Patent Publication Number: US-2020303037-A1

Title: The primary site of metastatic cancer identification method and system thereof

Description:
FIELD 
     The present disclosure relates to a method and a system for identifying a metastatic cancer, and more particularly to a method and a system for identifying a primary site of metastatic cancer. 
     BACKGROUND 
     Finding the primary site for metastatic cancers was mandatory and is still necessary for physicians to prescribe proper treatment for their patients. However, identifying the primary site for some of the poorly developed cancers or the so-called “cancer of unknown primary” (CUP) can sometimes be challenging. 
     For the CUPs where it is difficult to identify the primary site under the currently available technologies, patients will resort to additional procedures such as random biopsies in the hope to find the origin of the metastatic cancer. The chances of finding the primary site of the metastatic tumor after all such procedures, however, remain relatively unoptimistic. 
     Accordingly, it is desirable to develop a method to accurately and efficiently identify the primary site of a metastatic cancer. 
     SUMMARY 
     The present disclosure provides a method for developing a plurality of candidate probes to identify at least one primary site of a selected disease, disorder or genetic disorder in a mammalian subject. The method comprises the following steps: (a) generating a plurality of gene expression from a standard sample of a subject having a selected disease, disorder or genetic disorder by using a detecting chip; (b) comparing the plurality of gene expression to generate a comparison result by using a processing module; and (c) developing an array containing the plurality of candidate probes based on the comparison result. The standard sample is diagnosed with a metastasis cancer with at least one known primary site. The detecting chip is electrically connected to the processing module. The plurality of candidate probes in the array are capable of binding a plurality of polynucleotide sequences selected from any one of SEQ ID No.1 to 695 or from any fragment of SEQ ID No.1 to 695. 
     In one embodiment, the number of the candidate probes is about 650. 
     In one embodiment, the number of the candidate probes is about 100. 
     In one embodiment, the number of the candidate probes is about 50. 
     In one embodiment, the detecting chip includes a microarray, a next-generation sequencing device, quantitative PCR and magnetic beads. 
     In one embodiment, the processing module is a central processing unit (CPU). 
     In one embodiment, the standard sample includes blood, blood plasma, serum, urine, tissue, cells, organs, seminal fluids or any combination thereof. 
     In one embodiment, the selected disease, disorder or genetic pathology includes hematologic malignancies or solid tumors. 
     In one embodiment, a length of the candidate probes is at least 20 nucleotides. 
     In one embodiment, the candidate probes are approximately 695 genes selected from the group consisting of those given in Table 1, and more preferably 50 genes or less. 
     The present disclosure further provides a method for identifying a primary site of a selected disease, disorder or genetic disorder in a mammalian subject. The method comprises the following steps: (a) analysing expression levels of an array of a test sample by using a detecting chip that contains a plurality of candidate probes developed by the procedures described above; and (b) predicting a primary site of the test sample based on the array&#39;s expression levels by using a processing module. The test sample is diagnosed with a metastasis cancer with at least one unknown primary site, and the plurality of candidate probes are capable of binding the plurality of polynucleotide sequence selected from any one of SEQ ID No.1 to 695 or from any fragment of SEQ ID No.1 to 695. 
     In one embodiment, the test sample includes blood, blood plasma, serum, urine, tissue, cells, organs, seminal fluids or any combination thereof. 
     The present disclosure also provides a system for identifying a primary site of a selected disease, disorder or genetic disorder in a mammalian subject. The system comprises a detecting chip that contains a plurality of candidate probes and a processing module. The detecting chip and the processing module are electrically connected to each other. The plurality of candidate probes are capable of binding a plurality of polynucleotide sequence selected from any one of SEQ ID No.1 to 695 or from any fragment of SEQ ID No.1 to 695. 
     In some embodiments of the present disclosure, the tissue or organ may be any tissue or organ, for example, breast, stomach, colon, pancreas, bladder, thyroid, prostate, kidney, liver, ovary, germ cell, soft tissue, skin, lymph node or lung. 
     Those and other aspects of the present disclosure may be further clarified by the following descriptions and drawings of preferred embodiments. Although there may be changes or modifications therein, they would not betray the spirit and scope of the novel ideas disclosed in the present disclosure. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       One or more embodiments are illustrated by way of examples, and not by limitation, in the FIGURES of the accompanying drawings, wherein elements having the same reference numeral designations represent like elements throughout. 
         FIG. 1  illustrates the hierarchical clustering result of metastatic cancers with various primary sites using the expression profiles of the genes, which is acquired by using a microarray gene expression dataset. 
     
    
    
     The drawings are only schematic and are non-limiting. Any reference signs in the claims shall not be construed as limiting the scope. Like reference symbols in the various drawings indicate like elements 
     DETAILED DESCRIPTION 
     Unless defined otherwise, all technical and scientific terms used herein have the same meanings as commonly understood by one of skill in the art to which this disclosure belongs. It will be further understood that terms; such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the relevant art and the present disclosure, and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. 
     Reference throughout this specification to “one embodiment” or “an embodiment” means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases “in one embodiment” or “in an embodiment” in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, the particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. 
     Definition 
     Unless clearly specified herein, meanings of the articles “a,” “an,” and “said” all include the plural form of “more than one.” Therefore, for example, when the term “a component” is used, it includes multiple said components and equivalents known to those of common knowledge in said field. 
     The term “about,” as used herein, when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or ±10%, more preferably ±5%, even more preferably ±1%, and still more preferably ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. 
     A “disease” is a state of health of an animal wherein the animal cannot maintain homeostasis, and wherein if the disease is not ameliorated then the animal&#39;s health continues to deteriorate. In contrast, a “disorder” in an animal is a state of health in which the animal is able to maintain homeostasis, but in which the animal&#39;s state of health is less favorable than it would be in the absence of the disorder. Left untreated, a disorder does not necessarily cause a further decrease in the animal&#39;s state of health. 
     The term “cancer” and “tumor” as used herein are both defined as a disease characterized by the rapid and uncontrolled growth of aberrant cells. Therefore, the terms of “cancer” and “tumor” are interchangeable. Cancer cells can spread locally or through the bloodstream and lymphatic system to other parts of the body. Examples of various cancers include but are not limited to, breast cancer, prostate cancer, ovarian cancer, cervical cancer, skin cancer, pancreatic cancer, colorectal cancer, renal cancer, liver cancer, brain cancer, lymphoma, leukemia, lung cancer and the like. 
     The term “origin,” “originate” and “primary site” as used herein are all defined as the first location (i.e., tissue or organ) where a tumor/cancer developed. Therefore, the terms of “origin,” “originate” and “primary site” are interchangeable. 
     In the context of the present invention, the following abbreviations for the commonly occurring “nucleic acid bases” or “nucleotides” are used, “A” refers to adenosine, “C” refers to cytosine, “G” refers to guanosine, “T” refers to thymidine, and “U” refers to uridine. 
     Unless otherwise specified, a “nucleotide sequence encoding an amino acid sequence” includes all nucleotide sequences that are degenerate versions of each other and that encode the same amino acid sequence. The phrase nucleotide sequence that encodes a protein or an RNA may also include introns to the extent that the nucleotide sequence encoding the protein may in some version contain an intron(s). 
     The term “polynucleotide” as used herein is defined as a chain of nucleotides. Furthermore, nucleic acids are polymers of nucleotides. Thus, nucleic acids and polynucleotides as used herein are interchangeable. One skilled in the art has the general knowledge that nucleic acids are polynucleotides, which can be hydrolyzed into the monomeric “nucleotides.” The monomeric nucleotides can be hydrolyzed into nucleosides. As used herein polynucleotides include, but are not limited to, all nucleic acid sequences which are obtained by any means available in the art, including, without limitation, recombinant means, i.e., the cloning of nucleic acid sequences from a recombinant library or a cell genome, using ordinary cloning technology and PCR™, and the like, and by synthetic means. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 “Genes used as probes for identification” 
               
            
           
           
               
               
               
               
            
               
                 SEQ ID 
                   
                   
                   
               
               
                 No. 
                 Gene_Sym 
                 GENE_ID 
                 Gene_Title 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 103 
                 — 
                 — 
                 immunoglobulin kappa light chain variable 
               
               
                   
                   
                   
                 region 
               
               
                 105 
                 — 
                 — 
                 immunoglobulin heavy chain variable 
               
               
                   
                   
                   
                 region 
               
               
                 271 
                 ABAT 
                 18 
                 4-aminobutyrate aminotransferase 
               
               
                 488 
                 ABCA8 
                 10351 
                 ATP-binding cassette, sub-family A 
               
               
                   
                   
                   
                 (ABC1), member 8 
               
               
                 44 
                 ACE2 
                 59272 
                 angiotensin I converting enzyme (peptidyl- 
               
               
                   
                   
                   
                 dipeptidase A) 2 
               
               
                 512 
                 ACPP 
                 55 
                 acid phosphatase, prostate 
               
               
                 583 
                 ACTG2 
                 72 
                 actin, gamma 2, smooth muscle, enteric 
               
               
                 303 
                 ADAM28 
                 10863 
                 ADAM metallopeptidase domain 28 
               
               
                 377 
                 ADAMDEC1 
                 27299 
                 ADAM-like, decysin 1 
               
               
                 260/261 
                 ADH1B 
                 125 
                 alcohol dehydrogenase 1B (class I), beta 
               
               
                   
                   
                   
                 polypeptide 
               
               
                 365 
                 ADH1C 
                 126 
                 alcohol dehydrogenase 1C (class I), gamma 
               
               
                   
                   
                   
                 polypeptide 
               
               
                 288 
                 AGR2 
                 10551 
                 anterior gradient homolog 2 ( Xenopus   
               
               
                   
                   
                   
                 
                   laevis) 
                 
               
               
                 626 
                 AGTR2 
                 186 
                 angiotensin II receptor, type 2 
               
               
                 181 
                 AHNAK2 
                 113146 
                 AHNAK nucleoprotein 2 
               
               
                 210 
                 AHSG 
                 197 
                 alpha-2-HS-glycoprotein preproprotein 
               
               
                 344 
                 AKR1B10 
                 57016 
                 aldo-keto reductase family 1, member B10 
               
               
                   
                   
                   
                 (aldose reductase) 
               
               
                 197 
                 AKR1C2 
                 1646 
                 aldo-keto reductase family 1, member C2 
               
               
                   
                   
                   
                 (dihydrodiol dehydrogenase 2; bile acid 
               
               
                   
                   
                   
                 binding protein; 3-alpha hydroxysteroid 
               
               
                   
                   
                   
                 dehydrogenase, type III) 
               
               
                 292 
                 AKR1C3 
                 8644 
                 aldo-keto reductase family 1, member C3 
               
               
                   
                   
                   
                 (3-alpha hydroxysteroid dehydrogenase, 
               
               
                   
                   
                   
                 type II) 
               
               
                 131/206 
                 ALB 
                 213 
                 albumin 
               
               
                 189 
                 ALDH1A1 
                 216 
                 aldehyde dehydrogenase 1 family, member 
               
               
                   
                   
                   
                 A1 
               
               
                 40 
                 ALDH8A1 
                 64577 
                 aldehyde dehydrogenase 8 family, member 
               
               
                   
                   
                   
                 A1 
               
               
                 97 
                 ALDOB 
                 229 
                 fructose-bisphosphate aldolase B 
               
               
                 205/491  
                 ALDOB 
                 229 
                 aldolase B, fructose-bisphosphate 
               
               
                 510 
                 ALOX5 
                 240 
                 arachidonate 5-lipoxygenase 
               
               
                 272  
                 AMACR ///  
                 23600 /// 
                 alpha-methylacyl-CoA racemase isoform 3 
               
               
                   
                 C1QTNF3- 
                 100534612  
                 /// alpha-methyl acyl-CoA racemase 
               
               
                   
                 AMACR 
                   
                 isoform 1 /// alpha-methylacyl-CoA 
               
               
                   
                   
                   
                 racemase isoform 2 /// 
               
               
                 424 
                 AMBP 
                 259 
                 alpha-1-microglobulin/bikunin precursor 
               
               
                 298 
                 AMY1A /// 
                 276 /// 277 /// 
                 pancreatic alpha-amylase precursor /// 
               
               
                   
                 AMY1B /// 
                 278 /// 279 /// 
                 alpha-amylase 1 precursor /// alpha-amylase 
               
               
                   
                 AMY1C /// 
                 280 /// 281 
                 1 precursor /// alpha-amylase 1 precursor /// 
               
               
                   
                 AMY2A /// 
                   
                 alpha-amylase 1 precursor /// alpha-amylase 
               
               
                   
                 AMY2B /// 
                   
                 2B precursor /// /// 
               
               
                   
                 AMYP1 
                   
                   
               
               
                 354 
                 ANK3 
                 288 
                 ankyrin 3, node of Ranvier (ankyrin G) 
               
               
                 79 
                 ANO1 
                 55107 
                 anoctamin-1 
               
               
                 573 
                 ANPEP 
                 290 
                 alanyl (membrane) aminopeptidase 
               
               
                   
                   
                   
                 (aminopeptidase N, aminopeptidase M, 
               
               
                   
                   
                   
                 microsomal aminopeptidase, CD13, p150) 
               
               
                 226 
                 ANXA10 
                 11199 
                 annexin A10 
               
               
                 277 
                 ANXA3 
                 306 
                 annexin A3 
               
               
                 554 
                 AOC1 
                 26 
                 amiloride-sensitive amine oxidase [copper- 
               
               
                   
                   
                   
                 containing] isoform 2 precursor /// 
               
               
                   
                   
                   
                 amiloride-sensitive amine oxidase [copper- 
               
               
                   
                   
                   
                 containing] isoform 1 precursor 
               
               
                 454 
                 AOX1 
                 316 
                 aldehyde oxidase 1 
               
               
                 620 
                 AP3B2 
                 8120 
                 adaptor-related protein complex 3, beta 2 
               
               
                   
                   
                   
                 subunit 
               
               
                 358 
                 APCS 
                 325 
                 amyloid P component, serum 
               
               
                  99/509 
                 APOA1 
                 335 
                 apolipoprotein A-I 
               
               
                 68/69 
                 APOA2 
                 336 
                 apolipoprotein A-II 
               
               
                 453 
                 APOB 
                 338 
                 apolipoprotein B (including Ag(x) antigen) 
               
               
                 342 
                 APOBEC3B 
                 9582 
                 apolipoprotein B mRNA editing enzyme, 
               
               
                   
                   
                   
                 catalytic polypeptide-like 3B 
               
               
                 398 
                 APOC3 
                 345 
                 apolipoprotein C-III 
               
               
                 448 
                 APOH 
                 350 
                 apolipoprotein H (beta-2-glycoprotein I) 
               
               
                 4 
                 AQP3 
                 360 
                 aquaporin 3 (Gill blood group) 
               
               
                 445 
                 AREG 
                 374 
                 amphiregulin (schwannoma-derived growth 
               
               
                   
                   
                   
                 factor) 
               
               
                 372 
                 ARG1 
                 383 
                 arginase, liver 
               
               
                 538 
                 ARG2 
                 384 
                 arginase, type II 
               
               
                 374 
                 ARHGAP6 
                 395 
                 Rho GTPase activating protein 6 
               
               
                 35 
                 ARL14 
                 80117 
                 ADP-ribosylation factor-like 14 
               
               
                 238/239 
                 ASCL1 
                 429 
                 achaete-scute complex homolog 1 
               
               
                   
                   
                   
                 ( Drosophila ) 
               
               
                 75 
                 ASPN 
                 54829 
                 asporin 
               
               
                 179 
                 ATP8A1 
                 10396 
                 ATPase, aminophospholipid transporter 
               
               
                   
                   
                   
                 (APLT), class I, type 8A, member 1 
               
               
                 279 
                 AZGP1 
                 563 
                 alpha-2-glycoprotein 1, zinc-binding 
               
               
                 57 
                 BANK1 
                 55024 
                 B-cell scaffold protein with ankyrin repeats 
               
               
                   
                   
                   
                 1 
               
               
                 433 
                 BBOX1 
                 8424 
                 butyrobetaine (gamma), 2-oxoglutarate 
               
               
                   
                   
                   
                 dioxygenase (gamma-butyrob etaine 
               
               
                   
                   
                   
                 hydroxylase) 1 
               
               
                 144 
                 BCAT1 
                 586 
                 branched chain aminotransferase 1, 
               
               
                   
