Method For Identifying Whether A Patient Will Be Responder or Not to Immunotherapy

Information

  • Patent Application
  • 20100021424
  • Publication Number
    20100021424
  • Date Filed
    May 31, 2007
    17 years ago
  • Date Published
    January 28, 2010
    14 years ago
Abstract
The present invention relates to gene expression profiles, microarrays comprising nucleic acid sequences representing gene expression profiles and new diagnostic kits and methods. The invention further relates to treatment of specific populations of, for example, cancer patients, as characterised by their gene expression profile, suffering from Mage expressing tumours.
Description
FIELD OF THE INVENTION

The present invention relates to gene expression profiles; microarrays comprising nucleic acid sequences for identifying said profiles, for example, by analysing patient derived samples; new diagnostic kits and methods for identification of same. The invention further relates to treatment of specific populations of patients, for example cancer patients, characterised as a responder by their gene expression profile, such as patients suffering from Mage expressing tumours. The invention further includes methods of inducing a responder's profile in a patient initially or originally designated as a non-responder.


BACKGROUND

Melanomas are tumors originating from melanocyte cells in the epidermis. Patients with malignant melanoma in distant metastasis (stage IV according to the American Joint Commission on Cancer (AJCC) classification) have a median survival time of one year, with a long-term survival rate of only 5%. Even the standard chemotherapy for stage IV melanoma has therapeutic response rates of only 8-25%, but with no effect on overall survival. Patients with regional metastases (stage III) have a median survival of two to three years with very low chance of long-term survival, even after an adequate surgical control of the primary and regional metastases (Balch et al., 1992). Most Patients with stage I to III melanoma have their tumour removed surgically, but these patients maintain a substantial risk of relapse. Thus there remains a need to prevent melanoma progression, and to have improved treatment regimes for metastatic melanoma and adjuvant treatments for patients having had a primary tumour removed.


There are two types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). The names simply describe the type of cell found in the tumours. NSCLC includes squamous-cell carcinoma, adenocarcinoma, and large-cell carcinoma and accounts for around 80% of lung cancers. NSCLC is hard to cure and treatments available tend to have the aim of prolonging life, as far as possible, and relieving symptoms of disease. NSCLC is the most common type of lung cancer and is associated with poor outcomes (Gatzmeier et al., 1994). Of all NSCLC patients, only about 25% have loco-regional disease at the time of diagnosis and are still amenable to surgical excision (stages IB, IIA or IIB according to the AJCC classification). However, more than 50% of these patients will relapse within the two years following the complete surgical resection. There is therefore a need to provide better treatment for these patients.


Traditional chemotherapy is based on administering toxic substances to the patient and relying, in part, on the aggressive uptake of the toxic agent by the tumour/cancer cells. These toxic substances adversely affect the patient's immune system, leaving the individual physically weakened and susceptible to infection.


It is known that not all patients with cancer respond to current cancer treatments. It is thought that only 30% or less of persons suffering from a cancer will respond to any given treatment. The cancers that do not respond to treatment are described as resistant. In many instances there have not been reliable methods for establishing if the patients will respond to treatment. However, administering treatment to patients who are both responders and non-responders because they cannot be differentiated is an inefficient use of resources and, even worse, can be damaging to the patient because, as discussed already, many cancer treatments have significant side effects, such as severe immunosuppression, emesis and/or alopecia. It is thought that in a number of cases patients receive treatment, when it is not necessary or when it will not be effective.


Cells including cancer/tumour cells express many hundreds even thousands of genes.


A large amount of work has been done in recent times to assist in the diagnosis and prognosis of cancer patients, for example to identify those patients who do not require further treatment because they have no risk of metastasis, recurrence or progression of the disease.


WO 2006/124836 identifies certain gene expression signatures over several oncogenic pathways, thereby defining the prognosis of the patient and sensitivity to therapeutic agents that target these pathways. The specific oncogenes are; Myc, Ras, E2, S3, Src and beta-catenin.


US 2006/0265138 discloses a method of generating a genetic profile, generally for identifying the primary tumour so that appropriate treatment can be given.


US 2006/0240441 and US 2006/0252057 describe methods of diagnosing lung cancer based on the differential expression of certain genes.


