# Patent

## Title
Gene expression profiles associated with chronic allograft nephropathy

## Abstract

By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified a consensus set of gene expression-based molecular biomarkers associated with chronic allograft nephropathy and/or interstitial fibrosis and tubular atrophy CAN/IFTA and subtypes thereof. These genes sets are useful for diagnosis, prognosis, monitoring and/or subtyping of CAN/IFTA.

## Background
CROSS-REFERENCE TO RELATED APPLICATIONS
The present application is a nonprovisional and claims the benefit of U.S. Ser. No. 61/224,328 and 61/224,317 each filed Jul. 9, 2009, and incorporated by reference in its entirety for all purposes.


STATEMENT AS TO RIGHTS TO INVENTIONS MADE UNDER FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT
This invention was made with government support under grant numbers AI063603 and AI084146 awarded by the National Institutes of Health. The US Government has certain rights in the invention.


BACKGROUND OF THE INVENTION
Kidney transplantation offers a significant improvement in life expectancy and quality of life for patients with end stage renal disease[1]. Unfortunately, a chronic, progressive allograft dysfunction of uncertain etiology continues to be a primary cause of graft loss[2,3]. There has been some evolution of terminology for describing the histological basis of this chronic, progressive nephropathy, which is still commonly referred to as chronic allograft nephropathy (CAN) and more recently as interstitial fibrosis and tubular atrophy (IFTA)[4-6]. In current practice CAN refers to a clinical entity of a chronic progressive loss of kidney transplant function associated with a rising serum creatinine and a falling creatinine clearance. In current practice, IFTA refers to the histological findings based on review of a kidney transplant biopsy. Immunologic factors linked to CAN/IFTA are acute, sub-clinical and CAN/IFTA, HLA mismatching and circulating donor-specific anti-HLA antibodies[7,8]. Non-immunologic factors include hypertension, chronic toxicity of calcineurin inhibitors, hyperfiltration and diabetes mellitus[9-12]. The unifying mechanism is thought to be a progressive cycle of vascular and tissue injury, incomplete repair, compensatory hypertrophy, progressive interstitial fibrosis and nephron loss[13]. Moreover, increasing evidence is suggesting that the primary mechanism of CAN/IFTA is a chronic immunological injury mediated by a combination of T cell and antibody-mediated immunity, in other words, chronic rejection.
As early as two years post kidney transplant, protocol biopsies have shown that more than 50% of recipients have mild CAN/IFTA[2,15,16] and by 10 years over 50% of kidney transplant recipients have severe CAN/IFTA that is associated with diminishing graft function[2]. Traditional kidney function measurements like serum creatinine and glomerular filtration rates used to predict CAN/IFTA have poor predictive values[17] and a diagnosis requires a transplant biopsy[18,19]. Predicting graft outcomes strictly based on the kidney biopsy is difficult and this invasive procedure has significant costs and risks for patients. Thus, there is a pressing medical need to identify minimally invasive biomarkers that are able to identify early stages of CAN/IFTA at a time that changes in therapy may alter outcomes.
Rapidly evolving technologies for genomics have created new opportunities to develop minimally invasive biomarkers. Recent studies, including our own, have reported genes that are differentially expressed at the mRNA level in kidney biopsies in the presence of CAN/IFTA[16,20,21]. The limitation of these studies is that they require an invasive transplant biopsy. Others have reported analyzing urine and peripheral blood using RT-qPCR or proteomics to identify small numbers of potential biomarkers for CAN/IFTA, though none is validated for clinical use[22,23].
BRIEF SUMMARY OF THE INVENTION
The invention provides methods of prognosing, diagnosing or monitoring chronic allograft nephropathy and/or interstitial fibrosis and tubular atrophy (CAN/IFTA). The methods entail (a) determining expression levels in a subject of at least 5 genes selected from the genes in Table A, B, C, D, E, F, G, H, I and/or J; and (b) prognosing diagnosing or monitoring CAN/IFTA in a subject from the expression levels. Optionally, for each of the at least five genes, step (b) comprises comparing the expression level of the gene in the subject to one or more reference expression levels of the gene associated with CAN/IFTA or lack of CAN/IFTA. Optionally, step (b) further comprises for each of the at least five genes assigning the expression level of the gene in the subject a value or other designation providing an indication whether the subject has or is at risk of CAN/IFTA. Optionally, the expression level of each of the at least five genes is assigned a value on a normalized scale of values associated with a range of expression levels in kidney transplant patients with and without CAN/IFTA. Optionally, the expression level of each of the at least five genes is assigned a value or other designation providing an indication that the subject has is at risk of CAN/IFTA, lacks and is not at risk of CAN/IFTA, or that the expression level is uninformative. Optionally, step (b) further comprises, combining the values or designations for each of the genes to provide a combined value or designation providing an indication whether the subject has or is at risk of CAN/IFTA. Optionally, the method is repeated at different times on the subject.
In some methods, the subject is receiving a drug, and a change in the combined value or designation over time provides an indication of the effectiveness of the drug. Optionally, the subject has undergone a kidney transplant within 1-10 years of performing step (a). Optionally, step (a) is performed on a blood sample of the subject. Optionally, the blood sample is a plasma sample. Optionally, step (a) is performed on at least ten, 20, 40, or 100 genes from Table A, B, C, D, E, F, G, H, I and/or J.
Some methods further comprise changing the treatment regime of the patient responsive to the prognosing, diagnosing or monitoring step. In some methods, the subject has received a drug before performing the methods, and the change comprises administering an additional drug or administering a higher dose of the same drug. Some methods, further comprise performing an additional procedure, such as a kidney biopsy, to detect CAN/IFTA or risk thereof if the determining step provides an indication the subject has or is at risk of CAN/IFTA.
In some methods, the at least five genes are from Table A, B, C and/or D expression levels are determined at the mRNA level. In some methods, the at least five genes are from Tables E, F, G, H, I, and/or J and expression levels are determined at the protein level. In some methods, step (b) is performed by a computer. In some methods, the at least five genes are selected from Tables C and D. In some methods, the at least five genes are selected from Table C. In some methods, the at least five genes are selected from Table D. In some methods, the at least five genes are selected from Table E and F or H and I and expression levels are determined at the protein level.
The invention further provides an array, comprising a support or supports bearing a plurality of nucleic acid probes complementary to a plurality of mRNAs fewer than 5000 in number, wherein the plurality of mRNAs includes mRNAs expressed by at least five genes selected from Tables A, B, C, D. Optionally, the plurality of mRNAs are fewer than 1000, or 100 in number. Optionally a plurality of nucleic acid probes are attached to a planar support or to beads. Optionally, the at least five genes are selected from Table C and D. Optionally, the at least five genes are selected from Table C. Optionally, the at least five genes are selected from Table D.
The invention further provides an array, comprising a support or supports bearing a plurality of ligands that specifically bind to a plurality of proteins fewer than 5000 in number, wherein the plurality of proteins includes at least five proteins selected from Tables E, F, G, H, I and/or J. Optionally, the plurality of proteins are fewer than 1000 or 100 in number. Optionally, the plurality of ligands are attached to a planar support or to beads. Optionally, the at least five proteins are selected from Tables E and F and/or I and J. Optionally, the ligands are different antibodies, wherein the different antibodies bind to different proteins of the plurality of proteins.
The invention further provides a method of expression analysis, comprising determining expression levels of up to 5000 genes in a sample from a subject having a kidney transplant, wherein the genes include at least 5 genes selected from Table A, B, C, D, E, F, G, H, I and/or J. Optionally, the expression levels of up to 1000 or 100 genes are determined. The expression levels can be determined at the mRNA or protein level. The levels can be determined by, for example, quantitative PCR or hybridization to an array.
The invention further provides methods of screening a compound for activity in inhibiting or treating CAN/IFTA. The methods entail (a) administering the compound to a subject having or at risk of CAN/IFTA; (b) determining expression levels of at least five genes in the subject selected from Table A, B, C, D, E, F, G, H, I, and/or J and species variants thereof before and after administering the drug to the subject, and (c) determining whether the compound has activity in inhibiting or treating CAN/IFTA from a change in expression levels of the genes after administering the compound. Optionally, step (c) comprises for each of the at least five changes assigning a value or designation depending on whether the change in the expression level of the gene relative to one or more reference levels indicating presence or absence of CAN/IFTA. Optionally, the method further comprises determining a combined value or designation for the at least five genes from the values or designations determined for each gene. Optionally, the subject is human or a nonhuman animal model of CAN/IFTA.
The invention further provides methods of subtyping CAN/IFTA. The methods entail (a) determining expression levels in a subject of at least 5 genes selected from the genes in Tables A, B, C, D; E, F, G, H, I and/or J; and (b) determining a subtype of CAN/IFTA from the expression levels. The subtype can be selected from the group consisting of stage 0, 1, 2, or 3 of CAN/IFTA. Optionally, the subtype is stage 0, stage 1 or stage 2 and/or 3. In some methods for each of the at least five genes, step (b) comprises comparing the expression level of the gene in the subject to one or more reference expression levels of the gene associated with the subtype of CAN/IFTA or lack of CAN/IFTA. Some methods further comprise for each of the at least five genes assigning the expression level of the gene in the subject a value or other designation providing an indication whether the subject has or is at risk of the subtype of CAN/IFTA. In some methods, the expression level of each of the at least five genes is assigned a value on a normalized scale of values associated with a range of expression levels in kidney transplant patients with the subtype and without CAN/IFTA. In some methods, the expression level of each of the at least five genes is assigned a value or other designation providing an indication that the subject has or is at risk of the subtype of CAN/IFTA, lacks and is not at risk of the subtype of CAN/IFTA, or that the expression level is uninformative. In some methods, step (b) further comprises, combining the values or designations for each of the genes to provide a combined value or designation providing an indication whether the subject has or is at risk of the subtype of CAN/IFTA. Some methods are repeated at different times on the subject. In some methods, the subject is receiving a drug, and a change in the combined value or designation over time provides an indication of the effectiveness of the drug. In some methods, the subject has undergone a kidney transplant within 1-10 years of performing step (a). Some methods are performed on a blood sample of the subject, such as a plasma or whole blood sample. Some methods are performed on at least ten, 20, 40 or 100 genes selected from Tables A, B, C, D, E, F, G, H, I and/or J. Some methods further comprise changing the treatment regime of the patient responsive to the whether the subtype is present. In some methods, the subject has received a drug before performing the methods, and the change comprises administering an additional drug or administering a higher dose of the same drug. Some methods further comprise performing an additional procedure, such as a kidney biopsy, to detect CAN/IFTA or risk thereof if the determining step provides an indication the subject has or is at risk of the subtype of CAN/IFTA. Expression levels can be determined at the mRNA or protein level. In some methods, step (b) is performed by a computer. In some methods, the at least five genes are selected from Table C. In some methods, the at least five genes are selected from Table D. In some methods, the at least five genes are selected from Table E and expression levels are determined at the protein level. In some methods, the at least five genes are selected from Table F and the expression levels are determined at the protein level. In some methods, the at least five genes are selected from Table H and the expression levels are determined at the protein level. In some methods, the at least five genes are selected from Table I and the expression levels are determined at the protein level.



BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1: Class prediction analysis of Banff 0 vs. Banff 1 (mild CAN/IFTA) based on Diagonal Linear Discriminant Analysis for the top 50 Banff 0 vs. Banff 1 consensus genes ranked by p values. A) depicts the Receiver Operating Characteristic (ROC) curves and provides the Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV);
FIG. 2: Class prediction analysis of Banff 0 vs. Banff 2,3 (moderate to severe CAN/IFTA) based on Diagonal Linear Discriminant Analysis for the top 50 Banff 0 vs. Banff 2,3 consensus genes ranked by p values. A) depicts the Receiver Operating Characteristic (ROC) curves and provides the Sensitivity, Specificity, Positive Predictive Value (PPV) and Negative Predictive Value (NPV); B) depicts the heat map classifying Banff 0 vs. Banff 2,3 using the top 50 consensus genes where (red) is up-regulated and (green) is down-regulated.