                   
                   
                 cytosolic 
               
               
                 429 
                 BCHE 
                 590 
                 butyrylcholinesterase 
               
               
                 408 
                 BCL2A1 
                 597 
                 BCL2-related protein A1 
               
               
                 602 
                 BCLAF1 
                 9774 
                 BCL2-associated transcription factor 1 
               
               
                 85 
                 BEX1 
                 55859 
                 brain expressed, X-linked 1 
               
               
                 48 
                 BHMT2 
                 23743 
                 betaine-homocysteine methyltransferase 2 
               
               
                 213 
                 BIRC3 
                 330 
                 baculoviral IAP repeat-containing 3 
               
               
                 319 
                 BLNK 
                 29760 
                 B-cell linker 
               
               
                 42 
                 C14orf105 
                 55195 
                 chromosome 14 open reading frame 105 
               
               
                 67 
                 C1orf116 
                 79098 
                 chromosome 1 open reading frame 116 
               
               
                 14 
                 C1orf186 /// 
                 440712 /// 
                 uncharacterized protein C1orf186 
               
               
                   
                 LOC100505650 
                 100505650  
                   
               
               
                 567 
                 C7 
                 730 
                 complement component 7 
               
               
                 82 
                 C8orf4 
                 56892 
                 chromosome 8 open reading frame 4 
               
               
                 332 
                 C9 
                 735 
                 complement component 9 
               
               
                 280 
                 CA2 
                 760 
                 carbonic anhydrase II 
               
               
                 412/413 
                 CALB1 
                 793 
                 calbindin 1, 28 kDa 
               
               
                  90/211 
                 CALCA 
                 796 
                 calcitonin/calcitonin-related polypeptide, 
               
               
                   
                   
                   
                 alpha 
               
               
                 632 
                 CAPN11 
                 11131 
                 calpain 11 
               
               
                 140 
                 CAPN3 
                 825 
                 calpain 3, (p94) 
               
               
                 569 
                 CAPN6 
                 827 
                 calpain 6 
               
               
                 561 
                 CAV2 
                 858 
                 caveolin 2 
               
               
                 216 
                 CCL15 /// 
                 6359 /// 
                 C—C motif chemokine ligand 15 
               
               
                   
                 CCL15- 
                 348249 
                   
               
               
                   
                 CCL14 
                   
                   
               
               
                 12 
                 CCL18 
                 6362 
                 chemokine (C—C motif) ligand 18 
               
               
                   
                   
                   
                 (pulmonary and activation-regulated) 
               
               
                 231 
                 CCL19 
                 6363 
                 chemokine (C—C motif) ligand 19 
               
               
                 425 
                 CCL20 
                 6364 
                 chemokine (C—C motif) ligand 20 
               
               
                 359 
                 CCR7 
                 1236 
                 chemokine (C—C motif) receptor 7 
               
               
                 94 
                 CD22 
                 933 
                 CD22 molecule 
               
               
                 13 
                 CD24 
                 100133941  
                 signal transducer CD24 isoform a 
               
               
                   
                   
                   
                 preproprotein /// signal transducer CD24 
               
               
                   
                   
                   
                 isoform a preproprotein /// signal transducer 
               
               
                   
                   
                   
                 CD24 isoform b /// signal transducer CD24 
               
               
                   
                   
                   
                 isoform a preproprotein /// /// /// 
               
               
                 296 
                 CD24 
                 934 
                 CD24 molecule 
               
               
                 267 
                 CD36 
                 948 
                 CD36 molecule (thrombospondin receptor) 
               
               
                 527 
                 CD37 
                 951 
                 CD37 molecule 
               
               
                 10 
                 CD52 
                 1043 
                 CAMPATH-1 antigen precursor 
               
               
                 252 
                 CD69 
                 969 
                 CD69 molecule 
               
               
                 594 
                 CDH1 
                 999 
                 cadherin 1, type 1, E-cadherin (epithelial) 
               
               
                 248 
                 CDH17 
                 1015 
                 cadherin 17, LI cadherin (liver-intestine) 
               
               
                 328 
                 CDH19 
                 28513 
                 cadherin 19, type 2 
               
               
                 557 
                 CDH2 
                 1000 
                 cadherin 2, type 1, N-cadherin (neuronal) 
               
               
                 528 
                 CDO1 
                 1036 
                 cysteine dioxygenase, type I 
               
               
                 589 
                 CEACAM5 
                 1048 
                 carcinoembryonic antigen-related cell 
               
               
                   
                   
                   
                 adhesion molecule 5 
               
               
                 196/551 
                 CEACAM6 
                 4680 
                 carcinoembryonic antigen-related cell 
               
               
                   
                   
                   
                 adhesion molecule 6 (non-specific cross 
               
               
                   
                   
                   
                 reacting antigen) 
               
               
                 371 
                 CEACAM7 
                 1087 
                 carcinoembryonic antigen-related cell 
               
               
                   
                   
                   
                 adhesion molecule 7 
               
               
                 388 
                 CEL 
                 1056 
                 carboxyl ester lipase (bile salt-stimulated 
               
               
                   
                   
                   
                 lipase) 
               
               
                 308 
                 CFHR5 
                 81494 
                 complement factor H-related 5 
               
               
                 273/274 
                 CHI3L1 
                 1116 
                 chitinase 3-like 1 (cartilage glycoprotein- 
               
               
                   
                   
                   
                 39) 
               
               
                 498 
                 CHL1 
                 10752 
                 cell adhesion molecule with homology to 
               
               
                   
                   
                   
                 L1CAM (close homolog of L1) 
               
               
                 92 
                 CLCA2 
                 9635 
                 chloride channel, calcium activated, family 
               
               
                   
                   
                   
                 member 2 
               
               
                 685 
                 CLDN16 
                 10686 
                 claudin 16 
               
               
                 29/30/151 
                 CLDN18 
                 51208 
                 claudin 18 
               
               
                 537 
                 CLDN3 
                 1365 
                 claudin-3 
               
               
                 137 
                 CLDN8 
                 9073 
                 claudin 8 
               
               
                 41 
                 CLEC2D 
                 29121 
                 C-type lectin domain family 2, member D 
               
               
                 396 
                 CLGN 
                 1047 
                 calmegin 
               
               
                 65 
                 CLIC3 
                 9022 
                 chloride intracellular channel 3 
               
               
                 176 
                 CLIC5 
                 53405 
                 chloride intracellular channel 5 
               
               
                 130 
                 CNIH3 
                 149111 
                 cornichon homolog 3 ( Drosophila ) 
               
               
                 173 
                 CNR1 
                 1268 
                 cannabinoid receptor 1 (brain) 
               
               
                 93 
                 COL10A1 
                 1300 
                 collagen, type X, alpha 1(Schmid 
               
               
                   
                   
                   
                 metaphyseal chondrodysplasia) 
               
               
                 5/517/ 
                 COL11A1 
                 1301 
                 collagen, type XI, alpha 1 
               
               
                 183 
                 COL14A1 
                 7373 
                 collagen, type XIV, alpha 1 (undulin) 
               
               
                 581 
                 COL1A1 
                 1277 
                 collagen, type I, alpha 1 
               
               
                   
                   
                   
                 collagen, type II, alpha 1 (primary 
               
               
                 171 
                 COL2A1 
                 1280 
                 osteoarthritis, spondyloepiphyseal 
               
               
                   
                   
                   
                 dysplasia, congenital) 
               
               
                 15 
                 COL4A3 
                 1285 
                 collagen, type IV, alpha 3 (Goodpasture 
               
               
                   
                   
                   
                 antigen) 
               
               
                 178 
                 COL4A5 
                 1287 
                 collagen, type IV, alpha 5 (Alport 
               
               
                   
                   
                   
                 syndrome) 
               
               
                 405 
                 COMP 
                 1311 
                 cartilage oligomeric matrix protein 
               
               
                 481 
                 CP 
                 1356 
                 ceruloplasmin (ferroxidase) 
               
               
                 422 
                 CPB1 
                 1360 
                 carboxypeptidase B1 (tissue) 
               
               
                 338 
                 CPB2 
                 1361 
                 carboxypeptidase B2 (plasma) 
               
               
                 595 
                 CPE 
                 1363 
                 carboxypeptidase E 
               
               
                 379 
                 CPM 
                 1368 
                 carboxypeptidase M 
               
               
                 89/476 
                 CPS1 
                 1373 
                 carbamoyl-phosphate synthetase 1, 
               
               
                   
                   
                   
                 mitochondrial 
               
               
                 419 
                 CR2 
                 1380 
                 complement component (3d/Epstein Barr 
               
               
                   
                   
                   
                 virus) receptor 2 
               
               
                 316 
                 CRISP3 
                 10321 
                 cysteine-rich secretory protein 3 
               
               
                 7 
                 CRP 
                 1401 
                 C-reactive protein, pentraxin-related 
               
               
                 451 
                 CSF2RB 
                 1439 
                 colony stimulating factor 2 receptor, beta, 
               
               
                   
                   
                   
                 low-affinity (granulocyte-macrophage) 
               
               
                 367 
                 CST1 
                 1469 
                 cystatin SN 
               
               
                 465 
                 CSTA 
                 1475 
                 cystatin A (stefin A) 
               
               
                 195/212 
                 CTAG1A/// 
                 246100///1485 
                 cancer/testis antigen 1A///cancer/testis 
               
               
                   
                 CTAG1B 
                   
                 antigen 1B 
               
               
                 633 
                 CTNND1 /// 
                 1500 /// 
                 catenin delta-1 isoform 1ABC /// catenin 
               
               
                   
                 TMX2- 
                 100528016 
                 delta-1 isoform 1AB /// catenin delta-1 
               
               
                   
                 CTNND1 
                   
                 isoform 1A /// catenin delta-1 isoform 1A /// 
               
               
                   
                   
                   
                 catenin delta-1 isoform 1A /// catenin delta- 
               
               
                   
                   
                   
                 1 isoform 3ABC /// catenin delta-1 isoform 
               
               
                   
                   
                   
                 3AB /// catenin delta-1 isoform 3B /// 
               
               
                   
                   
                   
                 catenin delta-1 isoform 3AC /// catenin 
               
               
                   
                   
                   
                 delta-1 isoform 3A /// catenin delta-1 
               
               
                   
                   
                   
                 isoform 3A /// catenin delta-1 isoform 3A/// 
               
               
                   
                   
                   
                 catenin delta-1 isoform 2ABC /// catenin 
               
               
                   
                   
                   
                 delta-1 isoform 2AC /// catenin delta-1 
               
               
                   
                   
                   
                 isoform 1AC /// catenin delta-1 isoform 
               
               
                   
                   
                   
                 2AB /// catenin delta-1 isoform 2B /// 
               
               
                   
                   
                   
                 catenin delta-1 isoform 2A /// catenin delta- 
               
               
                   
                   
                   
                 1 isoform 2A /// catenin delta-1 isoform 3A 
               
               
                   
                   
                   
                 /// catenin delta-1 isoform 2A /// catenin 
               
               
                   
                   
                   
                 delta-1 isoform 1B /// 
               
               
                 604 
                 CTR9 
                 9646 
                 Ctr9, Paf1/RNA polymerase II complex 
               
               
                   
                   
                   
                 component, homolog ( S. cerevisiae)   
               
               
                 385 
                 CTSE 
                 1510 
                 cathepsin E 
               
               
                 630 
                 CUL1 
                 8454 
                 cullin 1 
               
               
                 161 
                 CUX2 
                 23316 
                 cut-like homeobox 2 
               
               
                 32 
                 CWH43 
                 80157 
                 PGAP2-interacting protein isoform 2 /// 
               
               
                   
                   
                   
                 PGAP2-interacting protein isoform 1 
               
               
                 505 
                 CXCL1 
                 2919 
                 chemokine (C-X-C motif) ligand 1 
               
               
                   
                   
                   
                 (melanoma growth stimulating activity, 
               
               
                   
                   
                   
                 alpha) 
               
               
                 207/224/641 
                 CXCL11 
                 6373 
                 chemokine (C-X-C motif) ligand 11 
               
               
                 257 
                 CXCL12 
                 6387 
                 stromal cell-derived factor 1 isoform beta 
               
               
                   
                   
                   
                 precursor /// stromal cell-derived factor 1 
               
               
                   
                   
                   
                 isoform gamma precursor /// stromal cell- 
               
               
                   
                   
                   
                 derived factor 1 isoform delta precursor /// 
               
               
                   
                   
                   
                 stromal cell-derived factor 1 isoform 5 
               
               
                   
                   
                   
                 precursor /// stromal cell-derived factor 1 
               
               
                   
                   
                   
                 isoform alpha precursor 
               
               
                 444 
                 CXCL13 
                 10563 
                 chemokine (C-X-C motif) ligand 13 (B-cell 
               
               
                   
                   
                   
                 chemoattractant) 
               
               
                 88 
                 CXCL14 
                 9547 
                 chemokine (C-X-C motif) ligand 14 
               
               
                 253 
                 CXCL2 
                 2920 
                 chemokine (C-X-C motif) ligand 2 
               
               
                 314 
                 CXCL3 
                 2921 
                 chemokine (C-X-C motif) ligand 3 
               
               
                 127/129 
                 CXCL5 
                 6374 
                 chemokine (C-X-C motif) ligand 5 
               
               
                 202/574 
                 CXCL8 
                 3576 
                 interleukin-8 precursor 
               
               
                 578 
                 CYP1B1 
                 1545 
                 cytochrome P450, family 1, subfamily B, 
               
               
                   
                   
                   
                 polypeptide 1 
               
               
                 307 
                 CYP2C8 
                 1558 
                 cytochrome P450 2C8 isoform a precursor 
               
               
                   
                   
                   
                 /// cytochrome P450 2C8 isoform b /// 
               
               
                   
                   
                   
                 cytochrome P450 2C8 isoform c /// 
               
               
                   
                   
                   
                 cytochrome P450 2C8 isoform b 
               
               
                 240/241/597 
                 CYP2E1 
                 1571 
                 cytochrome P450, family 2, subfamily E, 
               
               
                   
                   
                   
                 polypeptide 1 
               
               
                 148/149/401 
                 CYP3A5 
                 1577 
                 cytochrome P450, family 3, subfamily A, 
               
               
                   
                   
                   
                 polypeptide 5 
               
               
                   
                 CYP3A5P2 
                 79424 
                 cytochrome P450, family 3, subfamily A, 
               
               
                   
                   
                   
                 polypeptide 5 pseudogene 2 
               
               
                 230 
                 CYP4B1 
                 1580 
                 cytochrome P450, family 4, subfamily B, 
               
               
                   
                   
                   
                 polypeptide 1 
               
               
                 643 
                 CYP4F8 
                 11283 
                 cytochrome P450, family 4, subfamily F, 
               
               
                   
                   
                   
                 polypeptide 8 
               
               
                 302/313 
                 DAZ1 /// 
                 1617 /// 
                 deleted in azoospermia protein 4 isoform 1 
               
               
                   
                 DAZ2 /// 
                 57054 /// 
                 /// deleted in azoospermia protein 2 isoform 
               
               
                   
                 DAZ3 /// 
                 57055 /// 
                 2 /// deleted in azoospermia protein 2 
               
               
                   
                 DAZ4 
                 57135 
                 isoform 3 /// deleted in azoospermia protein 
               
               
                   
                   
                   
                 1 /// deleted in azoospermia protein 2 
               
               
                   
                   
                   
                 isoform 1 /// deleted in azoospermia protein 
               
               
                   
                   
                   
                 3 /// deleted in azoospermia protein 4 
               
               
                   
                   
                   
                 isoform 2 
               
               
                 106 
                 DCT 
                 1638 
                 L-dopachrome tautomerase isoform 2 
               
               
                   
                   
                   
                 precursor /// L-dopachrome tautomerase 
               
               
                   
                   
                   
                 isoform 1 precursor 
               
               
                 107 
                 DCT 
                 1638 
                 L-dopachrome tautomerase isoform 2 
               
               
                   
                   
                   
                 precursor /// L-dopachrome tautomerase 
               
               
                   
                   
                   
                 isoform 1 precursor 
               
               
                 437 
                 DCT 
                 1638 
                 dopachrome tautomerase (dopachrome 
               
               
                   
                   
                   
                 delta-isomerase, tyrosine-related protein 2) 
               
               
                 438/440 
                 DDC 
                 1644 
                 dopa decarboxylase (aromatic L-amino acid 
               
               
                   
                   
                   
                 decarboxylase) 
               
               
                 463 
                 DDX3Y 
                 8653 
                 DEAD (Asp-Glu-Ala-Asp) box polypeptide 
               
               
                   
                   
                   
                 3, Y-linked 
               
               
                 215 
                 DEFB1 
                 1672 
                 defensin, beta 1 
               
               
                 154 
                 DHRS2 
                 10202 
                 dehydrogenase/reductase (SDR family) 
               
               
                   
                   
                   
                 member 2 
               
               
                 497 
                 DKK1 
                 22943 
                 dickkopf homolog 1 ( Xenopus laevis ) 
               
               
                   