US 2006/0234259 relates to the identification and use of certain gene expression profiles of relevance to prostate cancer.


WO 2006/103442 describes gene expression profiles expressed in a subset of estrogen receptor (ER) positive tumours, which act, as a predictive signature for response to certain hormone therapies such as tamoxifen and also certain chemotherapies.


WO 2006/093507 describes a gene profile useful for characterising a patient with colorectal cancer as having a good prognosis or a bad prognosis, wherein patients with a good prognosis are suitable for chemotherapy.


WO 2006/092610 describes a method for monitoring melanoma progression based on differential expression of certain genes and novel markers for the disease, in particular TSBY1, CYBA and MT2A.


WO 2005/049829 describes an isolated set of marker genes that may be employed to predict the sensitivity of certain cancers to a chemotherapeutic agent, which is an erbB receptor kinase inhibitor, such as gefitinib.


Generally, these cases relate to markers for one or more cancers based on biological markers for the identification and/or progression of the cancer. In some instances these pathways are modulated by so-called oncogenes. Diagnosis employing the above techniques allows those patients who are likely to relapse and/or suffer metastasis to be identified and targeted for further therapy. In other instances a specific marker relevant to resistance to a specific treatment is identified.


A new generation of cancer treatments based on antigens, peptides, DNA and the like is currently under investigation by a number of groups. The strategy behind many of these therapies, often referred to as cancer immunotherapy, is to stimulate the patient's immune system into fighting the cancer. These therapies are likely to be advantageous because the side effects, of taking such treatments, are expected to be minimal in comparison to the side effects currently encountered by patients undergoing cancer treatment. An antigen used in a cancer immunotherapy may be referred to as an ASCI, that is antigen-specific cancer immunotherapeutic.


In the early 1980s, Van Pel and Boon published the discovery of cytolytic T cells directed against an antigen presented on tumour cells. This led to the characterization of the first tumour-specific, shared antigen: Melanoma AGE-1 (MAGE-1, subsequently renamed MAGE-A1). It was followed by the identification of a large number of genes sharing the same expression pattern: they are expressed in a wide range of tumour types such as, melanoma, lung, bladder, breast, head and neck cancers. They are not expressed in normal cells, except testis. However, this expression in the testis does not normally lead to antigen expression, as these germ line cells do not express MHC class I molecules. From their peculiar expression profile, the name of Cancer Testis (CT) genes was proposed for these genes.


MAGE antigens are antigens encoded by the family of Melanoma-associated antigen genes (MAGE). MAGE genes are predominately expressed on melanoma cells (including malignant melanoma) and some other cancers including NSCLC (non small cell lung cancer), head and neck squamous cell carcinoma, bladder transitional cell carcinoma and oesophagus carcinoma, but are not detectable on normal tissues except in the testis and the placenta (Gaugler et al Human gene MAGE-3 codes for an antigen recognized on a melanoma by autologous cytolytic T lymphocytes J Exp Med. 1994 Mar. 1; 179(3):921-930); Weynants et al Expression of mage genes by non-small-cell lung carcinomas Int. J. Cancer. 1994 Mar. 15; 56(6):826-829, Patard et al Int J. Cancer 64: 60, 1995). MAGE-A3 is expressed in 69% of melanomas (Gaugler, 1994), and can also be detected in 44% of NSCLC (Yoshimatsu 1988), 48% of head and neck squamous cell carcinoma, 34% of bladder transitional cell carcinoma, 57% of oesophageal carcinoma, 32% of colon cancers and 24% of breast cancers (Van Pel, et al Genes coding for tumor antigens recognized by cytolytic T lymphocytes Immunological Reviews 145, 229-250, 1995, 1995.); Inoue 1995; Fujie 1997; Nishimura 1997). Cancers expressing MAGE proteins are known as Mage associated tumours.


SUMMARY

In one aspect the invention provides a method for detection of a gene signature, indicative of a responder or non-responder to immunotherapy, such as cancer immunotherapy, in a biological sample. Thus the invention provides a method of screening patients to establish if they are suitable for treatment, for example with a cancer immunotherapy.