DEFINITIONS
The term Chronic Allograft Nephropathy/Interstitial Fibrosis and Tubular Atrophy (CAN/IFTA) refers to a progressive, chronic, kidney tissue injury that eventually causes a progressive, chronic deterioration of kidney transplant function. The histological changes of CAN/IFTA can be found in protocol kidney transplant biopsies as early as 6 months post transplant and frequently the clinical changes of progressive kidney transplant dysfunction evolve subsequently over the next year or several years (e.g., six months to ten years). CAN/IFTA is usually a consequence of combined immunological injury (e.g. chronic rejection) and non-immunological damage (e.g. hypertensive nephrosclerosis, or nephrotoxicity of immunosuppressants like cyclosporine A), taking place months or years after transplantation and ultimately leading to histologically detectable fibrosis and sclerosis of the transplant and progressive loss of kidney function. Chronic rejection of a transplanted kidney is increasingly thought to be the major mechanism of CAN/IFTA mediated through both T cell mediated immunity and antibodies directed at antigens expressed in the kidney transplant. The hybrid term, CAN/IFTA includes histological changes and/or functional deterioration of the kidneys or both. In some patients, the present methods can provide an indication of histological changes before detectable functional deterioration of the kidneys has occurred, thereby allowing early therapeutic intervention.
Transplantation is the transfer of tissues, cells or an organ from a donor into a recipient. If the donor and recipient as the same person, the graft is referred to as an autograft and as is usually the case between different individuals of the same species an allograft. Transfer of tissue between species is referred to as a xenograft.
A biopsy is a specimen obtained from a living patient for diagnostic evaluation. Kidney biopsies can be obtained with a needle.
An average value can refer to any of a mean, median or mode.
A gene expression level is associated with a particular phenotype e.g., presence of CAN/IFTA or a subtype thereof if the gene is differentially expressed in a patient having the phenotype relative to a patient lacking the phenotype to a statistically significant extent. Unless otherwise apparent from the context a gene expression level can be measured at the mRNA and/or protein level.
A target nucleic acids is a nucleic acid (often derived from a biological sample), to which a polynucleotide probe is designed to specifically hybridize. The probe can detect presence, absence and/or amount of the target. The term can refer to the specific subsequence of a larger nucleic acid to which the probe is directed or to the overall sequence (e.g., c DNA or mRNA) whose expression level it is desired to detect.
The term subject or patient can include human or non-human animals. Thus, the methods and described herein are applicable to both human and veterinary disease and animal models. Preferred subjects are “patients,” i.e., living humans that are receiving medical care for a disease or condition. This includes persons with no defined illness who are being investigated for signs of pathology.
Diagnosis refers to methods of estimating or determining whether or not a patient is suffering from a given disease or condition or severity of the condition. Diagnosis does not require ability to determine the presence or absence of a particular disease with 100% accuracy, or even that a given course or outcome is more likely to occur than not. Instead, the “diagnosis” refers to an increased probability that a certain disease or condition is present in the subject compared to the probability before the diagnostic test was performed.
Similarly, a prognosis signals an increased probability that a given course or outcome will occur in a patient relative to the probability before the prognostic test.
A probe or polynucleotide probe is an 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, usually through hydrogen bond formation, thus forming a duplex structure. The probe binds or hybridizes to a “probe binding site.” A probe can include natural (i.e., A, G, C, or T) or modified bases (e.g., 7-deazaguanosine, inosine.). A probe can be an oligonucleotide which is a single-stranded DNA. Polynucleotide probes can be synthesized or produced from naturally occurring polynucleotides. In addition, the bases in a probe can be joined by a linkage other than a phosphodiester bond, so long as it does not interfere with hybridization. Thus, probes can include, for example, peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages (see, e.g., Nielsen et al., Science 254, 1497-1500 (1991)). Some probes can have leading and/or trailing sequences of noncomplementarity flanking a region of complementarity.
A perfectly matched probe has a sequence perfectly complementary to a particular target sequence. The probe is typically perfectly complementary to a portion (subsequence) of a target sequence. The term “mismatch probe” refer to probes whose sequence is deliberately selected not to be perfectly complementary to a particular target sequence.
The term “isolated,” “purified” or “substantially pure” means an object species (e.g., a nucleic acid sequence described herein or a polypeptide encoded thereby) has been at least partially separated from the components with which it is naturally associated.
Differential expression refers to a statistically significant difference in expression levels of a gene between two populations of samples (e.g., samples with and without CAN/IFTA). The expression levels can differ for example by at least a factor of 1.5 or 2 between such populations of samples. Differential expression includes genes that are expressed in one population and are not expressed (at least at detectable levels) in the other populations. Unique expression refers to detectable expression in one population and undetectable expression (i.e., insignificantly different from background) in the other population using the same technique (e.g., as in the present example for detection).
Control populations for comparison with populations undergoing CAN/IFTA are usually referred to as being without CAN/IFTA. Unless otherwise indicated, such a control population also means subjects without acute kidney rejection.
Hybridization reactions are preferably performed under stringent conditions in which probes or primers hybridize to their intended target with which they have perfect complementarity and not to or at least to a reduced extent to other targets. An example of stringent hybridization conditions are hybridization in 6× sodium chloride/sodium citrate (SSC) at about 45° C., followed by one or more washes in 0.2×SSC, 0.1% SDS at 50° C., 55° C., 60° C., and even more or 65° C.
Statistical significance means p<0.05 or <0.01 or even <0.001 level.
DETAILED DESCRIPTION OF THE INVENTION
I. General
By a genome-wide gene analysis of expression profiles of over 50,000 known or putative gene sequences in peripheral blood, the present inventors have identified consensus sets of gene expression-based molecular biomarkers associated with CAN/IFTA. A set of 393 genes has differential expression levels between mild chronic allograft nephropathy (CAN/IFTA) and non-rejected transplants. A set of 63 genes have differential expression between moderate or severe CAN/IFTA and non-rejected transplants. Additional set of protein markers showing differential or unique expression between CAN/IFTA and non rejected transplants are also provided.
II. Genes in Profiles
Table A lists 393 genes whose expression changes significantly between kidney transplant patients undergoing mild CAN/IFTA, Banff stage 1 compared with patients not undergoing such rejection (Banff stage 0) one year post transplant. The columns in the table have the following meanings: column 1 is a number assigned to a gene, column 2 is a measure of the statistical significance of change in gene expression between the above populations, column 3 is a mean expression level of a gene in kidney transplant patients undergoing chronic rejection (normalized as described below), column 4 is mean expression level of the gene in kidney transplant patients not undergoing CAN/IFTA (similarly normalized), column 5 is a ratio of the expression levels, column 6 is an Affymetrix number indicating a set of probes suitable for measuring expression of the gene, column 7 is a gene name (recognized names of HUGO or similar bodies are used when available), and column 8 is a further description of the gene. Table B provides similar information for 62 genes that show differential expression between kidney transplant patients undergoing moderate or severe CAN/IFTA (Banff stage 2 or 3) with kidney transplant patients not undergoing CAN/IFTA. Tables C and D provide subsets of 50 preferred genes from Tables A and B respectively.
Table E provides 117 genes and corresponding proteins for which the proteins is uniquely expressed in patients not undergoing CAN/IFTA and not at detectable levels in patients undergoing CAN/IFTA level 1. Column 1 is a sequential number for a gene/protein, column 2 is a protein symbol, column 3 is a gene symbol, and column 4 is a gene name. Table F provides similar information about 143 proteins uniquely expressed in patients undergoing CAN/IFTA and not at detectable levels in kidney transplant patients without CAN/IFTA. Table G provides similar information regarding 188 proteins that are differentially expressed between CAN/IFTA levels 0 and 1. The right hand column of the table indicates the degree of differential expression with positive numbers being upregulated in Banff stage 1 patients. Table H provides similar information to Table E for 28 genes uniquely expressed in kidney transplant patients not undergoing CAN/ITFA and not at detectable levels in patients undergoing CAN/IFTA level 2 or 3. Table I provides similar information to Table F for 510 proteins uniquely expressed in CAN/IFTA level 2 or 3 and not detectable in kidney transplant patients not undergoing CAN/IFTA. Table J provides similar information to Table G for 284 proteins differentially expressed between kidney transplant patients at CAN/IFTA level 0 versus level 2 or 3. If a gene symbol or gene name is not available, the protein symbol should be understood as referring to both the genes.
The genes referred to in the above tables are human genes. In some methods, species variants or homologs of these genes are used in a non-human animal model. Species variants are the genes in different species having greatest sequence identity and similarity in functional properties to one another. Many species variants of the above human genes are listed in the Swiss-Prot database.
Raw gene expression levels are comparable between different genes in the same sample but not necessarily between different samples. As noted above, values given for gene expression levels can be normalized so that values for particular genes are comparable within and between the populations being analyzed. The normalization eliminates or at least reduces to acceptable levels any sample to sample differences arising from factors other than CAN/IFTA (e.g. differences in overall transcription levels of patients due to general state of health and differences in sample preparation or nucleic acid amplification between samples). The normalization effectively applies a correction factor to the measured expression levels from a given array such that a profile of many expression levels in the array are the same between different patient samples. Software for normalizing overall expression patterns between different samples is both commercially and publically available (e.g., XRAY from Biotique Systems or BRB ArrayTools from the National Cancer Institute). After applying appropriate normalizing factors to the measured expression value of a particular gene in different samples, an average value of the expression level is determined for the samples in a population. The average values between different populations are then compared to determine whether expression level has changed significantly between the populations. The changes in expression level indicated for a given gene represent the relative expression level of that gene in samples from a population of individuals with a defined condition (e.g., transplant patients with CAN/IFTA of specified Banff stage) relative to samples from a control population (kidney transplant patients not undergoing CAN/IFTA). Similar principles apply in normalizing gene expression levels at the mRNA and protein levels. Comparisons between populations are made at the same level (e.g., mRNA levels in one population are compared with mRNA levels in another population or protein levels in one population with protein levels in another population).
III. Subject Population
The methods are particularly useful on human subjects who have undergone a kidney transplant although can also be used on subjects who have gone other types of transplant (e.g., heart, liver, lungs, stem cell) or on non-humans who have undergone kidney or other transplant. Gene expression levels in such subjects can be measured, for example, within, three months, six months, one year, two years, five years or ten years after a kidney transplant. In some methods, gene expression levels are determined at regular intervals, e.g., every 3 months, 6 months or every year posttransplant, either indefinitely, or until evidence of CAN/IFTA is observed, in which case the frequency of monitoring is sometimes increased. In some methods, baseline values of expression levels are determined in a subject before a kidney transplant in combination with determining expression levels at one or more time points thereafter. In other methods, a measurement is initiated responsive to some other indication of potential kidney impairment, such as a rise in levels of creatinine or BUN or a decrease in glomerular filtration rate. Similar methods can be practiced in non-human species, in which cases, the expression levels measured are the species equivalent of the human genes referenced above.
IV. Chronic Allograft Nephropathy (Can/IFTA) and its Subtypes
The methods are particularly useful for detecting CAN/IFTA. CAN/IFTA can be further classified by histological analysis of kidney transplant biopsies based on the Banff 2007 schema and the following four subtypes or stages are recognized indicating severity: 0 (no CAN/IFTA), 1 (mild CAN/IFTA), 2 (moderate CAN/IFTA) and 3 (severe CAN/IFTA) [4]. An alternative and complementary histology grading schema is the Chronic Allograft Damage Index (CADI) score and this score is often provided by pathologists with the Banff classification score as supplemental information (for example, see Yilmaz et al, J Am Soc Nephrol 2003 14: 773-779). There is also a Banff 2007 classification for acute rejection [4]. Acute rejection is characterized histologically by an active, inflammatory/immune cell infiltration comprised of various numbers of T cells and B cells as well as sometimes plasma cells, eosinophils, neutrophils and macrophages.
V. Methods of Measuring Profiles
The preferred sample type for analysis is a blood sample, which refers to whole blood or fractions thereof, such as plasma, or lymphocytes. Other samples that can be analyzed include urine, feces, saliva, and a kidney biopsy. The samples are typically isolated from a subject, particularly as a peripheral blood sample, and not returned to the subject. The analytes of interests in the samples can be analyzed with or without further processing of the sample, such as purification and amplification. Samples not requiring biopsy to obtain, particularly peripheral blood, are preferred.
Expression profiles are preferably measured at the nucleic acid level, meaning that levels of mRNA or nucleic acid derived therefrom (e.g., cDNA or cRNA). An expression profile refers to the expression levels of a plurality of genes in a sample. A nucleic derived from mRNA means a nucleic acid synthesized using mRNA as a template. Methods of isolation and amplification of mRNA are well known as described for example WO 97/10365, WO 97/27317, Chapter 3 of Laboratory Techniques in Biochemistry and Molecular Biology Hybridization With Nucleic Acid Probes, Part I. Theory and Nucleic Acid Preparation, (P. Tijssen, ed.) Elsevier, N.Y. (1993). If mRNA or a nucleic acid therefrom is amplified, the amplification is performed under conditions that approximately preserve the relative proportions of mRNA in the original samples, such that the levels of the amplified nucleic acids can be used to establish phenotypic associations representative of the mRNAs.
A variety of approaches are available for determining mRNA levels including probe arrays and quantitative PCR. A number of distinct array formats are available. Some arrays, such as an Affymetrix GeneChip® array, have different probes occupying discrete known areas of a contiguous support. Other arrays, such as arrays from Illumina, have different probes attached to different particles or beads. In such arrays, the identity of which probe is attached to which particle or beads is usually determinable from an encoding system. The probes can be oligonucleotides. In such case, typically several match probes are included with perfect complementarity to a given target mRNA together, optionally together with mismatch probes differing from the match probes are a known number of oligonucleotides (Lockhart, et al., Nature Biotechnology 14:1675-1680 (1996); and Lipschutz, et al., Nature Genetics Supplement 21: 20-24, 1999). Other arrays including full length cDNA sequences with perfect or near perfect complementarity to a particular cDNA (Schena et al. (Science 270:467-470 (1995); and DeRisi et al. (Nature Genetics 14:457-460 (1996)). Such arrays can also include various control probes, such as a probe complementarity with a house keeping gene likely to be expressed in most samples. Regardless of the specifics of array design, an array contains one or more probes either perfectly complementary to a particular target mRNA or sufficiently complementarity to the target mRNA to distinguish it from other mRNAs in the sample, and the presence of such a target mRNA can be determined from the hybridization signal of such probes, optionally by comparison with mismatch or other control probes included in the array. Typically, the target bears a fluorescent label, in which case hybridization intensity can be determined by, for example, a scanning confocal microscope in photon counting mode. Appropriate scanning devices are described by e.g., U.S. Pat. No. 5,578,832, and U.S. Pat. No. 5,631,734. The intensity of labeling of probes hybridizing to a particular mRNA or its amplification product provides a raw measure of expression level.
In other methods, expression levels are determined by so-called “real time amplification” methods also known as quantitative PCR or Taqman (see, e.g., U.S. Pat. No. 5,210,015 to Gelfand, U.S. Pat. No. 5,538,848 to Livak, et al., and U.S. Pat. No. 5,863,736 to Haaland, as well as Heid, C. A., et al., Genome Research, 6:986-994 (1996); Gibson, U. E. M, et al., Genome Research 6:995-1001 (1996); Holland, P. M., et al., Proc. Natl. Acad. Sci. USA 88:7276-7280, (1991); and Livak, K. J., et al., PCR Methods and Applications 357-362 (1995)). The basis for this method of monitoring the formation of amplification product is to measure continuously PCR product accumulation using a dual-labeled fluorogenic oligonucleotide probe. The probe used in such assays is typically a short (ca. 20-25 bases) polynucleotide that is labeled with two different fluorescent dyes. The 5′ terminus of the probe is typically attached to a reporter dye and the 3′ terminus is attached to a quenching dye The probe is designed to have at least substantial sequence complementarity with a site on the target mRNA or nucleic acid derived from. Upstream and downstream PCR primers that bind to flanking regions of the locus are also added to the reaction mixture. When the probe is intact, energy transfer between the two fluorophors occurs and the quencher quenches emission from the reporter. During the extension phase of PCR, the probe is cleaved by the 5′ nuclease activity of a nucleic acid polymerase such as Taq polymerase, thereby releasing the reporter from the polynucleotide-quencher and resulting in an increase of reporter emission intensity which can be measured by an appropriate detector. The recorded values can then be used to calculate the increase in normalized reporter emission intensity on a continuous basis and ultimately quantify the amount of the mRNA being amplified. mRNA levels can also be measured without amplification by hybridization to a probe, for example, using a branched nucleic acid probe, such as a QuantiGene® Reagent System from Panomics.
Alternatively or additionally, expression levels of genes can be determined at the protein level, meaning that levels of proteins encoded by the genes discussed above are measured. Several methods and devices are well known for determining levels of proteins including immunoassays such as described in e.g., U.S. Pat. Nos. 6,143,576; 6,113,855; 6,019,944; 5,985,579; 5,947,124; 5,939,272; 5,922,615; 5,885,527; 5,851,776; 5,824,799; 5,679,526; 5,525,524; and 5,480,792. These assays include various sandwich, competitive, or non-competitive assay formats, to generate a signal that is related to the presence or amount of an protein analyte of interest. Any suitable immunoassay may be utilized, for example, lateral flow, enzyme-linked immunoassays (ELISA), radioimmunoassays (RIAs), competitive binding assays, and the like. Numerous formats for antibody arrays have been described proposed employing antibodies. Such arrays typically include different antibodies having specificity for different proteins intended to be detected. For example, usually at least one hundred different antibodies are used to detect one hundred different protein targets, each antibody being specific for one target. Other ligands having specificity for a particular protein target can also be used, such as the synthetic antibodies disclosed in WO/2008/048970. Other compounds with a desired binding specificity can be selected from random libraries of peptides or small molecules. U.S. Pat. No. 5,922,615 describes a device that utilizes multiple discrete zones of immobilized antibodies on membranes to detect multiple target antigens in an array. U.S. Pat. Nos. 5,458,852, 6,019,944, U.S. Pat. No. 6,143,576. Microtiter plates or automation can be used to facilitate detection of large numbers of different proteins. Protein levels can also be determined by mass spectrometry as described in the examples.
The selection of genes for determination of expression levels depends on the particular application (e.g., analysis of CAN/IFTA in general or one of the subtypes described above). In general, the genes are selected from one of the tables indicated above as appropriate for the application. In some methods, expression levels of at least 2, 3, 4, 5, 10, 20, 25, 50, 100, 150, 250 (e.g. 100-250) genes shown in any of Table A, B, C or D are determined. In some methods, expression levels of at least 2, 3, 4, 5, 10, 20, 25, 50, 100, 150, 250 or all genes shown in Table A are determined and/or expression levels of 2, 3, 4, 5, 10, 20, 25, 50 or all genes shown in Table B are determined. In some methods, expression levels of at least 2, 3, 4, 5, 10, 20, 25, or all 50 genes in Table C and at least 2, 3, 4, 5, 10, 20, 25, or all 50 genes in Table D are determined. In some methods, expression levels of 2, 3, 4, 5, 10, 20, 25, 50 or all genes shown in Tables 2, 3, 4, 5 and/or 6 are determined (genes for which both mRNAs and proteins are differentially expressed). In some methods, all genes are from the same table (i.e., all genes with differential expression associated with mild CAN/IFTA). In some methods, genes from different tables (i.e., including genes associated with mild CAN/IFTA and moderate/severe CAN/IFTA) are tested. In some methods, genes are selected such that genes from several different pathways are represented (e.g., at least one gene from at least 2, 3, 5, or 10 pathways, such as those described in the Examples). The genes within a pathway tend to be expressed in a co-ordinated expression whereas genes from different pathways tend to be expressed more independently. Thus, changes in expression based on the aggregate changes of genes from different pathways can have greater statistical significance than aggregate changes of genes within a pathway.
In some methods, expression levels of at least 2, 3, 4, 5, 10, 20, 25, 50, 100, or 150 proteins or corresponding genes shown in any of Tables E, F, G, H, I and/or J are determined. In some methods, expression levels of at least 2, 3, 4, 5, 10, 20, 25, 50, 100, 150 or all proteins or genes shown in Table E, F, and/or G are determined and/or expression levels of 2, 3, 4, 5, 10, 20, 25, 50 or all proteins or genes shown in Tables H, I and/or J are determined. In some methods, proteins or genes are selected from the same table (e.g., proteins uniquely expressed in Banff stage 1, or corresponding genes). In some methods, proteins or genes are selected from two tables (e.g., proteins uniquely expressed in Banff stage 0 (or corresponding genes) and proteins uniquely expressed in Banff stage 1 (or corresponding genes). In some methods, proteins or genes are selected from three tables (e.g., proteins uniquely expressed in Banff stage 0 or corresponding genes, proteins uniquely expressed in Banff stage 1 and corresponding genes, and proteins differentially expressed between Banff stages 1 and 0. Analogous selections of proteins can be made from Tables H-J for purposes of distinguishing Banff stages 0 and 2/3. In some methods, proteins or corresponding genes are selected such that proteins from several different pathways are represented (e.g., at least one gene from at least 2, 3, 5, or 10 pathways, such as those described in the Examples).
Expression levels of the present genes and/or proteins can be combined with or without determination of expression levels of any other genes or proteins of interest (e.g., genes or proteins associated with rejection of kidneys or other organs in WO 2007/104537, WO 2009/060035), Anglicheau et al., PNAS 106, 5330-5335 (2009)) and references, 16, 20, 21, 22, 23, 25, 26, 37 and 39. In some methods, the gene is not DPYD or IRS2 or the method includes determining the expression level of at least 5, 10, 25 or 50 genes other than DPYD and IRS2.
Regardless of the format adopted, the present methods can (but need not) be practiced by detection expression levels of a relatively small number of genes or proteins compared with the whole genome level expression analysis described in the Examples. In some methods, the total number of genes whose expression levels are determined is less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3. In some methods, the total number of genes whose expression level is determined is 100-1500, 100-250, 500-1500 or 750-1250. In some methods, the total number of proteins whose expression levels are determined is less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3. In some methods, the total number of proteins whose expression level is determined is 100-1500, 100-250, 500-1500 or 750-1250. Correspondingly, when an array form is used for detection of expression levels, the array includes probes or probes sets for less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 genes. Thus, for example, an Affymetrix GeneChip® expression monitoring array contains a set if about 20-50 oligonucleotide probes (half match and half-mismatch) for monitoring each gene of interest. Such an array design would include less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 such probes sets for detecting less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 genes. By further example, an alternative array including one cDNA for each gene whose expression level is to be detected would contain less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 such cDNAs for analyzing less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 genes. By further example, an array containing a different antibody for each protein to be detected would containing less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 different antibodies for analyzing less than 5000, 1000, 500, 200, 100, 50, 25, 10, 5 or 3 gene products.
VI. Analysis of Expression Levels
Analysis of expression levels initially provides a measurement of the expression level of each of several individual genes. The expression level can be absolute in terms of a concentration of an expression product, or relative in terms of a relative concentration of an expression product of interest to another expression product in the sample. For example, relative expression levels of genes can be expressed with respect to the expression level of a house-keeping gene in the sample. Relative expression levels can also be determined by simultaneously analyzing differentially labeled samples hybridized to the same array. Expression levels can also be expressed in arbitrary units, for example, related to signal intensity.
The individual expression levels, whether absolute or relative, can be converted into values or other designations providing an indication of presence or risk of CAN/IFTA by comparison with one or more reference points. The principles are first discussed with respect to CAN/IFTA without regarding to subtype. However, the same principles apply for analysis of subtypes except that the gene sets used may be different. For example, mild CAN/IFTA can be determined using genes or proteins from Tables A, C, E, F and/or G. Mid to severe CAN/IFTA can be determine using genes or proteins from Tables B, D, H, I and/or J. Genes or proteins from any of the tables can be used in analyzing CAN/IFTA without regard to subtype. Preferably, genes in both Tables A/C and B/D or proteins occurring in at least one of Tables E-G and at least one of Tables H-J are used for such analysis. Genes or proteins are found in both Banff 1 and Banff 2,3 CAN/IFTA but not found in Banff 0 are also useful in distinguishing the presence of CAN/IFTA in a patient. A combination of genes and/or proteins associated with mild CAN/IFTA and genes and/or proteins associated with mid to severe CAN/IFTA can be used.
The reference points can include a measure of an average expression level of a gene in subjects having had a kidney transplant without CAN/IFTA, and/or an average value of expression levels in subjects having had a kidney transplant with CAN/IFTA. The reference points can also include a scale of values found in kidney transplant patients including patients having and not having CAN/IFTA. The reference points can also or alternatively include a reference value in the subject before kidney transplant, or a reference value in a population of a patients who have not undergone kidney transplant. Such reference points can be expressed in terms of absolute or relative concentrations of gene products as for measured values in a sample.
For comparison between a measured expression level and reference level(s), the measured level sometimes needs to be normalized for comparison with the reference level(s) or vice versa. The normalization serves to eliminate or at least minimize changes in expression level unrelated to CAN/IFTA (e.g., from differences in overall health of the patient or sample preparation). Normalization can be performed by determining what factor is needed to equalize a profile of expression levels measured from different genes in a sample with expression levels of these genes in a set of reference samples from which the reference levels were determined. Commercial software is available for performing such normalizations between different sets of expression levels.
Comparison of the measured expression level of a gene with one or more of the above reference points provides a value (i.e., numerical) or other designation (e.g., symbol or word(s)) of presence or susceptibility to CAN/IFTA. In some methods, a binary system is used; that is a measured expression level of a gene is assigned a value or other designation indicating presence or susceptibility to CAN/IFTA or lack thereof without regard to degree. For example, the expression level can be assigned a value of 1 to indicate presence or susceptibility to CAN/IFTA and −1 to indicate absence or lack of susceptibility to CAN/IFTA. Such assignment can be based on whether the measured expression level is closer to an average level in kidney transplant patients having or not having CAN/IFTA. In other methods, a ternary system is used in which an expression level is assigned a value or other designation indicating presence or susceptibility to CAN/IFTA or lack thereof or that the expression level is uninformative. Such assignment can be based on whether the expression level is closer to the average level in kidney transplant patient undergoing CAN/IFTA, closer to an average level in kidney transplant patients lacking CAN/IFTA or intermediate between such levels. For example, the expression level can be assigned a value of +1, −1 or 0 depending on whether it is closer to the average level in patients undergoing CAN/IFTA, is closer to the average level in patients not undergoing CAN/IFTA or is intermediate. In other methods, a particular expression level is assigned a value on a scale, where the upper level is a measure of the highest expression level found in kidney transplant patients and the lowest level of the scale is a measure of the lowest expression level found in kidney transplant patients at a defined time point at which patients may be susceptible to CAN/IFTA (e.g., one year post transplant). Preferably, such a scale is normalized scale (e.g., from 0-1) such that the same scale can be used for different genes. Optionally, the value of a measured expression level on such a scale is indicated as being positive or negative depending on whether the upper level of the scale associates with presence or susceptibility to CAN/IFTA or lack thereof. It does not matter whether a positive or negative sign is used for chronic ejection or lack thereof as long as the usage is consistent for different genes.
Values or other designation can also be assigned based on a change in expression level of a gene relative to a previous measurement of the expression level of gene in the same patient. Here as elsewhere expression level of a gene can be measured at the protein or nucleic acid level. Such a change can be characterized as being toward, away from or neutral with respect to average expression levels of the gene in kidney transplant patients undergoing or not undergoing CAN/IFTA. For example, a gene whose expression level changes toward an average expression level in kidney transplant patients undergoing CAN/IFTA can be assigned a value of 1 and a gene whose express level changes way from an average expression level in kidney transplant patients undergoing CAN/IFTA and toward an average expression level in kidney transplant patients not undergoing CAN/IFTA can be assigned a value −1. Of course, more sophisticated systems of assigning values are possible based on the magnitude of changes in expression of a gene in a patient.
Having determined values or other designations of expression levels of individual genes providing an indication of presence or susceptibility to chronic ejection or lack thereof, the values or designations are combined to provide an aggregate value for all of the genes being analyzed. If each gene is assigned a score of +1 if its expression level indicates presence or susceptibility to CAN/IFTA and −1 if its expression level indicates absence or lack of susceptibility to CAN/IFTA and optionally zero if uninformative, the different values can be combined by addition. The same approach can be used if each gene is assigned a value on the same normalized scale and assigned as being positive or negative depending whether the upper point of the scale is associate with presence or susceptibility to CAN/IFTA or lack thereof. Other methods of combining values for individual markers of disease into a composite value that can be used as a single marker are described in US20040126767 and WO/2004/059293.
VII. Subtyping
CAN/IFTA can be classified into three subtypes, mild, mid and severe by the Banff scheme. These subtypes differ by histology and severity. The subtypes can be distinguished by the same principles and strategy as just discussed for presence or absence of CAN/IFTA, except that the set of genes whose expression levels is determined may be different for presence and absence of CAN/IFTA overall and each of the subtypes as indicated above. In some methods, one first analyzes CAN/IFTA independent of subtype and then looks at profiles of one or more sets of genes characteristic of one of the above subtypes. In some methods, detection of CAN/IFTA and subtypes are performed simultaneously, for example, by including probes for the sets of genes required for each analysis on the same array. In other methods, analysis of multiple subtypes is performed sequentially or simultaneously and analysis of overall CAN/IFTA is performed by aggregating the results from the different subtypes.
The principles for subtyping are closely analogous to those for analyzing CAN/IFTA independent of subtype. For example, to analyze whether mild CAN/IFTA is present, one determines expression levels of a set of genes whose expression levels are characterized of this subtype (Tables A, C, E, F and/or G). The measured expression levels are then compared with one or more reference levels of the genes. The reference levels can, for example, represent an average expression level of a gene in kidney transplant patients undergoing mild CAN/IFTA with borderline phenotype and an average expression level of the gene in kidney transplant patients not undergoing any kidney rejection, an average expression level of the gene in kidney transplant patients undergoing CAN/IFTA of a different subtype, or an earlier measurement of expression level of the gene in the same patient. The same principles are used for analyzing combined moderate/severe CAN/IFTA except that the set of genes is selected from Tables B, D, H, I and/or J and the reference levels represent an average expression level of a gene in transplant patients undergoing CAN/IFTA with Banff subtype 2 or 3, an average expression level of the gene in kidney transplant patients not undergoing kidney rejection of any kind, an average expression level of the gene in kidney transplant patients undergoing CAN/IFTA of a different subtype, or an earlier measurement of expression level of the gene in the same patient.
If subtyping is performed for both mild CAN/IFTA and moderate/severe CAN/IFTA, the aggregate of the results also indicates overall CAN/IFTA. For example, if the patient is assigned a value or other designation indicating absence or relatively low risk of developing mild CAN/IFTA and a value or other designation indicating absence or relatively low risk of developing moderate/severe CAN/IFTA, then the patient is also indicated as having absence of overall CAN/IFTA and/or a relatively low risk of developing the same. Conversely, if the patient is assigned a value or other designation indicating presence or enhanced risk to either mild CAN/IFTA or mid/severe CAN/IFTA, or both, the patients is also indicated as having presence or enhanced risk of overall CAN/IFTA.
VIII. Diagnosis, Prognosis and Monitoring
The above described methods can provide a value or other designation for a patient which indicates whether the aggregate measured expression levels in a patient is more like kidney transplant patients with or without CAN/IFTA or a subtype thereof. Such a value provides an indication that the patient either has or is at enhanced risk of CAN/IFTA or a subtype thereof, or conversely does not have or is at reduced risk of CAN/IFTA or a subtype thereof. Risk is a relative term in which risk of one patient is compared with risk of other patients either qualitatively or quantitatively. For example, the a value of one patient can be compared with a scale of values for a population of patients having undergone kidney transplant to determine whether the patient's risk relative to that of other patients. In general, diagnosis is the determination of the present condition of a patient (e.g., presence or absence of CAN/IFTA) and prognosis is developing future course of the patient (e.g., risk of developing CAN/IFTA in the future or likelihood of improvement in response to treatment); however, the analyses contemplated by these terms may overlap or even be the same. For example, the present methods alone do not necessarily distinguish between presence and enhanced risk of CAN/IFTA or a subtype thereof. However, these possibilities can be distinguished by additional testing.
If a patient is indicated as having or being at enhanced risk of CAN/IFTA or a subtype thereof, the physician can subject the patient to additional testing including performing a kidney biopsy or performing other analyses such as creatinine, BUN or glomerular filtration rate at increased frequency. Additionally or alternatively, the physician can change the treatment regime being administered to the patient. A change in treatment regime can include administering an additional or different drug, or administering a higher dosage or frequency of a drug already being administered to the patient. Many different drugs are available for treating rejection, such as immunosuppressive drugs used to treat transplant rejection calcineurin inhibitors (e.g., cyclosporine, tacrolimus), mTOR inhibitors (e.g., sirolimus and everolimus), anti-proliferatives (e.g., azathioprine, mycophenolic acid), corticosteroids (e.g., prednisolone and hydrocortisone) and antibodies (e.g., basiliximab, daclizumab, Orthoclone, anti-thymocyte globulin and anti-lymphocyte globulin). Conversely, if the value or other designation of aggregate expression levels of a patient indicates the patient does not have or is at reduced risk of CAN/IFTA, the physician need not order further diagnostic procedures, particularly not invasive ones such as biopsy. Further, the physician can continue an existing treatment regime, or even decrease the dose or frequency of an administered drug.
In some methods, expression levels are determined at intervals in a particular patient (i.e., monitoring). Such methods can provide a series of values changing over time indicating whether the aggregate expression levels in a particular patient are more like the expression levels in patients undergoing CAN/IFTA or not undergoing CAN/IFTA. Movement in value toward or away from CAN/IFTA or a subtype can provide an indication whether an existing immunosuppressive regime is working, whether the immunosuppressive regime should be changed or whether a biopsy or increased monitoring by markers such as creatinine or glomerular filtration rate should be performed.
Information from subtyping analysis can provide further guidance in whether to perform additional diagnostic measures and/or change the immunosuppressive regime administered to a subject. For example, presence or risk of subtype 2 or 3 is more suggestive of performing an additional diagnostic procedure (e.g., biopsy) and/or increasing the rigor of an immunosuppressive regime that is the presence or risk of subtype 1.
IX. Drug Screening
The expression profiles associated with CAN/IFTA (including subtypes) or lack thereof provided by the invention are useful in screening drugs, either in clinical trials or in animal models of CAN/IFTA. A clinical trial can be performed on a drug in similar fashion to the monitoring of a individual patient described above, except that drug is administered in parallel to a population of kidney transplant patients, usually in comparison with a control population administered a placebo.
The changes in expression levels of genes can be analyzed in individual patients and across a treated or control population. Analysis at the level of an individual patient provides an indication of the overall status of the patient at the end of the trial (i.e., whether gene expression profile indicates presence or enhanced susceptibility to CAN/IFTA) and/or an indication whether that profile has changed toward or away from such indication in the course of the trial. Results for individual patients can be aggregated for a population allowing comparison between treated and control population.
Similar trials can be performed in non-human animal models of chronic kidney disease, e.g., the mouse model of Mannon et al., Kidney International (1999) 55, 1935-1944 In this case, the expression levels of genes detected are the species variants or homologs of the human genes referenced above in whatever species of non-human animal on which tests are being conducted. Although the average expression levels of human genes determined in human kidney transplant patients undergoing or not undergoing CAN/IFTA are not necessarily directly comparable to those of homolog genes in an animal model, the human values can nevertheless be used to provide an indication whether a change in expression level of a non-human homolog is in a direction toward or away from CAN/IFTA or susceptibility thereto. The expression profile of individual animals in a trial can provide an indication of the status of the animal at the end of the trial with respect to presence or susceptibility to CAN/IFTA and/or change in such status during the trial. Results from individual animals can be aggregated across a population and treated and control populations compared. Average changes in the expression levels of genes can then be compared between the two populations.
X. Computer Implemented Methods
Expression levels can be analyzed and associated with status of a subject (e.g., presence or susceptibility to chronic kidney infection) in a digital computer. Optionally, such a computer is directly linked to a scanner or the like receiving experimentally determined signals related to expression levels. Alternatively, expression levels can be input by other means. The computer can be programmed to convert raw signals into expression levels (absolute or relative), compare measured expression levels with one or more reference expression levels, or a scale of such values, as described above. The computer can also be programmed to assign values or other designations to expression levels based on the comparison with one or more reference expression levels, and to aggregate such values or designations for multiple genes in an expression profile. The computer can also be programmed to output a value or other designation providing an indication of presence or susceptibility to CAN/IFTA as well as any of the raw or intermediate data used in determining such a value or designation.
A typically computer (see U.S. Pat. No. 6,785,613 FIGS. 4 and 5) includes a bus which interconnects major subsystems such as a central processor, a system memory, an input/output controller, an external device such as a printer via a parallel port, a display screen via a display adapter, a serial port, a keyboard, a fixed disk drive and a floppy disk drive operative to receive a floppy disk. Many other devices can be connected such as a scanner via I/O controller, a mouse connected to serial port or a network interface. The computer contains computer readable media holding codes to allow the computer to perform a variety of functions. These functions include controlling automated apparatus, receiving input and delivering output as described above. The automated apparatus can include a robotic arm for delivering reagents for determining expression levels, as well as small vessels, e.g., microtiter wells for performing the expression analysis.
EXAMPLES
Materials and Methods:
Patient Populations: Test Set 1 comprised 42 kidney transplant patients randomized to either cyclosporine or de novo rapamycin at the Cleveland Clinic, whose clinical courses have been previously, described [15,16,24]. Density gradient-purified peripheral blood lymphocytes (PBL) were collected at the time of protocol two-year biopsies. Test Set 2 comprised 35 patients from 3 clinical centers (St. Vincent's Medical Center, Scripps Clinic, and Cleveland Clinic). All patients were on FK506. Whole blood was collected directly into PaxGene Tubes (PreAnalytix) at the time of biopsies for suspected CAN/IFTA or protocol one-year biopsies. All the studies in this manuscript were covered by Human Subjects Research Protocols approved by each Center's Institutional Review Board and by the IRB of The Scripps Research Institute as the parent institution. Informed consent was obtained from all study subjects in the study.
Pathology: Banff IF/TA grades based on tubulointerstitial features were determined for all patients by kidney biopsies: grade 0 (no evidence CAN/IFTA), 1 (mild CAN/IFTA), and 2 (moderate CAN/IFTA) and 3 (severe CAN/IFTA). We merged patients with Banff 2 and Banff 3 IF/TA to increase numbers. Diagnosis was done first by local pathologists and reviewed in a blinded fashion. C4d staining was only available in the more recently acquired Test Set 2.
Gene expression profiling and analysis: RNA was extracted from Test Set 1 using Trizol (Invitrogen) and in Test Set 2 using Paxgene Blood RNA system (PreAnalytix) and globin transcripts were reduced using GlobinClear (Ambion). Biotinylated cRNA was prepared using Ambion MessageAmp Biotin II (Ambion) and hybridized to Affymetrix Human Genome U133 Plus 2.0 GeneChips. Normalized signals that were generated using a quantile normalization strategy (RMAExpress[25]) were used for class comparisons (ANOVA) and class predictions (BRB Array Tools; linus.nci.nih.gov/BRB-ArrayTools.html). We chose the Diagonal Linear Discriminant Analysis (DLDA) method for class predictions, which is based on maximum likelihood discriminant rules that give consistently good results with our data set and others[26]. Receiver Operating Characteristics (ROC) analysis was done using JROCFIT (rad.jhmi.edu/jeng/javarad/roc/JROCFITi.html). Heatmaps were generated using Cluster and Treeview[27] and functional analysis was performed using Gene Ontology (GO) (geneontology.org/) and Ingenuity Pathway Analysis (IPA). Consensus analysis was designed to identify true classifiers in the two independently collected data sets. Variability between the two test sets within each class (i.e. Banff 1/Test Set 1 vs. Banff 1/Test Set 2) was eliminated by removing all genes with a Student's t-test p-value of <0.05 after which the remaining genes were used to identify consensus candidates by class comparisons. All the microarray data for this study is available for review at the private GEO accession site ncbi.nlm.nih.gov/geo/query/acc.cgi?token=vbgvzkwuggqiqpy&acc=GSE12187.
Shotgun LC/MS/MS proteomics: All protein samples were prepared from density gradient-purified PBL. Individual patient samples were pooled within each Test Set (3 samples/pool) based on Banff classifications and pools were run in triplicates. Total protein was proteolytically digested with trypsin and samples run using Multidimensional Protein Identification Tool (MudPIT) protocol as previously described[28] using an LTQ XL mass spectrometer (ThermoFisher). Raw data were searched against the EBI-IPI_human_12_01_2006 database supplemented with a decoy database where each entry of the original protein contains its reversed sequence. Database searching used SEQUEST (v27)[29] and outcomes were filtered using DTASelect[30]. Relative quantifications were done using spectral counts nothialized to the median of the total spectral counts[31]. Pair-wise comparisons between CAN/IFTA biopsy classes were done by differentially expressed proteins (Student's t-test, p≦0.05) and as all-or-none/unique events.
Results:
Study Population
Recipients in both Test Sets were sex and age matched (Table 1). The only significant differences in Test Set 1 were Donor age between Banff 0 and Banff 1 groups. In Test Set 2 there were significant differences in induction therapy between Banff 0 and Banff 1 and between Banff 0 and the Banff 2,3; time to biopsy between Banff 0 and Banff 1 and between Banff 0 and the Banff 2,3; and steroid use between Banff 0 and Banff 1 and between Banff 0 and Banff 2,3. Only the Banff 2,3 group in Test Set 2 had a significantly higher serum creatinine compared to the Banff 0, thus, renal function levels per se were not a major determinant of the gene profiles. The higher creatinine levels in the Banff 2,3 group of Test Set 2 most likely reflect the fact that this group was “biopsy for cause,” whereas Test Set 1 were all protocol biopsies done regardless of any renal function change. However, by design, the two Test Sets differed significantly in recipient age, HLA mismatch, induction therapy, clinical center, immunosuppression, serum creatinines, and time to biopsy.
Gene Expression Profiling of Mild CAN/IFTA
We performed ANOVA-based class comparisons between Banff 0 (no histological evidence of CAN/IFTA) and Banff 1 (mild CAN/IFTA). At p-values<0.005, 1066 genes (1307 probe sets) were differentially expressed. Annotation of function by Gene Ontology (GO) shows 8 categories comprised of >25 genes each including 58 genes linked to immunity and inflammation. The percentage of genes in each category was immune/inflammatory 5%, apoptosis, 4%, cell adhesion 3%, signal transduction 5%, regulation of transcription 6%, protein phosphorylation 3%, cell cycle 3%, metabolism 11%, other functions 40%, unknown functions 20%. IPA shows that these 1066 genes fall into 27 networks with >15 genes per network. The top network was immune response and two additional networks in the top 10 were also immune response with 27 and 22 focus genes, respectively. The top canonical pathway was Toll-like Receptor Signaling followed by SAPK/JNK, Apoptosis, Notch and Death Receptor and Interferon Signaling. Finding 1066 significantly differentially expressed genes is a first indication that PBL transcript profiling is capable of classifying subjects defined by CAN/IFTA biopsy histology. Class prediction using DLDA demonstrates 90% mean correct classification[32,33]. Supervised hierarchical clustering shows misclassification of only 2 samples.
Based on gene expression profiles of the whole blood samples in Test Set 2, there were 1429 genes (1591 probe sets) differentially expressed at p-values<0.005. GO annotation of gene functions revealed the same groups as PBL including 50 immune response genes. The percentage of genes in each category was immune/inflammatory 4%, apoptosis, 2%, cell adhesion 2%, signal transduction 8%, regulation of transcription 6%, protein phosphorylation 1%, cell cycle 1%, metabolism 4%, other functions 35%, unknown functions 37%. IPA reveals 30 networks with ≧15 genes per network. The top canonical pathways were: B Cell Receptor, Toll-like Receptor, Death Receptor, Chemokine, Glucocorticoid Receptor, and IL-4 Signaling. DLDA demonstrates 88% mean correct classification. Supervised hierarchical clustering shows misclassification of only 1 sample.
A consensus analysis for Banff 0 vs. Banff 1 was performed with these two independently collected data sets by a class comparison at p-values<0.005 and identified 393 genes (424 probe sets) significantly differentially expressed in both data sets. This “consensus” gene list represents the intersection of these two significantly different test sets classifying mild CAN/IFTA by blood transcription profiling. We then combined all the samples of both Test Sets (n=55) and performed class predictions using the top 50 differentially expressed, consensus genes ranked by p values to obtain a class prediction accuracy of 80% depicted as a ROC curve (FIG. 1). A heat map classifying Banff 0 vs. Banff 1 using the 50 genes shows there are large “blocks” of up- or down-regulated genes that classify the Banff 0 vs. Banff 1 (mild CAN/IFTA). However, signatures of multiple genes are advantageous to achieve high class predictive accuracies in heterogeneous clinical populations that are the reality of transplantation medicine. We took the top 10 and top 3 genes from our consensus set for mild CAN/IFTA and performed class prediction using the DLDA method. The top 10 had a predictive accuracy of 80%, sensitivity of 85% and specificity of 77%, whereas the top 3 genes had a predictive accuracy of 80%, sensitivity of 74% and specificity of 86%.
Gene Expression Profiling of Moderate/Severe CAN/IFTA
Class comparisons between Banff 0 and Banff 2,3 identified genes differentially expressed between patients without CAN/IFTA and those with moderate to severe CAN/IFTA. In Test Set 1, 172 genes were differentially expressed (p<0.005) and classified the samples by DLDA with 78% accuracy. In Test Set 2 there were 545 differentially expressed genes. DLDA classified 95% of the samples accurately. The percentage of genes in each category for sets 1 and 2 was immune/inflammatory 4%, 3%, apoptosis, 2%, 3%, cell adhesion 2%, 3%, signal transduction 8%, 7%, regulation of transcription 6%, 8%, protein phosphorylation 1%, 3%, cell cycle 1%, 1%, metabolism 4%, 6% other functions 33%, 30%, unknown functions 37%, 36%. A consensus analysis was done as already described to yield 62 differentially expressed genes (p<0.005) shared for both Test Sets of moderate/severe CAN/IFTA (n=49). The ROC curve for the top 50 genes from this consensus gene set shows a class prediction accuracy of 92% (FIG. 2).
Proteomic Expression of Mild and Moderate/Severe CAN/IFTA
To investigate using proteomics to define blood cell biomarkers for CAN/IFTA, we performed shotgun tandem mass spectrometry. All samples represented purified PBL obtained at the same time as biopsies. We did not use the whole blood samples from Test Set 2 because high quality protein preparations cannot be obtained from PaxGene tubes. Differential protein expression was performed using a relative quantification strategy based on normalized spectral counts [31]. We identified 206 differentially expressed proteins (p<0.05) for Banff 0 vs. Banff 1 (mild CAN/IFTA). In addition, we identified 135 proteins unique to Banff 0 and 167 proteins unique to Banff 1. Class comparisons for Banff 0 vs. Banff 2,3 (moderate/severe CAN/IFTA) yielded 282 differentially expressed proteins (p<0.05) and 509 proteins unique to Banff 2,3. We found 95 proteins differentially expressed in mild and moderate/severe CAN/IFTA as compared to Banff 0, representing candidate protein markers for any stage of CAN/IFTA. In parallel, 94 proteins were differentially expressed only in mild CAN/IFTA and these were linked to cell death, cell signaling, and post-translational protein modifications. The 168 proteins differentially expressed only in moderate/severe CAN/IFTA were linked to cellular morphology, growth and proliferation and signaling via ERK/MAPK, acute phase responses, IGF1 and PPARa/RXRa.
There were 135 proteins unique to mild CAN/IFTA and 322 proteins unique to moderate/severe CAN/IFTA. Both mild and moderate/severe CAN/IFTA had immune and inflammation related proteins (20 and 37, respectively) but many of these proteins are not mapped to the same functional pathways (e.g. calcium signaling in mild CAN/IFTA and apoptosis, NK cell and PTEN signaling for moderate/severe CAN/IFTA). In other cases, such as signaling via T and B cell receptors, IL4 and JAK/STAT, the same canonical pathways were found but different unique proteins were identified.
Using only the differentially expressed proteins, DLDA obtained a 64% mean correct classification of mild CAN/IFTA and an 83% correct classification for moderate/severe CAN/IFTA. In contrast, the unique proteins identified only in the blood of patients with biopsy-documented mild (n=135) or moderate/severe CAN/IFTA (n=322), represent candidate biomarkers with a 100% class prediction value in this data set.
We compiled the matches between proteins identified by mass spectrometry and mRNA transcripts identified using microarrays. The premise is that protein/transcript matches are a form of candidate biomarker validation based on two independent technologies. There were 11 matches for the 393 consensus genes for mild CAN/IFTA, 32 matches for the 1066 genes for mild CAN/IFTA in Test Set 1 and 40 matches for the 1429 genes for mild CAN/IFTA in Test Set 2. There were no matches for the 62 consensus genes for moderate/severe CAN/IFTA but 9 matches in the 172 genes for moderate/severe CAN/IFTA in Test Set 1 and 9 matches in the 545 genes for moderate/severe CAN/IFTA in Test Set 2. All protein/transcript matches are listed in Tables 2-6.
Discussion
The primary objective of this study (also reported as [40]) was the discovery of biomarkers in the peripheral blood of kidney transplant patients with biopsy-documented interstitial fibrosis and tubular atrophy (IF/TA) and no known cause, which we refer to here as Chronic Allograft Nephropathy (CAN/IFTA)[14]. To this end, we integrated the results of two, independently collected sets of patient samples that were significantly different in multiple clinical elements. Thus, the selection of biomarker candidates was not significantly influenced by the time of biopsy (ranging from 1 to 6 years post-transplant), the specific immunosuppressive protocols (use of different calcineurin inhibitors vs. sirolimus) or the technology used to purify the mRNA transcripts (density gradient-separated cells vs. whole blood). This experimental design was chosen for its advantages in defining a consensus set of robust candidate biomarkers for CAN/IFTA suitable for clinical use.
Using more closely matched sets of patient samples, for example, patients only 2 years post-transplant or only one source of blood cell RNA such as the PaxGene tubes might have resulted in higher total numbers of differentially expressed candidate mRNA transcripts and proteins. However, classifications for CAN/IFTA based on the consensus mRNA candidates described here for these otherwise very heterogeneous clinical data sets are 80% for mild CAN/IFTA and 92% for moderate/severe CAN/IFTA. By contrast, the widely used prostate specific antigen (PSA) biomarker, tested in an equally heterogenous human population, was originally introduced with a predictive value of 28-35%[34] because there was no other minimally invasive option for early detection of prostate cancer at that time, which is true for CAN/IFTA today.
We obtain very reasonable predictive accuracy, sensitivity and specificity with 150, 100 and 50 total genes per signature. There are now several technology platforms perfectly suitable for point of clinical service implementation that can measure 100 genes or more cost effectively and within hours. In clinical practice, the differentially expressed genes and proteins can be used for serial, prospective measurements of the signature at regular intervals for the life of the kidney transplant. The absence of a positive CAN/IFTA signature at any point in time will indicate adequate immunosuppression or over-immunosuppression. Careful reductions in immunosuppressive drug doses can then be used with repeat monitoring of the signature to establish the optimal drug combination and level for each patient to prevent CAN/IFTA and ensure the long term safety of the therapy.
Biomarker discovery has been reported using peripheral blood profiling for acute rejection in heart transplantation[35,36]. Peripheral blood studies of kidney transplant patients with “operational tolerance” included 22 patients with biopsy-documented CAN/IFTA[37]. Two of the genes (DPYD, IRS2) reported to distinguish “operational tolerance” are identified in our consensus sets. Our earlier study of 42 kidney biopsies showed that gene expression profiles of CAN/IFTA had significant up-regulation of immune/inflammation, fibrosis and tissue remodeling genes[16]. However, only 5 genes from these CAN/IFTA biopsies were identified in the current peripheral blood consensus sets. A study of 11 CAN/IFTA biopsies identified 3 genes linked to immunity and fibrosis that were tested by quantitative PCR in urine and peripheral blood with good correlations in urine but none in peripheral blood[38]. Therefore, gene biomarkers identified in peripheral blood are mostly distinct from those identified in tissue.
Although practice of the invention is not dependent on an understanding of mechanism, we propose that the peripheral blood represents a fully functional and distinct compartment of the immune system that actively serves to traffic and modulate all the components of effector immunity. Although the tissue injury that causes the progression of CAN/IFTA is occurring in the kidney, we believe that a significant determinant of the phenotype of the host immune response, either acceptance of the graft or CAN/IFTA, is actually established and subsequently regulated within the peripheral blood compartment, lymph nodes and spleen.
Urine based proteomics have been used to report biomarkers for acute rejection using SELDI-TOF mass spectroscopy[23,39] but to our knowledge this is the first study to identify blood cell-based proteomic markers for transplantation using tandem mass spectroscopy. We have identified several hundred proteins that are significantly differentially expressed in peripheral blood of patients with CAN/IFTA as a function of histology grade, mild to moderate/severe. The group of uniquely identified proteins potentially represents the highest value biomarker candidates giving 100% accuracy in our tests. Integrating proteomics with gene expression, we identified over 80 protein/transcript matches for CAN/IFTA providing candidate validation based on two independent technologies. However, genes in which differential expression is found only at the gene or protein level but not both also allow accurate analyses.
Although the invention has been described with reference to the presently preferred embodiments, it should be understood that various modifications can be made without departing from the invention. Unless otherwise apparent from the context any step, element, embodiment, feature or aspect of the invention can be used with any other.
All publications (including GenBank Accession numbers, UniProtKB/Swiss-Prot accession numbers and the like), patents and patent applications cited are herein incorporated by reference in their entirety for all purposes to the same extent as if each individual publication, patent and patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes. In the event of any variance in sequences associated with Genbank, Unigene, International Protein Index, Entrez, UniProtKB/Swiss-Prot accession numbers and the like, the application refers to the sequences associated with the cited accession numbers as of Jul. 9, 2009.
REFERENCES


    1. Meier-Kriesche (2001) J Am Soc Nephrol 12: 1293-1296.
    2. Nankivell (2003) N Engl J Med 349: 2326-2333.
    3. Pascual (2002) N Engl J Med 346: 580-590.
    4. Solez (2008) Am J Transplant 8: 753-760.
    5. Racusen (1999) Kidney Int 55: 713-723.
    6. Solez K, (2007) Am J Transplant 7: 518-526.
    7. Banasik M, Klinger M (2006) Ann Transplant 11: 7-10.
    8. Yates (2006) Transpl Immunol 16: 148-157.
    9. Caine (1978) Lancet 2: 1323-1327.
    10. de Mattos (2000) Am J Kidney Dis 35: 333-346.
    11. Jevnikar (2008) Clin J Am Soc Nephrol 3 Suppl 2: S56-67.
    12. Pascual. (1998) Immunol Today 19: 514-519.
    13. Nankivell (2006) Transplantation 81: 643-654.
    14. Colvin RB (2003) N Engl J Med 349: 2288-2290.
    15. Flechner (2007) Transplantation 83: 883-892.
    16. Flechner (2004) Am J Transplant 4: 1776-1785.
    17. Yilmaz (2007) Transpl Int 20: 608-615.
    18. Lachenbruch (2004) Am J Transplant 4: 451-457.
    19. Pascual (1999) Transplantation 67: 737-741.
    20. Kurian (2005) Current Opinion in Organ Transplantation 10: 193-197.
    21. Kurian (2007) Int Immunopharmacol 7: 1948-1960.
    22. Oetting (2006) Am J Kidney Dis 47: 898-904.
    23. Schaub (2005) Am J Transplant 5: 729-738.
    24. Flechner (2004) Am J Transplant 4: 1475-1489.
    25. Bolstad (2003) Bioinformatics 19: 185-193.
    26. Dudoit (2002) Journal of the American Statistical Association 97: 77-87.
    27. Eisen (1998) Proc Natl Acad Sci USA 95: 14863-14868.
    28. Washburn (2001) Nat Biotechnol 19: 242-247.
    29. Sadygov (2002) J Proteome Res 1: 211-215.
    30. Tabb (2002) J Proteome Res 1: 21-26.
    31. Liu (2004) Anal Chem 76: 4193-4201.
    32. Guo (2007) Biostatistics 8: 86-100.
    33. Huang (2006) Pediatr Blood Cancer 46: 728-738.
    34. Woolf (1995) N Engl J Med 333: 1401-1405.
    35. Deng (2006) Am J Transplant 6: 150-160.
    36. Horwitz (2004) Circulation 110: 3815-3821.
    37. Brouard (2007) Proc Natl Acad Sci USA 104: 15448-15453.
    38. Mas (2007) Transplantation 83: 448-457.
    39. Clarke (2003) Ann Surg 237: 660-664; discussion 664-665.
    40. Kurian et al., PLoS One. 2009 Jul. 10; 4(7):e6212









TABLE 1







Clinical Characteristics of the Study Populations.