                   
                   
                 dickkopf-related protein 3 precursor /// 
               
               
                 667 
                 DKK3 
                 27122 
                 dickkopf-related protein 3 precursor /// 
               
               
                   
                   
                   
                 dickkopf-related protein 3 precursor /// 
               
               
                 266 
                 DLK1 
                 8788 
                 delta-like 1 homolog ( Drosophila ) 
               
               
                 545 
                 DMD 
                 1756 
                 dystrophin (muscular dystrophy, Duchenne 
               
               
                   
                   
                   
                 and Becker types) 
               
               
                 612 
                 DMXL1 
                 1657 
                 Dmx-like 1 
               
               
                 203/552 
                 DPP4 
                 1803 
                 dipeptidyl-peptidase 4 (CD26, adenosine 
               
               
                   
                   
                   
                 deaminase complexing protein 2) 
               
               
                 180 
                 DPT 
                 1805 
                 dermatopontin 
               
               
                 508 
                 DST 
                 667 
                 dystonin 
               
               
                 532 
                 DUSP4 
                 1846 
                 dual specificity phosphatase 4 
               
               
                 300 
                 EDN3 
                 1908 
                 endothelin 3 
               
               
                 334/520/522 
                 EDNRB 
                 1910 
                 endothelin receptor type B 
               
               
                 50 
                 EHF 
                 26298 
                 ets homologous factor 
               
               
                 511 
                 EIF1AY 
                 9086 
                 eukaryotic translation initiation factor 1A, 
               
               
                   
                   
                   
                 Y-linked 
               
               
                 678 
                 EIF4G2 
                 1982 
                 eukaryotic translation initiation factor 4 
               
               
                   
                   
                   
                 gamma 2 isoform 2 /// eukaryotic translation 
               
               
                   
                   
                   
                 initiation factor 4 gamma 2 isoform 1 /// 
               
               
                   
                   
                   
                 eukaryotic translation initiation factor 4 
               
               
                   
                   
                   
                 gamma 2 isoform 1 
               
               
                 66 
                 ELL3 
                 80237 
                 elongation factor RNA polymerase II-like 3 
               
               
                 168 
                 ELOVL2 
                 54898 
                 elongation of very long chain fatty acids 
               
               
                   
                   
                   
                 (FEN1/Elo2, SUR4/Elo3, yeast)-like 2 
               
               
                 17 
                 EMX2 
                 2018 
                 empty spiracles homeobox 2 
               
               
                 482/483 
                 ENPEP 
                 2028 
                 glutamyl aminopeptidase (aminopeptidase 
               
               
                   
                   
                   
                 A) 
               
               
                 591 
                 EPCAM 
                 4072 
                 epithelial cell adhesion molecule precursor 
               
               
                 380 
                 EPHA3 
                 2042 
                 EPH receptor A3 
               
               
                 348 
                 EPYC 
                 1833 
                 epiphycan 
               
               
                 446 
                 ESR1 
                 2099 
                 estrogen receptor 1 
               
               
                 610 
                 ETFB 
                 2109 
                 electron-transfer-flavoprotein, beta 
               
               
                   
                   
                   
                 polypeptide 
               
               
                 19 
                 ETV1 
                 2115 
                 ets variant gene 1 
               
               
                 192 
                 EVI2B 
                 2124 
                 ecotropic viral integration site 2B 
               
               
                 170 
                 F2RL1 
                 2150 
                 proteinase-activated receptor 2 precursor 
               
               
                 489 
                 F5 
                 2153 
                 coagulation factor V (proaccelerin, labile 
               
               
                   
                   
                   
                 factor) 
               
               
                 325 
                 F9 
                 2158 
                 coagulation factor IX (plasma 
               
               
                   
                   
                   
                 thromboplastic component, Christmas 
               
               
                   
                   
                   
                 disease, hemophilia B) 
               
               
                 390 
                 FABP1 
                 2168 
                 fatty acid binding protein 1, liver 
               
               
                 534 
                 FABP4 
                 2167 
                 fatty acid binding protein 4, adipocyte 
               
               
                 460/461 
                 FABP7 
                 2173 
                 fatty acid binding protein 7, brain 
               
               
                 249 
                 FAM65B 
                 9750 
                 protein FAM65B isoform 3 /// protein 
               
               
                   
                   
                   
                 FAM65B isoform 4 /// protein FAM65B 
               
               
                   
                   
                   
                 isoform 5 /// protein FAM65B isoform 1 /// 
               
               
                   
                   
                   
                 protein FAM65B isoform 2 
               
               
                 566 
                 FBLN1 
                 2192 
                 fibulin 1 
               
               
                 563 
                 FBN2 
                 2201 
                 fibrillin 2 (congenital contractural 
               
               
                   
                   
                   
                 arachnodactyly) 
               
               
                 533/615 
                 FCGR3B 
                 2215 
                 Fc fragment of IgG, low affinity IIIb, 
               
               
                   
                   
                   
                 receptor (CD16b) 
               
               
                 1 
                 FERMT1 
                 55612 
                 fermitin family homolog 1 
               
               
                 410/411 
                 FGA 
                 2243 
                 fibrinogen alpha chain 
               
               
                 112/464 
                 FGB 
                 2244 
                 fibrinogen beta chain 
               
               
                 515 
                 FGFR3 
                 2261 
                 fibroblast growth factor receptor 3 
               
               
                   
                   
                   
                 (achondroplasia, thanatophoric dwarfism) 
               
               
                 59 
                 FGG 
                 2266 
                 fibrinogen gamma chain 
               
               
                 218 
                 FHL1 
                 2273 
                 four and a half LIM domains 1 
               
               
                 526 
                 FLI1 
                 2313 
                 Friend leukemia virus integration 1 
               
               
                 72 
                 FLRT3 
                 23767 
                 fibronectin leucine rich transmembrane 
               
               
                   
                   
                   
                 protein 3 
               
               
                  3/347 
                 FMO3 
                 2328 
                 flavin containing monooxygenase 3 
               
               
                 121/393 
                 FOLH1 /// 
                 2346 /// 
                 folate hydrolase 1 
               
               
                   
                 FOLH1B 
                 219595 
                   
               
               
                 492 
                 FOXA1 
                 3169 
                 forkhead box A1 
               
               
                 599 
                 FOXE1 
                 2304 
                 forkhead box E1 (thyroid transcription 
               
               
                   
                   
                   
                 factor 2) 
               
               
                 553 
                 FRZB 
                 2487 
                 frizzled-related protein 
               
               
                 156 
                 FUT9 
                 10690 
                 fucosyltransferase 9 (alpha (1,3) 
               
               
                   
                   
                   
                 fucosyltransferase) 
               
               
                 27 
                 FZD5 
                 7855 
                 frizzled-5 precursor /// 
               
               
                 391 
                 GABBR1 /// 
                 2550 /// 
                 gamma-aminobutyric acid type B receptor 
               
               
                   
                 UBD 
                 10537 
                 subunit 1 isoform a precursor /// ubiquitin D 
               
               
                   
                   
                   
                 /// gamma-aminobutyric acid type B 
               
               
                   
                   
                   
                 receptor subunit 1 isoform b precursor /// 
               
               
                   
                   
                   
                 gamma-aminobutyric acid type B receptor 
               
               
                   
                   
                   
                 subunit 1 isoform c precursor 
               
               
                 237 
                 GABBR2 
                 9568 
                 gamma-aminobutyric acid (GABA) B 
               
               
                   
                   
                   
                 receptor, 2 
               
               
                 457 
                 GABRP 
                 2568 
                 gamma-aminobutyric acid (GABA) A 
               
               
                   
                   
                   
                 receptor, pi 
               
               
                 326 
                 GAGE1 /// 
                 2543 /// 2574 
                 G antigen 1 /// G antigen 12F///G antigen 
               
               
                   
                 GAGE12B 
                 /// 2576 /// 
                 12J /// G antigen 2D /// G antigen 
               
               
                   
                 /// 
                 2577 /// 2578 
                 12B/C/D/E /// G antigen 12G /// G antigen 
               
               
                   
                 GAGE12C 
                 /// 2579 /// 
                 12H///G antigen 2B/2C///G antigen 13 /// 
               
               
                   
                 /// 
                 26748 /// 
                 G antigen 12B/C/D/E /// G antigen 
               
               
                   
                 GAGE12D 
                 26749 /// 
                 12B/C/D/E /// G antigen 2E /// G antigen 
               
               
                   
                 /// 
                 645037 /// 
                 2A/2B /// G antigen 12B/C/D/E /// /// G 
               
               
                   
                 GAGE12E 
                 645051 /// 
                 antigen 2B/2C ///G antigen 4 /// G antigen 
               
               
                   
                 /// 
                 645073 /// 
                 5 /// G antigen 6 /// G antigen 12I /// G 
               
               
                   
                 GAGE12F 
                 729396 /// 
                 antigen 2D /// G antigen 12G 
               
               
                   
                 /// 
                 729408 ///  
                   
               
               
                   
                 GAGE12G 
                 729422 /// 
                   
               
               
                   
                 /// 
                 729428 /// 
                   
               
               
                   
                 GAGE12H 
                 729431 /// 
                   
               
               
                   
                 /// 
                 729442 /// 
                   
               
               
                   
                 GAGE12I 
                 729447 /// 
                   
               
               
                   
                 /// 
                 100008586 /// 
                   
               
               
                   
                 GAGE12J 
                 100101629 /// 
                   
               
               
                   
                 /// GAGE13 
                 100132399 
                   
               
               
                   
                 /// GAGE2A 
                   
                   
               
               
                   
                 /// GAGE2B 
                   
                   
               
               
                   
                 /// GAGE2C 
                   
                   
               
               
                   
                 /// GAGE2D  
                   
                   
               
               
                   
                 /// GAGE2E 
                   
                   
               
               
                   
                 /// GAGE4 
                   
                   
               
               
                   
                 /// GAGE5 
                   
                   
               
               
                   
                 /// GAGE6 
                   
                   
               
               
                   
                 /// GAGE7 
                   
                   
               
               
                   
                 /// GAGE8 
                   
                   
               
               
                 318 
                 GAGE1 /// 
                 2543 /// 2574 
                 G antigen 1 /// G antigen 12F /// G antigen 
               
               
                   
                 GAGE12D 
                 /// 2575 /// 
                 12J /// G antigen 2D /// G antigen 12G /// G 
               
               
                   
                 /// 
                 2576 /// 2577 
                 antigen 2B/2C///G antigen 13 /// G antigen 
               
               
                   
                 GAGE12F 
                 /// 2578 /// 
                 12B/C/D/E /// G antigen 2E /// G antigen 
               
               
                   
                 /// 
                 2579 /// 
                 2A/2B /// /// G antigen 2B/2C /// G antigen 
               
               
                   
                 GAGE12G 
                 26748 /// 
                 4 /// G antigen 5 /// G antigen 6 /// G antigen 
               
               
                   
                 /// 
                 26749 /// 
                 12I /// G antigen 2D /// G antigen 12G 
               
               
                   
                 GAGE12I 
                 645037 /// 
                   
               
               
                   
                 /// 
                 645051 ///  
                   
               
               
                   
                 GAGE12J 
                 645073 /// 
                   
               
               
                   
                 /// GAGE13 
                 729396 /// 
                   
               
               
                   
                 /// GAGE2A 
                 729408 /// 
                   
               
               
                   
                 /// GAGE2B 
                 729447 /// 
                   
               
               
                   
                 /// GAGE2C 
                 100008586 /// 
                   
               
               
                   
                 /// GAGE2D 
                 100101629 /// 
                   
               
               
                   
                 /// GAGE2E 
                 100132399 
                   
               
               
                   
                 /// GAGE3 
                   
                   
               
               
                   
                 /// GAGE4 
                   
                   
               
               
                   
                 /// GAGE5 
                   
                   
               
               
                   
                 /// GAGE6 
                   
                   
               
               
                   
                 /// GAGE7 
                   
                   
               
               
                   
                 /// GAGE8 
                   
                   
               
               
                 306 
                 GAGE1 /// 
                 2543 /// 2576 
                 G antigen 1 /// G antigen 12F /// G antigen 
               
               
                   
                 GAGE12D 
                 ///2577 /// 
                 12J /// G antigen 2D /// G antigen 12G /// G 
               
               
                   
                 /// 
                 2578 /// 2579 
                 antigen 2B/2C /// G antigen 13 /// G antigen 
               
               
                   
                 GAGE12F 
                 ///26748 /// 
                 12B/C/D/E /// G antigen 2E /// /// G antigen 
               
               
                   
                 /// 
                 26749 /// 
                 4 /// G antigen 5 /// G antigen 6 /// G antigen 
               
               
                   
                 GAGE12G 
                 645037 /// 
                 12I /// G antigen 12G 
               
               
                   
                 /// 
                 645051 /// 
                   
               
               
                   
                 GAGE12I 
                 645073 /// 
                   
               
               
                   
                 /// 
                 729396 ///  
                   
               
               
                   
                 GAGE12J 
                 729408 /// 
                   
               
               
                   
                 /// GAGE13 
                 100008586 /// 
                   
               
               
                   
                 /// GAGE2B 
                 100132399 
                   
               
               
                   
                 /// GAGE2D 
                   
                   
               
               
                   
                 /// GAGE2E  
                   
                   
               
               
                   
                 /// GAGE4 
                   
                   
               
               
                   
                 /// GAGE5 
                   
                   
               
               
                   
                 /// GAGE6 
                   
                   
               
               
                   
                 /// GAGE7 
                   
                   
               
               
                 340 
                 GAGE12B 
                 2574 /// 2576 
                 G antigen 12F /// G antigen 2D /// G antigen 
               
               
                   
                 /// 
                 /// 2577 /// 
                 12B/C/D/E /// G antigen 12G /// G antigen 
               
               
                   
                 GAGE12C 
                 2578///2579 
                 12H /// G antigen 12B/C/D/E /// G antigen 
               
               
                   
                 /// 
                 /// 26748 /// 
                 12B/C/D/E /// G antigen 2E /// G antigen 
               
               
                   
                 GAGE12D 
                 26749 /// 
                 2A/2B /// G antigen 12B/C/D/E /// G antigen 
               
               
                   
                 /// 
                 645073 /// 
                 2B/2C /// G antigen 4 /// G antigen 5 /// G 
               
               
                   
                 GAGE12E 
                 729408 /// 
                 antigen 6 /// G antigen 12I /// G antigen 2D 
               
               
                   
                 /// 
                 729422 /// 
                 /// G antigen 12G /// /// 
               
               
                   
                 GAGE12F 
                 729428 /// 
                   
               
               
                   
                 /// 
                 729431 /// 
                   
               
               
                   
                 GAGE12G 
                 729442 /// 
                   
               
               
                   
                 /// 
                 729447 /// 
                   
               
               
                   
                 GAGE12H 
                 100008586 /// 
                   
               
               
                   
                 /// 
                 100101629 /// 
                   
               
               
                   
                 GAGE12I 
                 100132399 
                   
               
               
                   
                 /// GAGE2A 
                   
                   
               
               
                   
                 /// GAGE2C 
                   
                   
               
               
                   
                 /// GAGE2D 
                   
                   
               
               
                   
                 /// GAGE2E 
                   
                   
               
               
                   
                 /// GAGE4 
                   
                   
               
               
                   
                 /// GAGE5 
                   
                   
               
               
                   
                 /// GAGE6 
                   
                   
               
               
                   
                 /// GAGE7 
                   
                   
               
               
                   
                 /// GAGE8 
                   
                   
               
               
                 304 
                 GAGE7 
                 2579 
                 G antigen 7 
               
               
                 560 
                 GALNT3 
                 2591 
                 UDP-N-acetyl-alpha-D- 
               
               
                   
                   
                   
                 galactosamine: polypeptide N- 
               
               
                   
                   
                   
                 acetylgalactosaminyltransferase 3 
               
               
                   
                   
                   
                 (GalNAc-T3) 
               
               
                 504 
                 GAP43 
                 2596 
                 growth associated protein 43 
               
               
                 263 
                 GATA3 
                 2625 
                 GATA binding protein 3 
               
               
                 236 
                 GATA6 
                 2627 
                 GATA binding protein 6 
               
               
                 564 
                 GATM 
                 2628 
                 glycine amidinotransferase (L- 
               
               
                   
                   
                   
                 arginine:glycine amidinotransferase) 
               
               
                 466 
                 GC 
                 2638 
                 group-specific component (vitamin D 
               
               
                   
                   
                   
                 binding protein) 
               
               
                 351 
                 GCG 
                 2641 
                 glucagon 
               
               
                 25 
                 GDF15 
                 9518 
                 growth differentiation factor 15 
               
               
                 661 
                 GDPD5 
                 81544 
                 glycerophosphodiester phosphodiesterase 
               
               
                   