In one aspect the invention provides a diagnostic kit comprising one or more nucleotide probes capable of hybridising to the mRNA or cDNA of one or more immune activation genes relevant to the profile.


In one aspect the invention provides one or more probes for identifying said one or more immune activation genes relevant to the profile.


In one aspect the invention provides a microarray of said probes suitable for the detection of said gene(s)/profile.


In another aspect the invention provides use of a microarray, including known microarrays, for the identification of said immune gene(s)/profile.


In one aspect the invention provides use of PCR (or other known techniques) for identification of differential expression (such as upregulation) of one or more of said genes.


In one aspect the invention provides a method of treating a patient with an appropriate immunotherapy after screening to identify the patient as a responder to said treatment.


In another aspect the invention provides a method of increasing the efficacy of an immunotherapy in a patient population comprising the step of first screening the population for the differential expression of one or more immune genes/said profile, and a second step of characterising the patient as a responder or non-responder.


In a further aspect the invention provides a method of generating a list of differentially expressed immune genes (ie a profile of immune genes) indicative of a responder or non-responder to immunotherapy.





BRIEF DESCRIPTION OF THE FIGURES, SEQUENCES & TABLES


FIG. 1 is a diagrammatic representation of hierarchical clustering using Spotfire analysis linking the clinical outcome of 31 patients found to be responders (defined herein to include responder, mixed responder and stable disease) or non-responders, to Mage immunotherapy in the MAGE008 clinical trial, with the gene profile identified by microarray analysis and employing the 148 top probe sets.



FIG. 2 is a diagrammatic representation of the same analysis as FIG. 1, wherein the hierarchical clustering was performed using the BaldiBH analysis using 100 probes sets.



FIG. 3 is a diagrammatic representation of the same analysis as FIG. 1, wherein the hierarchical clustering was performed using Arrayminer Classmaker gene list.



FIG. 4 is a Venn diagram representing the comparison of gene lists used in FIG. 1, FIG. 2 and FIG. 3.



FIG. 5 is a visual representation of the expression profile of various genes (36 probe sets) for 30 different patients (patients are along the X-axis and the various probe sets extend along the Y-axis).



FIG. 5
a is a visual representation of the expression of 2 genes for 30 different patients (patients along the X-axis).



FIG. 6 shows the Principal Component Analysis using PRF1, GZMB, GNLY, CD8A, PRKCQ, FOXP3, IFNG, CCL5, GPR171 and TRBV19 genes.



FIG. 7 is a visual representation of the expression profile of various genes (41 probe sets) for 33 different patients (patient identification numbers are along the X-axis) from the MAGE008 clinical trial using the adjuvant AS15.



FIG. 8 is a diagrammatic representation of hierarchical clustering for patients in the AS15 arm of the MAGE008 clinical trial.



FIG. 9 is a visual representation of the expression profile of various genes (41 probe sets) for 33 different patients (patient identification numbers are along the X-axis) from the MAGE008 clinical trial using the adjuvant AS02b.



FIG. 10 is a diagrammatic representation of hierarchical clustering for patients in the AS02b arm of the MAGE008 clinical trial.





In the heat maps herein upregulated genes are represented in red which in greyscale tends to be presented by darker shades. Lighter shades in greyscale tend to present green on the heat map (genes which are not upregulated).