Test Set 1





vs.



Test Set 1
Test Set 2
Test Set 2




















Signifi-



Signifi-
Signifi-



Banff 0
Banff 1
Banff 2, 3
cance
Banff 0
Banff 1
Banff 2, 3
cance
cance




















Number
18
15
9
NA
8
14
13
NA
NS


Recipient age
42.61 ± 12.8
48.47 ± 11.6
45.67 ± 17.5
NS
56.88 ± 12.2
51.36 ± 12.6
49.08 ± 12.9
NS
Banff0 =











0.01


Recipient
38.9
20
44.4
NS
62.5
35.7
53.8
NS
NS


gender


(% female)


Recipient race
22.22
13.33
11.11
NS
0
14.3
7.7
NS
NS


African


American


Pre tx diabetes
16.7
26.7
22.2
NS
25
14.3
7.7
NS
NS


PRA >20% (%)
5.6
6.7
11.1
NS
12.5
7.1
15.4
NS
NS


HLA mismatch
3.06 ± 1.7
2.66 ± 1.6
2.67 ± 2.2
NS
3.43 + 2.4
4.33 + 1.4
3.58 + 1.6
NS
Banff1 =











0.008


Deceased donor
55.6
73.3
77.8
NS
75
71.4
46.2
NS
NS


% re-transplant
0
0
0
—
0
14.3
15.4
NS
NS


Donor age
32.39 ± 15.7
42.33 ± 11.8
37.11 ± 12.1
Banff0 vs.
31.25 ± 19.3
41.54 ± 17.7
44.62 ± 13.4
NS
NS






Banff1






p = 0.05


Donor gender
50
53.3
33.3
NS
12.5
57
53.8
NS
NS


female


Donor race
16.7
13.3
11.1
NS
0
7.1
7.7
NS
NS


African


American


Induction
100
100
100
NS
75
21.4
23.1
Banff0 vs.
Banff1 =










Banff1
0.0001










p = 0.026;
Banff2, 3 =










Banff0 vs.
0.0005










Banff2, 3










p = 0.032


Serum
 1.32 ± 0.38
 1.45 ± 0.51
 1.84 ± 0.77
NS
1.70 + 1.3
2.41 + 0.7
3.09 + 1.2
Banff0 vs.
Banff1 =


Creatinine







Banff2, 3
0.0002










p = 0.025
Banff2, 3 =











0.007


Time to Biopsy
 755 ± 101
 710 ± 109
 659 ± 133
NS
 420 ± 309
 1664 ± 1364
 2398 ± 1120
Banff0 vs.
Banff0 =










Banff1
0.05










p = 0.005;
Banff 1 =










Banff0 vs.
0.02










Banff2, 3
Banff2, 3 =










p = 0.00002
0.0001


CNI
38.9
60
77.8
NS
100
100
84.6
NS
Banff0 =











0.007


MMF
100
93.3
88.9
NS
75
78.6
76.9
NS
NS


Steroids
100
100
100
NS
37.5
100
92.3
Banff0 vs.
Banff1 =










Banff1
0.0009










p = 0.0002;










Banff0 vs.










Banff2, 3










p = 0.0022


C4d+ staining*
ND
ND
ND
NA
NA
2
3
NS
NA





ND—Not Done


NA—Not Applicable


NS—Not Significant













TABLE A







Differentially expressed consensus genes for mild CAN for both Test


Mild CAN = CAN Banff Class 1; No evidence of CAN = CAN Banff Class 0


Probesets with positive fold changes are upregulated in mild CAN

















Geom








Geom mean
mean of




of intensities
intensities



Parametric
in class 1:
in class 2:
Fold



p-value
Banff 0
Banff 1
Change
Probe Set ID
Gene Symbol
Gene Title

















1
0.000002
27.9
19.3
−1.45
203796_s_at
BCL7A
B-cell CLL/lymphoma 7A


2
2.1E−06
11.6
16.7
1.44
233650_at
CEP63
centrosomal protein 63 kDa


3
3.2E−06
50.5
40.1
−1.26
1552892_at
TNFRSF13C
tumor necrosis factor receptor superfamily, member









13C


4
5.9E−06
19.2
33.6
1.75
1565597_at
EST1
Homo sapiens, clone IMAGE: 4275461, mRNA


5
8.3E−06
15.1
23.5
1.56
241752_at
SLC8A1
solute carrier family 8 (sodium/calcium exchanger),









member 1


6
1.25E−05
803.7
1050.5
1.31
213702_x_at
ASAH1
N-acylsphingosine amidohydrolase (acid ceramidase) 1


7
1.61E−05
224.8
174.8
−1.29
223259_at
ORMDL3
ORM1-like 3 (S. cerevisiae)


8
1.84E−05
135.4
189.9
1.40
204054_at
PTEN
phosphatase and tensin homolog (mutated in multiple









advanced cancers 1)


9
1.86E−05
26
46
1.77
239012_at
IBRDC2
IBR domain containing 2


10
2.39E−05
1182
1724.7
1.46
200975_at
PPT1
Palmitoyl-protein thioesterase 1 (ceroid-lipofuscinosis,









neuronal 1, infantile)


11
0.000024
174.3
363.5
2.09
206584_at
LY96
Lymphocyte antigen 96


12
3.35E−05
9
7.6
−1.18
228044_at
C13orf21
Chromosome 13 open reading frame 21


13
4.41E−05
250.1
327.6
1.31
225492_at
EST2
—


14
4.53E−05
7828
10660.2
1.36
202917_s_at
S100A8
S100 calcium binding protein A8


15
0.000047
374.1
724.5
1.94
223501_at
TNFSF13B
Tumor necrosis factor (ligand) superfamily, member









13b


16
4.75E−05
112.7
204
1.81
222496_s_at
FLJ20273
RNA-binding protein


17
5.11E−05
22.4
38.8
1.73
224996_at
EST3
CDNA FLI39064 fis, clone NT2RP7014583


18
5.13E−05
21.6
17.5
−1.23
244863_at
EST4
Transcribed locus


19
0.000052
7.5
9
1.20
238791_at
ZNF100
Zinc finger protein 100


20
5.66E−05
85.2
123.8
1.45
218177_at
CHMP1B
Chromatin modifying protein 1B


21
5.67E−05
203.3
336.4
1.65
226208_at
ZSWIM6
Zinc finger, SWIM-type containing 6


22
7.26E−05
180.8
237.2
1.31
203778_at
MANBA
Mannosidase, beta A, lysosomal


23
0.000089
86.6
123.4
1.42
238903_at
LOC137886
Hypothetical protein LOC137886


24
0.000094
19.7
14.5
−1.36
214308_s_at
HGD
Homogentisate 1,2-dioxygenase (homogentisate









oxidase)


25
0.000103
492.9
744.6
1.51
211368_s_at
CASP1
Caspase 1, apoptosis-related cysteine peptidase









(interleukin 1, beta, convertase)


26
0.000103
132.8
184.8
1.39
227017_at
ERICH1
Glutamate-rich 1


27
0.000107
10.3
15.5
1.50
228624_at
TMEM144
Transmembrane protein 144


28
0.000108
128.7
170.2
1.32
232149_s_at
NSMAF
Neutral sphingomyelinase (N-SMase) activation









associated factor


29
0.000112
26.4
35.2
1.33
243287_s_at
OSTM1
Osteopetrosis associated transmembrane protein 1


30
0.000116
59.5
134.7
2.26
1552773_at
CLEC4D
C-type lectin domain family 4, member D


31
0.000121
2887.4
3972.4
1.38
202902_s_at
CTSS
Cathepsin S


32
0.000125
142.4
229
1.61
211744_s_at
CD58
CD58 molecule


33
0.000133
35.6
26.9
−1.32
243507_s_at
C20orf196
Chromosome 20 open reading frame 196


34
0.000137
101.9
77.4
−1.32
228832_at
FLJ20021
Hypothetical LOC90024


35
0.000149
1057.6
1433.5
1.36
202727_s_at
IFNGR1
Interferon gamma receptor 1


36
0.000169
40.5
55.5
1.37
213952_s_at
ALOX5
Arachidonate 5-lipoxygenase


37
0.000174
364.6
288.1
−1.27
219045_at
RHOF
Ras homolog gene family, member F (in filopodia)


38
0.000175
666
974.1
1.46
212268_at
SERPINB1
Serpin peptidase inhibitor, clade B (ovalbumin),









member 1


39
0.00018
80.3
119.4
1.49
203276_at
LMNB1
Lamin B1


40
0.00019
347.2
814.1
2.34
219666_at
MS4A6A
Membrane-spanning 4-domains, subfamily A, member









6A


41
0.000204
54.9
110.9
2.02
204860_s_at
NAIP ///
NLR family, apoptosis inhibitory protein /// neuronal








NAIP1B
apoptosis inhibitory protein (centromeric)


42
0.000212
3812.4
4958.6
1.30
202388_at
RGS2
Regulator of G-protein signaling 2, 24 kDa


43
0.000226
24.5
43.9
1.79
1553514_a_at
VNN3
Vanin 3


44
0.000239
84.6
108.3
1.28
218364_at
LRRFIP2
Leucine rich repeat (in FLII) interacting protein 2


45
0.000242
15.5
21.5
1.39
218888_s_at
NETO2
Neuropilin (NRP) and tolloid (TLL)-like 2


46
0.000258
64.6
87.8
1.36
204108_at
NFYA
Nuclear transcription factor Y, alpha


47
0.000273
35.6
50.1
1.41
213935_at
ABHD5
Abhydrolase domain containing 5


48
0.000278
54
75.5
1.40
208883_at
UBR5
Ubiquitin protein ligase E3 component n-recognin 5


49
0.000282
334.9
425
1.27
222148_s_at
RHOT1
Ras homolog gene family, member T1


50
0.000284
564.8
712.6
1.26
227266_s_at
FYB
FYN binding protein (FYB-120/130)


51
0.000287
75.4
138.6
1.84
204714_s_at
F5
Coagulation factor V (proaccelerin, labile factor)


52
0.000302
6.3
5.6
−1.13
229777_at
CLRN3
Clarin 3


53
0.000302
16.9
19.2
1.14
241073_at
EST5
Transcribed locus


54
0.000309
29.8
52.7
1.77
1558549_s_at
VNN1
Vanin 1


55
0.000319
584.3
710
1.22
201007_at
HADHB
Hydroxyacyl-Coenzyme A dehydrogenase/2-ketoacyl-









Coenzyme A thiolase/enoyl-Coenzyme A hydratase









(trifunctional protein), beta subunit


56
0.000323
9
7.8
−1.15
241171_at
EST6
Transcribed locus


57
0.000328
18.4
33.5
1.82
239759_at
EST7
Transcribed locus


58
0.000368
44.5
76.4
1.72
209684_at
RIN2
Ras and Rab interactor 2


59
0.000369
22.6
18.4
−1.23
240654_at
EST8
Transcribed locus


60
0.00037
356
693
1.95
217738_at
PBEF1
Pre-B-cell colony enhancing factor 1


61
0.000377
48.8
73.7
1.51
228540_at
QKI
Quaking homolog, KH domain RNA binding (mouse)


62
0.000386
24.1
20
−1.21
221261_x_at
MAGED4 ///
Melanoma antigen family D, 4B///melanoma antigen








MAGED4B
family D, 4


63
0.000393
8.3
9.9
1.19
1562458_at
UBE2W
Ubiquitin-conjugating enzyme E2W (putative)


64
0.000399
28.9
40.2
1.39
227403_at
PIGX
Phosphatidylinositol glycan anchor biosynthesis, class X


65
0.000406
21.6
27.6
1.28
226827_at
TMEM165
Transmembrane protein 165


66
0.000418
61.4
54.1
−1.13
1568691_at
EST9
CDNA clone IMAGE: 3613441


67
0.000444
31
51.9
1.67
230343_at
EST10
Transcribed locus


68
0.000445
10.3
8.2
−1.26
212650_at
EHBP1
EH domain binding protein 1


69
0.000448
168.6
306.1
1.82
238066_at
RBP7
Retinol binding protein 7, cellular


70
0.000451
69.6
97.7
1.40
213292_s_at
SNX13
Sorting nexin 13


71
0.000463
38.7
63.7
1.65
228362_s_at
FAM26F
Family with sequence similarity 26, member F


72
0.000477
30
23.6
−1.27
236139_at
EST11
Transcribed locus


73
0.000486
15.4
20.2
1.31
220775_s_at
UEVLD
UEV and lactate/malate dehydrogenase domains


74
0.000493
55.2
46.9
−1.18
221189_s_at
TARS2
Threonyl-tRNA synthetase 2, mitochondrial (putative)


75
0.000497
24.5
20
−1.23
210150_s_at
LAMA5
Laminin, alpha 5


76
0.000509
49.3
41.2
−1.20
211304_x_at
KCNJ5
Potassium inwardly-rectifying channel, subfamily J,









member 5


77
0.000524
5.4
4.7
−1.15
233609_at
PTPRK
Protein tyrosine phosphatase, receptor type, K


78
0.000538
12.2
17.6
1.44
202422_s_at
ACSL4
Acyl-CoA synthetase long-chain family member 4


79
0.000539
360.3
442.2
1.23
225284_at
DNAJC3 ///
DnaJ (Hsp40) homolog, subfamily C, member








LOC144871
3///hypothetical protein LOC144871


80
0.000549
10.4
8.7
−1.20
204983_s_at
GPC4
Glypican 4


81
0.000555
15.5
13.4
−1.16
231318_at
C15orf51
Chromosome 15 open reading frame 51


82
0.000564
59.4
83.9
1.41
208158_s_at
OSBPL1A
Oxysterol binding protein-like 1A


83
0.000571
9.2
8.1
−1.14
205542_at
STEAP1
Six transmembrane epithelial antigen of the prostate 1


84
0.000573
186.9
235.8
1.26
218905_at
INTS8
Integrator complex subunit 8


85
0.000588
100.3
177.5
1.77
212820_at
DMXL2
Dmx-like 2


86
0.000594
160.5
341.8
2.13
215049_x_at
CD163
CD163 molecule


87
0.000595
20.8
34.4
1.65
206674_at
FLT3
Fms-related tyrosine kinase 3


88
0.000595
52.3
40.2
−1.30
233487_s_at
LRRC8A
Leucine rich repeat containing 8 family, member A


89
0.000607
17.5
21.1
1.21
33197_at
MYO7A
Myosin VIIA


90
0.000642
26.5
23.5
−1.13
203793_x_at
PCGF2
Polycomb group ring finger 2


91
0.000648
9.1
8.2
−1.11
1566935_at
TYRO3P
TYRO3P protein tyrosine kinase pseudogene


92
0.000663
10.8
15.2
1.41
203767_s_at
STS
Steroid sulfatase (microsomal), isozyme S


93
0.000668
303.5
421.8
1.39
226136_at
GLIPR1
GLI pathogenesis-related 1 (glioma)


94
0.00067
52.1
81.1
1.56
216252_x_at
FAS
Fas (TNF receptor superfamily, member 6)


95
0.000694
244.7
420.5
1.72
221724_s_at
CLEC4A
C-type lectin domain family 4, member A


96
0.000696
11.6
13.1
1.13
230419_at
FLJ37644
Hypothetical gene supported by AK094963


97
0.000701
26.8
33.2
1.24
225778_at
FUT1
Fucosyltransferase ! (galactoside 2-alpha-L-









fucosyltransferase, H blood group)


98
0.000702
14.8
10.3
−1.44
216063_at
HBBP1
Hemoglobin, beta pseudogene 1


99
0.000745
6.9
6.2
−1.11
207516_at
CHRNB4
Cholinergic receptor, nicotinic, beta 4


100
0.000749
21.8
17.3
−1.26
216910_at
XPNPEP2
X-prolyl aminopeptidase (aminopeptidase P) 2,









membrane-bound


101
0.00075
14.7
12.5
−1.18
1555655_at
OR10A4
Olfactory receptor, family 10, subfamily A, member 4


102
0.000755
266.1
339
1.27
225606_at
BCL2L11
BCL2-like 11 (apoptosis facilitator)


103
0.000768
17
14.8
−1.15
207967_at
VPS45
Vacuolar protein sorting 45 homolog (S. cerevisiae)


104
0.000775
253.9
336.8
1.33
219079_at
CYB5R4
Cytochrome b5 reductase 4


105
0.000803
94.6
134.1
1.42
222498_at
AZI2
5-azacytidine induced 2


106
0.00081
570.4
686.2
1.20
210817_s_at
CALCOCO2
Calcium binding and coiled-coil domain 2


107
0.00082
344.4
494.4
1.44
211404_s_at
APLP2
Amyloid beta (A4) precursor-like protein 2


108
0.000824
9.6
16.4
1.71
1562481_at
EST12
—


109
0.000834
78.3
105.7
1.35
203693_s_at
E2F3
E2F transcription factor 3


110
0.00084
23.2
33.6
1.45
205841_at
JAK2
Janus kinase 3 (a protein tyrosine kinase)


111
0.000847
10.2
9.1
−1.12
1553504_at
MRGPRX4
MAS-related GPR, member X4


112
0.00085
140.6
212.9
1.51
203139_at
DAPK1
Death-associated protein kinase 1


113
0.000864
186.1
235.2
1.26
226850_at
SUMF1
Sulfatase modifying factor 1


114
0.000896
4.9
5.4
1.10
230684_at
GTPBP10
GTP-binding protein 10 (putative)


115
0.000907
34.8
21.7
−1.60
228802_at
RBPMS2
RNA binding protein with multiple splicing 2


116
0.000969
7.6
6.8
−1.12
204596_s_at
STC1
Stanniocalcin 1


117
0.000972
45.3
57
1.26
228061_at
CCDC126
Coiled-coil domain containing 126


118
0.000979
31.4
22.6
−1.39
244876_at
EST13
—


119
0.000992
12.4
10.7
−1.16
233015_at
MBNL1
Muscleblind-like (Drosophila)


120
0.001033
21.6
14.5
−1.49
234284_at
GNG8
Guanine nucleotide binding protein (G protein),









gamma 8


121
0.001036
38.2
24.8
−1.54
1560262_at
EST14
Homo sapiens, clone IMAGE: 5751523, mRNA


122
0.001037
5.4
4.8
−1.13
1562902_at
EST15
Homo sapiens, clone IMAGE: 5176738, mRNA


123
0.001045
1215.1
2084.9
1.72
205863_at
S100A12
S100 calcium binding protein A12


124
0.001057
37.8
31.9
−1.18
222302_at
EST16
—


125
0.001065
44.9
51.1
1.14
212932_at
RAB3GAP1
RAB3 GTPase activating protein subunit 1 (catalytic)


126
0.001066
36.3
49.6
1.37
233924_s_at
EXOC6
Exocyst complex component 6


127
0.001087
34.5
41.5
1.20
230209_at
EST17
CDNA FLI36477 fis, clone THYMU2017158


128
0.001103
498.4
419.3
−1.19
41047_at
C9orf16
Chromosome 9 open reading frame 16


129
0.001136
57.1
40.8
−1.40
200884_at
CKB
Creatine kinase, brain


130
0.001137
177
245.9
1.39
219157_at
KLHL2
Kelch-like 2, Mayven (Drosophila)


131
0.001153
7.3
6.4
−1.14
207818_s_at
HTR7
5-hydroxytryptamine (serotonin) receptor 7









(adenylate cyclase-coupled)


132
0.001162
13.3
16.1
1.21
234977_at
ZADH2
Zinc binding alcohol dehydrogenase, domain









containing 2


133
0.001164
4.6
4.3
−1.07
238391_at
EST18
Transcribed locus


134
0.001173
125.2
160.3
1.28
222759_at
SUV420H1
Suppressor of variegation 4-20 homolog 1 (Drosophila)


135
0.001197
16.5
13.5
−1.22
233962_at
C20orf120
Chromosome 20 open reading frame 120


136
0.001212
183
250.9
1.37
204526_s_at
TBC1D8
TBC1 domain family, member 8 (with GRAM domain)


137
0.001214
39.9
31.5
−1.27
235417_at
SPOCD1
SPOC domain containing 1


138
0.001228
67.2
87.8
1.31
1552472_a_at
CENTB2
Centaurin, beta 2


139
0.001232
423
513.3
1.21
200768_s_at
MAT2A
Methionine adenosyltransferase II, alpha


140
0.001246
17
14.7
−1.16
229536_at
REC8
REC8 homolog (yeast)


141
0.001283
1790.8
2281.3
1.27
204220_at
GMFG
Glia maturation factor, gamma


142
0.001291
41.6
35.4
−1.18
234958_at
EST19
Clone HQ0352 PRO0352


143
0.001294
1519.9
1803
1.19
207168_s_at
H2AFY
H2A histone family, member Y


144
0.001329
9.9
8.3
−1.19
1557235_at
EST20
CDNA FLI44051 fis, clone TESTI4033433


145
0.001329
7.7
6.8
−1.13
207120_at
ZNF667
Zinc finger protein 667


146
0.001348
12
15.3
1.28
226688_at
C3orf23
Chromosome 3 open reading frame 23


147
0.001363
201.6
311.2
1.54
224374_s_at
EMILIN2
Elastin microfibril interfacer 2


148
0.001364
79.4
48.9
−1.62
244523_at
MMD
Monocyte to macrophage differentiation-associated


149
0.001415
10.4
9.1
−1.14
226533_at
HINT3
Histidine triad nucleotide binding protein 3


150
0.001421
505.7
358.5
−1.41
202074_s_at
OPTN
Optineurin


151
0.001438
10.9
9.6
−1.14
234372_at
LOC644728
Similar to Glyceraldehyde-3-phosphate









dehydrogenase (GAPDH) (38 kDa 8FA-dependent ADP-









ribosylation substrate) (BARS-38)


152
0.001448
239.8
331.7
1.38
202192_s_at
GAS7
Growth arrest-specific 7


153
0.001464
16.6
20.7
1.25
1559052_s_at
PAK2
p21 (CDKN1A)-activated kinase 2


154
0.001472
32.5
47.6
1.46
223304_at
SLC37A3
Solute carrier family 37 (glycerol-3-phosphate









transporter), member 3


155
0.001491
43.1
58.5
1.36
213582_at
ATP11A
ATPase, Class VI, type 11A


156
0.001507
6.5
5.8
−1.12
233770_at
EST21
CDNA FLI12077 fis, clone HEMBB1002453


157
0.001515
14.1
12.7
−1.11
234627_at
FLJ21408
Hypothetical gene supported by AK025061


158
0.00152
815.3
1047.6
1.28
209007_s_at
C1orf63
Chromosome 1 open reading frame 63


159
0.00153
15.6
11.2
−1.39
214502_at
HIST1H2BJ
Histone cluster 1, H2bj


160
0.001533
206.6
140.7
−1.47
202124_s_at
TRAK2
Trafficking protein, kinesin binding 2


161
0.001538
16.1
12.9
−1.25
223709_s_at
WNT10A
Wingless-type MMTV integration site family, member









10A


162
0.001544
143.1
194.3
1.36
219132_at
PELI2
Pellino homolog 2 (Drosophila)


163
0.001561
556.9
684.6
1.23
217492_s_at
LOC731292
Phosphatase and tensin homolog (mutated in multiple








/// PTEN ///
advanced cancers 1) ///phosphatase and tensin








PTENP1
homolog (mutated in multiple advanced cancers 1),









pseudogene 1///similar to Phosphatidylinositol-3,4,5-









trisphosphate 3-phosphatase and dual-specificity









protein phosphatase PTEN (Phosphatase and tensin









homolog) (Mutated in multiple advanced cancers1)


164
0.001562
7.4
6.7
−1.10
241226_at
EST22
Transcribed locus


165
0.001565
12.1
10.6
−1.14
231965_at
FAM113A
Family with sequence similarity 113, member A


166
0.00157
39.4
69.3
1.76
207605_x_at
ZNF117
Zinc finger protein 117


167
0.001602
22.4
19.4
−1.15
232249_at
FMNL3
Formin-like 3


168
0.001612
81.2
116
1.43
205698_s_at
MAP2K6
Mitogen-activated protein kinase kinase 6


169
0.001613
110.4
140.3
1.27
229798_s_at
EST23
—


170
0.00162
21
17.7
−1.19
219554_at
RHCG
Rh family, C glycoprotein


171
0.001625
7
6.1
−1.15
244690_at
EST24
Transcribed locus


172
0.00163
343.7
497.4
1.45
225919_s_at
C9orf72
Chromosome 9 open reading frame 72


173
0.001642
74.3
101.7
1.37
213792_s_at
INSR
Insulin receptor


174
0.001677
23.1
26.8
1.16
208328_s_at
MEF2A
Myocyte enhancer factor 2A


175
0.00168
6.9
6.2
−1.11
207362_at
SLC30A4
Solute carrier family 30 (zinc transporter), member 4


176
0.001709
17.5
15.4
−1.14
206521_s_at
GTF2A1
General transcription factor IIA, 1, 19/37 kDa


177
0.001735
100.2
142
1.42
218027_at
MRPL15
Mitochondrial ribosomal protein L15


178
0.001737
19.6
22.8
1.16
224198_at
ELA1
Elastase 1, pancreatic


179
0.001741
69.6
97.1
1.40
212572_at
STK38L
Serine/threonine kinase 38 like


180
0.001743
22.3
18.6
−1.20
206993_at
ATP5S
ATP synthase, H+ transporting, mitochondrial F0









complex, subunit s (factor B)


181
0.001788
45.4
36.5
−1.24
203479_s_at
OTUD4
OTU domain containing 4


182
0.001835
13.4
11
−1.22
232820_s_at
FAM112A
Family with sequence similarity 112, member A


183
0.001854
7.2
6.6
−1.09
1558621_at
CABLES1
Cdk5 and Abl enzyme substrate 1


184
0.001854
59.1
49.6
−1.19
220765_s_at
LIMS2
LIM and senescent cell antigen-like domains 2


185
0.001859
24.3
20.6
−1.18
205477_s_at
AMBP
Alpha-1-microglobulin/bikunin precursor


186
0.00189
102.8
59
0.57
207826_s_at
ID3
Inhibitor of DNA binding 3, dominant negative helix-









loop-helix protein


187
0.001892
10.5
17.8
1.70
209992_at
PFKFB2
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2


188
0.001928
207.8
151.9
−1.37
201841_s_at
HSPB1
Heat shock 27 kDa protein 1


189
0.001936
61.4
83.5
1.36
210768_x_at
TMCO1
Transmembrane and coiled-coil domains 1


190
0.001951
43.1
63.6
1.48
242794_at
MAML3
Mastermind-like 3 (Drosophila)


191
0.001976
58.7
79.2
1.35
213379_at
COQ2
Coenzyme Q2 homolog, prenyltransferase (yeast)


192
0.001983
425.9
650.8
1.53
202446_s_at
PLSCR1
Phospholipid scramblase 1


193
0.001984
24.7
28.7
1.16
204210_s_at
PCYT1A
Phosphate cytidylyltransferase 1, choline, alpha


194
0.001993
31.8
58.3
1.83
236898_at
EST25
Transcribed locus. strongly similar to









XP_0011011634.1 similar to tripartite motif-containing









25 (Macaca mulatta)


195
0.002
8.8
7.4
−1.19
242661_x_at
ALS2CR12
Amyotrophic lateral sclerosis 2 (juvenile) chromosome









region, candidate 12


196
0.002013
19.4
15.4
−1.26
1558773_s_at
RANBP10
RAN binding protein 10


197
0.002032
63.6
79.5
1.25
218896_s_at
C17orf85
Chromosome 17 open reading frame 85


198
0.002033
27.8
37.2
1.34
220865_s_at
PDSS1
Prenyl (decaprenyl) diphosphate synthase, subunit 1


199
0.002038
214.1
282.4
1.32
224511_s_at
TXNDC17
Thioredoxin domain containing 17


200
0.002045
7.6
6.4
−1.19
243347_at
EST26
—


201
0.002054
8.1
7
−1.16
236336_at
EST27
CDNA clone IMAGE: 4796690


202
0.002098
153.9
205.6
1.34
224983_at
SCARB2
Scavenger receptor class B, member 2


203
0.002099
30.1
26
−1.16
1569144_a_at
LOC653325
Similar to RIKEN cDNA 2310002J15








///
gene///hypothetical LOC653325








MGC59937


204
0.002104
15.9
13.7
−1.16
234511_at
C20orf86
Chromosome 20 open reading frame 86