                   
                   
                 domain containing 5 
               
               
                 649 
                 GGA3 
                 23163 
                 golgi associated, gamma adaptin ear 
               
               
                   
                   
                   
                 containing, ARF binding protein 3 
               
               
                 423 
                 GHR 
                 2690 
                 growth hormone receptor 
               
               
                 54 
                 GIMAP6 
                 474344 
                 GTPase, IMAP family member 6 
               
               
                 663 
                 GLB1L2 
                 89944 
                 beta-galactosidase-1-like protein 2 
               
               
                   
                   
                   
                 precursor 
               
               
                 623 
                 GNAL 
                 2774 
                 guanine nucleotide binding protein (G 
               
               
                   
                   
                   
                 protein), alpha activating activity 
               
               
                   
                   
                   
                 polypeptide, olfactory type 
               
               
                 289 
                 GPM6B 
                 2824 
                 neuronal membrane glycoprotein M6-b 
               
               
                   
                   
                   
                 isoform 4 /// neuronal membrane 
               
               
                   
                   
                   
                 glycoprotein M6-b isoform 1 /// neuronal 
               
               
                   
                   
                   
                 membrane glycoprotein M6-b isoform 2 /// 
               
               
                   
                   
                   
                 neuronal membrane glycoprotein M6-b 
               
               
                   
                   
                   
                 isoform 3 
               
               
                 290 
                 GPM6B 
                 2824 
                 neuronal membrane glycoprotein M6-b 
               
               
                   
                   
                   
                 isoform 4 /// neuronal membrane 
               
               
                   
                   
                   
                 glycoprotein M6-b isoform 1 /// neuronal 
               
               
                   
                   
                   
                 membrane glycoprotein M6-b isoform 2 /// 
               
               
                   
                   
                   
                 neuronal membrane glycoprotein M6-b 
               
               
                   
                   
                   
                 isoform 3 
               
               
                 291 
                 GPM6B 
                 2824 
                 glycoprotein M6B 
               
               
                 336 
                 GPR143 
                 4935 
                 G protein-coupled receptor 143 
               
               
                 220 
                 GPR18 
                 2841 
                 G protein-coupled receptor 18 
               
               
                 259 
                 GPR37 
                 2861 
                 prosaposin receptor GPR37 precursor 
               
               
                 141 
                 GPR65 
                 8477 
                 G protein-coupled receptor 65 
               
               
                 47 
                 GPR87 
                 53836 
                 G protein-coupled receptor 87 
               
               
                 369 
                 GRB14 
                 2888 
                 growth factor receptor-bound protein 14 
               
               
                 392 
                 GREB1 
                 9687 
                 GREB1 protein 
               
               
                 83/84/680 
                 GREM1 
                 26585 
                 gremlin 1, cysteine knot superfamily, 
               
               
                   
                   
                   
                 homolog ( Xenopus laevis ) 
               
               
                 434 
                 GRIA2 
                 2891 
                 glutamate receptor, ionotropic, AMPA 2 
               
               
                 646 
                 GRM1 
                 2911 
                 glutamate receptor, metabotropic 1 
               
               
                 689 
                 GRWD1 
                 83743 
                 glutamate-rich WD repeat containing 1 
               
               
                 539 
                 GSTA2 
                 2939 
                 glutathione S-transferase A2 
               
               
                 525 
                 GULP1 
                 51454 
                 GULP, engulfment adaptor PTB domain 
               
               
                   
                   
                   
                 containing 1 
               
               
                 223 
                 GZMB 
                 3002 
                 granzyme B (granzyme 2, cytotoxic T- 
               
               
                   
                   
                   
                 lymphocyte-associated serine esterase 1) 
               
               
                 682 
                 HEATR3 
                 55027 
                 HEAT repeat-containing protein 3 
               
               
                 543 
                 HEPH 
                 9843 
                 hephaestin 
               
               
                 447 
                 HGD 
                 3081 
                 homogentisate 1,2-dioxygenase 
               
               
                   
                   
                   
                 (homogentisate oxidase) 
               
               
                 113 
                 HHEX 
                 3087 
                 hematopoietically expressed homeobox 
               
               
                 165/562 
                 HLA-DQA1 
                 3117 
                 major histocompatibility complex, class II, 
               
               
                   
                   
                   
                 DQ alpha 1 
               
               
                 185 
                 HLA-DQA1 
                 3117 /// 3118 
                 HLA class II histocompatibility antigen, 
               
               
                   
                 /// HLA- 
                   
                 DQ alpha 1 chain precursor /// HLA class II 
               
               
                   
                 DQA2 
                   
                 histocompatibility antigen, DQ alpha 2 
               
               
                   
                   
                   
                 chain precursor 
               
               
                 269 
                 HLA-DQB1 
                 3119 
                 major histocompatibility complex, class II, 
               
               
                   
                   
                   
                 DQ beta 1 
               
               
                 26 
                 HLA-DQB1 
                 3119 /// 3123 
                 HLA class II histocompatibility antigen, 
               
               
                   
                 /// HLA- 
                 /// 3124 /// 
                 DQ beta 1 chain isoform 2 precursor /// 
               
               
                   
                 DRB1 /// 
                 3125 /// 3126 
                 HLA class II histocompatibility antigen, 
               
               
                   
                 HLA-DRB2 
                 /// 3127 /// 
                 DQ beta 1 chain isoform 1 precursor /// 
               
               
                   
                 /// HLA- 
                 3128 /// 3129 
                 major histocompatibility complex, class II, 
               
               
                   
                 DRB3 /// 
                 /// 3130 /// 
                 DR beta 1 precursor /// HLA class II 
               
               
                   
                 HLA-DRB4 
                 105369230 
                 histocompatibility antigen, DQ beta 1 chain 
               
               
                   
                 /// HLA- 
                   
                 isoform 1 precursor /// major 
               
               
                   
                 DRB5 /// 
                   
                 histocompatibility complex, class II, DR 
               
               
                   
                 HLA-DRB6 
                   
                 beta 1 precursor /// major histocompatibility 
               
               
                   
                 /// HLA- 
                   
                 complex, class II, DR beta 5 precursor /// 
               
               
                   
                 DRB7 /// 
                   
                 major histocompatibility complex, class II, 
               
               
                   
                 HLA-DRB8 
                   
                 DR beta 4 precursor /// major 
               
               
                   
                 /// 
                   
                 histocompatibility complex, class II, DR 
               
               
                   
                 LOC105369 
                   
                 beta 3 precursor 
               
               
                   
                 230 
                   
                   
               
               
                 309 
                 HMGA2 
                 8091 
                 high mobility group AT-hook 2 
               
               
                 496 
                 HMGCS2 
                 3158 
                 3-hydroxy-3-methylglutaryl-Coenzyme A 
               
               
                   
                   
                   
                 synthase 2 (mitochondrial) 
               
               
                 627 
                 HMX1 
                 3166 
                 H6 family homeobox 1 
               
               
                 133 
                 HOXA9 
                 3205 
                 homeobox A9 
               
               
                 335 
                 HP 
                 3240 
                 haptoglobin 
               
               
                 299 
                 HP /// HPR  
                 3240 /// 3250 
                 haptoglobin isoform 2 preproprotein /// 
               
               
                   
                   
                   
                 haptoglobin isoform 1 preproprotein /// 
               
               
                   
                   
                   
                 haptoglobin-related protein precursor 
               
               
                 383 
                 HPD 
                 3242 
                 4-hydroxyphenylpyruvate dioxygenase 
               
               
                 201 
                 HPGD 
                 3248 
                 15-hydroxyprostaglandin dehydrogenase 
               
               
                   
                   
                   
                 [NAD(+)] isoform 1 /// 15- 
               
               
                   
                   
                   
                 hydroxyprostaglandin dehydrogenase 
               
               
                   
                   
                   
                 [NAD(+)] isoform 2 /// 15- 
               
               
                   
                   
                   
                 hydroxyprostaglandin dehydrogenase 
               
               
                   
                   
                   
                 [NAD(+)] isoform 3 /// 15- 
               
               
                   
                   
                   
                 hydroxyprostaglandin dehydrogenase 
               
               
                   
                   
                   
                 [NAD(+)] isoform 4 /// 15- 
               
               
                   
                   
                   
                 hydroxyprostaglandin dehydrogenase 
               
               
                   
                   
                   
                 [NAD(+)] isoform 5 /// 15- 
               
               
                   
                   
                   
                 hydroxyprostaglandin dehydrogenase 
               
               
                   
                   
                   
                 [NAD(+)] isoform 3 
               
               
                 540/541 
                 HPGD 
                 3248 
                 hydroxyprostaglandin dehydrogenase 15- 
               
               
                   
                   
                   
                 (NAD) 
               
               
                 484 
                 HSD17B2 
                 3294 
                 hydroxysteroid (17-beta) dehydrogenase 2 
               
               
                  6/406 
                 HSD17B6 
                 8630 
                 hydroxysteroid (17-beta) dehydrogenase 6 
               
               
                   
                   
                   
                 homolog (mouse) 
               
               
                 639 
                 HSF2 
                 3298 
                 heat shock transcription factor 2 
               
               
                 608 
                 HSPA13 
                 6782 
                 heat shock 70 kDa protein 13 precursor 
               
               
                 281/282 
                 ID4 
                 3400 
                 inhibitor of DNA binding 4, dominant 
               
               
                   
                   
                   
                 negative helix-loop-helix protein 
               
               
                 607 
                 IFI27 
                 3429 
                 interferon, alpha-inducible protein 27 
               
               
                 268 
                 IGF1 
                 3479 
                 insulin-like growth factor I isoform 4 
               
               
                   
                   
                   
                 preproprotein /// insulin-like growth factor I 
               
               
                   
                   
                   
                 isoform 1 preproprotein /// insulin-like 
               
               
                   
                   
                   
                 growth factor I isoform 2 precursor /// /// /// 
               
               
                   
                   
                   
                 /// 
               
               
                 547 
                 IGF2BP3 
                 10643 
                 insulin-like growth factor 2 mRNA-binding 
               
               
                   
                   
                   
                 protein 3 
               
               
                 548 
                 IGF2BP3 
                 10643 
                 insulin-like growth factor 2 mRNA binding 
               
               
                   
                   
                   
                 protein 3 
               
               
                 441 
                 IGFBP1 
                 3484 
                 insulin-like growth factor binding protein 1 
               
               
                 125 
                 IGH 
                 3492 
                 immunoglobulin heavy locus 
               
               
                 100/108 
                 IGHAl /// 
                 3493 /// 3500 
                 zinc finger CW-type PWWP domain 
               
               
                   
                 IGHG1 /// 
                 /// 3507 /// 
                 protein 2 
               
               
                   
                 IGHM /// 
                 28396 ///  
                   
               
               
                   
                 IGHV3-23 
                 28442 ///  
                   
               
               
                   
                 /// IGHV4- 
                 50802 /// 
                   
               
               
                   
                 31 /// IGK 
                 152098 
                   
               
               
                   
                 /// 
                   
                   
               
               
                   
                 ZCWPW2 
                   
                   
               
               
                 109/276 
                 IGHM 
                 3507 
                 immunoglobulin heavy constant mu 
               
               
                 200 
                 IGHM /// 
                 3507 /// 
                 immunoglobulin heavy constant mu 
               
               
                   
                 IGHV1-69 
                 28458 /// 
                   
               
               
                   
                 /// IGHV1- 
                 28461 
                   
               
               
                   
                 69-2 
                   
                   
               
               
                 692 
                 IGHMBP2 
                 3508 
                 immunoglobulin mu binding protein 2 
               
               
                 199 
                 IGKC 
                 3514 
                 immunoglobulin kappa constant 
               
               
                 198 
                 IGKV1-17 
                 28937 
                 immunoglobulin kappa variable 1-17 
               
               
                 110 
                 IGKV1-37 
                 28894 /// 
                 immunoglobulin kappa variable 1D- 
               
               
                   
                 /// 
                 28931 
                 37///immunoglobulin kappa variable 1-37 
               
               
                   
                 IGKV1D-37 
                   
                   
               
               
                 123 
                 IGKV1-39 
                 28893 /// 
                 immunoglobulin kappa variable 1D-39 
               
               
                   
                 /// 
                 28930 
                   
               
               
                   
                 IGKV1D-39 
                   
                   
               
               
                 122 
                 IGLV3-25 
                 28793 
                 immunoglobulin lambda variable 3-25 
               
               
                 373 
                 IL13RA2 
                 3598 
                 interleukin 13 receptor, alpha 2 
               
               
                 674 
                 IL9R 
                 3581 
                 interleukin-9 receptor isoform 1 precursor 
               
               
                   
                   
                   
                 /// interleukin-9 receptor isoform 2 
               
               
                 690 
                 IMP3 
                 55272 
                 IMP3, U3 small nucleolar 
               
               
                   
                   
                   
                 ribonucleoprotein, homolog (yeast) 
               
               
                 343 
                 INS 
                 3630 
                 insulin 
               
               
                 378 
                 ISL1 
                 3670 
                 ISL LIM homeobox 1 
               
               
                 402 
                 ITIH3 
                 3699 
                 inter-alpha (globulin) inhibitor H3 
               
               
                 576 
                 ITM2A 
                 9452 
                 integral membrane protein 2A 
               
               
                 186 
                 JCHAIN 
                 3512 
                 immunoglobulin J chain precursor 
               
               
                 658 
                 JMJD6 
                 23210 
                 jumonji domain containing 6 
               
               
                 228 
                 KCNJ15 
                 3772 
                 potassium inwardly-rectifying channel, 
               
               
                   
                   
                   
                 subfamily J, member 15 
               
               
                 63 
                 KCNJ16 
                 3773 
                 potassium inwardly-rectifying channel, 
               
               
                   
                   
                   
                 subfamily J, member 16 
               
               
                 34 
                 KHDC1L 
                 100129128  
                 putative KHDC1-like protein 
               
               
                 2 
                 KIAA0226L 
                 80183 
                 uncharacterized protein KIAA0226-like 
               
               
                   
                   
                   
                 isoform a /// uncharacterized protein 
               
               
                   
                   
                   
                 KIAA0226-like isoform b /// 
               
               
                   
                   
                   
                 uncharacterized protein KIAA0226-like 
               
               
                   
                   
                   
                 isoform c /// uncharacterized protein 
               
               
                   
                   
                   
                 KIAA0226-like isoform d /// 
               
               
                   
                   
                   
                 uncharacterized protein KIAA0226-like 
               
               
                   
                   
                   
                 isoform e /// uncharacterized protein 
               
               
                   
                   
                   
                 KIAA0226-like isoform f /// 
               
               
                   
                   
                   
                 uncharacterized protein KIAA0226-like 
               
               
                   
                   
                   
                 isoform a 
               
               
                 670 
                 KIAA1024 
                 23251 
                 KIAA1024 protein 
               
               
                 659 
                 KIAA1109 
                 84162 
                 KIAA1109 
               
               
                 611 
                 KIF3C 
                 3797  
                 kinesin family member 3C 
               
               
                 287 
                 KLF5 
                 688  
                 Kruppel-like factor 5 (intestinal) 
               
               
                 426/600 
                 KLK2 
                 3817 
                 kallikrein-related peptidase 2 
               
               
                 499/500 
                 KLK3 
                 354 
                 kallikrein-related peptidase 3 
               
               
                 382 
                 KNG1 
                 3827 
                 kininogen 1 
               
               
                 311 
                 KRT13 
                 3860 
                 keratin 13 
               
               
                 278 
                 KRT14 
                 3861 
                 keratin 14 (epidermolysis bullosa simplex, 
               
               
                   
                   
                   
                 Dowling-Meara, Koebner) 
               
               
                 487 
                 KRT15 
                 3866 
                 keratin 15 
               
               
                 452 
                 KRT17 
                 3872 
                 keratin 17 
               
               
                 592 
                 KRT19 
                 3880 
                 keratin 19 
               
               
                 159 
                 KRT20 
                 54474 
                 keratin 20 
               
               
                 77 
                 KRT23 
                 25984 
                 keratin 23 (histone deacetylase inducible) 
               
               
                 293 
                 KRT6A 
                 3853 
                 keratin 6A 
               
               
                 295 
                 KRT7 
                 3855 
                 keratin 7 
               
               
                 96 
                 KYNU 
                 8942 
                 kynureninase (L-kynurenine hydrolase) 
               
               
                 45 
                 L1TD1 
                 54596 
                 LINE-1 type transposase domain containing 
               
               
                   
                   
                   
                 1 
               
               
                 143 
                 LBP 
                 3929 
                 lipopolysaccharide binding protein 
               
               
                 188 
                 LCN2 
                 3934 
                 lipocalin 2 (oncogene 24p3) 
               
               
                 442 
                 LCP2 
                 3937 
                 lymphocyte cytosolic protein 2 (SH2 
               
               
                   
