATTTCATT360
GGACTCTGAG
ATTTCTAGCTTCCACCTTCA CAAGGAGGGCCCACCTCAGCTCCTCTGCTC420
CCAAGGCAGA
CCCCTCCCTTTCCCACCTAT AAGAGTGCCCTGTCCCACAGAACACGGGGA480
TCATGTGTGC
6SACAACCATCTCAATGACAAG GGCAAGGCTCAACAGGACTCAGATGTCCCC540
GACAGCAGGT
CCAGGGTTAACTCATGAAAC GCCTGCTGCTCACCCCTCCCTCAAGGCAAG600
CCTCCATGAA
CCCTGCACCTGGGTCTGAGG CAGTGAAAATTAGGCCAGTGACATCATTTT660
ATGAGGGTGG
CAGCCAGCTAGTGCCAAAAA GTGTTCATCAAATAAGCCGAGCCAACCGGT720
ATATCAGGTG
GATGAGGATGGTAGTGTGAG CAGGTGAGGAATGAAAACAGAGTGCCCGAG780
TCATGTGTGA
7OAGCTTCTATTTCCTTGAGGC CATCTTATAAAAGCCAGCTGGCCATTGCCT840
AGGGCTCATT
TCACACCAAACCCAAGGGAC ATTCTGCTCCGTATACCAGGTAAGTCTCTG900
CACACAGCCC
ATTGCAACAAACTGGCAATT TTTTCATTATTAGAAATTAGCTAAAGGCAA960
CTAGTGTACT
ATATGTGTAAGCAGGTTAAT AATGGGAGATAGAGAATAGTGGAATATCTT1020
CCAGGGTTTC
TATTTTAAGTTAAATTACAG AAAGGACCTTAGAGATGGTTAGGGCTCCCA1080
TCTGGATTTG
7SCCTCAGTAGATAGTCATTGA CTGGAGAAGATTGTTCAAATGCCCATGGGA1140
ACTGGGAGTC
AGTTCATAGCAGAACTAGAA AGCACTCTCAGTAACACTGCAATTTCCCCC1200
CTCAGGCCAG
TGACAAGATATTTATAGAAA TTAGATGGATCTCTACTGAGCATTTATTCC1260
TTTTAATTTA
ATTTAAGGCAGTATGCTAGG AAATCAATGCCCTAACGTACTTACTTAACA1320
CACTTTGGAC
AACATAAAACCTAGCAGGAA ATATATAAATAAATGAAATGCAAAGTAGAT1380
GGTAATACAT
S AGTAATTGGCATGACGGAGA AGGGCTGTGCACTTTTGGGAGACTTGCTCA1440
O TGGGCAGAGA
AGGAGACCTCTAGGGTGTCA GCTATGATGGAGGGGTATTTGGACAAGCAG1500
AGTGATGTGA
AGATGGGAAGAAAAGCATTT GTGTAAGCACAGACCAGAAGCAAAACCATA1560
GGAAGGGACT
GAGGCTTAGATGAATATAAA AAGTCACAGGCTTTCTACATGGTACTAGGA1620
GCCATCCTAT
GAGGAAAGTGGTCTGATGCC AGACCTAATATGCGGACCTCATGTCCCTCA1680
ATTTTCCAAA
S GAAGCCAGCTTTAGTAGGGC AACAGATATAAGGTGCCTTGGGTAGGAAGG1740
S ATTTTTCCAG
GAGCCAAGAAGAGAACTCCA GCAGAAGAAATTGCCTTTTAGCTCCTCCTC1800
ATAAAATGGA
TTCAAAGGGCCTGAAAATTA TTTCATTTTTAAATGTAATGGGGGAGCTAA1860
TCCAAGCTTA
207
DEMANDE OU BREVET VOLUMINEUX
LA PRESENTE PARTIE DE CETTE DEMANDE OU CE BREVET COMPREND
PLUS D'UN TOME.
CECI EST LE TOME 1 DE 3
CONTENANT LES PAGES 1 A 207
NOTE : Pour les tomes additionels, veuillez contacter 1e Bureau canadien des
brevets
JUMBO APPLICATIONS/PATENTS
THIS SECTION OF THE APPLICATION/PATENT CONTAINS MORE THAN ONE
VOLUME
THIS IS VOLUME 1 OF 3
CONTAINING PAGES 1 TO 207
NOTE: For additional volumes, please contact the Canadian Patent Office
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