205
0.002106
20.3
17.2
−1.18
237254_at
SLC5A11
Solute carrier family 5 (sodium/glucose cotransporter),









member 11


206
0.002112
9.3
10.5
1.13
231310_at
EST28
Transcribed locus


207
0.002171
15.7
13
−1.21
244226_s_at
EST29
—


208
0.0022
13.3
11.4
−1.17
230957_at
PCDHB19P
Protocadherin beta 19 pseudogene


209
0.002206
10.8
9.5
−1.14
232321_at
MUC17
Mucin 17, cell surface associated


210
0.00221
27.4
19.8
−1.38
235557_at
LOC150763
Hypothetical protein LOC150763


211
0.002218
11251.4
8508.5
−1.32
214414_x_at
HBA2
Hemoglobin, alpha 2


212
0.00222
16.1
13.8
−1.17
1558118_at
DGCR5
DiGeorge syndrome critical region gene 5 (non-coding)


213
0.002223
18.1
15.9
−1.14
231994_at
CHDH
Choline dehydrogenase


214
0.002229
29.1
34.7
1.19
212710_at
CAMSAP1
Calmodulin regulated spectrin-associated protein 1


215
0.002253
94.3
73.7
−1.28
243579_at
MSI2
Musashi homolog 2 (Drosophila)


216
0.002256
446.2
305.3
−1.46
200702_s_at
DDX24
DEAD (Asp-Glu-Ala-Asp) box polypeptide 24


217
0.002266
94.9
124.4
1.31
227046_at
SLC39A11
Solute carrier family 39 (Metal ion transporter),









member 11


218
0.002294
36
31.2
−1.15
40020_at
CELSR3
Cadherin, EGF LAG seven-pass G-type receptor 3









(flamingo homolog, Drosophila)


219
0.002303
27.6
22.9
−1.21
218903_s_at
OBFC2B
Oligonucleotide/oligosaccharide-binding fold









containing 2B


220
0.002329
5.5
6.7
1.22
223861_at
HORMAD1
HORMA domain containing 1


221
0.002348
508.5
692.2
1.36
201926_s_at
CD55
CD55 molecule, decay accelerating factor for









complement (Cromer blood group)


222
0.00235
1265.9
1098.5
−1.15
209075_s_at
ISCU
Iron-sulfur cluster scaffold homolog (E. coli)


223
0.002351
7.1
6
−1.18
231721_at
JAM3
Junctional adhesion molecule 3


224
0.002354
8.2
7.4
−1.11
237505_at
EST30
Transcribed locus


225
0.002368
67.4
100.4
1.49
201952_at
ALCAM
Activated leukocyte cell adhesion molecule


226
0.002389
10
8.7
−1.15
211896_s_at
DCN
Decorin


227
0.002394
40.2
31.8
−1.26
216080_s_at
FADS3
Fatty acid desaturase 3


228
0.002427
252.5
326.4
1.29
202277_at
SPTLC1
Serine palmitoyltransferase, long chain base subunit 1


229
0.002435
37.7
56.3
1.49
208488_s_at
CR1
Complement component (3b/4b) receptor 1 (Knops









blood group)


230
0.002437
100.3
135.1
1.35
213868_s_at
DHRS7
Deydrogenase/reductase (SDR family) member 7


231
0.002443
314.9
419.1
1.33
225921_at
NIN
Ninein (GSK3B interacting protein)


232
0.002447
56.7
82.8
1.46
233329_s_at
KRCC1
Lysine-rich coiled-coil 1


233
0.002472
28.3
24.6
−1.15
232663_s_at
LOC390595
Similar to ubiquitin-associated protein 1 (predicted)


234
0.002474
88.9
143.5
1.61
204150_at
STAB1
Stabilin 1


235
0.002511
10
11.5
1.15
219831_at
CDKL3
Cyclin-dependent kinase-like 3


236
0.002528
69.8
101.9
1.46
216202_s_at
SPTLC2
Serine palmitoyltransferase, long chain base subunit 2


237
0.002536
28.7
24.3
−1.18
233381_at
RUFY1
RUN and FYVE domain containing 1


238
0.002552
67.7
84
1.24
222842_at
EIF2C4
Eukaryotic translation initiation factor 2C, 4


239
0.002566
13.7
10.6
−1.29
1554413_s_at
RUNDC2B ///
RUN domain containing 2B///RUN domain containing








RUNDC2C
2C


240
0.002598
13.9
12.2
−1.14
202403_s_at
COL1A2
Collagen, type 1, alpha 2


241
0.002603
531.4
440.6
−1.21
210950_s_at
FDFT1
Farnesyl-diposphate farnesyltransferase 1


242
0.002605
10.1
8.5
−1.19
215742_at
EST31
CDNA FLI12157 fis, clone MAMMA1000500


243
0.002672
35.9
42.2
1.18
221567_at
NOL3
Nucleolar protein 3 (apoptosis repressor with CARD









domain)


244
0.002691
16
12
−1.33
203151_at
MAP1A
Microtubule-associated protein 1A


245
0.002693
406.6
540.5
1.33
208864_s_at
TXN
Thioredoxin


246
0.002706
83
62.3
−1.33
201072_s_at
SMARCC1
SWI/SNF related, matrix associated, actin dependent









regulator of chromatin, subfamily c, member 1


247
0.002715
77.7
63.5
−1.22
211358_s_at
CIZ1
CDKN1A interacting zinc finger protein 1


248
0.002724
11.1
13.7
1.23
205416_s_at
ATXN3
Ataxin 3


249
0.002731
27
23.9
−1.13
244694_at
LOC402665
hCG1651476


250
0.002731
94.6
135.6
1.43
212511_at
PICALM
Phosphatidylinositol binding clathrin assembly protein


251
0.002736
81.1
112.4
1.39
223978_s_at
CRLS1
Cardiolipin synthase 1


252
0.002737
12.1
10.7
−1.13
210923_at
SLC1A7
Solute carrier family 1 (glutamate transporter),









member 7


253
0.002738
5.6
5.1
−1.10
204320_at
COL11A1
Collagen, type XI, alpha 1


254
0.002739
61
83.3
1.37
209666_s_at
CHUK
Conserved helix-loop-helix ubiquitous kinase


255
0.002747
29.9
24.5
−1.22
238097_at
EST32
—


256
0.002749
10.1
8.6
−1.17
205295_at
CKMT2
Creatine kinase, mitochondrial 2 (sarcomeric)


257
0.002773
240.1
331.4
1.38
1555797_a_at
ARPC5
Actin related protein 2/3 complex, subunit 5, 16 kDa


258
0.002776
32.5
28.1
−1.16
235402_at
C11orf66
Chromosome 11 open reading frame 66


259
0.002793
30.8
25.5
−1.21
216562_at
EST33
—


260
0.002823
19.6
17.1
−1.15
1553967_at
ADAT3
Adenosine deaminase, tRNA-specific 3, TAD3 homolog









(S. cerevisiae)


261
0.002831
883.8
1069.3
1.21
226525_at
EST34
Transcribed locus


262
0.002853
65.1
109.4
1.68
220034_at
IRAK3
Interleukin-1 receptor-associated kinase 3


263
0.002856
7.7
7.1
−1.08
1563656_at
EST35
MRNA; cDNA DKFZp586H1217 (from clone









DKFZp586H1217)


264
0.002859
60.5
53.8
−1.12
233235_x_at
EST36
CDNA: FLI21443 fis, clone COL04430


265
0.002876
5
5.5
1.10
1558640_a_at
LOC728411
Similar to Beta-glucuronidase precursor


266
0.00288
143.4
216.8
1.51
204646_at
DPYD
Dihydropyrimidine dehydrogenase


267
0.002888
52.8
83.6
1.58
207719_x_at
CEP170
Centrosomal protein 170 kDa


268
0.00289
41.3
50.9
1.23
228791_at
C15orf38
Chromosome 15 open reading frame 38


269
0.002915
17.6
15
−1.17
240705_at
CYP19A1
Cytochrome P450, family 19, subfamily A, polypeptide 1


270
0.002927
50.7
42.9
−1.18
218725_at
SLC25A22
Solute carrier family 25 (mitochondrial









carrier:glutamate), member 22


271
0.002996
105.1
163.4
1.55
201328_at
ETS2
v-ets erythroblastosis virus E26 oncogene homolog 2









(avian)


272
0.002997
13.9
16.3
1.17
239332_at
EST37
Homo sapiens, clone IMAGE: 3897156, mRNA


273
0.00302
14
16.9
1.21
240394_at
EST38
Transcribed locus


274
0.003049
60.3
51.8
−1.16
1556900_at
LOC149773
Hypothetical protein LOC149773


275
0.003057
43.4
33.4
−1.30
220588_at
BCAS4
Breast carcinoma amplified sequence 4


276
0.003067
10.1
8.4
−1.20
210127_at
RAB6B
RAB6B, member RAS oncogene family


277
0.003068
5.5
4.9
−1.12
1559450_at
EST39
CDNA clone IMAGE: 5286225


278
0.003109
22
36.6
1.66
1558920_at
EST40
CDNA FLI43417 fis, clone OCBBF2026025


279
0.003116
9.2
8.2
−1.12
206847_s_at
HOXA7
Homeobox A7


280
0.003117
12.9
11.3
−1.14
216303_s_at
MTMR1
Myotubularin related protein 1


281
0.003131
14
12.3
−1.14
216799_at
EST41
MRNA; cDNA DKFZp547G044 (from clone









DKFZp547G044)


282
0.003131
5.8
5.3
−1.09
242130_at
EST42
Transcribed locus


283
0.003145
10.6
9.4
−1.13
1562106_at
EST43
Homo sapiens, clone IMAGE: 5240933, mRNA


284
0.003147
40.2
46.9
1.17
224416_s_at
MED28
Mediator complex subunit 28


285
0.003153
441.7
716.5
1.62
203799_at
CD302
CD302 molecule


286
0.00318
23.2
19.5
−1.19
243062_at
FLCN
Folliculin


287
0.003188
15.1
19.7
1.30
239574_at
EST44
Transcribed locus


288
0.003189
5.7
5.2
−1.10
1559518_at
HSD17B12
Hydroxysteroid (17-beta) dehydrogenase 12


289
0.0032
27.3
38.8
1.42
207601_at
SULT1B1
Sulfotransferase family, cytosolic, 1B, member 1


290
0.003219
14.6
13
−1.12
219576_at
MAP7D3
MAP7 domain containing 3


291
0.003229
98.4
127.1
1.29
209234_at
KIF1B
Kinesin family member 1B


292
0.003234
151.4
100.7
−1.50
225775_at
TSPAN33
Tetraspanin 33


293
0.003255
10.8
12.9
1.19
238921_at
LOC641767
Hypothetical protein LOC641767///hypothetical








///
LOC644794








LOC644794


294
0.003276
5.2
5.8
1.12
236262_at
MMRN2
Multimerin 2


295
0.003296
20.4
16.2
−1.26
215526_at
EST45
MRNA; cDNA DKFZp586C2020 (from clone









DKFZp586C2020)


296
0.003296
14.9
13.2
−1.13
236914_at
EST46
Transcribed locus, moderately similar to









XP_001137307.1 hypothetical protein (Pan









troglodytes)


297
0.003306
43.6
58.4
1.34
236465_at
RNF175
Ring finger protein 175


298
0.00334
106.2
210.1
1.98
204619_s_at
VCAN
Versican


299
0.003365
15.3
12.5
−1.22
243365_s_at
AUTS2
Autism susceptibility candidate 2


300
0.003378
165.7
146
−1.13
201618_x_at
GPAA1
Glycosylphosphatidylinositol anchor attachment









protein 1 homolog (yeast)


301
0.003383
82.2
97.6
1.19
209445_x_at
C7orf44
Chromosome 7 open reading frame 44


302
0.003388
66.1
101.4
1.53
1552485_at
LACTB
Lactamase, beta


303
0.003393
6
5.5
−1.09
1558010_s_at
SLC1A2
Solute carrier family 1 (glial high affinity glutamate









transporter), member 2


304
0.003404
8
11
1.38
225008_at
EST47
CDNA FLI39064 fis, clone NT2RP7014583


305
0.003412
13.5
11.3
−1.19
1560108_at
EST48
CDNA FLI30757 fis, clone FEBRA2000468


306
0.003423
29.3
27.2
−1.08
244055_at
EST49
Transcribed locus


307
0.003447
16.6
20
1.20
233750_s_at
C1orf25
Chromosome 1 open reading frame 25


308
0.00346
5.4
5
−1.08
220361_at
IQCH
IQ motif containing H


309
0.003472
110
181.2
1.65
222303_at
EST50
—


310
0.003502
58.3
80.3
1.38
230937_at
LOC285835
Hypothetical protein LOC285835


311
0.003535
39.4
52
1.32
207627_s_at
TFCP2
Transcription factor CP2


312
0.003539
20.3
17.5
−1.16
1555752_at
STH
Saitohin


313
0.003542
3088.2
3805.3
1.23
212501_at
CEBPB
CCAAT/enhancer binding protein (C/EBP), beta


314
0.003551
6.2
5.7
−1.09
244675_at
RGS8
Regulator of G-protein signaling 8


315
0.003571
12.7
11.2
−1.13
208275_x_at
UTF1
Undifferentiated embryonic cell transcription factor 1


316
0.003572
397.4
524.7
1.32
210951_x_at
RAB27A
RAB27A, member RAS oncogene family


317
0.003582
7.8
6.7
−1.16
219840_s_at
TCL6
T-cell leukemia/lymphoma 6


318
0.003626
124.1
166.3
1.34
219256_s_at
SH3TC1
SH3 domain and tetratricopeptide repeats 1


319
0.003657
5.3
4.8
−1.10
1558778_s_at
MKL2
MKL/myocardin-like 2


320
0.00366
32.1
27.1
−1.18
218480_at
AGBL5
ATP/GTP binding protein-like 5


321
0.003672
118
176.7
1.50
204099_at
SMARCD3
SWI/SNF related, matrix associated, actin dependent









regulator of chromatin, subfamily d, member 3


322
0.003678
480.1
579
1.21
225750_at
EST51
CDNA FLI14162 fis, clone NT2RM4002504


323
0.003715
50.7
43.5
−1.17
214253_s_at
DTNB
Dystrobrevin, beta


324
0.003718
12.1
10.8
−1.12
243048_at
CECR7
Cat eye syndrome chromosome region, candidate 7


325
0.003757
9
7.9
−1.14
1556012_at
KLHDC7A
Kelch domain containing 7A


326
0.003773
17.6
23.4
1.33
215285_s_at
PHTF1
Putative homeodomain transcription factor 1


327
0.00378
64.4
81.7
1.27
231321_s_at
PHCA
Phytoceramidase, alkaline


328
0.003783
5.4
4.9
−1.10
238901_at
EST52
Full length insert cDNA clone ZE01A04


329
0.003793
25.4
21.4
−1.19
214595_at
KCNG1
Potassium voltage-gated channel, subfamily G,









member 1


330
0.0038
10.5
9.4
−1.12
216470_x_at
PRSS1 ///
Protease, serine, 1 (trypsin1)///protease, serine, 2








PRSS2 ///
(trypsin2)///protease, serine, 3 (mesotrypsin)








PRSS3 ///
trypsinogen 3








TRY6


331
0.003819
36.6
59.4
1.62
204787_at
VSIG4
V-set and immunoglobulin domain containing 4


332
0.003841
11.7
10.2
−1.15
216101_at
EST53
Full length insert cDNA clone YR67C11


333
0.003845
51
75.1
1.47
224862_at
GNAQ
Guanine nucleotide binding protein (G protein), q









polypeptide


334
0.003873
17.6
23.6
1.34
234664_at
LOC284701
Hypothetical protein LOC284701


335
0.003878
16.8
14
−1.20
202796_at
SYNPO
Synaptopodin


336
0.003884
11.4
10
−1.14
238217_at
EST54
Transcribed locus


337
0.003905
559.2
823.8
1.47
209184_s_at
IRS2
Insulin receptor substrate 2


338
0.003905
5.6
5.2
−1.08
1565578_at
EST55
CDNA FLI34486 fis, clone HLUNG2004217


339
0.003909
202.6
269.2
1.33
217823_s_at
UBE2J1
Ubiquitin-conjugating enzyme E2, J1 (UBC6 homolog,









yeast)


340
0.003952
7
6.2
−1.13
240873_x_at
DAB2
Disabled homolog 2, mitogen-responsive









phosphoprotein (Drosophila)


341
0.003967
206.9
281.1
1.36
212795_at
KIAA1033
KIAA1033


342
0.003968
36
48.9
1.36
239085_at
EST56
Transcribed locus


343
0.003972
110.8
171.2
1.55
223423_at
GPR160
G protein-coupled receptor 160


344
0.003992
12.3
10.8
−1.14
238917_s_at
MGC24039
Hypothetical protein MGC24039


345
0.003999
36.9
48.4
1.31
226395_at
LOC286170
Hypothetical protein LOC286170


346
0.004021
155.6
222.8
1.43
215000_s_at
FEZ2
Fasciculation and elongation protein zeta 2 (zygin II)


347
0.004032
196.3
235.6
1.20
203605_at
SRP54
Signal recognition particle 54 kDa


348
0.004054
7.7
6.6
−1.17
242805_at
EST57
—


349
0.004085
50.4
66.2
1.31
204043_at
TCN2
Transcobalamin II; macrocytic anemia


350
0.004142
9.8
11.4
1.16
237845_at
EST58
Transcribed locus, moderately similar to









XP_001103240.1 similar to kinesin family member 27









(Macaca mulatta)


351
0.004144
28.5
22.5
−1.27
1569499_at
EST59
CDNA clone IMAGE: 3840913


352
0.004179
21.1
18.5
−1.14
217876_at
GTF3C5
General transcription factor IIIC, polypeptide 5, 63 kDa


353
0.004185
9.9
15.3
1.55
223660_at
ADORA3
Adenosine A3 receptor


354
0.004186
5.8
6.3
1.09
231160_at
EST60
Transcribed locus


355
0.00419
9.7
15.7
1.62
236901_at
EST61
Transcribed locus


356
0.0042
20.9
18
−1.16
215979_s_at
SLC7A1
Solute carrier family 7 (cationic amino acid









transporter, y+ system), member 1


357
0.004234
1525.2
1779.3
1.17
208736_at
ARPC3
Actin related protein 2/3 complex, subunit 3, 21 kDa


358
0.004238
82.6
123.2
1.49
229383_at
EST62
CDNA FLI34016 fis, clone FCBBF2002541


359
0.004265
32
27.2
−1.18
32137_at
JAG2
Jagged 2


360
0.004278
7.6
6.9
−1.10
213249_at
FBXL7
F-box and leucine-rich repeat protein 7


361
0.004288
2770.3
3252
1.17
202803_s_at
ITGB2
Integrin, beta 2 (complement component 3 receptor 3









and 4 subunit)


362
0.004321
119
159.5
1.34
203310_at
STXBP3
Syntaxin binding protein 3


363
0.004335
798.5
1181
1.48
202295_s_at
CTSH
Cathespin H


364
0.004354
10.4
9.1
−1.14
220994_s_at
STXBP6
Syntaxin binding protein 6 (amisyn)


365
0.004355
49
90.4
1.84
212224_at
ALDH1A1
Aldehyde dehydrogenase 1 family, member A1


366
0.004381
208.3
260.9
1.25
212120_at
RHOQ
Ras homolog gene family, member Q


367
0.004435
32.8
29.9
−1.10
37586_at
ZNF142
Zinc finger protein 142


368
0.004453
285.1
404.8
1.42
219356_s_at
CHMP5
Chromatin modifying protein 5


369
0.004458
118.6
152.6
1.29
241370_at
LOC286052
Hypothetical protein LOC286052


370
0.004465
13.1
11.4
−1.15
1558476_at
C1orf165
Chromosome 1 open reading frame 165


371
0.004485
5.5
6.2
1.13
206533_at
CHRNA5
Cholinergic receptor, nicotinic, alpha 5


372
0.004489
33.2
28.8
−1.15
229979_x_at
EST63
Transcribed locus


373
0.004526
66.2
83.5
1.26
200764_s_at
CTNNA1
Catenin (cadherin-associated protein), alpha 1, 102 kDa


374
0.004556
7.3
6.5
−1.12
240874_at
EST64
Transcribed locus


375
0.004558
20.4
17.2
−1.19
1556672_a_at
RBM6
RNA binding motif protein 6


376
0.004559
13.6
10.9
−1.25
236268_at
SEC22C
SEC22 vesicle trafficking protein homolog C (S. cerevisiae)


377
0.004594
68.3
57
−1.20
220968_s_at
TSPAN9
Tetraspanin 9


378
0.004616
363.3
284.7
−1.28
223042_s_at
FUNDC2
FUN14 domain containing 2


379
0.004683
6.9
9.4
1.36
226311_at
EST65
CDNA clone IMAGE: 30924414


380
0.004699
5
4.7
−1.06
1570482_at
EST66
Pp14356


381
0.00476
5.9
6.6
1.12
1562274_at
EST67
MRNA; cDNA DKFZp 313I0929 (from clone









DKFZp313I0929)


382
0.004769
40.5
32.8
−1.23
201792_at
AEBP1
AE binding protein 1


383
0.004776
11.7
13.7
1.17
229671_s_at
C21orf45
Chromosome 21 open reading frame 45


384
0.004783
23
15.8
−1.46
208501_at
GFI1B
Growth factor independent 1B (potential regulator of









CDKN1A, translocated in CML)


385
0.004788
6.6
5.9
−1.12
206142_at
ZNF135
Zing finger protein 135


386
0.004813
6.9
6.4
−1.08
233594_at
EST68
CDNA clone IMAGE: 4823221


387
0.004845
9
8
−1.13
1565407_at
LHX9
LIM homeobox 9


388
0.004861
7.1
6.3
−1.13
1559634_at
CHRM3
Cholinergic receptor, muscarinic 3


389
0.004927
23.8
36.5
1.53
236297_at
EST69
CDNA FLI45742 fis, clone KIDNE2016327


390
0.004932
29.6
33.1
1.12
215930_s_at
CTAGE5
CTAGE family, member 5


391
0.004946
101.1
128.9
1.27
209463_s_at
TAF12
TAF12 RNA polymerase II, TATA box binding protein









(TBP)-associated factor, 20 kDa


392
0.004975
26.4
18.6
−1.42
206759_at
FCER2
Fc fragment of IgE, low affinity II, receptor for (CD23)


393
0.004988
14.3
12.3
−1.16
230950_at
EST70
Transcribed locus
















TABLE B







Differentially expressed consensus genes for moderate/severe CAN/IFTA for both Test Sets


Moderate/Severe CAN/IFTA = CAN/IFTA Banff Class 2, 3; No evidence of CAN/IFTA = CAN/IFTA Banff Class 0


Probesets with positive fold changes are upregulated in moderate/severe CAN
















Geom
Geom








mean of
mean of




intensities
intensities
Ratio of



Parametric
in class 1:
in class 2:
geom



p-value
Banff 0
Banff 2, 3
means
Probe Set ID
Gene Symbol
Gene Title

















1
0.0001775
11.1
9
−1.23
1566879_at
EST1
ATP/GTP binding protein-like 1


2
0.0003852
4.9
4.5
−1.09
241139_at
EST2
—


3
0.0004281
5.5
6.1
1.11
231591_at
BHMT
anthrax toxin receptor 2


4
0.0004852
20.5
26.2
1.28
242619_x_at
EST3
—


5
0.0005716
20.8
34.5
1.66
206674_at
FLT3
LIM homeobox 9


6
0.0005983
5.6
4.9
−1.14
204005_s_at
PAWR
—


7
0.0006361
23
39.6
1.72
220112_at
ANKRD55
—


8
0.0006841
6.6
5.9
−1.12
239312_at
EST4
Phospholipase C epsilon


9
0.0007962
21.4
28.1
1.31
205977_s_at
EPHA1
—


10
0.0008868
9.3
8.1
−1.15
210412_at
GRIN2B
olfactory receptor, family 8, subfamily G, member 1


11
0.0008881
5
4.5
−1.11
216089_at
MCFD2L
—


12
0.0009531
10
8.5
−1.18
226211_at
MEG3
PRKC, apoptosis, WT1, regulator


13
0.001086
58.7
72.7
1.24
226856_at
MUSTN1
CUG triplet repeat, RNA binding protein 1


14
0.001156
11.7
14.7
1.26
229671_s_at
C21orf45
PBX/knotted 1 homeobox 1


15
0.001212
10
11.6
1.16
219831_at
CDKL3
cleavage stimulation factor, 3′ pre-RNA, subunit 2, 64 kDa


16
0.0013123
8.7
10
1.15
233429_at
FLJ23577
matrix metallopeptidase 1 (interstitial collagenase)


17
0.0013489
14
19
1.36
210896_s_at
ASPH
IKAROS family zinc finger 1 (Ikaros)


18
0.0014846
9.7
15
1.55
236901_at
EST5
EPH receptor A1


19
0.0015437
7.7
6.8
−1.13
213994_s_at
SPON1
fms-related tyrosine kinase 3


20
0.0015498
11
9.5
−1.16
242417_at
LOC283278
cytochrome P450, family 4, subfamily B, polypeptide 1


21
0.0015652
6.3
5.6
−1.13
229777_at
CLRN3
glutamate receptor, ionotropic, N-methyl D-aspartate 2B


22
0.0016885
311.3
218.7
−1.42
205039_s_at
IKZF1
aspartate beta-hydroxylase


23
0.0017597
18.8
22.5
1.20
204113_at
CUGBP1
nuclear factor of kappa light polypeptide gene enhancer in









B-cells 2 (p49/p100)


24
0.0019344
11.6
14.8
1.28
233650_at
CEP63
met proto-oncogene (hepatocyte growth factor receptor)


25
0.0019513
42.8
57
1.33
236832_at
LOC221442
spondin 1, extracellular matrix protein


26
0.0019757
21.9
18.6
−1.18
228721_at
C3orf41
—


27
0.0020356
6.9
8.9
1.29
226311_at
EST6
secretogranin III


28
0.0020555
5.5
4.6
−1.20
1566428_at
EST7
cyclin-dependent kinase-like 3


29
0.0020848
18.7
15
−1.25
229532_at
ZNF502
ankyrin repeat domain 55


30
0.0021794
10.6
12
1.13
1554615_at
EST8
heparan-alpha-glucosaminide N-acetyltransferase


31
0.0022636
5.9
5.4
−1.09
230650_at
EST9
family with sequence similarity 135, member A


32
0.0022797
76.1
62.4
−1.22
204459_at
CSTF2
maternally expressed 3 (non-protein coding)


33
0.0023808
5.3
4.8
−1.10
1570050_at
EST10
—


34
0.0023855
4.7
4.3
−1.09
1566096_x_at
EST11
musculoskeletal, embryonic nuclear protein 1


35
0.0025531
9
8
−1.13
1565407_at
LHX9
hexokinase domain containing 1


36
0.0025848
5.1
5.6
1.10
232770_at
TUSC3
—


37
0.0026131
6.4
5.6
−1.14
204475_at
MMP1
hypothetical protein LOC90784


38
0.0026527
11.3
14.3
1.27
243349_at
KIAA1324
thyroid hormone receptor, beta (erythroblastic leukemia









viral (v-erb-a) oncogene homolog 2, avian)


39
0.0027257
5.7
5.1
−1.12
240604_at
EXOD1
chromosome 3 open reading frame 41


40
0.0027342
6
5.6
−1.07
210096_at
CYP4B1
RNA binding protein with multiple splicing 2


41
0.0027896
39.3
22
−1.79
228390_at
EST12
hypothetical protein LOC729680


42
0.0027907
6.3
6.9
1.10
228977_at
LOC729680
nuclear receptor subfamily 2, group F, member 2


43
0.0028215
9.5
10.6
1.12
213807_x_at
MET
zinc finger protein 502


44
0.0028343
7.9
6.7
−1.18
228716_at
THRB
CDNA FU90800 fis, clone Y79AA1000127


45
0.0029105
6.1
10.7
1.75
1560800_at
EST13
clarin 3


46
0.0031196
12.6
14.3
1.13
1567060_at
OR8G1
—


47
0.0033408
24.1
19.6
−1.23
223497_at
FAM135A
Betaine:homocysteine methyltransferase


48
0.0039416
5.3
5.9
1.11
211524_at
NFKB2
tumor suppressor candidate 3


49
0.0039539
14.2
12.3
−1.15
241261_x_at
EST14
sperm flagellar 2


50
0.003958
12.1
10.5
−1.15
243048_at
CECR7
centrosomal protein 63 kDa


51
0.0040206
34.8
22.1
−1.57
228802_at
RBPMS2
—


52
0.004032
4.7
4.4
−1.07
219196_at
SCG3
hypothetical LOC221442


53
0.0041033
18.9
24.7
1.31
227614_at
HKDC1
—


54
0.0041799
39.2
46
1.17
204195_s_at
PKNOX1
—


55
0.0042431
25
30.2
1.21
228515_at
LOC90784
exoribonuclease 2


56
0.0042468
9.7
8.7
−1.11
1566739_at
PLCE1
—


57
0.0043315
27.7
33.5
1.21
222491_at
HGSNAT
—


58
0.0044839
7.3
8.1
1.11
1553447_at
AGBL1
—


59
0.0045669
6.7
6.2
−1.08
229092_at
EST15
hypothetical protein LOC283278


60
0.0047554
9.7
11.1
1.14
233993_at
EST16
—


61
0.004775
17.7
21
1.19
242264_at
EST17
cat eye syndrome chromosome region, candidate 7


62
0.0048752
34.1
38.1
1.12
1555536_at
ANTXR2
KIAA1324
















TABLE C







Differentially expressed consensus genes for mild CAN/IFTA for both Test Sets


Mild CAN/IFTA = CAN/IFTA Banff Class 1; No evidence of CAN/IFTA = CAN/IFTA Banff Class 0


Probesets with positive fold changes are upregulated in mild CAN
















Geom
Geom








mean of
mean of




intensities
intensities



Parametric
in class 1:
in class 2:
Fold



p-value
Banff 0
Banff 1
Change
Probe Set ID
Gene Symbol
Gene Title

















1
0.000002
27.9
19.3
−1.45
203796_s_at
BCL7A
B-cell CLL/lymphoma 7A


2
2.1E−06
11.6
16.7
1.44
233650_at
CEP63
centrosomal protein 63 kDa


3
3.2E−06
50.5
40.1
−1.26
1552892_at
TNFRSF13C
tumor necrosis factor receptor superfamily, member 13C


4
5.9E−06
19.2
33.6
1.75
1565597_at
EST1
Homo sapiens, clone IMAGE: 4275461, mRNA


5
8.3E−06
15.1
23.5
1.56
241752_at
SLC8A1
solute carrier family 8 (sodium/calcium exchanger),









member 1


6
1.25E−05
803.7
1050.5
1.31
213702_x_at
ASAH1
N-acylsphingosine amidohydrolase (acid ceramidase) 1


7
1.61E−05
224.8
174.8
−1.29
223259_at
ORMDL3
ORM1-like 3 (S. cerevisiae)


8
1.84E−05
135.4
189.9
1.40
204054_at
PTEN
phosphatase and tensin homolog (mutated in multiple









advanced cancers 1)


9
1.86E−05
26
46
1.77
239012_at
IBRDC2
IBR domain containing 2


10
2.39E−05
1182
1724.7
1.46
200975_at
PPT1
palmitoyl-protein thioesterase 1 (ceroid-lipofuscinosis,









neuronal 1, infantile)


11
0.000024
174.3
363.5
2.09
206584_at
LY96
lymphocyte antigen 96


12
3.35E−05
9
7.6
−1.18
228044_at
C13orf21
chromosome 13 open reading frame 21


13
4.41E−05
250.1
327.6
1.31
225492_at
EST2
—


14
4.53E−05
7828
10660.2
1.36
202917_s_at
S100A8
S100 calcium binding protein A8


15
0.000047
374.1
724.5
1.94
223501_at
TNFSF13B
tumor necrosis factor (ligand) superfamily, member 13b


16
4.75E−05
112.7
204
1.81
222496_s_at
FLJ20273
RNA-binding protein


17
5.11E−05
22.4
38.8
1.73
224996_at
EST3
CDNA FLJ39064 fis, clone NT2RP7014583


18
5.13E−05
21.6
17.5
−1.23
244863_at
EST4
Transcribed locus


19
0.000052
7.5
9
1.20
238791_at
ZNF100
zinc finger protein 100


20
5.66E−05
85.2
123.8
1.45
218177_at
CHMP1B
chromatin modifying protein 1B


21
5.67E−05
203.3
336.4
1.65
226208_at
ZSWIM6
zinc finger, SWIM-type containing 6