                   
                   
                 domain containing leukocyte protein of 
               
               
                   
                   
                   
                 76 kDa) 
               
               
                 605 
                 LDLR 
                 3949 
                 low density lipoprotein receptor (familial 
               
               
                   
                   
                   
                 hypercholesterolemia) 
               
               
                 364 
                 LEFTY1 
                 10637 
                 left-right determination factor 1 
               
               
                 244 
                 LEPR 
                 3953 
                 leptin receptor 
               
               
                 609 
                 LEPROTL1 
                 23484 
                 leptin receptor overlapping transcript-like 1 
               
               
                 521 
                 LGALS4 
                 3960 
                 lectin, galactoside-binding, soluble, 4 
               
               
                   
                   
                   
                 (galectin 4) 
               
               
                 164 
                 LGR5 
                 8549 
                 leucine-rich repeat-containing G protein- 
               
               
                   
                   
                   
                 coupled receptor 5 
               
               
                 52 
                 LIN28A 
                 79727 
                 protein lin-28 homolog A 
               
               
                 360 
                 LIPF 
                 8513 
                 lipase, gastric 
               
               
                 102 
                 LOC100126 
                 100126583/// 
                 hypothetical 
               
               
                   
                 583///IGHA 
                 3494///3493 
                 LOC100126583///immunoglobulin heavy 
               
               
                   
                 2///IGHA1 
                   
                 constant alpha 2 (A2m 
               
               
                   
                   
                   
                 marker)///immunoglobulin heavy constant 
               
               
                   
                   
                   
                 alpha 1 
               
               
                 117 
                 LOC101929 
                 101929272  
                 LOC101929272 
               
               
                   
                 272 
                   
                   
               
               
                 636 
                 LOC103021 
                 7326 /// 
                 ubiquitin-conjugating enzyme E2 G1 
               
               
                   
                 295 /// 
                 103021295 
                   
               
               
                   
                 UBE2G1 
                   
                   
               
               
                 118 
                 LOX 
                 4015 
                 lysyl oxidase 
               
               
                 555 
                 LPL 
                 4023 
                 lipoprotein lipase 
               
               
                 55 
                 LRAP 
                 64167 
                 leukocyte-derived arginine aminopeptidase 
               
               
                 9 
                 LRMP 
                 4033 
                 lymphoid-restricted membrane protein 
               
               
                 587 
                 LTF 
                 4057 
                 lactotransferrin 
               
               
                 409 
                 LY75 
                 4065 
                 lymphocyte antigen 75 
               
               
                 323 
                 MAGEA1 
                 4100 
                 melanoma antigen family A, 1 (directs 
               
               
                   
                   
                   
                 expression of antigen MZ2-E) 
               
               
                 134 
                 MAGEA12 
                 4111 
                 melanoma antigen family A, 12 
               
               
                 214 
                 MAGEA2B 
                 266740///139  
                 melanoma antigen family A, 
               
               
                   
                 ///psMAGE 
                 041///4101 
                 2B///melanoma antigen pseudogene, family 
               
               
                   
                 A///MAGE 
                   
                 A///melanoma antigen family A, 2 
               
               
                   
                 A2 
                   
                   
               
               
                 136 
                 MAGEA3 
                 4102 
                 melanoma antigen family A, 3 
               
               
                 242 
                 MAGEA4 
                 4103 
                 melanoma antigen family A, 4 
               
               
                 147 
                 MAGEA5 
                 4104 
                 melanoma antigen family A, 5 
               
               
                 135 
                 MAGEA6 
                 4105 
                 melanoma antigen family A, 6 
               
               
                 368 
                 MAGEB2 
                 4113 
                 melanoma antigen family B, 2 
               
               
                 485 
                 MAL 
                 4118 
                 mal, T-cell differentiation protein 
               
               
                 513/514 
                 MAOA 
                 4128 
                 monoamine oxidase A 
               
               
                 572 
                 MAP7 
                 9053 
                 microtubule-associated protein 7 
               
               
                 579 
                 MATN2 
                 4147 
                 matrilin 2 
               
               
                 644 
                 MAX 
                 4149 
                 MYC associated factor X 
               
               
                 324 
                 MBL2 
                 4153 
                 mannose-binding lectin (protein C) 2, 
               
               
                   
                   
                   
                 soluble (opsonic defect) 
               
               
                 294 
                 MBP 
                 4155 
                 myelin basic protein 
               
               
                 672 
                 MCM5 
                 4174 
                 minichromosome maintenance complex 
               
               
                   
                   
                   
                 component 5 
               
               
                 20 
                 MECOM 
                 2122 
                 MDS1 and EVI1 complex locus 
               
               
                 370 
                 MEOX2 
                 4223 
                 mesenchyme homeobox 2 
               
               
                 427 
                 MFAP3L 
                 9848 
                 microfibrillar-associated protein 3-like 
               
               
                 167 
                 MFAP5 
                 8076 
                 microfibrillar associated protein 5 
               
               
                 345 
                 MIA 
                 8190 
                 melanoma inhibitory activity 
               
               
                 652 
                 MKI67 
                 4288 
                 antigen identified by monoclonal antibody 
               
               
                   
                   
                   
                 Ki-67 
               
               
                 349/350 
                 MLANA 
                 2315 
                 melan-A 
               
               
                 558 
                 MME 
                 4311 
                 membrane metallo-endopeptidase 
               
               
                 503 
                 MMP1 
                 4312 
                 matrix metallopeptidase 1 (interstitial 
               
               
                   
                   
                   
                 collagenase) 
               
               
                 501 
                 MMP12 
                 4321 
                 matrix metallopeptidase 12 (macrophage 
               
               
                   
                   
                   
                 elastase) 
               
               
                 524 
                 MMP7 
                 4316 
                 matrix metallopeptidase 7 (matrilysin, 
               
               
                   
                   
                   
                 uterine) 
               
               
                 468 
                 MNDA 
                 4332 
                 myeloid cell nuclear differentiation antigen 
               
               
                 430 
                 MPPED2 
                 744 
                 metallophosphoesterase domain containing 
               
               
                   
                   
                   
                 2 
               
               
                 550 
                 MPZL2 
                 10205 
                 myelin protein zero-like 2 
               
               
                  95/217 
                 MS4A1 
                 931 
                 membrane-spanning 4-domains, subfamily 
               
               
                   
                   
                   
                 A, member 1 
               
               
                 60 
                 MS4A4A 
                 51338 
                 membrane-spanning 4-domains, subfamily 
               
               
                   
                   
                   
                 A, member 4 
               
               
                 660 
                 MSH5- 
                 401251 /// 
                 suppressor APC domain-containing protein 
               
               
                   
                 SAPCD1 /// 
                 100532732  
                 1 /// 
               
               
                   
                 SAPCD1 
                   
                   
               
               
                 479 
                 MSLN 
                 10232 
                 mesothelin 
               
               
                 219/321 
                 MSMB 
                 4477 
                 microseminoprotein, beta- 
               
               
                 91 
                 MT1M 
                 4499 
                 metallothionein 1M 
               
               
                 647 
                 MTAP 
                 4507 
                 methylthioadenosine phosphorylase 
               
               
                 315 
                 MUC1 
                 4582 
                 mucin 1, cell surface associated 
               
               
                 81 
                 MUC13 
                 56667 
                 mucin 13, cell surface associated 
               
               
                 38 
                 MUC16 
                 94025 
                 mucin 16, cell surface associated 
               
               
                 98 
                 MUC4 
                 4585 
                 mucin 4, cell surface associated 
               
               
                 162 
                 MYBL1 
                 4603 
                 v-myb myeloblastosis viral oncogene 
               
               
                   
                   
                   
                 homolog (avian)-like 1 
               
               
                 153 
                 MYBPC1 
                 4604 
                 myosin binding protein C, slow type 
               
               
                 653 
                 MYH10 
                 4628 
                 myosin, heavy chain 10, non-muscle 
               
               
                 593 
                 MYH11 
                 4629 
                 myosin, heavy chain 11, smooth muscle 
               
               
                 677 
                 MYRF 
                 745 
                 myelin regulatory factor isoform 2 
               
               
                   
                   
                   
                 precursor /// myelin regulatory factor 
               
               
                   
                   
                   
                 isoform 1 
               
               
                 39 
                 NANOG 
                 79923 
                 Nanog homeobox 
               
               
                 467 
                 NCF1 /// 
                 653361 /// 
                 neutrophil cytosol factor 1 
               
               
                   
                 NCF1B /// 
                 654816 /// 
                   
               
               
                   
                 NCF1C 
                 654817 
                   
               
               
                 535/536 
                 NEBL 
                 10529 
                 nebulette 
               
               
                 11 
                 NEFH 
                 4744 
                 neurofilament, heavy polypeptide 200 kDa 
               
               
                 22 
                 NEFL 
                 4747 
                 neurofilament, light polypeptide 68 kDa 
               
               
                 657 
                 NEMP1 
                 23306 
                 nuclear envelope integral membrane protein 
               
               
                   
                   
                   
                 1 isoform a precursor /// nuclear envelope 
               
               
                   
                   
                   
                 integral membrane protein 1 isoform b 
               
               
                 208 
                 NKX2-1 
                 7080 
                 NK2 homeobox 1 
               
               
                 256 
                 NKX3-1 
                 4824 
                 NK3 homeobox 1 
               
               
                 389 
                 NLGN1 
                 22871 
                 neuroligin 1 
               
               
                 18 
                 NLGN4X 
                 57502 
                 neuroligin 4, X-linked 
               
               
                 146 
                 NOV 
                 4856 
                 nephroblastoma overexpressed gene 
               
               
                 622 
                 NOVA1 
                 4857 
                 neuro-oncological ventral antigen 1 
               
               
                 352 
                 NOX1 
                 27035 
                 NADPH oxidase 1 
               
               
                 28 
                 NPL 
                 80896 
                 N-acetylneuraminate pyruvate lyase 
               
               
                   
                   
                   
                 (dihydrodipicolinate synthase) 
               
               
                 172 
                 NPTX2 
                 4885 
                 neuronal pentraxin II 
               
               
                 428 
                 NPY1R 
                 4886 
                 neuropeptide Y receptor Y1 
               
               
                 111 
                 NR4A2 
                 4929 
                 nuclear receptor subfamily 4, group A, 
               
               
                   
                   
                   
                 member 2 
               
               
                 264/265 
                 NSG1 
                 27065 
                 neuron-specific protein family member 1 
               
               
                   
                   
                   
                 isoform a /// neuron-specific protein family 
               
               
                   
                   
                   
                 member 1 isoform a /// neuron-specific 
               
               
                   
                   
                   
                 protein family member 1 isoform b /// 
               
               
                   
                   
                   
                 neuron-specific protein family member 1 
               
               
                   
                   
                   
                 isoform a 
               
               
                  23/625 
                 NTRK2 
                 4915 
                 neurotrophic tyrosine kinase, receptor, type 
               
               
                   
                   
                   
                 2 
               
               
                 362 
                 NTS 
                 4922 
                 neurotensin 
               
               
                 664 
                 NUP210 
                 23225 
                 nucleoporin 210 kDa 
               
               
                 638 
                 NXT2 
                 55916 
                 nuclear transport factor 2-like export factor 
               
               
                   
                   
                   
                 2 
               
               
                 80 
                 OGN 
                 4969 
                 osteoglycin 
               
               
                 645 
                 OLFM1 
                 10439 
                 olfactomedin 1 
               
               
                 184 
                 OLFM4 
                 10562 
                 olfactomedin 4 
               
               
                 459 
                 ORM1 
                 5004 
                 orosomucoid 1 
               
               
                 142 
                 ORM1 /// 
                 5004 /// 5005  
                 alpha-1-acid glycoprotein 1 precursor /// 
               
               
                   
                 ORM2 
                   
                 alpha-1-acid glycoprotein 2 precursor 
               
               
                 458 
                 ORM2 
                 5005 
                 orosomucoid 2 
               
               
                 341 
                 P2RY14 
                 9934 
                 purinergic receptor P2Y, G-protein coupled, 
               
               
                   
                   
                   
                 14 
               
               
                 404 
                 PAH 
                 5053 
                 phenylalanine hydroxylase 
               
               
                 16 
                 PAX5 
                 5079 
                 paired box 5 
               
               
                 138 
                 PAX8 
                 7849 
                 paired box 8 
               
               
                 73 
                 PBK 
                 55872 
                 PDZ binding kinase 
               
               
                 64 
                 PBLD 
                 64081 
                 phenazine biosynthesis-like protein domain 
               
               
                   
                   
                   
                 containing 
               
               
                 683 
                 PCDH12 
                 51294 
                 protocadherin 12 
               
               
                 420 
                 PCDH7 
                 5099 
                 protocadherin 7 
               
               
                 301 
                 PCK1 
                 5105 
                 phosphoenolpyruvate carboxykinase 1 
               
               
                   
                   
                   
                 (soluble) 
               
               
                 418 
                 PCP4 
                 5121 
                 Purkinje cell protein 4 
               
               
                 397 
                 PCSK1 
                 5122 
                 proprotein convertase subtilisin/kexin type 
               
               
                   
                   
                   
                 1 
               
               
                 417 
                 PCSK5 
                 5125 
                 proprotein convertase subtilisin/kexin type 
               
               
                   
                   
                   
                 5 
               
               
                 654 
                 PDCD11 
                 22984 
                 programmed cell death 11 
               
               
                 432 
                 PDZK1 
                 5174 
                 PDZ domain containing 1 
               
               
                 58 
                 PDZK1IP1 
                 10158 
                 PDZK1 interacting protein 1 
               
               
                 182 
                 PDZRN3 
                 23024 
                 PDZ domain containing RING finger 3 
               
               
                 190 
                 PEG10 
                 23089 
                 paternally expressed 10 
               
               
                 285/286 
                 PEG3 
                 5178 
                 paternally expressed 3 
               
               
                 631 
                 PFKFB2 
                 5208 
                 6-phosphofructo-2-kinase/fructose-2,6- 
               
               
                   
                   
                   
                 biphosphatase 2 
               
               
                 621 
                 PGAM2 
                 5224 
                 phosphoglycerate mutase 2 (muscle) 
               
               
                 169 
                 PHACTR1 
                 221692 
                 phosphatase and actin regulator 1 
               
               
                 320 
                 PIR 
                 8544 
                 pirin (iron-binding nuclear protein) 
               
               
                 61 
                 PLA1A 
                 51365 
                 phospholipase A1 member A 
               
               
                 225 
                 PLA2G4A 
                 5321 
                 phospholipase A2, group IVA (cytosolic, 
               
               
                   
                   
                   
                 calcium-dependent) 
               
               
                 76 
                 PLAC8 
                 51316 
                 placenta-specific 8 
               
               
                 327 
                 PLAGL1 
                 5325 
                 pleiomorphic adenoma gene-like 1 
               
               
                 590 
                 PLAT 
                 5327 
                 plasminogen activator, tissue 
               
               
                 614 
                 PLCB4 
                 5332 
                 phospholipase C, beta 4 
               
               
                 470/471/472 
                 PLN 
                 5350 
                 phospholamban 
               
               
                 222 
                 PLP1 
                 5354 
                 proteolipid protein 1 (Pelizaeus- 
               
               
                   
                   
                   
                 Merzbacher disease, spastic paraplegia 2, 
               
               
                   
                   
                   
                 uncomplicated) 
               
               
                 449 
                 PLS1 
                 5357 
                 plastin 1(1 isoform) 
               
               
                 688 
                 PLXNA1 
                 5361 
                 plexin A1 
               
               
                 519 
                 PMAIP1 
                 5366 
                 phorbol-12-myristate-13-acetate-induced 
               
               
                   
                   
                   
                 protein 1 
               
               
                 247 
                 PMEL 
                 6490 
                 melanocyte protein PMEL isoform 2 
               
               
                   
                   
                   
                 precursor /// melanocyte protein PMEL 
               
               
                   
                   
                   
                 isoform 1 precursor /// melanocyte protein 
               
               
                   
                   
                   
                 PMEL isoform 3 preproprotein 
               
               
                 387 
                 PNLIP 
                 5406 
                 pancreatic lipase 
               
               
                 191 
                 PNLIPRP2 
                 5408 
                 pancreatic lipase-related protein 2 
               
               
                 679 
                 POMGNT1 
                 55624 
                 protein O-linked mannose beta1,2-N- 
               
               
                   
                   
                   
                 acetylglucosaminyltransferase 
               
               
                 443 
                 POU2AF1 
                 5450 
                 POU class 2 associating factor 1 
               
               
                 628 
                 PPP1R2P9 
                 80316 
                 protein phosphatase 1 regulatory inhibitor 
               
               
                   