    • Seq ID No 1 Chromosome 6 open reading frame 190
    • Seq ID No 2 Hematopoietic cell-specific Lyn substrate 1
    • Seq ID No 3 Interleukin 2 receptor, gamma (severe combined immunodeficiency)
    • Seq ID No 4 CD52 antigen (CAMPATH-1 antigen) /// CD52 antigen (CAMPATH-1 antigen)
    • Seq ID No 5 CD2 antigen (p50), sheep red blood cell receptor /// CD2 antigen (p50), sheep red blood cell receptor
    • Seq ID No 6 Ubiquitin D
    • Seq ID No 7 Signal transducer and activator of transcription 4
    • Seq ID No 8 Granzyme K (granzyme 3; tryptase 11) /// granzyme K (granzyne 3; tryptase II)
    • Seq ID No 9 CD3G antigen, gamma polypeptide (TiT3 complex)
    • Seq ID No 10 G protein-coupled receptor 171
    • Seq ID No 11 Protein kinase C, beta 1
    • Seq ID No 12 Major histocompatibility complex, class II, DR alpha /// major histocompatibility complex, class II, DR alpha
    • Seq ID No 13 Major histocompatibility complex, class II, DQ beta /// Major histocompatibility complex, class II, DQ beta 1
    • Seq ID No 14 Alcohol dehydrogenase IB (class I), beta polypeptide
    • Seq ID No 15 T cell receptor alpha constant /// T cell receptor alpha constant
    • Seq ID No 16 CD69 antigen (p60, early T-cell activation antigen)
    • Seq ID No 17 Protein kinase C, theta
    • Seq ID No 18 T cell receptor beta variable 19 /// T cell receptor beta constant 1
    • Seq ID No 19 T cell receptor alpha locus /// T cell receptor delta variable 2 μl T cell receptor alpha variable 20 /// T cell receptor alpha joining 17 /// T cell receptor alpha constant
    • Seq ID No 20 T cell receptor gamma constant 2
    • Seq ID No 21 T cell receptor beta variable 21-1 /// T cell receptor beta variable 19 /// T cell receptor beta variable 5-4 μl T cell receptor beta variable 3-1 /// T cell receptor beta constant 1
    • Seq ID No 22 T cell receptor alpha locus
    • Seq ID No 23 T cell receptor beta variable 19 /// T cell receptor beta variable 19 /// T cell receptor beta constant 1 /// T cell receptor beta constant 1
    • Seq ID No 24 CD3D antigen, delta polypeptide (TiT3 complex)
    • Seq ID No 25 T cell receptor gamma constant 2 /// T cell receptor gamma variable 9 /// similar to T-cell receptor gamma chain C region PT-gamma-1/2 /// similar to T-cell receptor gamma chain V region PT-gamma-1/2 precursor /// TCR gamma alternate reading frame protein
    • Seq ID No 26 Pyrin and HIN domain family, member 1
    • Seq ID No 27 T cell receptor associated transmembrane adaptor 1
    • Seq ID No 28 SLAM family member 7
    • Seq ID No 29 Chromosome 4 open reading frame 7
    • Seq ID No 30 Major histocompatibility complex, class II, DQ alpha 1
    • Seq ID No 31 Transcribed locus
    • Seq ID No 32 Amphiphysin (Stiff-Man syndrome with breast cancer 128 kDa auto antigen)
    • Seq ID No 33 Dendritic cell-associated lectin-1


      Each sequences above is given in Table 1A below.
    • Seq ID No 34 Nucleotide sequence encoding fusion protein of Lipoprotein D fragment, Mage3 fragment, and histidine tail
    • Seq ID No 35 Amino acid sequence of the fusion protein of Lipoprotein D fragment, Mage3 fragment and histidine tails
    • Seq ID No.s 36 to 43 (found in the description) are peptide sequences relevant to MAGE A3.
    • Seq ID No.s 44 to 48 are examples of oliogionucleotide sequences containing a CpG motif.
    • Seq ID No.s 49 to 84 (listed in Table 1B) are probes sets suitable for hybridising to the genes listed in Table 1.
    • Seq ID No.s 85 to 97 (listed in Table 3A) are sequences for the genes listed in Table 3.


Tables 1 to 4, 11 and 12 provide lists of genes that are differentially regulated according to the present invention.


Table 1A provides the nucleotide sequence listing for each of the genes listed in Table 1.


Table 1B provides the probe set identifier number (a unique reference number for the probe) of probes (and sequence thereof) wherein each probe is suitable for identifying particular genes listed in Table 1.


Table 3A links the genes (and sequences thereof) of Table 3 and probes suitable for identifying said genes.


Table 5 provides a list of genes, primers and probes suitable for use in PCR analysis.


Table 6 is a list of gene included in the TaqMan® (Q-PCR) Immune Profiling Array.


Table 7 provides a list of genes according to one aspect of the invention.


Table 7A provides the geomean ratio between responders and non-responder groups for the genes listed in Table 7.