22
7.26E−05
180.8
237.2
1.31
203778_at
MANBA
mannosidase, beta A, lysosomal


23
0.000089
86.6
123.4
1.42
238903_at
LOC137886
hypothetical protein LOC137886


24
0.000094
19.7
14.5
−1.36
214308_s_at
HGD
homogentisate 1,2-dioxygenase (homogentisate oxidase)


25
0.000103
492.9
744.6
1.51
211368_s_at
CASP1
caspase 1, apoptosis-related cysteine peptidase









(interleukin 1, beta, convertase)


26
0.000103
132.8
184.8
1.39
227017_at
ERICH1
glutamate-rich 1


27
0.000107
10.3
15.5
1.50
228624_at
TMEM144
transmembrane protein 144


28
0.000108
128.7
170.2
1.32
232149_s_at
NSMAF
neutral sphingomyelinase (N-SMase) activation associated









factor


29
0.000112
26.4
35.2
1.33
243287_s_at
OSTM1
osteopetrosis associated transmembrane protein 1


30
0.000116
59.5
134.7
2.26
1552773_at
CLEC4D
C-type lectin domain family 4, member D


31
0.000121
2887.4
3972.4
1.38
202902_s_at
CTSS
cathepsin S


32
0.000125
142.4
229
1.61
211744_s_at
CD58
CD58 molecule


33
0.000133
35.6
26.9
−1.32
243507_s_at
C20orf196
chromosome 20 open reading frame 196


34
0.000137
101.9
77.4
−1.32
228832_at
FLJ20021
hypothetical LOC90024


35
0.000149
1057.6
1433.5
1.36
202727_s_at
IFNGR1
interferon gamma receptor 1


36
0.000169
40.5
55.5
1.37
213952_s_at
ALOX5
Arachidonate 5-lipoxygenase


37
0.000174
364.6
288.1
−1.27
219045_at
RHOF
ras homolog gene family, member F (in filopodia)


38
0.000175
666
974.1
1.46
212268_at
SERPINB1
serpin peptidase inhibitor, clade B (ovalbumin), member 1


39
0.00018
80.3
119.4
1.49
203276_at
LMNB1
lamin B1


40
0.00019
347.2
814.1
2.34
219666_at
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


41
0.000204
54.9
110.9
2.02
204860_s_at
NAIP ///
NLR family, apoptosis inhibitory protein /// neuronal








NAIP1B
apoptosis inhibitory protein (centromeric)


42
0.000212
3812.4
4958.6
1.30
202388_at
RGS2
regulator of G-protein signaling 2, 24 kDa


43
0.000226
24.5
43.9
1.79
1553514_a_at
VNN3
vanin 3


44
0.000239
84.6
108.3
1.28
218364_at
LRRFIP2
leucine rich repeat (in FLII) interacting protein 2


45
0.000242
15.5
21.5
1.39
218888_s_at
NETO2
neuropilin (NRP) and tolloid (TLL)-like 2


46
0.000258
64.6
87.8
1.36
204108_at
NFYA
nuclear transcription factor Y, alpha


47
0.000273
35.6
50.1
1.41
213935_at
ABHD5
abhydrolase domain containing 5


48
0.000278
54
75.5
1.40
208883_at
UBR5
ubiquitin protein ligase E3 component n-recognin 5


49
0.000282
334.9
425
1.27
222148_s_at
RHOT1
ras homolog gene family, member T1


50
0.000284
564.8
712.6
1.26
227266_s_at
FYB
FYN binding protein (FYB-120/130)
















TABLE D







Top 50 Differentially expressed consensus genes for moderate/severe CAN/IFTA for both Test Sets


Moderate/Severe CAN/IFTA = CAN/IFTA Banff Class 2, 3; No evidence of CAN/IFTA = CAN/IFTA Banff Class 0
















Geom
Geom








mean of
mean of




intensities
intensities
Ratio of



Parametric
in class 1:
in class 2:
geom



p-value
Banff 0
Banff 2, 3
means
Probe Set ID
Gene Symbol
Gene Title

















1
0.000178
11.1
9
−1.23
1566879_at
EST1
ATP/GTP binding protein-like 1


2
0.000385
4.9
4.5
−1.09
241139_at
EST2
—


3
0.000428
5.5
6.1
1.11
231591_at
BHMT
anthrax toxin receptor 2


4
0.000485
20.5
26.2
1.28
242619_x_at
EST3
—


5
0.000572
20.8
34.5
1.66
206674_at
FLT3
LIM homeobox 9


6
0.000598
5.6
4.9
−1.14
204005_s_at
PAWR
—


7
0.000636
23
39.6
1.72
220112_at
ANKRD55
—


8
0.000684
6.6
5.9
−1.12
239312_at
EST4
Phospholipase C epsilon


9
0.000796
21.4
28.1
1.31
205977_s_at
EPHA1
—


10
0.000887
9.3
8.1
−1.15
210412_at
GRIN2B
olfactory receptor, family 8, subfamily G, member 1


11
0.000888
5
4.5
−1.11
216089_at
MCFD2L
—


12
0.000953
10
8.5
−1.18
226211_at
MEG3
PRKC, apoptosis, WT1, regulator


13
0.001086
58.7
72.7
1.24
226856_at
MUSTN1
CUG triplet repeat, RNA binding protein 1


14
0.001156
11.7
14.7
1.26
229671_s_at
C21orf45
PBX/knotted 1 homeobox 1


15
0.001212
10
11.6
1.16
219831_at
CDKL3
cleavage stimulation factor, 3′ pre-RNA, subunit 2, 64 kDa


16
0.001312
8.7
10
1.15
233429_at
FLJ23577
matrix metallopeptidase 1 (interstitial collagenase)


17
0.001349
14
19
1.36
210896_s_at
ASPH
IKAROS family zinc finger 1 (Ikaros)


18
0.001485
9.7
15
1.55
236901_at
EST5
EPH receptor A1


19
0.001544
7.7
6.8
−1.13
213994_s_at
SPON1
fms-related tyrosine kinase 3


20
0.00155
11
9.5
−1.16
242417_at
LOC283278
cytochrome P450, family 4, subfamily B, polypeptide 1


21
0.001565
6.3
5.6
−1.13
229777_at
CLRN3
glutamate receptor, ionotropic, N-methyl D-aspartate 2B


22
0.001689
311.3
218.7
−1.42
205039_s_at
IKZF1
aspartate beta-hydroxylase


23
0.00176
18.8
22.5
1.20
204113_at
CUGBP1
nuclear factor of kappa light polypeptide gene enhancer in









B-cells 2 (p49/p100)


24
0.001934
11.6
14.8
1.28
233650_at
CEP63
met proto-oncogene (hepatocyte growth factor receptor)


25
0.001951
42.8
57
1.33
236832_at
LOC221442
spondin 1, extracellular matrix protein


26
0.001976
21.9
18.6
−1.18
228721_at
C3orf41
—


27
0.002036
6.9
8.9
1.29
226311_at
EST6
secretogranin III


28
0.002056
5.5
4.6
−1.20
1566428_at
EST7
cyclin-dependent kinase-like 3


29
0.002085
18.7
15
−1.25
229532_at
ZNF502
ankyrin repeat domain 55


30
0.002179
10.6
12
1.13
1554615_at
EST8
heparan-alpha-glucosaminide N-acetyltransferase


31
0.002264
5.9
5.4
−1.09
230650_at
EST9
family with sequence similarity 135, member A


32
0.00228
76.1
62.4
−1.22
204459_at
CSTF2
maternally expressed 3 (non-protein coding)


33
0.002381
5.3
4.8
−1.10
1570050_at
EST10
—


34
0.002386
4.7
4.3
−1.09
1566096_x_at
EST11
musculoskeletal, embryonic nuclear protein 1


35
0.002553
9
8
−1.13
1565407_at
LHX9
hexokinase domain containing 1


36
0.002585
5.1
5.6
1.10
232770_at
TUSC3
—


37
0.002613
6.4
5.6
−1.14
204475_at
MMP1
hypothetical protein LOC90784


38
0.002653
11.3
14.3
1.27
243349_at
KIAA1324
thyroid hormone receptor, beta (erythroblastic leukemia









viral (v-erb-a) oncogene homolog 2, avian)


39
0.002726
5.7
5.1
−1.12
240604_at
EXOD1
chromosome 3 open reading frame 41


40
0.002734
6
5.6
−1.07
210096_at
CYP4B1
RNA binding protein with multiple splicing 2


41
0.00279
39.3
22
−1.79
228390_at
EST12
hypothetical protein LOC729680


42
0.002791
6.3
6.9
1.10
228977_at
LOC729680
nuclear receptor subfamily 2, group F, member 2


43
0.002822
9.5
10.6
1.12
213807_x_at
MET
zinc finger protein 502


44
0.002834
7.9
6.7
−1.18
228716_at
THRB
CDNA FLJ90800 fis, clone Y79AA1000127


45
0.002911
6.1
10.7
1.75
1560800_at
EST13
clarin 3


46
0.00312
12.6
14.3
1.13
1567060_at
OR8G1
—


47
0.003341
24.1
19.6
−1.23
223497_at
FAM135A
Betaine:homocysteine methyltransferase


48
0.003942
5.3
5.9
1.11
211524_at
NFKB2
tumor suppressor candidate 3


49
0.003954
14.2
12.3
−1.15
241261_x_at
EST14
sperm flagellar 2


50
0.003958
12.1
10.5
−1.15
243048_at
CECR7
centrosomal protein 63 kDa




















TABLE E







International





Protein



Index/UniGene
Symbol
Entrez Gene Name



















1
Hs.103854
DOK1
docking protein 1, 62 kDa (downstream of tyrosine kinase 1)


2
Hs.109752
C6ORF108
chromosome 6 open reading frame 108


3
Hs.110675
APOC1
apolipoprotein C-I


4
Hs.116459
MAN2A2
mannosidase, alpha, class 2A, member 2


5
Hs.117331
TREML1
triggering receptor expressed on myeloid cells-like 1


6
Hs.119177
ARF3
ADP-ribosylation factor 3


7
Hs.123198
MYO9B
myosin IXB


8
Hs.134084
M6PR
mannose-6-phosphate receptor (cation dependent)


9
Hs.151135
FN3K
fructosamine 3 kinase


10
Hs.159509
SERPINF2
serpin peptidase inhibitor, clade F (alpha-2 antiplasmin, pigment epithelium derived factor),





member 2


11
Hs.190334
RAP1A
RAP1A, member of RAS oncogene family


12
Hs.191215
CYTH1
cytohesin 1


13
Hs.202
TSPO
translocator protein (18 kDa)


14
Hs.203637
PLS1
plastin 1 (I isoform)


15
Hs.226007
RDH11
retinol dehydrogenase 11 (all-trans/9-cis/11-cis)


16
Hs.24178
EML2
echinoderm microtubule associated protein like 2


17
Hs.24258
GUCY1A3
guanylate cyclase 1, soluble, alpha 3


18
Hs.24889
FMN2
formin 2


19
Hs.260750
SNX12
sorting nexin 12


20
Hs.277624
ZZEF1
zinc finger, ZZ-type with EF-hand domain 1


21
Hs.287714
RAB32
RAB32, member RAS oncogene family


22
Hs.301412
UFC1
ubiquitin-fold modifier conjugating enzyme 1


23
Hs.306327
RAB3GAP1
RAB3 GTPase activating protein subunit 1 (catalytic)


24
Hs.327527
SMARCA4
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a,





member 4


25
Hs.363396
CFH
complement factor H


26
Hs.368078
DNAJA2
DnaJ (Hsp40) homolog, subfamily A, member 2


27
Hs.368527
TOLLIP
toll interacting protein


28
Hs.368626
RTN1
reticulon 1


29
Hs.369840
NID2
nidogen 2 (osteonidogen)


30
Hs.376933
GUK1
guanylate kinase 1


31
Hs.38449
SERPINE2
serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2


32
Hs.390567
FYN
FYN oncogene related to SRC, FGR, YES


33
Hs.390667
GSTK1
glutathione S-transferase kappa 1


34
Hs.411312
ITGA2B
integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen CD41)




(includes




EG: 3674)


35
Hs.414795
SERPINE1
serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 1


36
Hs.416848
CTSW
cathepsin W


37
Hs.420529
UBE2V1
ubiquitin-conjugating enzyme E2 variant 1


38
Hs.429608
REEP5
receptor accessory protein 5


39
Hs.433068
PRKAR2B
protein kinase, cAMP-dependent, regulatory, type II, beta


40
Hs.435291
ARHGAP6
Rho GTPase activating protein 6


41
Hs.435512
PPP3CA
protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform


42
Hs.438906
C22ORF30
chromosome 22 open reading frame 30


43
Hs.443976
CEP250
centrosomal protein 250 kDa


44
Hs.458917
SCAMP2
secretory carrier membrane protein 2


45
Hs.460109
MYH11
myosin, heavy chain 11, smooth muscle


46
Hs.462379
TOM1L2
target of myb1-like 2 (chicken)


47
Hs.464813
PSMA8
proteasome (prosome, macropain) subunit, alpha type, 8


48
Hs.465295
LMAN1
lectin, mannose-binding, 1


49
Hs.466910
CDA
cytidine deaminase


50
Hs.477009
USP24
ubiquitin specific peptidase 24


51
Hs.477352
PDIA5
protein disulfide isomerase family A, member 5


52
Hs.4779
GATAD2B
GATA zinc finger domain containing 2B


53
Hs.480364
METAP1
methionyl aminopeptidase 1


54
Hs.481836
MTMR12
myotubularin related protein 12


55
Hs.481860
TARS
threonyl-tRNA synthetase


56
Hs.482873
TMED5
transmembrane emp24 protein transport domain containing 5


57
Hs.487540
RPA3
replication protein A3, 14 kDa


58
Hs.49582
PPP1R12A
protein phosphatase 1, regulatory (inhibitor) subunit 12A


59
Hs.501200
RGS10
regulator of G-protein signaling 10


60
Hs.502244
EIF3M
eukaryotic translation initiation factor 3, subunit M


61
Hs.50382
TJP2
tight junction protein 2 (zona occludens 2)


62
Hs.506603
APPL2
adaptor protein, phosphotyrosine interaction, PH domain and leucine zipper containing 2


63
Hs.513055
WDR61
WD repeat domain 61


64
Hs.513646
IVD
isovaleryl Coenzyme A dehydrogenase


65
Hs.514012
MAP2K3
mitogen-activated protein kinase kinase 3


66
Hs.514199
VAT1
vesicle amine transport protein 1 homolog (T. californica)


67
Hs.514870
ATP5F1
ATP synthase, H+ transporting, mitochondrial F0 complex, subunit B1


68
Hs.520048
HLA-DRA
major histocompatibility complex, class II, DR alpha


69
Hs.524518
STAT6
signal transducer and activator of transcription 6, interleukin-4 induced


70
Hs.525419
LIMA1
LIM domain and actin binding 1


71
Hs.528952
TRIM25
tripartite motif-containing 25


72
Hs.529023
ZNF532
zinc finger protein 532


73
Hs.530096
EIF3I (includes
eukaryotic translation initiation factor 3, subunit I




EG: 8668)


74
Hs.573495
SLC44A1
solute carrier family 44, member 1


75
Hs.578450
MESDC2
mesoderm development candidate 2


76
Hs.584790
PPP2R1B
protein phosphatase 2 (formerly 2A), regulatory subunit A, beta isoform


77
Hs.592771
DGKG
diacylglycerol kinase, gamma 90 kDa


78
Hs.620557
ANK2
ankyrin 2, neuronal


79
Hs.631569
PPP1R14A
protein phosphatase 1, regulatory (inhibitor) subunit 14A


80
Hs.63348
EMILIN1
elastin microfibril interfacer 1


80
Hs.63348
EMILIN1
elastin microfibril interfacer 1


81
Hs.64016
PROS1
protein S (alpha)


82
Hs.647018
CLIP2
CAP-GLY domain containing linker protein 2


83
Hs.647064
RARRES2
retinoic acid receptor responder (tazarotene induced) 2


84
Hs.653263
CEP110
centrosomal protein 110 kDa


85
Hs.654404
HLA-C
major histocompatibility complex, class I, C


86
Hs.654439
APOE
apolipoprotein E


87
Hs.654473
MAOB
monoamine oxidase B


88
Hs.654581
PRPS2
phosphoribosyl pyrophosphate synthetase 2


89
Hs.654634
CDC42BPB
CDC42 binding protein kinase beta (DMPK-like)


90
Hs.655207
F2
coagulation factor II (thrombin)


91
Hs.655361
HPR (includes
haptoglobin-related protein




EG: 3250)


92
Hs.656274
TNFAIP8
tumor necrosis factor, alpha-induced protein 8


93
Hs.656726
STRN
striatin, calmodulin binding protein


94
Hs.658434
PSIP1
PC4 and SFRS1 interacting protein 1


95
Hs.660130
CD226
CD226 molecule


96
Hs.695926
RASA1
RAS p21 protein activator (GTPase activating protein) 1


97
Hs.696074
DHX15
DEAH (Asp-Glu-Ala-His) box polypeptide 15


98
Hs.696326
ANO6
anoctamin 6


99
Hs.699154
LYN
v-yes-1 Yamaguchi sarcoma viral related oncogene homolog


100
Hs.7486
ETHE1
ethylmalonic encephalopathy 1


101
Hs.7753
CALU
calumenin


102
Hs.77741
KNG1 (includes
kininogen 1




EG: 3827)


103
Hs.79322
QARS
glutaminyl-tRNA synthetase


104
Hs.8004
KALRN
kalirin, RhoGEF kinase


105
Hs.81934
ACADSB
acyl-Coenzyme A dehydrogenase, short/branched chain


106
Hs.90061
PGRMC1
progesterone receptor membrane component 1


107
Hs.904
AGL
amylo-1,6-glucosidase, 4-alpha-glucanotransferase


108
IPI00010951
EPPK1
epiplakin 1


109
IPI00011891
PRKAA1
protein kinase, AMP-activated, alpha 1 catalytic subunit


110
IPI00165421
SERPINC1
serpin peptidase inhibitor, clade C (antithrombin), member 1


111
IPI00301271
RPN2
ribophorin II


112
IPI00382606
F7
coagulation factor VII (serum prothrombin conversion accelerator)


113
IPI00448925
IGHG1
immunoglobulin heavy constant gamma 1 (G1m marker)


114
IPI00783829
IPO5
importin 5


115
IPI00787190
HLA-B
major histocompatibility complex, class I, B


116
IPI00788786
VWF
von Willebrand factor


117
IPI00797856
HPSE
heparanase




















TABLE F







International





Protein



Index/UniGene
Symbol
Entrez Gene Name



















1
IPI00001753
MYH4
myosin, heavy chain 4, skeletal muscle


2
Hs.110837
TUBB4
tubulin, beta 4


3
Hs.132499
ARPC5L
actin related protein 2/3 complex, subunit 5-like




(includes




EG: 81873)


4
Hs.133892
TPM1
tropomyosin 1 (alpha)


5
Hs.143046
CORO6
coronin 6


6
Hs.1437
GAA
glucosidase, alpha; acid


7
Hs.143703
EHD4
EH-domain containing 4


8
Hs.147433
PCNA
proliferating cell nuclear antigen


9
Hs.148641
CTSH
cathepsin H


10
Hs.154078
LBP
lipopolysaccharide binding protein


11
Hs.156367
RPS29
ribosomal protein S29


12
Hs.158339
SERPINB10
serpin peptidase inhibitor, clade B (ovalbumin), member 10


13
Hs.161357
PDHB (includes
pyruvate dehydrogenase (lipoamide) beta




EG: 5162)


14
Hs.16355
MYH10
myosin, heavy chain 10, non-muscle


15
Hs.163867
CD14
CD14 molecule


16
Hs.164144
EIF5A2
eukaryotic translation initiation factor 5A2


17
Hs.169284
PRPS1L1
phosphoribosyl pyrophosphate synthetase 1-like 1


18
Hs.169900
PABPC4
poly(A) binding protein, cytoplasmic 4 (inducible form)


19
Hs.170310
CECR1
cat eye syndrome chromosome region, candidate 1


20
Hs.171626
SKP1
S-phase kinase-associated protein 1


21
Hs.173043
MTA2
metastasis associated 1 family, member 2


22
Hs.188401
ANXA10
annexin A10


23
Hs.189409
FNBP1
formin binding protein 1


24
Hs.196437
MOBKL1B
MOB1, Mps One Binder kinase activator-like 1B (yeast)


25
Hs.200333
APOB48R
apolipoprotein B48 receptor


26
Hs.213470
PSMB7
proteasome (prosome, macropain) subunit, beta type, 7


27
Hs.220594
CCDC58
coiled-coil domain containing 58


28
Hs.224171
ENO3
enolase 3 (beta, muscle)


29
Hs.236030
SMARCC2
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily c,




(includes
member 2




EG: 6601)


30
Hs.248746
AGXT2L2
alanine-glyoxylate aminotransferase 2-like 2


31
Hs.252549
CTSZ (includes
cathepsin Z




EG: 1522)


32
Hs.258314
BRE
brain and reproductive organ-expressed (TNFRSF1A modulator)


33
Hs.263812
NUDC
nuclear distribution gene C homolog (A. nidulans)


34
Hs.268963
UBAP1
ubiquitin associated protein 1


35
Hs.279640
TPR
translocated promoter region (to activated MET oncogene)


36
Hs.282901
RBM39
RNA binding motif protein 39


37
Hs.284491
PDXK
pyridoxal (pyridoxine, vitamin B6) kinase


38
Hs.309090
SFRS7
splicing factor, arginine/serine-rich 7, 35 kDa


39
Hs.3100
KARS
lysyl-tRNA synthetase


40
Hs.31053
TBCB
tubulin folding cofactor B


41
Hs.319334
NASP
nuclear autoantigenic sperm protein (histone-binding)


42
Hs.325978
NUMA1
nuclear mitotic apparatus protein 1


43
Hs.335034
DPYD
dihydropyrimidine dehydrogenase


44
Hs.337766
RPL18A
ribosomal protein L18a


45
Hs.3439
STOML2
stomatin (EPB72)-like 2


46
Hs.356604
WNK1
WNK lysine deficient protein kinase 1


47
Hs.368077
SERPINB8
serpin peptidase inhibitor, clade B (ovalbumin), member 8


48
Hs.368203
DOCK11
dedicator of cytokinesis 11


49
Hs.368266
CLTCL1
clathrin, heavy chain-like 1


50
Hs.36927
HSPH1
heat shock 105 kDa/110 kDa protein 1


51
Hs.369373
SEC23B
Sec23 homolog B (S. cerevisiae)


52
Hs.375957
ITGB2
integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)


53
Hs.376933
GUK1
guanylate kinase 1


54
Hs.388664
RPL11
ribosomal protein L11


55
Hs.403436
DCI
dodecenoyl-Coenzyme A delta isomerase (3,2 trans-enoyl-Coenzyme A isomerase)


56
Hs.406423
SF3B2
splicing factor 3b, subunit 2, 145 kDa


57
Hs.407190
FKBP5
FK506 binding protein 5


58
Hs.408061
FABP5
fatty acid binding protein 5 (psoriasis-associated)


59
Hs.408236
TXNDC17
thioredoxin domain containing 17


60
Hs.409834
PHPT1
phosphohistidine phosphatase 1


61
Hs.412117
ANXA6
annexin A6


62
Hs.429180
EIF2S2
eukaryotic translation initiation factor 2, subunit 2 beta, 38 kDa


63
Hs.432674
LARS
leucyl-tRNA synthetase


64
Hs.433222
NPC2
Niemann-Pick disease, type C2


65
Hs.434996
GIT2
G protein-coupled receptor kinase interacting ArfGAP 2


66
Hs.437385
NECAP2
NECAP endocytosis associated 2


67
Hs.440895
MYH3
myosin, heavy chain 3, skeletal muscle, embryonic


68
Hs.440932
9-Sep
septin 9


69
Hs.460002
FLJ11151
hypothetical protein FLJ11151


70
Hs.461925
RPA1
replication protein A1, 70 kDa


71
Hs.465224
NARS
asparaginyl-tRNA synthetase


72
Hs.465761
ARHGEF18
rho/rac guanine nucleotide exchange factor (GEF) 18


73
Hs.465924
SDHB (includes
succinate dehydrogenase complex, subunit B, iron sulfur (lp)




EG: 6390)


74
Hs.470627
LCK
lymphocyte-specific protein tyrosine kinase


75
Hs.471207
NDUFS1
NADH dehydrogenase (ubiquinone) Fe—S protein 1, 75 kDa (NADH-coenzyme Q reductase)


76
Hs.477126
ATG3
ATG3 autophagy related 3 homolog (S. cerevisiae)


77
Hs.484412
EXOC2
exocyst complex component 2


78
Hs.491440
PPP2CB
protein phosphatase 2 (formerly 2A), catalytic subunit, beta isoform


79
Hs.494496
FBP1
fructose-1,6-bisphosphatase 1


80
Hs.494595
TMOD1
tropomodulin 1


81
Hs.497599
WARS
tryptophanyl-tRNA synthetase


82
Hs.502328
CD44
CD44 molecule (Indian blood group)


83
Hs.502756
AHNAK
AHNAK nucleoprotein


84
Hs.505033
KRAS
v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog


85
Hs.5086
RBM42
RNA binding motif protein 42


86
Hs.508738
ARHGEF7
Rho guanine nucleotide exchange factor (GEF) 7


87
Hs.509736
HSP90AB1
heat shock protein 90 kDa alpha (cytosolic), class B member 1


88
Hs.513726
GBP5
guanylate binding protein 5


89
Hs.514495
SRP68
signal recognition particle 68 kDa


90
Hs.514581
ACTG1
actin, gamma 1


91
Hs.517307
MX1
myxovirus (influenza virus) resistance 1, interferon-inducible protein p78 (mouse)


92
Hs.517949
MAP4
microtubule-associated protein 4


93
Hs.518198
CSTA (includes
cystatin A (stefin A)




EG: 1475)


94
Hs.518662
FAM129A
family with sequence similarity 129, member A


95
Hs.521924
PUF60
poly-U binding splicing factor 60 KDa


96
Hs.529989
RNASET2
ribonuclease T2


97
Hs.531176
SARS
seryl-tRNA synthetase


98
Hs.531807
ARHGAP25
Rho GTPase activating protein 25


99
Hs.534350
SMARCB1
SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b,





member 1


100
Hs.534770
PKM2
pyruvate kinase, muscle


101
Hs.535581
TPM3
tropomyosin 3


102
Hs.55682
EIF3D
eukaryotic translation initiation factor 3, subunit D


103
Hs.583855
SNX6
sorting nexin 6


104
Hs.587558
NCF2
neutrophil cytosolic factor 2


105
Hs.591176
DYNLL2
dynein, light chain, LC8-type 2


106
Hs.591768
BTF3
basic transcription factor 3


107
Hs.591922
SLK
STE20-like kinase (yeast)


108
Hs.632733
ALDH2
aldehyde dehydrogenase 2 family (mitochondrial)


109
Hs.643487
ACAA1
acetyl-Coenzyme A acyltransferase 1


110
Hs.649475
RPL24
ribosomal protein L24


111
Hs.654404
HLA-C
major histocompatibility complex, class I, C


112
Hs.654408
NFKB1
nuclear factor of kappa light polypeptide gene enhancer in B-cells 1


113
Hs.654429
SEC24C
SEC24 family, member C (S. cerevisiae)




(includes




EG: 9632)


114
Hs.654521
WIPF1
WAS/WASL interacting protein family, member 1


115
Hs.654543
TUBB2A
tubulin, beta 2A


116
Hs.654597
ACAP2
ArfGAP with coiled-coil, ankyrin repeat and PH domains 2


117
Hs.655196
HP
haptoglobin


118
Hs.656726
STRN
striatin, calmodulin binding protein


119
Hs.656870
SLC25A24
solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 24


120
Hs.687055
PARP14
poly (ADP-ribose) polymerase family, member 14


121
Hs.68714
SFRS1
splicing factor, arginine/serine-rich 1


122
Hs.690634
HSPA1L
heat shock 70 kDa protein 1-like


123
Hs.69293
HEXB
hexosaminidase B (beta polypeptide)


124
Hs.695973
HNRNPK
heterogeneous nuclear ribonucleoprotein K


125
Hs.699408
CLINT1
clathrin interactor 1


126
Hs.699441
NFATC2
nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 2


127
Hs.73839
RNASE3
ribonuclease, RNase A family, 3 (eosinophil cationic protein)


128
Hs.74368
CKAP4
cytoskeleton-associated protein 4


129
Hs.77254
CBX1
chromobox homolog 1 (HP1 beta homolog Drosophila)


130
Hs.77897
SF3A3
splicing factor 3a, subunit 3, 60 kDa


131
Hs.78880
ILVBL
ilvB (bacterial acetolactate synthase)-like


132
Hs.79110
NCL
nucleolin


133
Hs.8360
C11ORF54
chromosome 11 open reading frame 54


134
Hs.83753
SNRPB
small nuclear ribonucleoprotein polypeptides B and B1


135
Hs.861
MAPK3
mitogen-activated protein kinase 3


136
Hs.99936
KRT10
keratin 10


137
IPI00074489
NDUFB10
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 10, 22 kDa


138
IPI00384938
IGHG1
immunoglobulin heavy constant gamma 1 (G1m marker)


139
IPI00396421
KIAA0776
KIAA0776


140
IPI00401105
RPS25
ribosomal protein S25


141
IPI00413108
RPSA (includes
ribosomal protein SA




EG: 3921)


142
IPI00456853
FAM21C
family with sequence similarity 21, member C


143
IPI00465022
SMCHD1
structural maintenance of chromosomes flexible hinge domain containing 1





















TABLE G










Fold Change



International


(positive numbers



Protein


are upregulated



Index/UniGene
Symbol
Entrez Gene Name
in B1)




















1
Hs.180062
PSMB8
proteasome (prosome, macropain) subunit, beta type, 8 (large
1.74748





multifunctional peptidase 7)


2
IPI00001539
ACAA2
acetyl-Coenzyme A acyltransferase 2
2.53112


3
Hs.412117
ANXA6
annexin A6
1.99146


4
Hs.90093
HSPA4
heat shock 70 kDa protein 4
2.72271


5
Hs.130316
DBN1
drebrin 1
−2.19867


6
IPI00003438
DNAJC8
DnaJ (Hsp40) homolog, subfamily C, member 8
2.74556


7
Hs.186350
RPL4
ribosomal protein L4
1.80696


8
Hs.175437
EPB41
erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked)
1.37195


9
Hs.2178
HIST2H2BE
histone cluster 2, H2be
1.73893


10
Hs.524630
UBE2N
ubiquitin-conjugating enzyme E2N (UBC13 homolog, yeast)
2.17574


11
Hs.411695
HK3
hexokinase 3 (white cell)
2.79458


12
Hs.489284
ARPC1B
actin related protein 2/3 complex, subunit 1B, 41 kDa
1.87474


13
Hs.514934
CAPZA1
capping protein (actin filament) muscle Z-line, alpha 1
1.77014


14
Hs.431279
NSF
N-ethylmaleimide-sensitive factor
4.20439


15
Hs.155975
PTPRCAP
protein tyrosine phosphatase, receptor type, C-associated protein
−1.77658


16
Hs.458272
MPO
myeloperoxidase
1.71345


17
Hs.433615
TUBB2C
tubulin, beta 2C
−1.76403


18
Hs.184233
HSPA9
heat shock 70 kDa protein 9 (mortalin)
6.35072


19
Hs.295917
ATP6V1B2
ATPase, H+ transporting, lysosomal 56/58 kDa, V1 subunit B2
2.24142


20
Hs.521640
RAD23B
RAD23 homolog B (S. cerevisiae)
1.96378


21
Hs.699880
RPS10
ribosomal protein S10
3.17111


22
Hs.546285
RPLP0 (includes
ribosomal protein, large, P0
2.03495




EG: 6175)


23
Hs.389649
EIF4A3 (includes
eukaryotic translation initiation factor 4A, isoform 3
1.89742




EG: 9775)


24
Hs.511251
SQRDL (includes
sulfide quinone reductase-like (yeast)
2.33602




EG: 58472)


25
Hs.26010
PFKP
phosphofructokinase, platelet
−2.73727


26
Hs.78888
DBI
diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme
2.47829





A binding protein)


27
Hs.405144
SFRS3
splicing factor, arginine/serine-rich 3
4.47655


28
Hs.413812
RAC1
ras-related C3 botulinum toxin substrate 1 (rho family, small GTP
2.76246





binding protein Rac1)