                   
                   
                 subunit 2 pseudogene 9 
               
               
                 529 
                 PRAME 
                 23532 
                 preferentially expressed antigen in 
               
               
                   
                   
                   
                 melanoma 
               
               
                 310 
                 PRKCB1 
                 5579 
                 protein kinase C, beta 1 
               
               
                 650 
                 PRLR 
                 5618 
                 prolactin receptor 
               
               
                 518 
                 PROM1 
                 8842 
                 prominin 1 
               
               
                 431 
                 PRS S2 
                 5645 
                 protease, serine, 2 (trypsin 2) 
               
               
                 439 
                 PSCA 
                 8000 
                 prostate stem cell antigen 
               
               
                 262 
                 PSCDBP 
                 9595 
                 pleckstrin homology, Sec7 and coiled-coil 
               
               
                   
                   
                   
                 domains, binding protein 
               
               
                 456 
                 PSPH 
                 5723  
                 phosphoserine phosphatase 
               
               
                 648 
                 PTGDS 
                 5730 
                 prostaglandin D2 synthase 21 kDa (brain) 
               
               
                 486 
                 PTGS2 
                 5743 
                 prostaglandin-endoperoxide synthase 2 
               
               
                   
                   
                   
                 (prostaglandin G/H synthase and 
               
               
                   
                   
                   
                 cyclooxygenase) 
               
               
                 193/270 
                 PTN 
                 5764 
                 pleiotrophin (heparin binding growth factor 
               
               
                   
                   
                   
                 8, neurite growth-promoting factor 1) 
               
               
                 187 
                 PTPRC 
                 5788 
                 protein tyrosine phosphatase, receptor type, 
               
               
                   
                   
                   
                 C 
               
               
                 506 
                 PTPRZ1 
                 5803 
                 protein tyrosine phosphatase, receptor-type, 
               
               
                   
                   
                   
                 Z polypeptide 1 
               
               
                 375 
                 PTX3 
                 5806 
                 pentraxin-related gene, rapidly induced by 
               
               
                   
                   
                   
                 IL-1 beta 
               
               
                 450 
                 QPCT 
                 25797 
                 glutaminyl-peptide cyclotransferase 
               
               
                   
                   
                   
                 (glutaminyl cyclase) 
               
               
                 86 
                 RAB25 
                 57111 
                 RAB25, member RAS oncogene family 
               
               
                 70 
                 RAB38 
                 23682 
                 RAB38, member RAS oncogene family 
               
               
                  21/353 
                 RARRES1 
                 5918 
                 retinoic acid receptor responder (tazarotene 
               
               
                   
                   
                   
                 induced) 1 
               
               
                 415 
                 RASGRP1 
                 10125 
                 RAS guanyl releasing protein 1 (calcium 
               
               
                   
                   
                   
                 and DAG-regulated) 
               
               
                 695 
                 RASSF4 
                 83937 
                 Ras association (RalGDS/AF-6) domain 
               
               
                   
                   
                   
                 family 4 
               
               
                 666 
                 RBM8A 
                 9939 
                 RNA-binding protein 8A 
               
               
                 74 
                 RBP4 
                 5950 
                 retinol binding protein 4, plasma 
               
               
                 254 
                 REG1A 
                 5967 
                 regenerating islet-derived 1 alpha 
               
               
                   
                   
                   
                 (pancreatic stone protein, pancreatic thread 
               
               
                   
                   
                   
                 protein) 
               
               
                 399 
                 REG3A 
                 5068 
                 regenerating islet-derived 3 alpha 
               
               
                 568 
                 RGS1 
                 5996 
                 regulator of G-protein signaling 1 
               
               
                 221 
                 RGS13 
                 6003 
                 regulator of G-protein signaling 13 
               
               
                 227 
                 RGS20 
                 8601 
                 regulator of G-protein signaling 20 
               
               
                 174 
                 RNASE4 
                 6038 
                 ribonuclease 4 precursor /// ribonuclease 4 
               
               
                   
                   
                   
                 precursor /// ribonuclease 4 precursor /// /// 
               
               
                   
                   
                   
                 ribonuclease 4 precursor 
               
               
                 71 
                 RNF128 
                 79589 
                 ring finger protein 128 
               
               
                 36 
                 ROPN1 
                 54763 
                 ropporin, rhophilin associated protein 1 
               
               
                 588 
                 RPS4Y1 
                 6192 
                 ribosomal protein S4, Y-linked 1 
               
               
                 687 
                 RRAGD 
                 58528 
                 Ras-related GTP binding D 
               
               
                 606 
                 RSRC2 
                 65117 
                 arginine/serine-rich coiled-coil 2 
               
               
                 673 
                 RTEL1///ST 
                 51750///50861  
                 regulator of telomere elongation helicase 
               
               
                   
                 MN3///ARF 
                 ///10139/// 
                 1///stathmin-like 3///ADP-ribosylation 
               
               
                   
                 RP1///TNF 
                 8771 
                 factor related protein 1///tumor necrosis 
               
               
                   
                 RSF6B 
                   
                 factor receptor superfamily, member 6b, 
               
               
                   
                   
                   
                 decoy 
               
               
                 523 
                 S100A2 
                 6273 
                 S100 calcium binding protein A2 
               
               
                 386 
                 S100A7 
                 6278 
                 S100 calcium binding protein A7 
               
               
                 571 
                 S100A8 
                 6279 
                 S100 calcium binding protein A8 
               
               
                 258 
                 S100B 
                 6285 
                 S100 calcium binding protein B 
               
               
                 516 
                 S100P 
                 6286 
                 S100 calcium binding protein P 
               
               
                 329 
                 SALL1 
                 6299 
                 sal-like 1 ( Drosophila ) 
               
               
                 37 
                 SAMSN1 
                 64092 
                 SAM domain, SH3 domain and nuclear 
               
               
                   
                   
                   
                 localization signals 1 
               
               
                 635 
                 SAP18 
                 10284 
                 Sin3A-associated protein, 18 kDa 
               
               
                 330 
                 SCEL 
                 8796 
                 sciellin 
               
               
                 531 
                 SCG2 
                 7857 
                 secretogranin II (chromogranin C) 
               
               
                 544 
                 SCG5 
                 6447 
                 secretogranin V (7B2 protein) 
               
               
                 331 
                 SCGB1D2 
                 10647 
                 secretoglobin, family 1D, member 2 
               
               
                 384 
                 SCGB2A1 
                 4246 
                 secretoglobin, family 2A, member 1 
               
               
                 355 
                 SCGB2A2 
                 4250 
                 secretoglobin, family 2A, member 2 
               
               
                 556/676 
                 SCNN1A 
                 6337 
                 sodium channel, nonvoltage-gated 1 alpha 
               
               
                 426 
                 SCRG1 
                 11341 
                 scrapie responsive protein 1 
               
               
                 549 
                 SEMA3C 
                 10512 
                 sema domain, immunoglobulin domain (Ig), 
               
               
                   
                   
                   
                 short basic domain, secreted, (semaphorin) 
               
               
                   
                   
                   
                 3C 
               
               
                 128 
                 SEMA6A 
                 57556 
                 sema domain, transmembrane domain 
               
               
                   
                   
                   
                 (TM), and cytoplasmic domain, 
               
               
                   
                   
                   
                 (semaphorin) 6A 
               
               
                 691 
                 SENP5 
                 205564 
                 SUMO1/sentrin specific peptidase 5 
               
               
                 575 
                 SERPINA1 
                 5265 
                 serpin peptidase inhibitor, clade A (alpha-1 
               
               
                   
                   
                   
                 antiproteinase, antitrypsin), member 1 
               
               
                 495 
                 SERPINB2 
                 5055 
                 serpin peptidase inhibitor, clade B 
               
               
                   
                   
                   
                 (ovalbumin), member 2 
               
               
                 255 
                 SERPINB3 
                 6317 
                 serpin peptidase inhibitor, clade B 
               
               
                   
                   
                   
                 (ovalbumin), member 3 
               
               
                 480 
                 SERPINB5 
                 5268 
                 serpin peptidase inhibitor, clade B 
               
               
                   
                   
                   
                 (ovalbumin), member 5 
               
               
                 235 
                 SERPINC1 
                 462 
                 serpin peptidase inhibitor, clade C 
               
               
                   
                   
                   
                 (antithrombin), member 1 
               
               
                 416 
                 SERPIND1 
                 3053 
                 serpin peptidase inhibitor, clade D (heparin 
               
               
                   
                   
                   
                 cofactor), member 1 
               
               
                 613 
                 SF3A3 
                 10946 
                 splicing factor 3a, subunit 3, 60 kDa 
               
               
                 584/585/586 
                 SFRP1 
                 6422 
                 secreted frizzled-related protein 1 
               
               
                 530/616 
                 SFRP4 
                 6424 
                 secreted frizzled-related protein 4 
               
               
                 601 
                 SFRS11 
                 9295 
                 splicing factor, arginine/serine-rich 11 
               
               
                 78 
                 SFTPA2 
                 729238 
                 pulmonary surfactant-associated protein A2 
               
               
                   
                   
                   
                 precursor 
               
               
                 8/251 
                 SFTPB 
                 6439 
                 surfactant, pulmonary-associated protein B 
               
               
                 229 
                 SH2D1A 
                 4068 
                 SH2 domain protein 1A, Duncan&#39;s disease 
               
               
                   
                   
                   
                 (lymphoproliferative syndrome) 
               
               
                 675 
                 SH3BP2 
                 6452 
                 SH3 domain-binding protein 2 isoform a 
               
               
                   
                   
                   
                 SH3 domain-binding protein 2 isoform c 
               
               
                   
                   
                   
                 SH3 domain-binding protein 2 isoform b /// 
               
               
                   
                   
                   
                 SH3 domain-binding protein 2 isoform a 
               
               
                 640 
                 SH3 GLB 1 
                 51100 
                 SH3-domain GRB2-like endophilin B1 
               
               
                 629 
                 SHE 
                 6469 
                 sonic hedgehog homolog ( Drosophila ) 
               
               
                 337 
                 SI 
                 6476 
                 sucrase-isomaltase (alpha-glucosidase) 
               
               
                 394 
                 SLC14A1 
                 6563 
                 solute carrier family 14 (urea transporter), 
               
               
                   
                   
                   
                 member 1 (Kidd blood group) 
               
               
                 634 
                 SLC14A2 
                 8170 
                 solute carrier family 14 (urea transporter), 
               
               
                   
                   
                   
                 member 2 
               
               
                 376 
                 SLC26A3 
                 1811 
                 solute carrier family 26, member 3 
               
               
                 31 
                 SLC38A4 
                 55089 
                 solute carrier family 38, member 4 
               
               
                 400 
                 SLC3A1 
                 6519 
                 solute carrier family 3 (cystine, dibasic and 
               
               
                   
                   
                   
                 neutral amino acid transporters, activator of 
               
               
                   
                   
                   
                 cystine, dibasic and neutral amino acid 
               
               
                   
                   
                   
                 transport), member 1 
               
               
                 414 
                 SLC44A4 
                 80736 
                 solute carrier family 44, member 4 
               
               
                 542 
                 SLC4A4 
                 8671 
                 solute carrier family 4, sodium bicarbonate 
               
               
                   
                   
                   
                 cotransporter, member 4 
               
               
                 53 
                 SLC6A14 
                 11254 
                 solute carrier family 6 (amino acid 
               
               
                   
                   
                   
                 transporter), member 14 
               
               
                 356 
                 SLC6A15 
                 55117 
                 solute carrier family 6, member 15 
               
               
                 565 
                 SLPI 
                 6590 
                 secretory leukocyte peptidase inhibitor 
               
               
                 507 
                 SNCA 
                 6622 
                 synuclein, alpha (non A4 component of 
               
               
                   
                   
                   
                 amyloid precursor) 
               
               
                 102 
                 SOD2 
                 6648 
                 superoxide dismutase 2, mitochondrial 
               
               
                 87 
                 SORBS1 
                 10580 
                 sorbin and SH3 domain containing 1 
               
               
                 477/478 
                 SOX11 
                 6664 
                 transcription factor SOX-11 
               
               
                 570 
                 SOX9 
                 6662 
                 transcription factor SOX-9 
               
               
                 317 
                 SP140 
                 11262 
                 SP140 nuclear body protein 
               
               
                 681 
                 SPATA5L1 
                 79029 
                 spermatogenesis associated 5-like 1 
               
               
                 366 
                 SPINK1 
                 6690 
                 serine peptidase inhibitor, Kazal type 1 
               
               
                 158 
                 SPON1 
                 10418 
                 spondin 1, extracellular matrix protein 
               
               
                 245 
                 SPP1 
                 6696 
                 secreted phosphoprotein 1 (osteopontin, 
               
               
                   
                   
                   
                 bone sialoprotein I, early T-lymphocyte 
               
               
                   
                   
                   
                 activation 1) 
               
               
                 166 
                 SPRR1A 
                 6698 
                 small proline-rich protein 1A 
               
               
                 455 
                 SPRR1B 
                 6699 
                 small proline-rich protein 1B (cornifin) 
               
               
                 469 
                 SRPX 
                 8406 
                 sushi-repeat-containing protein, X-linked 
               
               
                 160 
                 SST 
                 6750 
                 somatostatin 
               
               
                 175/209 
                 ST3GAL6 
                 10402 
                 ST3 beta-galactoside alpha-2,3- 
               
               
                   
                   
                   
                 sialyltransferase 6 
               
               
                 43 
                 STAP1 
                 26228 
                 signal transducing adaptor family member 1 
               
               
                 618 
                 STC1 
                 6781 
                 stanniocalcin-1 precursor 
               
               
                 619 
                 STK4 
                 6789 
                 serine/threonine kinase 4 
               
               
                 204/436 
                 SULT1C2 
                 6819 
                 sulfotransferase family, cytosolic, 1C, 
               
               
                   
                   
                   
                 member 2 
               
               
                 361 
                 SULT2A1 
                 6822 
                 sulfotransferase family, cytosolic, 2A, 
               
               
                   
                   
                   
                 dehydroepiandrosterone (DHEA)- 
               
               
                   
                   
                   
                 preferring, member 1 
               
               
                 582 
                 TACSTD2 
                 4070 
                 tumor-associated calcium signal transducer 
               
               
                   
                   
                   
                 2 
               
               
                 101 
                 TARP 
                 445347 
                 TCR gamma alternate reading frame protein 
               
               
                 114 
                 TARP /// 
                 6966 /// 6967 
                   
               
               
                   
                 TRCTC1 /// 
                 /// 6983 /// 
                 TCR gamma alternate reading frame protein 
               
               
                   
                 TRGC2 /// 
                 445347 
                 isoform 1 /// TCR gamma alternate reading 
               
               
                   
                 TRGV9 
                   
                 frame protein isoform 2 
               
               
                 250 
                 TARP /// 
                 6966 /// 6967 
                 TCR gamma alternate reading frame protein 
               
               
                   
                 TRCTC1 /// 
                 /// 6983 /// 
                 isoform 1 /// TCR gamma alternate reading 
               
               
                   
                 TRGC2 /// 
                 445347 
                 frame protein isoform 2 /// /// 
               
               
                   
                 TRGV9 
                   
                   
               
               
                 56 
                 TBX3 
                 6926 
                 T-box 3 (ulnar mammary syndrome) 
               
               
                 475 
                 TCF21 
                 6943 
                 transcription factor 21 
               
               
                 686 
                 TCF7L1 
                 83439 
                 transcription factor 7-like 1 (T-cell specific, 
               
               
                   
                   
                   
                 HMG-box) 
               
               
                 421 
                 TCN1 
                 6947 
                 transcobalamin I (vitamin B12 binding 
               
               
                   
                   
                   
                 protein, R binder family) 
               
               
                 363 
                 TDGF1 
                 6997 
                 teratocarcinoma-derived growth factor 1 
               
               
                 403 
                 TENM1 
                 10178 
                 teneurin-1 isoform 1 /// teneurin-1 isoform 
               
               
                   
                   
                   
                 2 /// teneurin-1 isoform 3 
               
               
                 155/559 
                 TF 
                 7018 
                 transferrin 
               
               
                 493 
                 TFAP2A 
                 7020 
                 transcription factor AP-2 alpha (activating 
               
               
                   
                   
                   
                 enhancer binding protein 2 alpha) 
               
               
                 145 
                 TFAP2B 
                 7021 
                 transcription factor AP-2 beta (activating 
               
               
                   
                   
                   
                 enhancer binding protein 2 beta) 
               