Table 8 provides a correlation matrix for 30 genes.


Table 9 provides a list of genes according to one aspect of the invention.


Table 9A logistical regression results for certain genes listed in Table 9


Table 10 shows the percentage of correct classification using a logistical regression model for the genes listed in Table 9.


Table 11 provides a list of genes according to one aspect of the invention.


Tables 11A & 11B show the level of gene expression (based on the results of 41 probe sets) for various patients.


Tables 12 and 13 show gene lists that form further aspects of the invention.


Table 14 provides a correlation between the gene expression levels given in Tables 11A & 11B with the clinical outcome for said patients.


Annexes A to C are computer code for assisting with stastical analysis of samples.


The MAGE-1 gene belongs to a family of 12 closely related genes, MACE 1, MAGE 2, MAGE 3, MAGE 4, MAGE 5, MAGE 6, MAGE 7, MAGE 8, MAGE 9, MAGE 10, MAGE 11, MAGE 12, located on chromosome X and sharing with each other 64 to 85% homology in their coding sequence (De Plaen, 1994). These are sometimes known as MAGE A1, MAGE A2, MAGE A3, MAGE A4, MAGE A5, MAGE A6, MAGE A7, MAGE A8, MAGE A9, MAGE A 10, MAGE A11, MAGE A12 (The MAGE A family).


Two other groups of proteins are also part of the MAGE family although more distantly related. These are the MAGE B and MAGE C group. The MAGE B family includes MAGE B1 (also known as MAGE Xp1, and DAM 10), MAGE B2 (also known as MAGE Xp2 and DAM 6) MAGE B3 and MAGE B4—the Mage C family currently includes MAGE C1 and MAGE C2.


In general terms, a MAGE A protein can be defined as containing a core sequence signature located towards the C-terminal end of the protein (for example with respect to MAGE A1 a 309 amino acid protein, the core signature corresponds to amino acid 195-279).


It does not simply follow that if the tumour expresses, for example, Mage that the patient will respond to immunotherapy based on a Mage antigen.


STATEMENT OF INVENTION

Analysis performed on cancers/tumours from patients prior to receiving immunotherapy, such as Mage immunotherapy, identified that certain genes were differentially expressed in patients that responded well to the treatment, in comparison to those patients who did not respond to the immunotherapy. The present inventors have discovered a gene signature/profile that is predictive of the likely response of the patient to an appropriate immunotherapy. More specifically the present inventors have discovered a gene signature that is predictive of improved survival after treatment with Mage antigen specific immunotherapy.


Thus the invention provides a gene profile, from a patient derived sample, which is indicative of an increased likelihood that the patient will be a responder (or alternatively a non-responder) to an immunotherapy, for example a cancer immunotherapy, such as Mage immunotherapy, wherein the profile comprises differential expression of at least one immune activation gene. The invention provides a gene profile, from a patient derived sample, which is indicative of an increased likelihood that the patient will be a responder to an immunotherapy, for example a cancer immunotherapy, such as Mage immunotherapy, wherein the profile comprises upregulation of at least one immune activation gene.


The present invention provides a predictive profile in contrast to a diagnostic or prognostic profile.


Whilst not wishing to be bound by theory it is hypothesised that the gene signature identified is in fact indicative of an immune/inflammatory, such as a T cell infiltration/activation response in the patients who are designated as responders, for example, the signature may represent a T-cell activation marker. The presence of this response is thought to assist the patient's body to fight the disease, such as cancer, after administration of the immunotherapy thereby rendering a patient more responsive to said immunotherapy.


Thus the signature of the present invention does not focus on markers/genes specifically associated with the diagnosis and/or prognosis of the relevant disease, for example cancer such as oncogenes, but rather is predictive of whether the patient will respond to an appropriate immunotherapy, such as cancer immunotherpay.


The gene profile identified herein for cancer and methods for identifying the same are thought to be indicative of the microenvironment of the tumor. The correct microenvironment of the tumor seems to be key to whether the patient responds to appropriate cancer immunotherapy. Immunotherapy in the context of the invention means therapy based on stimulating an immune response, generally to an antigen, wherein the response results in the treatment, amelioration and/or retardation of the progression of a disease associated therewith. Treatment in this context would not usually include prophylactic treatment.