29
Hs.558351
KIF2A
kinesin heavy chain member 2A
−1.41796


30
Hs.355934
SFPQ
splicing factor proline/glutamine-rich (polypyrimidine tract binding
2.45856





protein associated)


31
Hs.464336
P4HB
prolyl 4-hydroxylase, beta polypeptide
2.20506


32
Hs.131151
PSMD9
proteasome (prosome, macropain) 26S subunit, non-ATPase, 9
−1.67257


33
Hs.247362
DDAH2
dimethylarginine dimethylaminohydrolase 2
1.98084


34
Hs.356654
PSMC1
proteasome (prosome, macropain) 26S subunit, ATPase, 1
2.36445


35
Hs.527105
HNRPDL
heterogeneous nuclear ribonucleoprotein D-like
5.14561


36
Hs.472838
STK4
serine/threonine kinase 4
1.65603


37
Hs.373763
HNRNPR
heterogeneous nuclear ribonucleoprotein R
3.23939


38
Hs.440898
FCN1
ficolin (collagen/fibrinogen domain containing) 1
3.12337


39
Hs.178551
RPL8
ribosomal protein L8
2.39479


40
Hs.644646
KIF5B
kinesin family member 5B
−1.81795


41
Hs.153837
MNDA
myeloid cell nuclear differentiation antigen
2.21411


42
Hs.627414
RPS18
ribosomal protein S18
2.94127


43
Hs.546287
RPS7
ribosomal protein S7
1.83705


44
Hs.497788
EPRS
glutamyl-prolyl-tRNA synthetase
1.99658


45
Hs.511743
TUBB3
tubulin, beta 3
−1.48195


46
Hs.270291
ACTN4
actinin, alpha 4
2.09181


47
Hs.119251
UQCRC1
ubiquinol-cytochrome c reductase core protein I
2.05968


48
Hs.699298
CDV3
CDV3 homolog (mouse)
1.35707


49
Hs.111779
SPARC
secreted protein, acidic, cysteine-rich (osteonectin)
−3.78710


50
Hs.651923
CNN2
calponin 2
2.25485


51
Hs.465511
GZMM
granzyme M (lymphocyte met-ase 1)
2.38354


52
Hs.2853
PCBP1 (includes
poly(rC) binding protein 1
1.65937




EG: 5093)


53
Hs.690198
CDC42
cell division cycle 42 (GTP binding protein, 25 kDa)
1.59084


54
Hs.271510
GSR
glutathione reductase
2.59620


55
Hs.406277
SF3A1
splicing factor 3a, subunit 1, 120 kDa
2.92334


56
Hs.571177
SYNCRIP
synaptotagmin binding, cytoplasmic RNA interacting protein
3.05703


57
Hs.695941
HK1
hexokinase 1
1.48167


58
Hs.250758
PSMC3
proteasome (prosome, macropain) 26S subunit, ATPase, 3
1.90255


59
Hs.707
KRT2
keratin 2
3.19828


60
Hs.594444
LMNA
lamin A/C
2.42545


61
Hs.2490
CASP1
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,
2.18090





convertase)


62
Hs.75307
H1FX
H1 histone family, member X
2.60755


63
Hs.534639
HADHB
hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
2.04804





thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), beta





subunit


64
Hs.30054
F5
coagulation factor V (proaccelerin, labile factor)
−2.31510


65
Hs.533040
PDLIM7
PDZ and LIM domain 7 (enigma)
−2.15116


66
Hs.665429
DDX17
DEAD (Asp-Glu-Ala-Asp) box polypeptide 17
2.97738


67
Hs.695185
NAP1L1
nucleosome assembly protein 1-like 1
−1.56121


68
Hs.75841
ERP29
endoplasmic reticulum protein 29
3.53236


69
Hs.523302
PRDX3
peroxiredoxin 3
1.71589


70
IPI00024989
PCMT1
protein-L-isoaspartate (D-aspartate) O-methyltransferase
2.22172


71
Hs.430606
CS
citrate synthase
−2.53628


72
Hs.520973
HSPB1
heat shock 27 kDa protein 1
1.89406


73
Hs.118958
STX11
syntaxin 11
−1.57367


74
Hs.610830
PRKCSH
protein kinase C substrate 80K-H
2.25450


75
Hs.14601
HCLS1
hematopoietic cell-specific Lyn substrate 1
2.13579


76
Hs.632828
HNRNPH2
heterogeneous nuclear ribonucleoprotein H2 (H′)
3.09381


77
Hs.694128
RPS14
ribosomal protein S14
2.10304


78
Hs.356624
NID1
nidogen 1
−4.10930


79
Hs.12084
TUFM
Tu translation elongation factor, mitochondrial
1.77413


80
Hs.95990
PKLR
pyruvate kinase, liver and RBC
2.55932


81
Hs.654614
HSPA6
heat shock 70 kDa protein 6 (HSP70B′)
1.28057


82
Hs.471441
PSMB2
proteasome (prosome, macropain) subunit, beta type, 2
3.18295


83
Hs.7744
NDUFV1
NADH dehydrogenase (ubiquinone) flavoprotein 1, 51 kDa
2.82524


84
Hs.480073
HNRNPD
heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA
2.72172





binding protein 1, 37 kDa)


85
Hs.98791
ACTR1B (includes
ARP1 actin-related protein 1 homolog B, centractin beta (yeast)
3.00772




EG: 10120)


86
IPI00029625
FLOT2
flotillin 2
3.53456


87
Hs.11355
TMPO
thymopoietin
3.65290


88
Hs.571841
RPL7
ribosomal protein L7
1.81095


89
Hs.699271
STAT1
signal transducer and activator of transcription 1, 91 kDa
2.36973


90
Hs.529451
DIAPH1
diaphanous homolog 1 (Drosophila)
1.44181


91
Hs.516032
HADHA
hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
4.43165





thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha





subunit


92
Hs.503043
CPT1A
carnitine palmitoyltransferase 1A (liver)
−1.45507


93
Hs.475074
PARVB
parvin, beta
−1.93236


94
Hs.655396
PSMD11
proteasome (prosome, macropain) 26S subunit, non-ATPase, 11
1.89081


95
Hs.122523
SND1
staphylococcal nuclease and tudor domain containing 1
2.96927


96
Hs.444075
UBASH3B
ubiquitin associated and SH3 domain containing, B
−1.85814


97
Hs.473144
CASS4
Cas scaffolding protein family member 4
−2.58235


98
Hs.436186
CAST
calpastatin
1.48337


99
Hs.465808
HNRNPM
heterogeneous nuclear ribonucleoprotein M
2.64995


100
Hs.506759
ATP2A2
ATPase, Ca++ transporting, cardiac muscle, slow twitch 2
−1.44671


101
Hs.535581
TPM3
tropomyosin 3
2.05422


102
Hs.654720
KIAA1967
KIAA1967
3.42772


103
Hs.515517
RPL18
ribosomal protein L18
3.72595


104
Hs.438429
RPS19
ribosomal protein S19
4.78644


105
IPI00216134
TPM1
tropomyosin 1 (alpha)
−1.36995


106
Hs.128548
WDR1
WD repeat domain 1
4.48437


107
Hs.519320
VDAC1
voltage-dependent anion channel 1
1.94443


108
Hs.512675
RPS8
ribosomal protein S8
3.35144


109
IPI00216633
EPB49
erythrocyte membrane protein band 4.9 (dematin)
−1.84863


110
Hs.496622
PLS3
plastin 3 (T isoform)
3.79198


111
Hs.654438
ANK1
ankyrin 1, erythrocytic
2.45336


112
Hs.417303
SPTB
spectrin, beta, erythrocytic
1.95917


113
Hs.89497
LMNB1
lamin B1
2.53206


114
Hs.172631
ITGAM
integrin, alpha M (complement component 3 receptor 3 subunit)
6.14877


115
Hs.652308
MTHFD1
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1,
1.36675





methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate





synthetase


116
Hs.411312
ITGA2B (includes
integrin, alpha 2b (platelet glycoprotein IIb of IIb/IIIa complex, antigen
3.09010




EG: 3674)
CD41)


117
Hs.76392
ALDH1A1
aldehyde dehydrogenase 1 family, member A1
−1.59383


118
Hs.500756
GOT1
glutamic-oxaloacetic transaminase 1, soluble (aspartate
1.42300





aminotransferase 1)


119
Hs.514196
RPL27
ribosomal protein L27
2.67384


120
Hs.445351
LGALS1
lectin, galactoside-binding, soluble, 1
2.14691


121
Hs.80828
KRT1
keratin 1
3.95879


122
Hs.654559
HNRNPL
heterogeneous nuclear ribonucleoprotein L
−3.40543


123
Hs.119825
SPTA1
spectrin, alpha, erythrocytic 1 (elliptocytosis 2)
1.66210


124
Hs.446588
RPS13
ribosomal protein S13
3.62921


125
Hs.433427
RPS17 (includes
ribosomal protein S17
4.39840




EG: 6218)


126
Hs.483305
HINT1
histidine triad nucleotide binding protein 1
−2.04047


127
Hs.476448
FLNB
filamin B, beta (actin binding protein 278)
−1.82786


128
Hs.350899
CAPN2
calpain 2, (m/II) large subunit
2.86704


129
Hs.520967
MDH2
malate dehydrogenase 2, NAD (mitochondrial)
2.20250


130
Hs.371563
RAB14
RAB14, member RAS oncogene family
1.66010


131
Hs.83722
EPS15
epidermal growth factor receptor pathway substrate 15
2.14994


132
Hs.580681
SAMHD1
SAM domain and HD domain 1
2.17687


133
Hs.88778
CBR1
carbonyl reductase 1
1.69648


134
Hs.497599
WARS
tryptophanyl-tRNA synthetase
1.58361


135
Hs.517622
UNC84B
unc-84 homolog B (C. elegans)
1.78160


136
Hs.523145
DDOST
dolichyl-diphosphooligosaccharide-protein glycosyltransferase
1.71412


137
Hs.539684
EIF2S3
eukaryotic translation initiation factor 2, subunit 3 gamma, 52 kDa
2.09125


138
Hs.201978
PTGS1
prostaglandin-endoperoxide synthase 1 (prostaglandin G/H synthase
−1.72382





and cyclooxygenase)


139
Hs.370770
XPO1
exportin 1 (CRM1 homolog, yeast)
2.13295


140
Hs.696016
SNX2
sorting nexin 2
1.83066


141
Hs.181301
CTSS
cathepsin S
2.66342


142
Hs.204238
LCN2
lipocalin 2
−2.88567


143
Hs.212102
PDIA6
protein disulfide isomerase family A, member 6
2.67256


144
Hs.465041
HDHD2
haloacid dehalogenase-like hydrolase domain containing 2
1.58049


145
Hs.125113
CCT8
chaperonin containing TCP1, subunit 8 (theta)
2.74083


146
Hs.218040
ITGB3
integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)
−2.86872


147
Hs.126941
FAM49B
family with sequence similarity 49, member B
2.41970


148
Hs.140452
M6PRBP1
mannose-6-phosphate receptor binding protein 1
2.45483


149
Hs.591940
APOA4
apolipoprotein A-IV
2.29544


150
Hs.519756
STK10
serine/threonine kinase 10
2.91394


151
Hs.274402
HSPA1A
heat shock 70 kDa protein 1A
3.13788


152
Hs.571886
AKR7A2
aldo-keto reductase family 7, member A2 (aflatoxin aldehyde
2.51928





reductase)


153
Hs.599481
EIF4A2
eukaryotic translation initiation factor 4A, isoform 2
3.52387


154
Hs.352224
EDARADD
EDAR-associated death domain
7.46803


155
Hs.534385
THOC4
THO complex 4
−1.32827


156
Hs.528668
RPL6
ribosomal protein L6
3.03691


157
Hs.368084
LRPPRC
leucine-rich PPR-motif containing
−1.71518


158
Hs.632717
MYL6
myosin, light chain 6, alkali, smooth muscle and non-muscle
3.02347


159
Hs.482043
NNT
nicotinamide nucleotide transhydrogenase
2.26497


160
Hs.525600
HSP90AA1
heat shock protein 90 kDa alpha (cytosolic), class A member 1
2.84841


161
Hs.513530
TGFB1I1
transforming growth factor beta 1 induced transcript 1
−2.45685


162
Hs.369920
RAP1B
RAP1B, member of RAS oncogene family
−2.37368


163
Hs.148340
RPL10A (includes
ribosomal protein L10a
1.99620




EG: 4736)


164
Hs.200716
MECP2
methyl CpG binding protein 2 (Rett syndrome)
2.99376


165
Hs.642813
VIM
vimentin
1.75207


166
Hs.570791
LAP3
leucine aminopeptidase 3
2.49300


167
Hs.516539
HNRNPA3
heterogeneous nuclear ribonucleoprotein A3
1.70158


168
Hs.356572
RPS3A
ribosomal protein S3A
3.02357


169
Hs.518530
PAK2
p21 protein (Cdc42/Rac)-activated kinase 2
2.61046


170
Hs.37617
MYO1G
myosin IG
2.16324


171
Hs.467408
TRIM28
tripartite motif-containing 28
2.84983


172
Hs.136905
HUWE1
HECT, UBA and WWE domain containing 1
1.88641


173
IPI00464990
GP1BB
glycoprotein Ib (platelet), beta polypeptide
−1.88206


174
Hs.617193
CYCS (includes
cytochrome c, somatic
1.64385




EG: 54205)


175
Hs.595053
HSPD1
heat shock 60 kDa protein 1 (chaperonin)
1.76318


176
Hs.534770
PKM2
pyruvate kinase, muscle
1.27869


177
Hs.166463
HNRNPU
heterogeneous nuclear ribonucleoprotein U (scaffold attachment factor
2.79696





A)


178
Hs.2533
ALDH9A1
aldehyde dehydrogenase 9 family, member A1
1.38474


179
Hs.700575
STMN1
stathmin 1/oncoprotein 18
2.31540


180
Hs.530687
RNH1
ribonuclease/angiogenin inhibitor 1
1.64737


181
Hs.696144
TXNRD1
thioredoxin reductase 1
1.70635


182
Hs.502756
AHNAK
AHNAK nucleoprotein
6.50929


183
Hs.10842
RAN
RAN, member RAS oncogene family
2.05198


184
Hs.311609
DDX39
DEAD (Asp-Glu-Ala-Asp) box polypeptide 39
2.85922


185
Hs.533273
UBA1
ubiquitin-like modifier activating enzyme 1
1.88773


186
Hs.695946
ITGB1
integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29
−3.90341





includes MDF2, MSK12)


187
IPI00646888
1-Sep
septin 1
2.21854


188
Hs.546292
RPS27A
ribosomal protein S27a
−1.51316




















TABLE H







International





Protein



Index/



UniGene
Symbol
Entrez Gene Name



















1
Hs.1012
C4BPA
complement component 4 binding





protein, alpha


2
Hs.110675
APOC1
apolipoprotein C-I


3
Hs.116448
GLS
Glutaminase


4
Hs.191215
CYTH1
cytohesin 1


5
Hs.202
TSPO
translocator protein (18 kDa)


6
Hs.203637
PLS1
plastin 1 (I isoform)


7
Hs.24889
FMN2
formin 2


8
Hs.327527
SMARCA4
SWI/SNF related, matrix associated,





actin dependent regulator of chromatin,





subfamily a, member 4


9
Hs.352224
EDARADD
EDAR-associated death domain


10
Hs.464813
PSMA8
proteasome (prosome, macropain)





subunit, alpha type, 8


11
Hs.466910
CDA
cytidine deaminase


12
Hs.4779
GATAD2B
GATA zinc finger domain containing





2B


13
Hs.482873
TMED5
transmembrane emp24 protein





transport domain containing 5


14
Hs.501200
RGS10
regulator of G-protein signaling 10


15
Hs.518750
OCIAD1
OCIA domain containing 1


16
Hs.529023
ZNF532
zinc finger protein 532


17
Hs.594444
LMNA
lamin A/C


18
Hs.620557
ANK2
ankyrin 2, neuronal


19
Hs.653263
CEP110
centrosomal protein 110 kDa


20
Hs.654438
ANK1
ankyrin 1, erythrocytic


21
Hs.69771
CFB
complement factor B


22
Hs.77741
KNG1
kininogen 1




(includes




EG: 3827)


23
Hs.83634
HCFC1
host cell factor C1 (VP16-accessory





protein)


24
IPI00010951
EPPK1
epiplakin 1


25
IPI00382606
F7
coagulation factor VII (serum





prothrombin conversion accelerator)


26
IPI00641229
IGHA2
immunoglobulin heavy constant alpha





2 (A2m marker)


27
IPI00645452
TUBB
tubulin, beta


28
IPI00787190
HLA-B
major histocompatibility complex,





class I, B




















TABLE I







Unigene/IPI
Symbol
Entrez Gene Name



















1
Hs.406758
HIBADH
3-hydroxyisobutyrate dehydrogenase


2
Hs.656685
HIBCH
3-hydroxyisobutyryl-Coenzyme A hydrolase


3
Hs.643487
ACAA1
acetyl-Coenzyme A acyltransferase 1


4
Hs.558296
ACP1
acid phosphatase 1, soluble


5
Hs.514581
ACTG1
actin, gamma 1


6
Hs.461727
ACSF3
acyl-CoA synthetase family member 3


7
Hs.464137
ACOX1
acyl-Coenzyme A oxidase 1, palmitoyl


8
Hs.512815
AP3D1
adaptor-related protein complex 3, delta 1 subunit


9
Hs.470907
AK2
adenylate kinase 2


10
Hs.525330
ARF6
ADP-ribosylation factor 6


11
Hs.62578
ARFGEF2
ADP-ribosylation factor guanine nucleotide-exchange factor 2 (brefeldin A-inhibited)


12
Hs.418167
ALB
albumin


13
Hs.632733
ALDH2
aldehyde dehydrogenase 2 family (mitochondrial)


14
Hs.591631
AGPS
alkylglycerone phosphate synthase


15
Hs.499725
ANK3
ankyrin 3, node of Ranvier (ankyrin G)


16
Hs.696087
ANKFY1
ankyrin repeat and FYVE domain containing 1


17
Hs.412117
ANXA6
annexin A6


18
Hs.3346
ANXA9
annexin A9


19
Hs.435771
API5
apoptosis inhibitor 5


20
Hs.503165
ARAP1
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain 1


21
Hs.465224
NARS
asparaginyl-tRNA synthetase


22
Hs.477126
ATG3
ATG3 autophagy related 3 homolog (S. cerevisiae)


23
Hs.486063
ATG5 (includes
ATG5 autophagy related 5 homolog (S. cerevisiae)




EG: 9474)


24
Hs.584905
ATL1
atlastin GTPase 1


25
Hs.85539
ATP5I
ATP synthase, H+ transporting, mitochondrial F0 complex, subunit E


26
Hs.656515
ATP5J2
ATP synthase, H+ transporting, mitochondrial F0 complex, subunit F2


27
Hs.444957
ATP8A2
ATPase, aminophospholipid transporter-like, class I, type 8A, member 2


28
Hs.517338
ATP6V1E1
ATPase, H+ transporting, lysosomal 31 kDa, V1 subunit E1


29
Hs.491737
ATP6V1H
ATPase, H+ transporting, lysosomal 50/57 kDa, V1 subunit H


30
Hs.429294
ABCA1
ATP-binding cassette, sub-family A (ABC1), member 1


31
Hs.508423
ABCC4
ATP-binding cassette, sub-family C (CFTR/MRP), member 4


32
Hs.355983
BZW1
basic leucine zipper and W2 domains 1


33
Hs.591768
BTF3
basic transcription factor 3


34
Hs.494614
BAT2D1
BAT2 domain containing 1


35
Hs.631546
BAX
BCL2-associated X protein


36
Hs.654740
BRWD1
bromodomain and WD repeat domain containing 1


37
Hs.418533
BUB3
budding uninhibited by benzimidazoles 3 homolog (yeast)


38
IPI00797310
CLSTN3
calsyntenin 3


39
Hs.524809
CLIP1
CAP-GLY domain containing linker protein 1


40
Hs.699182
CPT2
carnitine palmitoyltransferase 2


41
Hs.504096
CBL
Cas-Br-M (murine) ecotropic retroviral transforming sequence


42
Hs.654616
CASP6
caspase 6, apoptosis-related cysteine peptidase


43
Hs.460232
CNOT1
CCR4-NOT transcription complex, subunit 1


44
Hs.485518
CD2AP
CD2-associated protein


45
Hs.502328
CD44
CD44 molecule (Indian blood group)


46
Hs.556638
CISD2
CDGSH iron sulfur domain 2


47
Hs.472027
CDS2
CDP-diacylglycerol synthase (phosphatidate cytidylyltransferase) 2


48
Hs.568242
CREG1
cellular repressor of E1A-stimulated genes 1


49
Hs.31819
C1ORF128
chromosome 1 open reading frame 128


50
Hs.368353
C1ORF71
chromosome 1 open reading frame 71


51
Hs.611057
C1ORF77
chromosome 1 open reading frame 77


52
Hs.462033
C1ORF93
chromosome 1 open reading frame 93


53
Hs.8360
C11ORF54
chromosome 11 open reading frame 54


54
Hs.530753
C11ORF59
chromosome 11 open reading frame 59


55
IPI00373869
C17ORF49
chromosome 17 open reading frame 49


56
Hs.368266
CLTCL1
clathrin, heavy chain-like 1


57
Hs.591506
MYCBP
c-myc binding protein


58
Hs.505652
COPZ1
coatomer protein complex, subunit zeta 1


59
Hs.655010
CHCHD3
coiled-coil-helix-coiled-coil-helix domain containing 3


60
Hs.369614
COPS2
COP9 constitutive photomorphogenic homolog subunit 2 (Arabidopsis)


61
Hs.502917
CCS
copper chaperone for superoxide dismutase


62
Hs.460923
CBFB
core-binding factor, beta subunit


63
Hs.372286
CUL3
cullin 3


64
Hs.518198
CSTA (includes
cystatin A (stefin A)




EG: 1475)


65
Hs.481898
CCBL2
cysteine conjugate-beta lyase 2


66
Hs.513803
CYBA
cytochrome b-245, alpha polypeptide


67
Hs.461131
CYB5B
cytochrome b5 type B (outer mitochondrial membrane)


68
IPI00017510
COX2
cytochrome c oxidase II


69
Hs.696092
CLASP2
cytoplasmic linker associated protein 2


70
Hs.99120
DDX3Y
DEAD (Asp-Glu-Ala-Asp) box polypeptide 3, Y-linked




(includes




EG: 8653)


71
Hs.75189
DAP
death-associated protein


72
Hs.368203
DOCK11
dedicator of cytokinesis 11


73
Hs.654567
DENND4A
DENN/MADD domain containing 4A


74
Hs.407618
DSG4
desmoglein 4


75
Hs.9857
DCXR
dicarbonyl/L-xylulose reductase


76
Hs.335551
DLAT
dihydrolipoamide S-acetyltransferase


77
Hs.37916
DPP7
dipeptidyl-peptidase 7


78
Hs.515210
DNAJB1
DnaJ (Hsp40) homolog, subfamily B, member 1


79
Hs.656476
DNAJC3
DnaJ (Hsp40) homolog, subfamily C, member 3


80
Hs.425801
DUSP23
dual specificity phosphatase 23


81
Hs.522413
DNM1
dynamin 1


82
Hs.529495
DYNC1LI1
dynein, cytoplasmic 1, light intermediate chain 1


83
Hs.591176
DYNLL2
dynein, light chain, LC8-type 2


84
Hs.4747
DKC1
dyskeratosis congenita 1, dyskerin


85
Hs.412103
EFHA1
EF-hand domain family, member A1


86
Hs.654553
ETFB (includes
electron-transfer-flavoprotein, beta polypeptide




EG: 2109)


87
Hs.509791
ERH
enhancer of rudimentary homolog (Drosophila)


88
Hs.429879
EHHADH
enoyl-Coenzyme A, hydratase/3-hydroxyacyl Coenzyme A dehydrogenase


89
Hs.419815
EGF
epidermal growth factor (beta-urogastrone)


90
Hs.477498
EEFSEC
eukaryotic elongation factor, selenocysteine-tRNA-specific


91
Hs.429180
EIF2S2
eukaryotic translation initiation factor 2, subunit 2 beta, 38 kDa


92
Hs.696322
EIF2C2
eukaryotic translation initiation factor 2C, 2


93
Hs.55682
EIF3D
eukaryotic translation initiation factor 3, subunit D


94
Hs.502244
EIF3M
eukaryotic translation initiation factor 3, subunit M


95
Hs.467084
EIF4G3
eukaryotic translation initiation factor 4 gamma, 3


96
Hs.433702
EIF5
eukaryotic translation initiation factor 5


97
Hs.483494
ETF1
eukaryotic translation termination factor 1


98
Hs.517293
F11R
F11 receptor


99
Hs.518662
FAM129A
family with sequence similarity 129, member A


100
Hs.490795
FAM62B
family with sequence similarity 62 (C2 domain containing) member B


101
Hs.335918
FDPS
farnesyl diphosphate synthase (farnesyl pyrophosphate synthetase,





dimethylallyltranstransferase, geranyltranstransferase)


102
Hs.86131
FADD (includes
Fas (TNFRSF6)-associated via death domain




EG: 8772)


103
Hs.408061
FABP5
fatty acid binding protein 5 (psoriasis-associated)


104
Hs.433300
FCER1G
Fc fragment of IgE, high affinity I, receptor for; gamma polypeptide


105
Hs.509343
FERMT2
fermitin family homolog 2 (Drosophila)


106
Hs.338207
FRAP1
FK506 binding protein 12-rapamycin associated protein 1


107
Hs.407190
FKBP5
FK506 binding protein 5


108
Hs.409065
FEN1
flap structure-specific endonuclease 1


109
Hs.494496
FBP1
fructose-1,6-bisphosphatase 1


110
Hs.654961
FUT8
fucosyltransferase 8 (alpha (1,6) fucosyltransferase)


111
Hs.390567
FYN
FYN oncogene related to SRC, FGR, YES


112
Hs.530024
GGCT
gamma-glutamyl cyclotransferase


113
Hs.27059
GMPPA
GDP-mannose pyrophosphorylase A


114
Hs.567488
GMPPB
GDP-mannose pyrophosphorylase B


115
Hs.591069
GBAS
glioblastoma amplified sequence


116
Hs.654465
GCLC
glutamate-cysteine ligase, catalytic subunit


117
Hs.390667
GSTK1
glutathione S-transferase kappa 1


118
Hs.59138
GYPC
glycophorin C (Gerbich blood group)


119
Hs.344151
GOLGA4
golgi autoantigen, golgin subfamily a, 4


120
Hs.431317
GORASP2
golgi reassembly stacking protein 2, 55 kDa


121
Hs.290243
GBF1
golgi-specific brefeldin A resistant guanine nucleotide exchange factor 1


122
Hs.485449
GTPBP2
GTP binding protein 2


123
Hs.495134
GAPVD1
GTPase activating protein and VPS9 domains 1


124
Hs.591450
GBP7
guanylate binding protein 7


125
Hs.655196
HP
haptoglobin


126
Hs.531785
HS1BP3
HCLS1 binding protein 3


127
Hs.36927
HSPH1
heat shock 105 kDa/110 kDa protein 1


128
Hs.690634
HSPA1L
heat shock 70 kDa protein 1-like


129
Hs.432648
HSPA2
heat shock 70 kDa protein 2


130
Hs.509736
HSP90AB1
heat shock protein 90 kDa alpha (cytosolic), class B member 1


131
Hs.525084
HECTD3
HECT domain containing 3


132
Hs.642618
HEBP1
heme binding protein 1


133
IPI00784636
HBB (includes
hemoglobin, beta




EG: 3043)


134
Hs.699280
HBD
hemoglobin, delta


135
Hs.502617
HNRNPCL1
heterogeneous nuclear ribonucleoprotein C-like 1


136
Hs.69293
HEXB
hexosaminidase B (beta polypeptide)


137
Hs.83634
HCFC1
host cell factor C1 (VP16-accessory protein)


138
Hs.460002
FLJ11151
hypothetical protein FLJ11151


139
Hs.78880
ILVBL
ilvB (bacterial acetolactate synthase)-like


140
IPI00384938
IGHG1
immunoglobulin heavy constant gamma 1 (G1m marker)


141
Hs.699240
IPO5
importin 5


142
Hs.434102
IKBKG
inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma


143
Hs.500546
IDE
insulin-degrading enzyme


144
Hs.513225
ITFG3
integrin alpha FG-GAP repeat containing 3


145
Hs.375957
ITGB2
integrin, beta 2 (complement component 3 receptor 3 and 4 subunit)


146
Hs.431460
ICAM2
intercellular adhesion molecule 2


147
Hs.591110
IDH3A
isocitrate dehydrogenase 3 (NAD+) alpha


148
Hs.515247
JAK3
Janus kinase 3 (a protein tyrosine kinase, leukocyte)


149
Hs.301613
JTV1
JTV1 gene


150
Hs.527919
KPNA3
karyopherin alpha 3 (importin alpha 4)


151
Hs.270043
KIAA0196
KIAA0196


152
Hs.368255
KIAA0368
KIAA0368


153
Hs.368282
KIAA0564
KIAA0564


154
IPI00396421
KIAA0776
KIAA0776


155
Hs.654497
LTBP1
latent transforming growth factor beta binding protein 1


156
Hs.478067
LXN
latexin


157
Hs.432674
LARS
leucyl-tRNA synthetase


158
Hs.700163
LY6G5B
lymphocyte antigen 6 complex, locus G5B


159
Hs.3100
KARS
lysyl-tRNA synthetase


160
Hs.654404
HLA-C
major histocompatibility complex, class I, C


161
Hs.75694
MPI
mannose phosphate isomerase


162
Hs.696082
MAPKSP1
MAPK scaffold protein 1


163
Hs.444969
MEMO1
mediator of cell motility 1




(includes




EG: 51072)


164
Hs.486189
MAGI3
membrane associated guanylate kinase, WW and PDZ domain containing 3


165
Hs.500842
MGEA5
meningioma expressed antigen 5 (hyaluronidase)


166
Hs.377155
MTDH
metadherin


167
Hs.516157
MAT2A
methionine adenosyltransferase II, alpha


168
Hs.252457
MVD
mevalonate (diphospho) decarboxylase


169
Hs.580782
MACF1
microtubule-actin crosslinking factor 1


170
Hs.517949
MAP4
microtubule-associated protein 4


171
Hs.515860
MAPRE3
microtubule-associated protein, RP/EB family, member 3


172
Hs.269944
MTCH2
mitochondrial carrier homolog 2 (C. elegans)


173
Hs.861
MAPK3
mitogen-activated protein kinase 3


174
Hs.507681
MAP3K7IP1
mitogen-activated protein kinase kinase kinase 7 interacting protein 1


175
Hs.643565
MAPKAPK2
mitogen-activated protein kinase-activated protein kinase 2


176
Hs.591221
MYCBP2
MYC binding protein 2


177
Hs.91531
MLLT6
myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila);





translocated to, 6


178
Hs.655278
MYOF
myoferlin


179
Hs.286226
MYO1C
myosin IC


180
IPI00719669
MRLC2
myosin regulatory light chain MRLC2


181
IPI00007858
MYH13
myosin, heavy chain 13, skeletal muscle


182
IPI00001753
MYH4
myosin, heavy chain 4, skeletal muscle


183
Hs.463300
MYL4
myosin, light chain 4, alkali; atrial, embryonic


184
Hs.926
MX2
myxovirus (influenza virus) resistance 2 (mouse)


185
Hs.527412
ASAH1
N-acylsphingosine amidohydrolase (acid ceramidase) 1


186
Hs.651219
NDUFA5
NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 5, 13 kDa


187
IPI00074489
NDUFB10
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 10, 22 kDa


188
Hs.532853
NDUFB7
NADH dehydrogenase (ubiquinone) 1 beta subcomplex, 7, 18 kDa


189
Hs.471207
NDUFS1
NADH dehydrogenase (ubiquinone) Fe—S protein 1, 75 kDa (NADH-coenzyme Q





reductase)


190
Hs.90443
NDUFS8
NADH dehydrogenase (ubiquinone) Fe—S protein 8, 23 kDa (NADH-coenzyme Q





reductase)