               
                 333 
                 TFEC 
                 22797 
                 transcription factor EC 
               
               
                 462 
                 TFF1 
                 7031 
                 trefoil factor 1 
               
               
                 139 
                 TFF2 
                 7032 
                 trefoil factor 2 (spasmolytic protein 1) 
               
               
                 283/284 
                 TFPI2 
                 7980 
                 tissue factor pathway inhibitor 2 
               
               
                 596 
                 THB S1 
                 7057 
                 thrombospondin 1 
               
               
                 275 
                 TM4SF1 
                 4071 
                 transmembrane 4 L six family member 1 
               
               
                 33 
                 TM4SF20 
                 79853 
                 transmembrane 4 L six family member 20 
               
               
                 243 
                 TM4SF4 
                 7104 
                 transmembrane 4 L six family member 4 
               
               
                 62 
                 TMC5 
                 79838 
                 transmembrane channel-like 5 
               
               
                 49 
                 TMEM255 
                 55026 
                 transmembrane protein 255A isoform 2 /// 
               
               
                   
                 A 
                   
                 transmembrane protein 255A isoform 3 /// 
               
               
                   
                   
                   
                 transmembrane protein 255A isoform 1 
               
               
                 177 
                 TMEM30B 
                 161291 
                 transmembrane protein 30B 
               
               
                 194 
                 TMPRSS2 
                 7113 
                 transmembrane protease, serine 2 
               
               
                 435 
                 TMSB15A 
                 11013 
                 thymosin beta-15A 
               
               
                 473/474 
                 TNFRSF11 
                 4982 
                 tumor necrosis factor receptor superfamily, 
               
               
                   
                 B 
                   
                 member 11b (osteoprotegerin) 
               
               
                 339 
                 TNFRSF17 
                 608 
                 tumor necrosis factor receptor superfamily, 
               
               
                   
                   
                   
                 member 17 
               
               
                 502 
                 TOX 
                 9760 
                 thymocyte selection-associated high 
               
               
                   
                   
                   
                 mobility group box 
               
               
                 104/126/132 
                 TOX3 
                 27324 
                 TOX high mobility group box family 
               
               
                   
                   
                   
                 member 3 
               
               
                 163 
                 TRAF3IP3 
                 80342 
                 TRAF3-interacting JNK-activating 
               
               
                   
                   
                   
                 modulator isoform 2 /// TRAF3-interacting 
               
               
                   
                   
                   
                 JNK-activating modulator isoform 1 
               
               
                 693 
                 TRAFD1 
                 10906 
                 TRAF-type zinc finger domain containing 1 
               
               
                 580 
                 TRIM2 
                 23321 
                 tripartite motif-containing 2 
               
               
                 305 
                 TRIM31 
                 11074 
                 tripartite motif-containing 31 
               
               
                 655 
                 TRIM33 
                 51592 
                 tripartite motif-containing 33 
               
               
                 624 
                 TRPC3 
                 7222 
                 transient receptor potential cation channel, 
               
               
                   
                   
                   
                 subfamily C, member 3 
               
               
                 119/120/ 
                 TSHR 
                 7253 
                 thyroid stimulating hormone receptor 
               
               
                 234/671  
                   
                   
                   
               
               
                 668 
                 TSPAN2 
                 10100 
                 tetraspanin 2 
               
               
                 546 
                 TSPAN8 
                 7103 
                 tetraspanin 8 
               
               
                 312 
                 TSPY1 
                 7258 
                 testis specific protein, Y-linked 1 
               
               
                 157 
                 TUBB2B 
                 347733 
                 tubulin, beta 2B 
               
               
                 665 
                 TWF1 
                 5756 
                 twinfilin, actin-binding protein, homolog 1 
               
               
                   
                   
                   
                 ( Drosophila ) 
               
               
                 603 
                 TWF2 
                 11344 
                 twinfilin, actin-binding protein, homolog 2 
               
               
                   
                   
                   
                 ( Drosophila ) 
               
               
                 152 
                 TXLNGY 
                 246126 
                 taxilin gamma pseudogene, Y-linked 
               
               
                 407 
                 TYRP1 
                 7306 
                 tyrosinase-related protein 1 
               
               
                 124/297 
                 UGT1A1 /// 
                 54575 /// 
                 UDP-glucuronosyltransferase 1-1 precursor 
               
               
                   
                 UGT1A10 
                 54576 /// 
                 /// UDP-glucuronosyltransferase 1-6 
               
               
                   
                 /// UGT1A3 
                 54577 /// 
                 isoform 1 precursor /// UDP- 
               
               
                   
                 /// UGT1A4 
                 54578 /// 
                 glucuronosyltransferase 1-4 precursor /// 
               
               
                   
                 ///UGT1A5 
                 54579 /// 
                 UDP-glucuronosyltransferase 1-10 
               
               
                   
                 /// UGT1A6 
                 54600 /// 
                 precursor /// UDP-glucuronosyltransferase 
               
               
                   
                 /// UGT1A7 
                 54657 /// 
                 1-8 precursor /// UDP- 
               
               
                   
                 /// UGT1A8 
                 54658 /// 
                 glucuronosyltransferase 1-7 precursor /// 
               
               
                   
                 /// UGT1A9 
                 54659 
                 UDP-glucuronosyltransferase 1-5 precursor 
               
               
                   
                   
                   
                 /// UDP-glucuronosyltransferase 1-3 
               
               
                   
                   
                   
                 precursor /// UDP-glucuronosyltransferase 
               
               
                   
                   
                   
                 1-9 precursor /// UDP- 
               
               
                   
                   
                   
                 glucuronosyltransferase 1-6 isoform 2 
               
               
                 46 
                 UGT2A3 
                 79799 
                 UDP glucuronosyltransferase 2 family, 
               
               
                   
                   
                   
                 polypeptide A3 
               
               
                 322 
                 UGT2B15 
                 7366 
                 UDP glucuronosyltransferase 2 family, 
               
               
                   
                   
                   
                 polypeptide B15 
               
               
                 346 
                 UGT2B4 
                 7363 
                 UDP glucuronosyltransferase 2 family, 
               
               
                   
                   
                   
                 polypeptide B4 
               
               
                 232/233 
                 UPK1B 
                 7348 
                 uroplakin 1B 
               
               
                 656 
                 USP33 
                 23032 
                 ubiquitin specific peptidase 33 
               
               
                 662 
                 VASH1- 
                 100506603 
                 VASH1 antisense RNA 1 
               
               
                   
                 AS1 
                   
                   
               
               
                 116/494 
                 VCAN 
                 1462 
                 versican 
               
               
                 115 
                 VGLL1 
                 51442 
                 vestigial like 1 ( Drosophila ) 
               
               
                 395 
                 VNN1 
                 8876 
                 vanin 1 
               
               
                 598 
                 VTN 
                 7448 
                 vitronectin 
               
               
                 637 
                 WDR46 
                 9277 
                 WD repeat domain 46 
               
               
                 694 
                 WDTC1 
                 23038 
                 WD and tetratricopeptide repeats 1 
               
               
                 490 
                 WIF1 
                 11197 
                 WNT inhibitory factor 1 
               
               
                 577 
                 WIPF1 
                 7456 
                 WAS/WASL interacting protein family, 
               
               
                   
                   
                   
                 member 1 
               
               
                 381 
                 WT1 
                 7490 
                 Wilms tumor 1 
               
               
                 24 
                 XIST 
                 7503 
                 X inactive specific transcript 
               
               
                 150 
                 XIST 
                 7503 
                 X (inactive)-specific transcript 
               
               
                 684 
                 YIF1B 
                 90522 
                 protein YIF1B isoform 3 /// protein YIF1B 
               
               
                   
                   
                   
                 isoform 5 /// protein YIF1B isoform 4 /// 
               
               
                   
                   
                   
                 protein YIF1B isoform 6 /// protein YIF1B 
               
               
                   
                   
                   
                 isoform 2 /// protein YIF1B isoform 7 
               
               
                 51 
                 ZBED2 
                 79413 
                 zinc finger, BED-type containing 2 
               
               
                 357 
                 ZIC1 
                 7545 
                 Zic family member 1 (odd-paired homolog, 
               
               
                   
                   
                   
                   Drosophila ) 
               
               
                 285/286 
                 ZIM2///PEG3 
                 23619///5178 
                 zinc finger, imprinted 2///paternally 
               
               
                   
                   
                   
                 expressed 3 
               
               
                 642 
                 ZNF174 
                 7727 
                 zinc finger protein 174 
               
               
                 669 
                 ZNF266 
                 10781 
                 zinc finger protein 266 /// zinc finger protein 
               
               
                   
                   
                   
                 266 
               
               
                 651 
                 ZNF471 
                 57573 
                 zinc finger protein 471 
               
               
                 617 
                 EBAG9 
                 9166 
                 estrogen receptor binding site associated, 
               
               
                   
                   
                   
                 antigen, 9 
               
               
                 55 
                 ERAP2 
                 6414767 
                 endoplasmic reticulum aminopeptidase 2 
               
               
                   
               
            
           
         
       
     
     DESCRIPTION 
     The present disclosure relates to a method for developing candidate probes to identify at least one primary site of a selected disease, disorder or genetic disorder in a mammalian subject. The method includes steps (a) to (c). In step (a), a detecting chip generates a plurality of gene expressions from a standard sample of a subject having a selected disease, disorder or genetic disorder, and the standard sample is diagnosed with a metastasis cancer with at least one known primary site. In step (b), a processing module compares the plurality of gene expression by using a meta-data analysis to generate a comparison result. In step (c), the processing module further develops an array that contains a plurality of candidate probes based on the comparison result. Moreover, the plurality of candidate probes are capable of binding a plurality of polynucleotide sequences selected from any one of SEQ ID No.1 to 695 or from any fragment of SEQ ID No.1 to 695. The detecting chip and the processing module are electrically connected to each other. Individually, the plurality of polynucleotides are the genes in Table 1. 
     In one embodiment, the number of the candidate probes used to identify primary site is about 650. In another embodiment, the number of the candidate probes is about 100. In one preferred embodiment, the number of the candidate probes is about 50. 
     In another embodiment, the length of the candidate probes is at least 20 nucleotides. 
     In one embodiment, the detecting chip used to identify the primary sites is a microarray chip or magnetic beads. In another embodiment, the processing module used to compare the plurality gene expressions or to develop the array containing the candidate probes is a central processing unit (CPU). 
     In one embodiment, the standard sample used to develop the candidate probes includes blood, blood plasma, serum, urine, tissue, cells, organs, seminal fluids or any combination thereof. In another embodiment, the selected disease, disorder or genetic disorder includes hematologic malignancies or solid tumors. 
     The present disclosure further relates to a method for identifying a primary site of a selected disease, disorder or genetic disorder in a mammalian subject. Specifically, the selected disease, disorder or genetic pathology in a mammalian subject may be a tumor. The method includes step (a′) and (b′). In step (a′), a detection chip containing the plurality of candidate probes developed by the method previously described is provided to analyse and measure the expression levels of an array of a test sample. The test sample may be obtained from a subject having a selected disease, disorder or genetic disorder. Such test sample is further diagnosed with a metastasis cancer with at least one unknown primary site. 
     In one embodiment, the test sample used to develop the candidate probes includes blood, blood plasma, serum, urine, tissue, cells, organs, seminal fluids or any combination thereof. In another embodiment, the selected disease, disorder or genetic disorder includes hematologic malignancies or solid tumors. 
     The present disclosure also related to a system for identifying a primary site of a selected disease, disorder or genetic disorder in a mammalian subject. The system includes a detecting chip and a processing module electrically connected to each other. The detecting chip contains a plurality of candidate probes for primary sites, and the candidate probes are capable of binding a plurality of polynucleotide sequence selected from any one of SEQ ID No.1 to 695 or from any fragment of SEQ ID No.1 to 695. Specifically, the plurality of polynucleotide are the genes list in the Table 1. That is, the candidate probes are capable of binding and further recognizing the genes in the Table 1. 
     Example 1 
     In the following content, all the statistical calculations are conducted through a processing module, which is a central processing unit (CPU). The candidate genes probes in Table 1 are hereinafter referred as “PH2”, “PH2 probes” or “the 695-gene transcription profiles.” 
     Developing the PH2 Probes 
     Step (a) of the present disclosure is to generate the whole genome expression profile of the cancer sample. Specifically, a group of transcriptomic microarray datasets derived from the metastatic cancer samples of different primary sites are collected from the public database Gene Expression Omnibus (GEO, https://www.ncbi.nlm.nih.gov/geo/). As seen in Table 2, a total of more than five hundreds samples of metastatic cancers originated from fifteen primary sites are used for probes finding and validation. 
     
       
         
           
               
               
               
               
               
               
             
               
                 TABLE 2 
               
               
                   
               
               
                   
                   
                 Number 
                   
                   
                   
               
               
                   
                 Sample 
                 of correct 
                   
                   
                   
               
               
                 Datasets 
                 number 
                 results 
                 Metastatic_site 
                 Cancer_type 
                 Reference 
               
               
                   
               
             
            
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 GSE12630 
                 187 
                 276 
                 See Note 1 
                 metastatic 
                 J Clin Oncol. 
               
               
                   
                   
                   
                   
                 cancers from 15 
                 2009 May 20; 
               
               
                   
                   
                   
                   
                 different origins 
                 27(15):2503-8. 
               
               
                 GSE14095 
                 189 
                 190 
                 liver metastasis 
                 colorectal cancer 
                 Clin Transl 
               
               
                   
                   
                   
                   
                   
                 Oncol. 2011 Jun; 
               
               
                   
                   
                   
                   
                   
                 13(6):419-25. 
               
               
                 GSE14108 
                 28 
                 9 
                 Brain 
                 lung 
                 Not Available 
               
               
                   
                   
                   
                 metastasized 
                 adenocarcinoma 
                   
               
               
                   
                   
                   
                 from lung 
                   
                   
               
               
                   
                   
                   
                 adenocarcinoma 
                   
                   
               
               
                 GSE14378 
                 20 
                 19 
                 lung 
                 clear-cell renal  
                 Wuttig et al. Int. 
               
               
                   
                   
                   
                   
                 cell carcinoma 
                 J. Cancer: 125, 
               
               
                   
                   
                   
                   
                   
                 474-482(2009) 
               
               
                 GSE15605 
                 12 
                 11 
                 lymph node, 
                 melanoma 
                 Raskin et al 
               
               
                   
                   
                   
                 subcutaneous 
                   
                 (2013), J Invest 
               
               
                   
                   
                   
                 soft tissue, 
                   
                 Dermatol, 
               
               
                   
                   
                   
                 spleen or small 
                   
                 133(11):2585-92 
               
               
                   
                   
                   
                 instestine 
                   
                   
               
               
                 GSE19949 
                 15 
                 15 
                 metastasis of 
                 renal cell 
                 Beleut M et al. 
               
               
                   
                   
                   
                 RCC to other 
                 carcinoma 
                 (2012), BMC 
               
               
                   
                   
                   
                 site 
                   
                 Cancer1 
               
               
                   
                   
                   
                   
                   
                 23; 12:310 
               
               
                 GSE20565 
                 44 
                 43 
                 ovary 
                 breast 
                 Meyniel et al. 
               
               
                   
                   
                   
                   
                   
                 (2010) BMC 
               
               
                   
                   
                   
                   
                   
                 Cancer 
               
               
                   
                   
                   
                   
                   
                 21; 10:222 
               
               
                 GSE22541 
                 44 
                 41 
                 lung 
                 clear-cell renal 
                 Wuttig et al. 
               
               
                   
                   
                   
                   
                 cell carcinoma 
                 (2012) Int J 
               
               
                   
                   
                   
                   
                   
                 Cancer 
               
               
                   
                   
                   
                   
                   
                 131(5):E693-704 
               
               
                 Total 
                 539 
                 1070 
                   
                   
                   
               
               
                   
               
               
                 Note 1: 
               
               
                 bladder, breast, colon, stomach, germ cell, kidney, liver, lung, lymph node, ovary, pancreas, prostate, skin, soft tissue, and thyroid. 
               
            
           
         
       
     
     For the purpose of generating the candidate probes of the present invention, 186 samples of distant metastasis originated from fifteen different tissue origins are first selected from the dataset GSE12630 to construct a training dataset. For this training dataset, the CEL files are acquired from GEO and then subjected to quality assessment by AffyQualityReport to remove the poor quality arrays. The data passing quality-control is then subjected to the Robust Multichip Average (RMA, Irizarry R et al.  Biostatistics  2003, 4(2):249-264) processing for data normalization. Both AffyQualityReport and RMA are obtained from the Bioconductor package in the R package (http://www.r-project.org/). Following the standard preprocessing procedure, the transcriptomic data is subjected to further statistical and bioinformatics analyses. 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 “The Example of the Expression Array of Training Gene Dataset” 
               
            
           
           
               
               
               
            
               
                   
                 Sample 
                   
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                   
                 Gene 
                 Liver 
                 Liver 
                 Breast 
                 Colon 
                 Colon 
                   
                   
                 CV 
               
               
                 No. 
                 Name 
                 1 
                 2 
                 1 
                 1 
                 2 
                 . . . 
                 others 
                 value 
               
               
                   
               
               
                 1 
                   
                   
                   
                   
                   
                   
                   
                   
                   
               
               
                 2 
               
               
                 3 
               
               
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
               
               
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
               
               
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
                 . 
               
               
                   
               
            
           
         
       
     
     Step (b) involves comparing the expression levels across different tumor samples for each gene. According to step (a), the expression levels for each gene in different tumor tissues are provided. To compare, the coefficients of variation (CV) value of the expression level in each tumor samples is obtained based on the following formula: 
     The coefficients of variation (CV) is defined as the ratio of the standard deviation σ to the mean μ: C V =σ/μ 
     Accordingly, the gene expression array which Table 3 is the exemplary format is developed. In Table 3, each row represents the expression levels of a specific gene in different tumor samples (e.g., Liver 1, Liver 2, etc.), while each column represents the different genes in the tumor samples. 
     More specifically, gene filtration is carried out by firstly selecting from the training dataset obtained in step (a) the genes whose CV value appeared in the top 5% of the entire transcriptome across different tissue types. The resulted highly variably expressed genes then becomes the set of candidate tissue-classifier genes which are later subjected to data redundancy elimination through hierarchical clustering against the 15 tissues using the open-source computer software MeV v4.8.1 (https://sourceforge.net/projects/mev-tm4/) where Pearson correlation and average linkage were chosen for Distance Metric and for Linkage method, respectively. 
     Following the hierarchical cluster analysis, one representative gene for each cluster is selected and additional genes with highly similar expression profiles are removed. Such procedure results the candidate genes as provided in Table 1. 
     The hierarchical cluster method (Pearson&#39;s correlation): 
     
       
         
           
             r 
             = 
             
               
                 
                   ∑ 
                   
                     i 
                     = 
                     1 
                   
                   n 
                 
                  
                 
                     
                 
                  
                 
                   
                     ( 
                     
                       
                         X 
                         i 
                       
                       - 
                       
                         X 
                         _ 
                       
                     
                     ) 
                   
                    
                   
                     ( 
                     
                       
                         Y 
                         i 
                       
                       - 
                       
                         Y 
                         _ 
                       
                     
                     ) 
                   
                 
               
               
                 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                      
                     
                         
                     
                      
                     
                       
                         ( 
                         
                           
                             X 
                             i 
                           
                           - 
                           
                             X 
                             _ 
                           
                         
                         ) 
                       
                       2 
                     
                   
                 
                  
                 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                      
                     
                         
                     
                      
                     
                       
                         ( 
                         
                           
                             Y 
                             i 
                           
                           - 
                           
                             Y 
                             _ 
                           
                         
                         ) 
                       
                       2 
                     
                   
                 
               
             
           
         
       
     
     Step (c) involves further developing the candidate probes of the present invention based on the previous candidate genes in Table 1. That is, the probe sequence is designed as the complementary sequence to SEQ ID No.1 to 695. Furthermore, the candidate probes sequence can be a long sequence that is entirely complementary to SEQ ID No.1 to 695, or a short sequence complementary only to a fragment of SEQ ID No.1 to 695. 
     Validation of the PH2 Probes on the Metastatic Cancerous Samples with the Oligonucleotide Microarrays 
     To validate the effects of the PH2 probes in identifying the primary sites of metastatic cancers, more of the whole-genome gene expression datasets with samples from metastatic cancers were collected from public database GEO. (See Table 2.) 
     The dataset GSE20565 (Meyniel et al. BMC Cancer 2010 May 21; 10: 222) contained 44 samples of ovarian cancers metastasized from breast. Applying the expression profiles of PH2, 43 out of 44 samples were correctly predicted with breast as their primary sites—reaching an accuracy of 97.7%. The dataset GSE22541 (Wuttig et al. Int. J. Cancer, 2009; 125: 474-482) contained 30 samples which were found in lung but metastasized from the clear-cell renal cell carcinoma. Among the 30 samples, 27 were correctly predicted to be originated from the kidney primary site, attaining a 90% of prediction accuracy. The dataset GSE15605 (Raskin L. et al. J Invest Dermatol 2013 November; 133(11): 2585-92) was predicted correctly on 11 of the 12 metastasized melanoma samples which were punch-biopsied at spleen, small intestine, lymph nodes and subcutaneous soft tissue. All of the 15 metastatic renal cell carcinoma from the dataset GSE19949 (Beleut M. et al. BMC Cancer 2012 Jul. 23; 12: 310) were successfully mapped to kidney by the PH2 probes. The lung metastasis of the renal cell carcinoma from the dataset GSE14378 19/20 (Wuttig et al. Int. J. Cancer 2009; 125: 474-482) was also confirmed by the 600-gene transcription profiles. 
     The Number of Genes was Reduced to Fit Different Experimental Platforms 
     To adapt to various experimental platforms such as using magnetic beads to identify of primary site of a metastatic cancer, the 695-gene transcription profiles may be reduced by eliminating genes with alike expression profiles. Particularly, further elimination by reducing the number of clusters at step (b) described above may result in a smaller group of classifier genes. Following validation on the test dataset with the computational process of primary-tissue-prediction, the present invention is able to reduce the gene set down to as small as 53 genes which were later proved to work efficiently on magnetic beads. As shown in Table 5 which provides the results of the validation tests, the prediction of the primary sites of metastatic cancers using a subset of the PH2 probes was highly satisfied. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 “Prediction of the primary site of a metastatic  
               
               
                 cancer with different versions of PH2” 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                 Samples 
                   
                   
                 correct_Q 
                 correct_Q 
               
               
                 Datasets 
                 (N) 
                 correct_600 
                 correct_100 
                 G (k = 1) 
                 G (k = 2) 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 GSE14095 
                 189 
                 169 
                 178 
                 177 
                 187 
               
               
                 GSE14108 
                 28 
                 24 
                 24 
                 18 
                 28 
               
               
                 GSE14378 
                 20 
                 19 
                 19 
                 19 
                 20 
               
               
                 GSE15605 
                 12 
                 11 
                 8 
                 11 
                 12 
               
               
                 GSE19949 
                 15 
                 15 
                 15 
                 14 
                 15 
               
               
                 GSE20565 
                 44 
                 43 
                 42 
                 43 
                 43 
               
               
                 GSE22541 
                 44 
                 41 
                 39 
                 42 
                 43 
               
               
                   
               
            
           
         
       
     
     For example, 42 out of 44 samples from the dataset GSE 20565 were correctly predicted, 15 out of 15 samples from the dataset GSE19949 were correctly predicted. 
     In some experimental platforms, smaller gene numbers is preferred. In one example, a group of around 53 genes (the subset of the PH2 probes) can be used to identify the primary site. While performing the validation method as described above with a larger group of genes, it was found that prediction accuracy using a subset of PH2 probes significantly dropped to 64% (18/28) from 86% (24/28) with the dataset GSE14108. However, if the parameter k of the KNN used in the prediction model changes from 1 to 2, the accuracy increases to 100% (28/28) for all test datasets. Such result suggests that a subset of the PH2 probes, if selected properly, can perform the primary site identification for metastatic cancers just as accurate as if using the entire PH2 markers. 
     Clinical Validation of QG on Primary Site Prediction for Metastatic Cancers 
     Patients and Samples: 
     The metastatic tumor specimens were taken from the cancer patients whose tumors were diagnosed as metastatic cancer by both oncologists and pathologists at the Tzu-Chi Hospital in Hualian, Taiwan. All the donors have signed informed consent forms before the tumors were removed at the surgery. The tissue samples (Table 6) extracted from the tumors were immersed into liquid nitrogen followed by RNAlater processing for later usage of PH2-QuantiGene assays. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Anatomic and Metastatic Sites of the Clinical Samples 
               
            
           
           
               
               
               
            
               
                   
                 Anatomic site 
                 Number of Samples 
               
               
                   
                   
               
            
           
           
               
               
               
            
               
                   
                 breast 
                 2 
               
               
                   
                 Colon/rectum 
                 1 
               
               
                   
                 liver 
                 7 
               
               
                   
                 gastric 
                 1 
               
               
                   
                 others 
                 4 
               
               
                   
                 Total 
                 15 
               
               
                   
                   
               
            
           
         
       
     
     Assay Kit and Signal Detection 
     The PH2-QuantiGene assay kit was custom-made by Affymetrix Inc. Affymetrix Inc. (the carrier of Panomics beads) designed the PH2 probes, conjugated the probes to the magnetic beads, assembled the necessary reagents and performed quality control on the final products. At the end of each assay, Luminex® 100/200™ is used to detect the hybridization signals. 
     The Quantigene assays on PH2 were performed in two separate experiments. The first experiment was carried out using the Luminex® 200™ to detect hybridization signals while the second experiment was performed using Luminex® 100™. Each sample was assayed in duplicates in both experiments for confirmation. For each assay, about a rice-grain size of sample was used. The Panomics-provided protocol was followed in order to measure the expression levels of each of the probes whose probes have been conjugated on the magnetic beads. 
     Analysis and Statistics 
     The data of the expression levels of each gene on the PH2-Quantigene beads output from the Luminex fluorescence reader was preprocessed and analyzed. The model then computes the probability for each of the 15 candidate tissues to become the primary site using k-nearest neighbor method (hereinafter “KNN”) as following mathematical equation at k=1, k=2 or k=3. It compares the c.f. (coefficient of correlation by Pearson&#39;s correlation) of the 600-gene profiles between a test tissue and each of our 15 tissue-specific gene expression profiles, one for each tissue type. The tissue type with highest correlation was nominated as our prediction. 
     The k-nearest neighbor method: 
     
       
         
           
             
               Sim 
                
               
                 ( 
                 
                   
                     d 
                     i 
                   
                   , 
                   
                     d 
                     j 
                   
                 
                 ) 
               
             
             = 
             
               
                 
                   ∑ 
                   
                     k 
                     = 
                     1 
                   
                   M 
                 
                  
                 
                     
                 
                  
                 
                   
                     W 
                     ik 
                   
                   × 
                   
                     W 
                     jk 
                   
                 
               
               
                 
                   
                     ( 
                     
                       
                         ∑ 
                         
                           k 
                           = 
                           1 
                         
                         M 
                       
                        
                       
                           
                       
                        
                       
                         W 
                         ik 
                         2 
                       
                     
                     ) 
                   
                    
                   
                     ( 
                     
                       
                         ∑ 
                         
                           k 
                           = 
                           1 
                         
                         M 
                       
                        
                       
                           
                       
                        
                       
                         W 
                         jk 
                         2 
                       
                     
                     ) 
                   
                 
               
             
           
         
       
     
     According to the present disclosure, the PH2 probes can identify the primary site of a metastatic cancer/tumor if the cancer/tumor originates from one of the tissues/organs including breast, stomach, colon, pancreas, bladder, thyroid, prostate, kidney, liver, ovary, germ cell, soft tissue, skin, lymph node and lung. The meta-data analysis demonstrated that a portion or an entire set of PH2 probes may perform the function with high accuracy. Clinical samples were used by some experiments to further validate the gene markers. 
     In the test using the magnetic-beads which had been conjugated with the oligonucleotides representing each of the PH2 probes, the magnetic beads were purchased from QuantiGene, which was developed by Panomics and distributed by eBioscience of Affymetrix Inc. Before applying to the clinical samples, PH2 probes have been validated on the transcriptomic datasets obtained from the public database GEO at NCBI (http://www.ncbi.nlm.nih.gov/geo/). The positive results (Tables 4, 5) from these analyses indicated the PH2 probes are applicable to real clinical samples. 
     A total of fifteen specimens from cancer patients were used. All the clinical information of the specimens and that of the donor patients were kept confidential. The pathological features and the diagnosis of each specimen had been confirmed by the pathologists and the surgeons. The fifteen specimens were dissected from various organs, including liver, colon, breast, spleen, pancreas, perineum etc. during a necessary surgery. Among the specimens, fourteen of them were confirmed as metastatic tumors while one of the specimen was found to be a benign tumor originated from soft tissue. Three of the fourteen metastatic specimens have primary sites other than the fifteen tissues/organs so were dropped from the study. 
     To perform the PH2/Quantigene analysis on the clinical specimens, the frozen tissue was firstly cut, thawed, and manually homogenized with micro pestles. Then the RNA was extracted and hybridized to the PH2/Quantigene beads. The manufacturer-provided standard protocol was followed until signal was acquired with the Luminex machine. The data output from the Luminex was then subjected to computer analysis with the PH2 probes which incorporates KNN method as the final step for the prediction. 
     A total of eleven specimens whose primary sites fell into the fifteen candidate primary sites were included for the final computing. For these eleven metastatic specimens, the primary site was predicted at k=1, k=2 and k=3 (that is, their correct primary site was ranked within one, two, or three highest scored tissues, respectively.) The overall accuracy of primary site prediction by PH2 probes in this study was 100% at k=3, see Tables 7 and 8. 
     
       
         
           
               
             
               
                 TABLE 7 
               
             
            
               
                   
               
               
                 “PH2 on Agilent: Tested with Clinical Specimens; Accuracy: 80% 
               
               
                 when k = 1 or k = 2; 100% when k = 3” 
               
            
           
           
               
               
               
               
               
            
               
                   
                   
                 Agilent_PH2 
                 Agilent_PH2 
                 Agilent_PH2 
               
               
                 Primary site 
                 Anatomic 
                 Rank_1 
                 Rank_2  
                 Rank_3 
               
               
                 answer 1   
                 Site 2   
                 (k = 1) 
                 (k = 2) 
                 (k = 3) 
               
               
                   
               
               
                 colon 
                 liver 
                 Colorectal 
                   
                   
               
               
                 colon 
                 liver 
                 Colorectal 
                   
                   
               
               
                 breast  
                 breast 
                 Breast 
                   
                   
               
               
                 recurrence 
                   
                   
                   
                   
               
               
                 gastric 
                 liver 
                 Liver 
                 Pancreas 
                 Gastric 
               
               
                 colon 
                 liver 
                 Colorectal 
               
               
                   
               
               
                   1 The primary site of the tumor sample. 
               
               
                   2 The organ where the tumor sample is taken. 
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 8 
               
             
            
               
                   
               
               
                 “PH2 on Clinical specimen using Quantigene or Agilent” 
               
            
           
           
               
               
               
               
            
               
                   
                 Test-1 
                 Test-2 
                 Agilent 
               
            
           
           
               
               
               
               
               
               
               
               
               
               
            
               
                 K value 
                 1 
                 2 
                 3 
                 1 
                 2 
                 3 
                 1 
                 2 
                 3 
               
               
                   
               
               
                 accuracy 
                 7/12 
                 9.5/12 
                 12/12 
                 5/8 
                 7.5/8 
                 8/8 
                 4/5 
                 4/5 
                 5/5 
               
               
                 (number) 
               
               
                 accuracy 
                 58% 
                 79% 
                 100% 
                 63% 
                 94% 
                 100% 
                 80% 
                 80% 
                 100% 
               
               
                 (%) 
               
               
                   
               
            
           
         
       
     
     The PH2 probes were confirmed by three platforms. A comparison between the results using three platforms is provided in Table 9. 
     
       
         
           
               
             
               
                 TABLE 9 
               
             
            
               
                   
               
               
                 “Comparison of PH2 prediction on three platforms” 
               
            
           
           
               
               
               
               
               
            
               
                   
                 K 
                 Affymetrix 
                 Agilent  
                 Magnetic 
               
               
                   
                 value 
                 array 
                 array 
                 beads (QGP) 
               
               
                   
               
            
           
           
               
               
               
               
               
            
               
                 Accuracy 
                 K = 1 
                 &gt;90 
                  80% 
                 ~60%   
               
               
                   
                 K = 2 
                   
                  80% 
                 &gt;80%   
               
               
                   
                 K = 3 
                   
                 100% 
                 100%  
               
            
           
           
               
               
               
               
            
               
                 Price 
                 ~30000 NT 
                 ~20000 NT 
                 &lt;3000~10000 NTD 
               
               
                 Sample amount 
                 ug 
                 ug 
                 ng 
               
               
                 Processing time 
                 &gt;5 days 
                 &gt;5 days 
                 1.5 days 
               
               
                   
               
            
           
         
       
     
     It will be appreciated by those skilled in the art that changes could be made to the embodiments described above without departing from the broad inventive concept thereof. It is understood, therefore, that this disclosure is not limited to the particular embodiments disclosed, but it is intended to cover modifications within the spirit and scope of the present disclosure as defined by the appended claims.