191
Hs.464572
NDUFV2
NADH dehydrogenase (ubiquinone) flavoprotein 2, 24 kDa


192
Hs.473937
NDUFV3
NADH dehydrogenase (ubiquinone) flavoprotein 3, 10 kDa


193
Hs.655006
NCKIPSD
NCK interacting protein with SH3 domain


194
Hs.603732
NCKAP1
NCK-associated protein 1


195
Hs.467759
NBAS
neuroblastoma amplified sequence


196
Hs.524116
NRGN
neurogranin (protein kinase C substrate, RC3)


197
Hs.587558
NCF2
neutrophil cytosolic factor 2


198
Hs.493164
NAPRT1
nicotinate phosphoribosyltransferase domain containing 1


199
Hs.696107
NEK9 (includes
NIMA (never in mitosis gene a)-related kinase 9




EG: 91754)


200
Hs.524082
NLRX1
NLR family member X1


201
Hs.532790
NMT1
N-myristoyltransferase 1


202
Hs.319334
NASP
nuclear autoantigenic sperm protein (histone-binding)


203
Hs.263812
NUDC
nuclear distribution gene C homolog (A. nidulans)


204
Hs.654408
NFKB1
nuclear factor of kappa light polypeptide gene enhancer in B-cells 1


205
Hs.325978
NUMA1
nuclear mitotic apparatus protein 1


206
Hs.79110
NCL
nucleolin


207
Hs.643487
NUP160
nucleoporin 160 kDa


208
Hs.555956
NUDT5
nudix (nucleoside diphosphate linked moiety X)-type motif 5


209
Hs.405410
OGT (includes
O-linked N-acetylglucosamine (GlcNAc) transferase (UDP-N-




EG: 8473)
acetylglucosamine:polypeptide-N-acetylglucosaminyl transferase)


210
Hs.695379
OPTN
optineurin


211
Hs.430849
OSBPL8
oxysterol binding protein-like 8


212
Hs.656789
PAK3
p21 protein (Cdc42/Rac)-activated kinase 3


213
Hs.98475
PNKD (includes
paroxysmal nonkinesigenic dyskinesia




EG: 25953)


214
Hs.495471
PMPCA
peptidase (mitochondrial processing) alpha


215
Hs.33455
PADI2
peptidyl arginine deiminase, type II


216
IPI00745933
PPIA (includes
peptidylprolyl isomerase A (cyclophilin A)




EG: 5478)


217
Hs.644938
PCYT2
phosphate cytidylyltransferase 2, ethanolamine


218
Hs.372295
PITPNM1
phosphatidylinositol transfer protein, membrane-associated 1


219
Hs.272759
PITPNM2
phosphatidylinositol transfer protein, membrane-associated 2


220
Hs.75812
PCK2
phosphoenolpyruvate carboxykinase 2 (mitochondrial)


221
Hs.75160
PFKM
phosphofructokinase, muscle


222
Hs.26612
PGM2L1
phosphoglucomutase 2-like 1


223
Hs.487296
PHGDH
phosphoglycerate dehydrogenase


224
IPI00786982
PGAM5
phosphoglycerate mutase family member 5


225
Hs.409834
PHPT1
phosphohistidine phosphatase 1


226
Hs.32942
PIK3CG
phosphoinositide-3-kinase, catalytic, gamma polypeptide


227
Hs.591953
PLCB3
phospholipase C, beta 3 (phosphatidylinositol-specific)


228
Hs.413111
PLCG2
phospholipase C, gamma 2 (phosphatidylinositol-specific)


229
Hs.517216
PEA15
phosphoprotein enriched in astrocytes 15


230
Hs.675491
PLXNA4
plexin A4


231
Hs.632833
PLXNB3
plexin B3


232
Hs.348609
PARP10
poly (ADP-ribose) polymerase family, member 10


233
Hs.482038
PAIP1
poly(A) binding protein interacting protein 1


234
Hs.507910
PGRMC2
progesterone receptor membrane component 2


235
Hs.567410
PSMD14
proteasome (prosome, macropain) 26S subunit, non-ATPase, 14


236
IPI00555590
PSMB2
proteasome (prosome, macropain) subunit, beta type, 2


237
IPI00064328
PRMT5
protein arginine methyltransferase 5


238
Hs.498570
PRKCQ
protein kinase C, theta


239
Hs.631923
PRKAR2A
protein kinase, cAMP-dependent, regulatory, type II, alpha


240
Hs.514323
PPP1R9B
protein phosphatase 1, regulatory (inhibitor) subunit 9B


241
Hs.400740
PPP2R4
protein phosphatase 2A activator, regulatory subunit 4


242
Hs.584019
PPP6C
protein phosphatase 6, catalytic subunit


243
Hs.591549
PTPN18
protein tyrosine phosphatase, non-receptor type 18 (brain-derived)


244
Hs.439152
PCDH12
protocadherin 12


245
Hs.78524
PRUNE
prune homolog (Drosophila)


246
Hs.41735
P2RX1
purinergic receptor P2X, ligand-gated ion channel, 1


247
Hs.284491
PDXK
pyridoxal (pyridoxine, vitamin B6) kinase


248
Hs.370781
PDXDC1
pyridoxal-dependent decarboxylase domain containing 1


249
Hs.470633
PDK1
pyruvate dehydrogenase kinase, isozyme 1


250
Hs.534770
PKM2
pyruvate kinase, muscle


251
Hs.321541
RAB11A
RAB11A, member RAS oncogene family


252
Hs.406799
RAB18
RAB18, member RAS oncogene family


253
Hs.369017
RAB2A
RAB2A, member RAS oncogene family


254
Hs.567328
RAB5B
RAB5B, member RAS oncogene family


255
Hs.650382
RAB5C
RAB5C, member RAS oncogene family


256
Hs.591552
RAB6C
RAB6C, member RAS oncogene family


257
Hs.644420
RAB8A
RAB8A, member RAS oncogene family


258
Hs.493867
RCSD1
RCSD domain containing 1


259
Hs.461925
RPA1
replication protein A1, 70 kDa


260
Hs.645283
RTN4
reticulon 4


261
Hs.368631
ARHGAP10
Rho GTPase activating protein 10


262
Hs.531807
ARHGAP25
Rho GTPase activating protein 25


263
Hs.508738
ARHGEF7
Rho guanine nucleotide exchange factor (GEF) 7


264
Hs.465761
ARHGEF18
rho/rac guanine nucleotide exchange factor (GEF) 18


265
Hs.73839
RNASE3
ribonuclease, RNase A family, 3 (eosinophil cationic protein)


266
Hs.388664
RPL11
ribosomal protein L11


267
Hs.374588
RPL17
ribosomal protein L17


268
Hs.337766
RPL18A
ribosomal protein L18a


269
IPI00741405
LOC391282
ribosomal protein L23a pseudogene 12


270
Hs.649475
RPL24
ribosomal protein L24


271
Hs.652114
RPL28
ribosomal protein L28


272
Hs.433701
RPL37A
ribosomal protein L37a




(includes




EG: 6168)


273
IPI00796861
LOC100130892
ribosomal protein L7 pseudogene 32


274
Hs.546289
RPS12
ribosomal protein S12




(includes




EG: 6206)


275
Hs.370504
RPS15A
ribosomal protein S15a


276
IPI00401105
RPS25
ribosomal protein S25


277
IPI00397963
RPS27
ribosomal protein S27


278
Hs.282376
RPS4Y1
ribosomal protein S4, Y-linked 1


279
Hs.367761
RPS4Y2
ribosomal protein S4, Y-linked 2


280
Hs.408073
RPS6
ribosomal protein S6


281
IPI00413108
RPSA (includes
ribosomal protein SA




EG: 3921)


282
Hs.553723
RNF123
ring finger protein 123




(includes




EG: 63891)


283
Hs.306769
RUFY1
RUN and FYVE domain containing 1


284
Hs.272822
RUVBL1
RuvB-like 1 (E. coli)


285
Hs.515846
RUVBL2
RuvB-like 2 (E. coli)


286
Hs.632438
SEC22B
SEC22 vesicle trafficking protein homolog B (S. cerevisiae)


287
Hs.654429
SEC24C
SEC24 family, member C (S. cerevisiae)




(includes




EG: 9632)


288
IPI00643835
SELP
selectin P (granule membrane protein 140 kDa, antigen CD62)


289
Hs.632460
SELENBP1
selenium binding protein 1


290
Hs.283743
5-Sep
septin 5


291
Hs.440932
9-Sep
septin 9


292
Hs.435661
SPTLC2
serine palmitoyltransferase, long chain base subunit 2


293
Hs.433343
SRRM2
serine/arginine repetitive matrix 2


294
Hs.409578
STK38
serine/threonine kinase 38


295
IPI00168350
RP6-213H19.1
serine/threonine protein kinase MST4


296
Hs.368077
SERPINB8
serpin peptidase inhibitor, clade B (ovalbumin), member 8


297
Hs.531176
SARS
seryl-tRNA synthetase


298
Hs.643526
SETDB1
SET domain, bifurcated 1


299
Hs.285666
SH3PXD2B
SH3 and PX domains 2B


300
Hs.601143
SH3BP1
SH3-domain binding protein 1


301
Hs.514495
SRP68
signal recognition particle 68 kDa


302
Hs.409223
SSR4
signal sequence receptor, delta (translocon-associated protein delta)


303
IPI00399212
LOC389842
similar to RanBP1


304
Hs.591680
SCYE1
small inducible cytokine subfamily E, member 1 (endothelial monocyte-activating)


305
Hs.356549
SNRPD3
small nuclear ribonucleoprotein D3 polypeptide 18 kDa


306
Hs.632166
SNRPN
small nuclear ribonucleoprotein polypeptide N


307
Hs.83753
SNRPB
small nuclear ribonucleoprotein polypeptides B and B1


308
Hs.350927
SLC25A6
solute carrier family 25 (mitochondrial carrier; adenine nucleotide translocator),





member 6


309
Hs.656870
SLC25A24
solute carrier family 25 (mitochondrial carrier; phosphate carrier), member 24


310
Hs.438723
SLC27A3
solute carrier family 27 (fatty acid transporter), member 3


311
Hs.656699
SLC27A4
solute carrier family 27 (fatty acid transporter), member 4


312
Hs.502769
SLC3A2
solute carrier family 3 (activators of dibasic and neutral amino acid transport),





member 2


313
Hs.469116
SLC9A1
solute carrier family 9 (sodium/hydrogen exchanger), member 1


314
Hs.878
SORD
sorbitol dehydrogenase


315
Hs.505824
SAMM50
sorting and assembly machinery component 50 homolog (S. cerevisiae)


316
Hs.32706
SPTBN4
spectrin, beta, non-erythrocytic 4


317
Hs.558463
SPEN
spen homolog, transcriptional regulator (Drosophila)


318
Hs.436306
SPHKAP
SPHK1 interactor, AKAP domain containing


319
Hs.406423
SF3B2
splicing factor 3b, subunit 2, 145 kDa


320
Hs.679714
SFRS1
splicing factor, arginine/serine-rich 1


321
Hs.309090
SFRS7
splicing factor, arginine/serine-rich 7.35 kDa


322
Hs.591922
SLK
STE20-like kinase (yeast)


323
Hs.3439
STOML2
stomatin (EPB72)-like 2


324
Hs.656726
STRN
striatin, calmodulin binding protein


325
Hs.440475
SDHA (includes
succinate dehydrogenase complex, subunit A, flavoprotein (Fp)




EG: 6389)


326
Hs.465924
SDHB (includes
succinate dehydrogenase complex, subunit B, iron sulfur (Ip)




EG: 6390)


327
Hs.494827
SUSD1
sushi domain containing 1


328
Hs.83734
STX4
syntaxin 4


329
Hs.530436
STXBP3
syntaxin binding protein 3


330
Hs.643566
TAOK3
TAO kinase 3


331
IPI00642032
TXNL1
thioredoxin-like 1


332
Hs.30345
TRAP1
TNF receptor-associated protein 1


333
Hs.87968
TLR9
toll-like receptor 9


334
Hs.475733
TOP2B
topoisomerase (DNA) II beta 180 kDa


335
Hs.496459
TOR1AIP1
torsin A interacting protein 1


336
Hs.34024
TNIK
TRAF2 and NCK interacting kinase


337
Hs.529618
TFRC
transferrin receptor (p90, CD71)


338
Hs.517033
TGM2
transglutaminase 2 (C polypeptide, protein-glutamine-gamma-glutamyltransferase)


339
Hs.96247
TSNAX
translin-associated factor X


340
Hs.654824
TM9SF2
transmembrane 9 superfamily member 2


341
Hs.502
TAP2
transporter 2, ATP-binding cassette, sub-family B (MDR/TAP)


342
IPI00018853
TPM1
tropomyosin 1 (alpha)


343
Hs.535581
TPM3
tropomyosin 3


344
Hs.497599
WARS
tryptophanyl-tRNA synthetase


345
Hs.31053
TBCB
tubulin folding cofactor B


346
Hs.279669
TUBG1
tubulin, gamma 1


347
Hs.473296
TPD52L2
tumor protein D52-like 2


348
IPI00794254
YWHAH
tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta





polypeptide


349
Hs.9589
UBQLN1
ubiquilin 1


350
Hs.5308
UBA52
ubiquitin A-52 residue ribosomal protein fusion product 1


351
Hs.474213
UFD1L
ubiquitin fusion degradation 1 like (yeast)


352
Hs.632370
UBE4B
ubiquitination factor E4B (UFD2 homolog, yeast)


353
IPI00019932
UBE2D2
ubiquitin-conjugating enzyme E2D 2 (UBC4/5 homolog, yeast)


354
Hs.50308
UBE2K
ubiquitin-conjugating enzyme E2K (UBC1 homolog, yeast)


355
IPI00216316
UROS
uroporphyrinogen III synthase


356
Hs.292689
USO1
USO1 homolog, vesicle docking protein (yeast)


357
Hs.499925
VPS26A
vacuolar protein sorting 26 homolog A (S. pombe)


358
Hs.418175
VPS28
vacuolar protein sorting 28 homolog (S. cerevisiae)


359
Hs.592009
VPS33A
vacuolar protein sorting 33 homolog A (S. cerevisiae)


360
Hs.631535
AKT2
v-akt murine thymoma viral oncogene homolog 2


361
Hs.632066
VCPIP1
valosin containing protein (p97)/p47 complex interacting protein 1


362
Hs.515469
VASP
vasodilator-stimulated phosphoprotein


363
Hs.66708
VAMP3
vesicle-associated membrane protein 3 (cellubrevin)


364
Hs.505033
KRAS
v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog


365
Hs.699154
LYN
v-yes-1 Yamaguchi sarcoma viral related oncogene homolog


366
Hs.635221
WASF3
WAS protein family, member 3


367
Hs.356604
WNK1
WNK lysine deficient protein kinase 1


368
Hs.390623
XPNPEP1
X-prolyl aminopeptidase (aminopeptidase P) 1, soluble


369
Hs.27239
ZDHHC5
zinc finger, DHHC-type containing 5


370
Hs.37003
Not Annotated
Not Annotated


371
Hs.102696
Not Annotated


372
Hs.10326
COPE


373
Hs.10649
C1orf38


374
Hs.108049
Not Annotated
Not Annotated


375
Hs.108957
Not Annotated
Not Annotated


376
Hs.111024
Not Annotated
Not Annotated


377
Hs.115242
Not Annotated
Not Annotated


378
Hs.116237
Not Annotated
Not Annotated


379
Hs.11638
ACSL5


380
Hs.119825
Not Annotated
Not Annotated


381
Hs.124027
Not Annotated
Not Annotated


382
Hs.124126
Not Annotated
Not Annotated


383
Hs.12865
NSFL1C


384
Hs.131255
Not Annotated
Not Annotated


385
Hs.131489
Not Annotated
Not Annotated


386
Hs.132499
Not Annotated
Not Annotated


387
Hs.132858
Not Annotated
Not Annotated


388
Hs.133512
Not Annotated
Not Annotated


389
Hs.134688
Not Annotated
Not Annotated


390
Hs.136309
Not Annotated
Not Annotated


391
Hs.138378
Not Annotated
Not Annotated


392
Hs.141125
Not Annotated
Not Annotated


393
Hs.142003
Not Annotated
Not Annotated


394
Hs.1422
FGR


395
Hs.1437
GAA


396
Hs.143703
EHD4


397
Hs.144011
CYTH2


398
Hs.144447
BRWD2


399
Hs.146406
DEDD


400
Hs.146602
UQCRQ


401
Hs.149957
RPS6KA1


402
Hs.150206
HIST1H1A


403
Hs.150718
JAM3 ///




LOC100133502


404
Hs.152944
VWA5A


405
Hs.154078
LBP


406
Hs.155975
PTPRCAP


407
Hs.158331
RENBP


408
Hs.15977
NDUFB9


409
Hs.161357
PDHB


410
Hs.162121
COPA


411
Hs.16355
MYH10


412
Hs.163867
CD14


413
Hs.166011
CTNND1


414
Hs.166551
FAM114A2


415
Hs.166924
SEC13


416
Hs.169284
PRPS1L1


417
Hs.169900
PABPC4


418
Hs.171626
SKP1


419
Hs.173043
MTA2


420
Hs.17614
ABCB10


421
Hs.179309
UBQLN2


422
Hs.18192
SRRM1


423
Hs.182625
VAPB


424
Hs.1872
Not Annotated
Not Annotated


425
Hs.188401
ANXA10


426
Hs.188882
NUDT3


427
Hs.189075
TWF1


428
Hs.18925
CRBN


429
Hs.189409
FNBP1


430
Hs.190086
MRCL3


431
Hs.191213
SNX9


432
Hs.194148
YES1


433
Hs.195080
ECE1


434
Hs.196437
MOBKL1B


435
Hs.200804
SDCBP


436
Hs.204041
AHSA1


437
Hs.2057
Not Annotated
Not Annotated


438
Hs.211463
DNM2


439
Hs.21160
ME1


440
Hs.212088
EPHX2


441
Hs.213389
GOLGB1


442
Hs.213470
PSMB7


443
Hs.214142
MTHFR


444
Hs.220594
CCDC58


445
Hs.224171
ENO3


446
Hs.238839
SCYL1


447
Hs.239818
PIK3CB


448
Hs.24956
INF2


449
Hs.271954
Not Annotated
Not Annotated


450
Hs.296422
Not Annotated
Not Annotated


451
Hs.301658
1554440_at
1554440_at


452
Hs.328865
Not Annotated
Not Annotated


453
Hs.351544
Not Annotated
Not Annotated


454
Hs.368359
Not Annotated
Not Annotated


455
Hs.370503
Not Annotated
Not Annotated


456
Hs.37712
AW006941
AW006941


457
Hs.43505
AF091453


458
Hs.435775
Not Annotated
Not Annotated


459
Hs.439474
Not Annotated
Not Annotated


460
Hs.440534
Not Annotated
Not Annotated


461
Hs.460988
Not Annotated
Not Annotated


462
Hs.470544
Not Annotated
Not Annotated


463
Hs.471528
Not Annotated
Not Annotated


464
Hs.486856
Not Annotated
Not Annotated


465
Hs.500674
Not Annotated
Not Annotated


466
Hs.590925
Not Annotated
Not Annotated


467
Hs.591005
Not Annotated
Not Annotated


468
Hs.591366
Not Annotated
Not Annotated


469
Hs.599301
Not Annotated
Not Annotated


470
Hs.632735
Not Annotated
Not Annotated


471
Hs.637017
Not Annotated
Not Annotated


472
Hs.645248
Not Annotated
Not Annotated


473
Hs.654497
Not Annotated
Not Annotated


474
Hs.659335
Not Annotated
Not Annotated


475
Hs.694210
Not Annotated
Not Annotated


476
Hs.696132
Not Annotated
Not Annotated


477
Hs.699333
Not Annotated
Not Annotated


478
Hs.699367
Not Annotated
Not Annotated


479
Hs.700648
Not Annotated
Not Annotated


480
Hs.700676
Not Annotated
Not Annotated


481
Hs.700760
Not Annotated
Not Annotated


482
IPI00011791
Not Annotated
Not Annotated


483
IPI00026138
Not Annotated
Not Annotated


484
IPI00027007
Not Annotated
Not Annotated


485
IPI00061977
Not Annotated
Not Annotated


486
IPI00140827
Not Annotated
Not Annotated


487
IPI00152990
Not Annotated
Not Annotated


488
IPI00165486
Not Annotated


489
IPI00167258
Not Annotated


490
IPI00176593
Not Annotated


491
IPI00176692
Not Annotated


492
IPI00176854
Not Annotated


493
IPI00332493
Not Annotated


494
IPI00386403
Not Annotated


495
IPI00397713
Not Annotated


496
IPI00397808
Not Annotated


497
IPI00398435
Not Annotated


498
IPI00412216
Not Annotated


499
IPI00457006
Not Annotated


500
IPI00478310
Not Annotated


501
IPI00556589
Not Annotated


502
IPI00738024
Not Annotated


503
IPI00745518
Not Annotated


504
IPI00746177
Not Annotated


505
IPI00788196
Not Annotated


506
IPI00792850
Not Annotated


507
IPI00796208
Not Annotated


508
IPI00797737
Not Annotated


509
IPI00807559
Not Annotated


510
IPI00807559
Not Annotated





















TABLE J










Fold Change



International


(positive numbers



Protein


are upregulated



Index/UniGene
Symbol
Entrez Gene Name
in B1)




















1
Hs.180946
RPL5 (includes
ribosomal protein L5
2.991594141




EG: 6125)


2
Hs.520026
VARS
valyl-tRNA synthetase
1.788666142


3
Hs.664670
Not Annotated

1.863546477


4
IPI00001539
ACAA2
acetyl-Coenzyme A acyltransferase 2
1.778012617


5
Hs.631827
ANXA7
annexin A7
1.962977658


6
Hs.466044
PKN1
protein kinase N1
2.926215231


7
Hs.90093
HSPA4
heat shock 70 kDa protein 4
2.324540439


8
Hs.185172
GNB2
guanine nucleotide binding protein (G protein), beta polypeptide 2
2.321199972


9
IPI00003438
DNAJC8
DnaJ (Hsp40) homolog, subfamily C, member 8
3.049698528


10
Hs.431850
MAPK1
mitogen-activated protein kinase 1
1.472676636


11
Hs.50382
TJP2
tight junction protein 2 (zona occludens 2)
2.014271952


12
Hs.180414
Not Annotated

1.683155132


13
Hs.186350
RPL4
ribosomal protein L4
2.710518039


14
Hs.699250
B2M
beta-2-microglobulin
2.103571916


15
Hs.591897
Not Annotated

2.715551514


16
Hs.489284
ARPC1B
actin related protein 2/3 complex, subunit 1B, 41 kDa
2.034992123


17
Hs.514934
CAPZA1
capping protein (actin filament) muscle Z-line, alpha 1
2.337884511


18
Hs.431279
NSF
N-ethylmaleimide-sensitive factor
2.608040048


19
Hs.700570
APP
amyloid beta (A4) precursor protein
−2.395893698


20
Hs.279259
EPX
eosinophil peroxidase
2.005473585


21
Hs.644618
SLC25A5
solute carrier family 25 (mitochondrial carrier; adenine nucleotide
2.377793261





translocator), member 5


22
Hs.477155
ATP6V1A
ATPase, H+ transporting, lysosomal 70 kDa, V1 subunit A
1.592166761


23
Hs.75318
TUBA4A
tubulin, alpha 4a
1.410317852


24
Hs.184233
HSPA9
heat shock 70 kDa protein 9 (mortalin)
3.890588764


25
Hs.521640
RAD23B
RAD23 homolog B (S. cerevisiae)
1.945040444


26
Hs.370581
CAP1
CAP, adenylate cyclase-associated protein 1 (yeast)
2.08626543


27
Hs.522969
PADI4
peptidyl arginine deiminase, type IV
−2.585597629


28
Hs.483408
Not Annotated

2.427608273


29
Hs.437594
RPLP2
ribosomal protein, large, P2
1.762376912


30
Hs.546285
RPLP0 (includes
ribosomal protein, large, P0
2.401809197




EG: 6175)


31
Hs.300816
RAB1B (includes
RAB1B, member RAS oncogene family
2.036788097




EG: 81876)


32
Hs.632535
SSB (includes
Sjogren syndrome antigen B (autoantigen La)
1.848049688




EG: 6741)


33
Hs.38449
SERPINE2
serpin peptidase inhibitor, clade E (nexin, plasminogen activator
1.839116473





inhibitor type 1), member 2


34
Hs.374596
TPT1 (includes
tumor protein, translationally-controlled 1
1.916065103




EG: 7178)


35
Hs.148559
IMMT
inner membrane protein, mitochondrial (mitofilin)
2.208812239


36
Hs.405144
SFRS3
splicing factor, arginine/serine-rich 3
1.854287873


37
Hs.274309
ERAF
erythroid associated factor
−2.404141665


38
Hs.413812
RAC1
ras-related C3 botulinum toxin substrate 1 (rho family, small GTP
3.007255119





binding protein Rac1)


39
Hs.25318
RAB27B
RAB27B, member RAS oncogene family
1.762079978


40
Hs.355934
SFPQ
splicing factor proline/glutamine-rich (polypyrimidine tract binding
2.033693659





protein associated)


41
Hs.464336
P4HB
prolyl 4-hydroxylase, beta polypeptide
2.058272651


42
Hs.247362
DDAH2
dimethylarginine dimethylaminohydrolase 2
2.191528732


43
Hs.527105
HNRPDL
heterogeneous nuclear ribonucleoprotein D-like
3.323650054


44
Hs.502842
CAPN1
calpain 1, (mu/l) large subunit
1.844181806


45
Hs.12970
PSMD3
proteasome (prosome, macropain) 26S subunit, non-ATPase, 3
1.509756576


46
IPI00011891
Not Annotated

1.949391219


47
Hs.373763
HNRNPR
heterogeneous nuclear ribonucleoprotein R
3.183271632


48
Hs.440898
FCN1
ficolin (collagen/fibrinogen domain containing) 1
−1.921894928


49
Hs.644646
KIF5B
kinesin family member 5B
−1.435375448


50
Hs.63348
EMILIN1
elastin microfibril interfacer 1
1.663039334


51
Hs.153837
MNDA
myeloid cell nuclear differentiation antigen
1.689289277


52
Hs.656176
RBM4
RNA binding motif protein 4
1.899826892


53
Hs.77793
CSK
c-src tyrosine kinase
1.724761961


54
Hs.627414
RPS18
ribosomal protein S18
3.348251322


55
Hs.497788
EPRS
glutamyl-prolyl-tRNA synthetase
1.466442524


56
Hs.698340
Not Annotated

1.921786734


57
Hs.699298
CDV3
CDV3 homolog (mouse)
1.486895919


58
Hs.111779
SPARC
secreted protein, acidic, cysteine-rich (osteonectin)
−2.780445145


59
IPI00011891
PRKAA1
protein kinase, AMP-activated, alpha 1 catalytic subunit
2.713587735


60
Hs.495541
C9ORF167
chromosome 9 open reading frame 167
1.599094872


61
Hs.651923
CNN2
calponin 2
1.731782614


62
Hs.131711
DLD
dihydrolipoamide dehydrogenase
1.948923988


63
Hs.644809
Not Annotated

2.338316865


64
Hs.643072
RAB10
RAB10, member RAS oncogene family
1.911187131


65
Hs.2853
PCBP1 (includes
poly(rC) binding protein 1
1.878028726




EG: 5093)


66
Hs.19121
AP2A2
adaptor-related protein complex 2, alpha 2 subunit
2.290995374


67
Hs.690198
CDC42
cell division cycle 42 (GTP binding protein, 25 kDa)
2.382171241


68
Hs.271510
GSR
glutathione reductase
2.161827645


69
Hs.524161
RSU1
Ras suppressor protein 1
1.436279998


70
Hs.406277
SF3A1
splicing factor 3a, subunit 1, 120 kDa
3.35665152


71
Hs.558314
CP
ceruloplasmin (ferroxidase)
−4.832439476


72
Hs.75514
NP (includes
nucleoside phosphorylase
1.500961251




EG: 4860)


73
Hs.501684
NAP1L4
nucleosome assembly protein 1-like 4
2.209825746


74
Hs.571177
SYNCRIP
synaptotagmin binding, cytoplasmic RNA interacting protein
2.269580549


75
Hs.695941
HK1
hexokinase 1
1.893698231


76
Hs.368149
CCT7
chaperonin containing TCP1, subunit 7 (eta)
1.433906814


77
Hs.695925
DUSP3
dual specificity phosphatase 3
2.286782204


78
Hs.75066
TSN
translin
−2.048787544


79
Hs.474751
MYH9
myosin, heavy chain 9, non-muscle
2.033216171


80
Hs.644809
Not Annotated

3.013475764


81
Hs.655207
F2
coagulation factor II (thrombin)
−2.861439244


82
Hs.143436
PLG
plasminogen
−1.893142835


83
Hs.420529
UBE2V1
ubiquitin-conjugating enzyme E2 variant 1
3.119742802


84
Hs.190028
GSTO1
glutathione S-transferase omega 1
1.353315555


85
Hs.20107
KLC1
kinesin light chain 1
1.756378314


86
Hs.626404
RAB11B
RAB11B, member RAS oncogene family
1.540804975


87
Hs.460109
MYH11
myosin, heavy chain 11, smooth muscle
2.332116359


88
Hs.490415
ZYX
zyxin
2.38059363


89
Hs.138860
ARHGAP1
Rho GTPase activating protein 1
1.851916091


90
Hs.646283
VISA
virus-induced signaling adapter
1.446706533


91
Hs.8004
KALRN
kalirin, RhoGEF kinase
4.58940432


92
Hs.594673
Not Annotated

1.559917838


93
Hs.707
KRT2
keratin 2
2.661810703


94
Hs.699367
Not Annotated

1.552098437


95
Hs.280342
PRKAR1A
protein kinase, cAMP-dependent, regulatory, type I, alpha (tissue
1.634710854





specific extinguisher 1)


96
Hs.73849
APOC3
apolipoprotein C-III
3.025507594


97
Hs.546255
FGG
fibrinogen gamma chain
2.194270748


98
Hs.75307
H1FX
H1 histone family, member X
2.411319459


99
Hs.632729
FAM62A
family with sequence similarity 62 (C2 domain containing), member A
1.737053335


100
Hs.120759
APOB
apolipoprotein B (including Ag(x) antigen)
−3.022308409


101
Hs.72933
PF4V1
platelet factor 4 variant 1
−1.667015899


102
Hs.507866
C130RF15
chromosome 13 open reading frame 15
2.508431485


103
Hs.203717
FN1
fibronectin 1
−2.170422372


104
Hs.324746
AHSG
alpha-2-HS-glycoprotein
−4.302298793


105
Hs.200770
SKAP2
src kinase associated phosphoprotein 2
1.755472125


106
Hs.30054
F5
coagulation factor V (proaccelerin, labile factor)
−1.567648564


107
Hs.372208
HSPC159
galectin-related protein
1.824854702


108
Hs.505735
NACA
nascent polypeptide-associated complex alpha subunit
1.652441243


109
Hs.491351
CLTC
clathrin, heavy chain (Hc)
1.743502579


110
Hs.480042
ANXA3
annexin A3
−3.143396399


111
Hs.509226
FKBP3
FK506 binding protein 3, 25 kDa
2.142363841


112
Hs.24258
GUCY1A3
guanylate cyclase 1, soluble, alpha 3
1.848134452


113
Hs.81934
ACADSB
acyl-Coenzyme A dehydrogenase, short/branched chain
1.352453174


114
Hs.429608
REEP5
receptor accessory protein 5
−1.629165972


115
Hs.75841
ERP29
endoplasmic reticulum protein 29
2.32777609


116
Hs.413482
C210RF33
chromosome 21 open reading frame 33
−1.338275818


117
Hs.502823
PRDX5
peroxiredoxin 5
1.612032187


118
Hs.523302
PRDX3
peroxiredoxin 3
1.609936792


119
Hs.408054
RPL12 (includes
ribosomal protein L12
2.804663051




EG: 6136)


120
IPI00024989
PCMT1
protein-L-isoaspartate (D-aspartate) O-methyltransferase
1.567802876


121
Hs.591095
PDIA3
protein disulfide isomerase family A, member 3
1.780599508


122
Hs.430606
CS
citrate synthase
−2.357926195


123
Hs.520973
HSPB1
heat shock 27 kDa protein 1
1.923931973


124
Hs.518244
RPN1
ribophorin I
2.112462414


125
Hs.695918
CAPZA2
capping protein (actin filament) muscle Z-line, alpha 2
2.146454384


126
Hs.632828
HNRNPH2
heterogeneous nuclear ribonucleoprotein H2 (H′)
1.609307106


127
Hs.430425
GNB1
guanine nucleotide binding protein (G protein), beta polypeptide 1
1.915685862


128
Hs.469473
RPL31
ribosomal protein L31
1.971237465


129
Hs.381072
PPIF
peptidylprolyl isomerase F
1.919712344


130
Hs.83190
FASN
fatty acid synthase
1.596744982


131
Hs.356624
NID1
nidogen 1
−1.567370157


132
Hs.12084
TUFM
Tu translation elongation factor, mitochondrial
1.443666367


133
Hs.95990
PKLR
pyruvate kinase, liver and RBC
2.624429792


134
Hs.489040
SRI
sorcin
−1.668251058


135
Hs.192374
HSP90B1
heat shock protein 90 kDa beta (Grp94), member 1
1.227206967


136
Hs.516155
CAPG
capping protein (actin filament), gelsolin-like
1.935086978


137
Hs.928
PRTN3
proteinase 3
−2.191302631


138
Hs.179986
FLOT1
flotillin 1
2.62551323


139
Hs.315137
AARS
alanyl-tRNA synthetase
2.138071963


140
Hs.275243
S100A6
S100 calcium binding protein A6
−2.091908363


141
Hs.656274
TNFAIP8
tumor necrosis factor, alpha-induced protein 8
1.848699684


142
Hs.654559
HNRNPL
heterogeneous nuclear ribonucleoprotein L
2.064236514


143
Hs.471441
PSMB2
proteasome (prosome, macropain) subunit, beta type, 2
3.189407689


144
Hs.594095
Not Annotated

1.541410846


145
Hs.7744
NDUFV1
NADH dehydrogenase (ubiquinone) flavoprotein 1, 51 kDa
1.859664494


146
Hs.517670
TTLL12
tubulin tyrosine ligase-like family, member 12
1.548669753


147
Hs.159494
BTK
Bruton agammaglobulinemia tyrosine kinase
1.744461371


148
Hs.153961
ACTR1A
ARP1 actin-related protein 1 homolog A, centractin alpha (yeast)
1.602174673


149
Hs.98791
ACTR1B (includes
ARP1 actin-related protein 1 homolog B, centractin beta (yeast)
2.447561282




EG: 10120)


150
IPI00029625
FLOT2
flotillin 2
2.779048389


151
Hs.232375
ACAT1
acetyl-Coenzyme A acetyltransferase 1
1.844709235


152
Hs.529451
DIAPH1
diaphanous homolog 1 (Drosophila)
1.472455435


153
Hs.477352
PDIA5
protein disulfide isomerase family A, member 5
2.417726204


154
Hs.516032
HADHA
hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A
2.919893077





thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha





subunit


155
Hs.528007
U2AF2 (includes
U2 small nuclear RNA auxiliary factor 2
2.33690845




EG: 11338)


156
Hs.655340
Not Annotated

1.994399205


157
Hs.546303
Not Annotated

1.993258019


158
Hs.191346
7-Sep
septin 7
1.426720758


159
Hs.556296
Not Annotated

1.918157196


160
Hs.546407
CAND1
cullin-associated and neddylation-dissociated 1
1.355594109


161
Hs.122523
SND1
staphylococcal nuclease and tudor domain containing 1
1.764952427


162
Hs.327252
Not Annotated

1.853845796


163
IPI00154742
IGL@
immunoglobulin lambda locus
−2.322679589


164
Hs.514412
PECAM1
platelet/endothelial cell adhesion molecule
1.521872894


165
Hs.248267
MPST
mercaptopyruvate sulfurtransferase
1.802723925


166
Hs.436186
CAST
calpastatin
1.877444004


167
Hs.390567
FYN
FYN oncogene related to SRC, FGR, YES
1.721126996


168
IPI00168728
IGHM
immunoglobulin heavy constant mu
−1.882125059


169
Hs.558799
PSMA3
proteasome (prosome, macropain) subunit, alpha type, 3
2.424171315


170
Hs.465808
HNRNPM
heterogeneous nuclear ribonucleoprotein M
1.745065443


171
Hs.149185
CNDP2
CNDP dipeptidase 2 (metallopeptidase M20 family)
1.639294303


172
IPI00179291
XPNPEP1
X-prolyl aminopeptidase (aminopeptidase P) 1, soluble
1.443429746


173
Hs.555895
TMSL3
thymosin-like 3
−2.986973706


174
Hs.126550
VPS4B
vacuolar protein sorting 4 homolog B (S. cerevisiae)
1.5707885


175
Hs.654720
KIAA1967
KIAA1967
3.861735646


176
Hs.49582
PPP1R12A
protein phosphatase 1, regulatory (inhibitor) subunit 12A
−1.985284505


177
Hs.63489
PTPN6
protein tyrosine phosphatase, non-receptor type 6
2.403072934


178
Hs.535581
TPM3
tropomyosin 3
−1.265339887


179
Hs.496984
MPP1
membrane protein, palmitoylated 1, 55 kDa
1.825563177


180
Hs.515517
RPL18
ribosomal protein L18
3.659413318


181
Hs.438429
RPS19
ribosomal protein S19
2.504016487


182
Hs.73722
APEX1
APEX nuclease (multifunctional DNA repair enzyme) 1
2.126641285


183
Hs.461047
G6PD
glucose-6-phosphate dehydrogenase
1.330805366


184
Hs.128548
WDR1
WD repeat domain 1
5.196770912


185
Hs.519320
VDAC1
voltage-dependent anion channel 1
2.440307464


186
Hs.512675
RPS8
ribosomal protein S8
2.401417871


187
Hs.494691
PFN1
profilin 1
1.824342002


188
Hs.180535
FERMT3
fermitin family homolog 3 (Drosophila)
1.933107142


189
Hs.417303
SPTB
spectrin, beta, erythrocytic
2.124657924


190
Hs.446628
Not Annotated

2.082461305


191
Hs.1869
PGM1
phosphoglucomutase 1
1.62661576


192
Hs.89497
LMNB1
lamin B1
1.892879233


193
Hs.652308
MTHFD1
methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 1,
1.965807135





methenyltetrahydrofolate cyclohydrolase, formyltetrahydrofolate





synthetase


194
Hs.446149
LDHB
lactate dehydrogenase B
1.507117812


195
Hs.87752
MSN
moesin
1.792183522


196
Hs.253903
STOM
stomatin
1.663466237


197
Hs.523836
GSTP1
glutathione S-transferase pi 1
3.12010713


198
Hs.573688
PRDX6
peroxiredoxin 6
1.768671919


199
Hs.80828
KRT1
keratin 1
2.488668295


200
Hs.289123
DCTN2
dynactin 2 (p50)
1.517636012


201
Hs.654554
Not Annotated

−3.221258193


202
Hs.90061
PGRMC1
progesterone receptor membrane component 1
1.645197721


203
Hs.514819
AP2B1
adaptor-related protein complex 2, beta 1 subunit
1.967752606


204
Hs.467284
RPS9
ribosomal protein S9
2.046621121


205
Hs.397609
RPS16
ribosomal protein S16
3.411967491


206
Hs.433427
RPS17 (includes
ribosomal protein S17
3.95408013




EG: 6218)


207
Hs.350899
CAPN2
calpain 2, (m/II) large subunit
1.680232488


208
Hs.363137
TCP1
t-complex 1
1.787923894


209
Hs.520967
MDH2
malate dehydrogenase 2, NAD (mitochondrial)
1.559612551


210
Hs.699180
VCL
vinculin
3.129938695


211
Hs.371563
RAB14
RAB14, member RAS oncogene family
2.101732978


212
Hs.83722
EPS15
epidermal growth factor receptor pathway substrate 15
1.373102908


213
Hs.277035
MGLL
monoglyceride lipase
1.805879512


214
Hs.64016
PROS1
protein S (alpha)
−2.623015853


215
Hs.584790
PPP2R1B
protein phosphatase 2 (formerly 2A), regulatory subunit A, beta
−1.810743224





isoform


216
Hs.580681
SAMHD1
SAM domain and HD domain 1
2.000782596


217
Hs.444770
SH3KBP1
SH3-domain kinase binding protein 1
2.069800255


218
Hs.88778
CBR1
carbonyl reductase 1
1.904274616


219
Hs.339278
COPB1
coatomer protein complex, subunit beta 1
1.443967836


220
Hs.592490
FH
fumarate hydratase
2.186123666


221
Hs.486458
ARHGAP18
Rho GTPase activating protein 18
2.274383381


222
Hs.335513
F13A1
coagulation factor XIII, A1 polypeptide
2.145284002


223
Hs.189772
CCT2
chaperonin containing TCP1, subunit 2 (beta)
1.435139731


224
Hs.539684
EIF2S3
eukaryotic translation initiation factor 2, subunit 3 gamma, 52 kDa
2.261012155


225
Hs.33642
ARCN1
archain 1
2.07225933


226
Hs.370770
XPO1
exportin 1 (CRM1 homolog, yeast)
2.343773987


227
Hs.573018
Not Annotated

1.456482565


228
Hs.291030
IQGAP2
IQ motif containing GTPase activating protein 2
1.646289191


229
Hs.212102
PDIA6
protein disulfide isomerase family A, member 6
2.480879671


230
Hs.499839
RPL7A
ribosomal protein L7a
1.726750017


231
Hs.465041
HDHD2
haloacid dehalogenase-like hydrolase domain containing 2
2.231113926


232
Hs.654957
PPA2
pyrophosphatase (inorganic) 2
2.076884027


233
Hs.660070
Not Annotated

2.0488303


234
Hs.125113
CCT8
chaperonin containing TCP1, subunit 8 (theta)
2.39782042


235
Hs.274402
HSPA1A
heat shock 70 kDa protein 1A
2.358211938


236
Hs.75285
ITIH2
inter-alpha (globulin) inhibitor H2
−2.825741915


237
Hs.571886
AKR7A2
aldo-keto reductase family 7, member A2 (aflatoxin aldehyde
2.166498126





reductase)


238
Hs.368794
AP1B1
adaptor-related protein complex 1, beta 1 subunit
1.872459483


239
Hs.599481
EIF4A2
eukaryotic translation initiation factor 4A, isoform 2
3.551326775


240
Hs.416848
CTSW
cathepsin W
−1.696934761


241
Hs.528668
RPL6
ribosomal protein L6
2.430141179


242
Hs.368084
LRPPRC
leucine-rich PPR-motif containing
−2.370581231


243
Hs.509736
HSP90AB1
heat shock protein 90 kDa alpha (cytosolic), class B member 1
2.408626383


244
Hs.632717
MYL6
myosin, light chain 6, alkali, smooth muscle and non-muscle
3.625359469


245
Hs.654614
HSPA6
heat shock 70 kDa protein 6 (HSP70B′)
2.880497988


246
Hs.567380
FUBP1
far upstream element (FUSE) binding protein 1
2.457237888


247
Hs.525600
HSP90AA1
heat shock protein 90 kDa alpha (cytosolic), class A member 1
2.30575168


248
Hs.699168
TUBA1B
tubulin, alpha 1b
1.343588946


249
IPI00398135
Not Annotated

1.706927145


250
Hs.128420
VPS4A
vacuolar protein sorting 4 homolog A (S. cerevisiae)
2.041670779


251
Hs.591054
BID
BH3 interacting domain death agonist
1.977789146


252
Hs.200716
MECP2
methyl CpG binding protein 2 (Rett syndrome)
2.115913201


253
Hs.155247
ALDOC
aldolase C, fructose-bisphosphate
2.390316052


254
Hs.570791
LAP3
leucine aminopeptidase 3
1.7773007


255
Hs.598115
PPIA (includes
peptidylprolyl isomerase A (cyclophilin A)
−1.252231897




EG: 5478)


256
Hs.356572
RPS3A
ribosomal protein S3A
3.364033062


257
Hs.518530
PAK2
p21 protein (Cdc42/Rac)-activated kinase 2
1.820573252


258
Hs.98510
WDR44
WD repeat domain 44
1.715515466


259
IPI00448925
IGHG1
immunoglobulin heavy constant gamma 1 (G1m marker)
−2.709398355


260
Hs.41045
UNC13D
unc-13 homolog D (C. elegans)
1.475081587


261
Hs.380956
Not Annotated

2.840678067


262
Hs.404321
GARS
glycyl-tRNA synthetase
2.140952373


263
Hs.306769
RUFY1
RUN and FYVE domain containing 1
2.531625079


264
Hs.292493
XRCC6
X-ray repair complementing defective repair in Chinese hamster cells 6
1.787163446


265
Hs.595053
HSPD1
heat shock 60 kDa protein 1 (chaperonin)
1.255650787


266
Hs.699280
HBD
hemoglobin, delta
−2.913740187


267
Hs.655361
HPR (includes
haptoglobin-related protein
−4.710560337




EG: 3250)


268
Hs.534770
PKM2
pyruvate kinase, muscle
1.537311441


269
Hs.2533
ALDH9A1
aldehyde dehydrogenase 9 family, member A1
2.429592013


270
Hs.530687
RNH1
ribonuclease/angiogenin inhibitor 1
1.905230817


271
Hs.517168
TAGLN2
transgelin 2
1.822335623


272
Hs.14770
BIN2
bridging integrator 2
1.68853164


273
Hs.436439
TWF2
twinfilin, actin-binding protein, homolog 2 (Drosophila)
1.884510405


274
Hs.433068
PRKAR2B
protein kinase, cAMP-dependent, regulatory, type II, beta
1.54914478


275
Hs.502756
AHNAK
AHNAK nucleoprotein
2.893577011


276
Hs.515876
NRBP1
nuclear receptor binding protein 1
2.746197889


277
Hs.132858
RAP1GDS1
RAP1, GTP-GDP dissociation stimulator 1
2.107982605


279
Hs.311609
DDX39
DEAD (Asp-Glu-Ala-Asp) box polypeptide 39
2.84761005


280
Hs.438678
TALDO1
transaldolase 1
2.691818999


282
IPI00746976
DNM1L
dynamin 1-like
1.617915807


283
Hs.270428
SUCLG1
succinate-CoA ligase, alpha subunit
2.37225264


284
Hs.471014
TLN1
talin 1
2.579118784
















TABLE 2







Protein Transcript Matches of 393 mild CAN consensus genes












Probe Set ID
UniGene ID
Gene Title
Gene Symbol















1
212224_at
Hs.76392
aldehyde dehydrogenase 1 family, member A1
ALDH1A1


2
209970_x_at
Hs.2490
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,
CASP1





convertase)


3
216799_at
Hs.24907
Coronin, actin binding protein, 2B
CORO2B


4
202902_s_at
Hs.181301
cathepsin S
CTSS


5
203276_at
Hs.89497
lamin B1
LMNB1


6
1559052_s_at
Hs.518530
p21 (CDKN1A)-activated kinase 2
PAK2


7
202803_s_at
Hs.375957
integrin, beta 2 (antigen CD18 (p95), lymphocyte function-associated antigen
ITGB2





1; macrophage antigen 1 (mac-1) beta subunit)


8
224511_s_at
Hs.408236
thioredoxin-like 5 /// thioredoxin-like 5
TXNL5


9
216063_at
Hs.20205
hemoglobin, beta pseudogene 1 /// hemoglobin, beta pseudogene 1
HBBP1


10
202277_at
Hs.90458
serine palmitoyltransferase, long chain base subunit 1
SPTLC1
















TABLE 3







Protein Transcript Matches of 1066 mild CAN Data Set 1 genes












Probe Set ID
UniGene ID
Gene Title
Gene Symbol















1
212224_at
Hs.76392
aldehyde dehydrogenase 1 family, member A1
ALDH1A1


2
201089_at
Hs.295917
ATPase, H+ transporting, lysosomal 56/58 kDa, V1 subunit B, isoform 2
ATP6V1B2


3
213312_at
Hs.70769
chromosome 6 open reading frame 162
C6orf162


4
206011_at
Hs.2490
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,
CASP1





convertase)


5
202902_s_at
Hs.181301
cathepsin S
CTSS


6
204714_s_at
Hs.30054
coagulation factor V (proaccelerin, labile factor)
F5


7
202957_at
Hs.14601
Hematopoietic cell-specific Lyn substrate 1
HCLS1


8
205936_s_at
Hs.411695
hexokinase 3 (white cell)
HK3


9
204959_at
Hs.153837
myeloid cell nuclear differentiation antigen /// myeloid cell nuclear
MNDA





differentiation antigen


10
208875_s_at
Hs.518530
p21 (CDKN1A)-activated kinase 2
PAK2


11
207668_x_at
Hs.212102
protein disulfide isomerase family A, member 6
PDIA6


12
227516_at
Hs.406277
splicing factor 3a, subunit 1, 120 kDa
SF3A1


13
217995_at
Hs.511251
sulfide quinone reductase-like (yeast)
SQRDL


14
220966_x_at
Hs.132499
actin related protein 2/3 complex, subunit 5-like /// actin related protein 2/3
ARPC5L





complex, subunit 5-like


15
219505_at
Hs.170310
cat eye syndrome chromosome region, candidate 1
CECR1


16
202295_s_at
Hs.148641
cathepsin H
CTSH


17
209759_s_at
Hs.403436
dodecenoyl-Coenzyme A delta isomerase (3,2 trans-enoyl-Coenzyme A
DCI





isomerase)


18
204646_at
Hs.335034
dihydropyrimidine dehydrogenase
DPYD


19
218610_s_at
Hs.460002
hypothetical protein FLJ11151
FLJ11151


20
209876_at
Hs.434996
G protein-coupled receptor kinase interactor 2
GIT2


21
201944_at
Hs.69293
hexosaminidase B (beta polypeptide)
HEXB


22
211023_at
Hs.161357
pyruvate dehydrogenase (lipoamide) beta
PDHB


23
202671_s_at
Hs.284491
pyridoxal (pyridoxine, vitamin B6) kinase
PDXK


24
225214_at
Hs.213470
Proteasome (prosome, macropain) subunit, beta type, 7
PSMB7


25
217983_s_at
Hs.529989
ribonuclease T2
RNASET2


26
206034_at
Hs.368077
serpin peptidase inhibitor, clade B (ovalbumin), member 8
SERPINB8


27
204981_at
Hs.50868
solute carrier family 22 (organic cation transporter), member 18
SLC22A18


28
219403_s_at
Hs.44227
heparanase
HPSE


29
232359_at
Hs.226007
Retinol dehydrogenase 11 (all-trans and 9-cis)
RDH11


30
203485_at
Hs.368626
reticulon 1
RTN1


31
221532_s_at
Hs.513055
WD repeat domain 61
WDR61


32
208857_s_at
Hs.279257
protein-L-isoaspartate (D-aspartate) O-methyltransferase
PCMT1
















TABLE 4







Protein Transcript Matches of 1429 mild CAN Data Set 2 genes












Probe Set ID
UniGene ID
Gene Title
Gene Symbol















1
201305_x_at
Hs.494604
acidic (leucine-rich) nuclear phosphoprotein 32 family, member B
ANP32B


2
216123_x_at
Hs.514934
Capping protein (actin filament) muscle Z-line, alpha 1
CAPZA1


3
209970_x_at
Hs.2490
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,
CASP1





convertase)


4
209789_at
Hs.24907
coronin, actin binding protein, 2B
CORO2B


5
237104_at
Hs.181301
Cathepsin S
CTSS


6
202428_x_at
Hs.78888
diazepam binding inhibitor (GABA receptor modulator, acyl-Coenzyme A
DBI





binding protein)


7
235999_at
Hs.480073
Heterogeneous nuclear ribonucleoprotein D (AU-rich element RNA binding
HNRPD





protein 1, 37 kDa)


8
243593_s_at
Hs.465808
Heterogeneous nuclear ribonucleoprotein M
HNRPM


9
201841_s_at
Hs.520973
heat shock 27 kDa protein 1
HSPB1


10
1566785_x_at
Hs.431279
Ribosomal protein S7
NSF


11
216253_s_at
Hs.475074
parvin, beta
PARVB


12
215628_x_at
Hs.483408
Protein phosphatase 2 (formerly 2A), catalytic subunit, alpha isoform
PPP2CA


13
200927_s_at
Hs.371563
RAB14, member RAS oncogene family
RAB14


14
213941_x_at
Hs.546287
ribosomal protein S7
RPS7


15
240855_at
Hs.417303
Spectrin, beta, erythrocytic (includes spherocytosis, clinical type I)
SPTB


16
237875_at
Hs.519756
Serine/threonine kinase 10
STK10


17
238749_at
Hs.258314
Brain and reproductive organ-expressed (TNFRSF1A modulator)
BRE


18
1565868_at
Hs.502328
CD44 antigen (homing function and Indian blood group system)
CD44


18
1565868_at
Hs.502328
CD44 antigen (homing function and Indian blood group system)
CD44


19
226875_at
Hs.368203
dedicator of cytokinesis 11
DOCK11


20
208000_at
Hs.86161
GPI anchored molecule like protein
GML


21
243147_x_at
Hs.432674
Leucyl-tRNA synthetase
LARS


22
226253_at
Hs.143774
leucine rich repeat containing 45
LRRC45


23
229851_s_at
Hs.8360
PTD012 protein
PTD012


24
208720_s_at
Hs.282901
RNA-binding region (RNP1, RRM) containing 2
RNPC2


25
201742_x_at
Hs.68714
splicing factor, arginine/serine-rich 1 (splicing factor 2, alternate splicing
SFRS1





factor)


26
215274_at
Hs.369271
solute carrier family 12 (sodium/chloride transporters), member 3
SLC12A3


27
231324_at
Hs.534350
SWI/SNF related, matrix associated, actin dependent regulator of chromatin,
SMARCB1





subfamily b, member 1


28
215416_s_at
Hs.3439
stomatin (EPB72)-like 2
STOML2


29
206116_s_at
Hs.133892
tropomyosin 1 (alpha)
TPM1


30
224511_s_at
Hs.408236
thioredoxin-like 5 /// thioredoxin-like 5
TXNL5


31
201266_at
Hs.337766
thioredoxin reductase 1
TXNRD1


32
243160_at
Hs.363396
Complement factor H
CFH


33
218218_at
Hs.506603
DIP13 beta
DIP13B


34
221942_s_at
Hs.24258
guanylate cyclase 1, soluble, alpha 3
GUCY1A3


35
232169_x_at
Hs.90443
NADH dehydrogenase (ubiquinone) Fe—S protein 8, 23 kDa (NADH-coenzyme Q
NDUFS8





reductase)


36
205190_at
Hs.203637
plastin 1 (l isoform)
PLS1


37
202429_s_at
Hs.435512
protein phosphatase 3 (formerly 2B), catalytic subunit, alpha isoform
PPP3CA





(calcineurin A alpha)


38
1555340_x_at
Hs.190334
RAP1A, member of RAS oncogene family
RAP1A


39
1569073_x_at
Hs.327527
SWI/SNF related, matrix associated, actin dependent regulator of chromatin,
SMARCA4





subfamily a, member 4


40
212577_at
Hs.8118
structural maintenance of chromosomes flexible hinge domain containing 1
SMCHD1
















TABLE 5







Protein Transcript Matches of 545 moderate/severe CAN Data Set 1 genes












Probe Set ID
UniGene ID
Gene Title
Gene Symbol















1
223598_at
Hs.521640
RAD23 homolog B (S. cerevisiae)
RAD23B


2
208000_at
Hs.86161
GPI anchored molecule like protein
GML


3
1557724_a_at
Hs.407190
hypothetical protein LOC285847
LOC285847


4
236356_at
Hs.471207
NADH dehydrogenase (ubiquinone) Fe—S protein 1, 75 kDa (NADH-coenzyme Q
NDUFS1





reductase)


5
238688_at
Hs.133892
Tropomyosin 1 (alpha)
TPM1


6
218090_s_at
Hs.144447
bromodomain and WD repeat domain containing 2
BRWD2


7
200898_s_at
Hs.500842
meningioma expressed antigen 5 (hyaluronidase)
MGEA5


8
201569_s_at
Hs.505824
sorting and assembly machinery component 50 homolog (S. cerevisiae)
SAMM50


9
1560854_s_at
Hs.50216
zinc finger protein 588
ZNF588
















TABLE 6







Protein Transcript Matches of 172 moderate/severe CAN Data Set 2 genes












Probe Set ID
UniGene ID
Gene Title
Gene Symbol















1
216251_s_at
Hs.517670
KIAA0153 protein
KIAA0153


2
204959_at
Hs.153837
myeloid cell nuclear differentiation antigen /// myeloid cell nuclear
MNDA





differentiation antigen


3
227770_at
Hs.128420
Vacuolar protein sorting 4A (yeast)
VPS4A


4
231324_at
Hs.534350
SWI/SNF related, matrix associated, actin dependent regulator of chromatin,
SMARCB1





subfamily b, member 1


5
209029_at
Hs.530823
COP9 constitutive photomorphogenic homolog subunit 7A (Arabidopsis)
COPS7A


6
218326_s_at
Hs.502176
leucine-rich repeat-containing G protein-coupled receptor 4
LGR4


7
1568619_s_at
Hs.530899
Hypothetical protein LOC162073
LOC162073


8
204994_at
Hs.926
myxovirus (influenza virus) resistance 2 (mouse)
MX2


9
205325_at
Hs.334688
phytanoyl-CoA hydroxylase interacting protein
PHYHIP

## Claims

1. A method of prognosing, diagnosing or monitoring CAN/IFTA (chronic allograft nephropathy, interstitial fibrosis and tubular atrophy, or chronic allograft nephropathy and interstitial fibrosis and tubular atrophy), comprising
(a) obtaining target nucleic acids, wherein the target nucleic acids comprise mRNA from a blood sample from a human subject or nucleic acids derived from the mRNA from the blood sample from the human subject, wherein the human subject is a recipient of a transplanted kidney and has received an immunosuppressant drug;
(b) contacting the target nucleic acids with at least ten probes, wherein the at least ten probes are specific for genes associated with the presence or absence of CAN/IFTA and are specific for at least genes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56;
(c) detecting expression levels in the human subject of the at least genes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56;
(d) prognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidney of the human subject when the expression levels of SYNPO and GFI1B detected in step (c) have a statistically significant negative-fold change relative to a kidney transplant patient without CAN/IFTA and the expression levels of ANXR2, VSIG4, SPTLC2, RNF17S, and EST56 detected in step (c) have a statistically significant positive-fold change relative to a kidney transplant patient without CAN/IFTA; and
(e) administering an increased dose of the immunosuppressant drug to the human subject in order to treat or prevent the CAN/IFTA prognosed, diagnosed or monitored in the transplanted kidney of the human subject in step (d) or administering a new immunosuppressant drug to the human subject in order to treat or prevent the CAN/IFTA prognosed, diagnosed or monitored in the transplanted kidney of the human subject in step (d).

2. The method of claim 1, wherein step (c) further comprises for each of the at least genes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56 assigning the expression level of the gene in the human subject a value or other designation providing an indication whether the human subject has or is at risk of CAN/IFTA.

3. The method of claim 2, wherein the expression level of each of the at least genes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and EST56 is assigned a value on a normalized scale of values associated with a range of expression levels in kidney transplant patients with and without CAN/IFTA.

4. The method of claim 2, wherein the expression level of each of the at least genes ANTXR2, SYNPO, VSIG4, GFI1B, SPTLC2, RNF175, and BST56 is assigned a value or other designation providing an indication that the human subject has or is at risk of CAN/IFTA, lacks and is not at risk of CAN/IFTA, or that the expression level is uninformative.

5. The method of claim 2, wherein (c) further comprises combining the values or designations for each of the genes to provide a combined value or designation providing an indication whether the human subject has or is at risk of CAN/IFTA.

6. The method of claim 5, wherein the method is repeated at different times on the human subject.

7. The method of claim 5, wherein a change in the combined value or designation over time provides an indication of the effectiveness of the immunosuppressant drug received by the human subject.

8. The method of claim 1, wherein the human subject has undergone a kidney transplant within 1-10 years of performing step (a).

9. The method of claim 1, wherein the blood sample is a peripheral blood sample.

10. The method of claim 9, wherein the peripheral blood sample is a peripheral blood lymphocyte sample.

11. The method of claim 1, wherein the blood sample is a blood plasma sample.

12. The method of claim 1, wherein the target nucleic acids are mRNA extracted from the blood sample from the human subject.

13. The method of claim 12, wherein the target nucleic acids are nucleic acids derived from the mRNA extracted from the blood sample from the human subject.

14. The method of claim 13, wherein the target nucleic acids are DNA derived from the mRNA extracted from the blood sample from the human subject.

15. The method of claim 13, wherein the detecting the expression levels in the human subject comprises one or more of the following: (a) hybridizing the mRNA to an array; (b) nucleic acid amplification; (c) monitoring the formation of an amplification product; or (d) synthesizing a nucleic acid using the mRNA as a template.

16. The method of claim 1, wherein the prognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidney of the human subject in step (d) further comprises performing an additional procedure to detect CAN/IFTA or risk thereof if the detecting expression levels provides an indication the subject has or is at risk of CAN/IFTA.

17. The method of claim 16, wherein the additional procedure is a kidney biopsy.

18. The method of claim 1, further comprising determining baseline values of expression levels in the human subject before a kidney transplant.

19. The method of claim 18, wherein prognosing, diagnosing or monitoring CAN/IFTA in the human subject comprises comparing the baseline values of expression levels in the human subject before the kidney transplant with the expression levels in the human subject after the kidney transplant.

20. The method of claim 16, wherein the additional procedure is a creatinine or glomerular filtration rate analysis.

21. The method of claim 12, wherein the detecting the expression levels in the human subject comprises hybridizing the mRNA to an array.

22. The method of claim 14, wherein the detecting the expression levels in the human subject comprises hybridizing the DNA to an array.

23. The method of claim 1, wherein the method comprises diagnosing CAN/IFTA in the human subject from the expression levels detected in step (c).

24. The method of claim 1, wherein the method comprises prognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidney of the human subject when the expression levels of at least 50 genes exhibit a statistically significant fold change.

25. The method of claim 1, wherein the method comprises prognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidney of the human subject when the expression levels of at least 100 genes exhibit a statistically significant fold change.

26. The method of claim 1, wherein the transplanted kidney is a transplanted kidney organ.

27. The method of claim 1, wherein the transplanted kidney is transplanted kidney tissues or cells.

28. The method of claim 1, wherein the method comprises administering an increased dose of the immunosuppressant drug to the human subject in order to treat or prevent the CAN/IFTA prognosed, diagnosed or monitored in the transplanted kidney of the human subject in step (d).

29. The method of claim 1, wherein the method comprises administering a new immunosuppressant drug to the human subject in order to treat or prevent the CAN/IFTA prognosed, diagnosed or monitored in the transplanted kidney of the human subject in step (d).

30. The method of claim 1, wherein the immunosuppressant drug or the new immunosuppressant drug is a calcineurin inhibitor.

31. The method of claim 30, wherein the calcineurin inhibitor is cyclosporin or tacrolimus.

32. The method of claim 1, wherein the immunosuppressant drug or the new immunosuppressant drug is an mTOR inhibitor.

33. The method of claim 32, wherein the mTOR inhibitor is sirolimus or everolimus.

34. The method of claim 1, wherein the immunosuppressant drug or new immunosuppressant drug is selected from the group consisting of: azathioprine, mycophenolic acid, prednisolone, hydrocortisone, basiliximab, daclizumab, orthoclone, anti-thymocyte globulin, anti-lymphocyte globulin, an anti-proliferative drug, and an anti-T cell antibody.

35. The method of claim 1, wherein the method comprises prognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidney of the human subject when the expression levels of at least 20 genes from Table A, B, C, D, E, F, G, H, I and/or J and less than 1000 total genes exhibit a statistically significant fold change.

36. The method of claim 1, wherein the method comprises prognosing, diagnosing or monitoring CAN/IFTA in the transplanted kidney of the human subject when the expression levels of at least 40 and up to 500 genes exhibit a statistically significant fold change.

37. The method of claim 1, wherein step (d) of the method comprises diagnosing CAN/IFTA in the transplanted kidney of the human subject.

38. The method of claim 36, wherein step (e) comprises administering the increased dose of the immunosuppressant drug to the human subject in order to treat the CAN/IFTA diagnosed in the transplanted kidney of the human subject in step (d).

39. The method of claim 36, wherein step (e) comprises administering the new immunosuppressant drug to the human subject in order to treat the CAN/IFTA diagnosed in the transplanted kidney of the human subject in step (d).