Cancer immunotherapy in the context of this specification means immunotherapy for the treatment of cancer. In one aspect the immunotherapy is based on a cancer testis antigen, such as Mage (discussed in more detail below).


This invention may be used for identifying cancer patients that are likely to respond to appropriate immunotherapy, for example patients with melanoma, breast, bladder, lung, NSCLC, head and neck cancer, squamous cell carcinoma, colon carcinoma and oesophageal carcinoma, such as in patients with MAGE-expressing cancers. In an embodiment, the invention may be used in an adjuvant (post-operative, for example disease-free) setting in such cancers, particularly lung and melanoma. The invention also finds utility in the treatment of cancers in the metastatic setting.


Thus in a first aspect the invention provides a signature indicative of a patient, such as a cancer patient, designated a responder or non-responder to treatment with an appropriate immunotherapy, the signature comprising differential expression of one or more genes selected from immune activation/immune response/inflammatory response genes, for example, the group of genes indicative of T cell infiltration/activation, such as a gene listed (or a gene list comprising or consisting) those listed in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 such as Table 1 or 2. Differential expression in the context of the present invention means the gene is upregulated or downregulated in comparison to its normal expression. Statistical methods for calculating gene differentiation are discussed below.


Immune activation gene is intended to mean a gene that facilitates, increases or stimulates an appropriate immune response. Immune response gene and immune activation gene are used interchangeably herein.


An important technique for the analysis of the genes expressed by cells, such as cancer/tumour cells, is DNA microarray (also known as gene chip technology), where hundreds or more probe sequences (such as 55,000 probe sets) are attached to a glass surface. The probe sequences are generally all 25 mers or 60 mers and are sequences from known genes. These probes are generally arranged in a set of 11 individual probes (a probe set) and are fixed in a predefined pattern on the glass surface. Once exposed to an appropriate biological sample these probes hybridise to the relevant RNA or DNA of a particular gene. After washing, the chip is “read” by an appropriate method and a quantity such as colour intensity recorded. The differential expression of a particular gene is proportional to the measure/intensity recorded. This technology is discussed in more detail below.


Once a target gene profile has been identified there are several analytical methods to measure whether the gene(s) is/are differentially expressed. These analytical techniques include real-time polymerase chain reaction, also called quantitative real time polymerase chain reaction (QRT-PCR or Q-PCR), which is used to simultaneously quantify and amplify a specific part of a given DNA molecule present in the sample.


The procedure follows the general pattern of polymerase chain reaction, but the DNA is quantified after each round of amplification (the “real-time” aspect). Two common methods of quantification are the use of fluorescent dyes that intercalate with double-strand DNA, and modified DNA oligonucleotide probes that fluoresce when hybridized with a complementary DNA.


The basic idea behind real-time polymerase chain reaction is that the more abundant a particular cDNA (and thus mRNA) is in a sample, the earlier it will be detected during repeated cycles of amplification. Various systems exist which allow the amplification of DNA to be followed and they often involve the use of a fluorescent dye which is incorporated into newly synthesised DNA molecules during real-time amplification. Real-time polymerase chain reaction machines, which control the thermocycling process, can then detect the abundance of fluorescent DNA and thus the amplification progress of a given sample. Typically, amplification of a given cDNA over time follows a curve, with an initial flat-phase, followed by an exponential phase. Finally, as the experiment reagents are used up, DNA synthesis slows and the exponential curve flattens into a plateau.


Alternatively the mRNA or protein product of the target gene(s) may be measured by Northern Blot analysis, Western Blot and/or immunohistochemistry.


In one aspect the analysis to identify the profile/signature is performed on a patient sample wherein a cancer testis antigen is expressed.


If a gene is always upregulated or always down regulated in patients that are deemed to be responders (or alternatively non-responders) then this single gene can be used to establish if the patient is a responder or a non-responder once a threshold is established and provided the separation of the two groups is adequate.


When a single gene is analysed, for example, by Q-PCR then the gene expression can be normalised by reference to a gene that remains constant, for example genes with the symbol H3F3A, GΔPDH, TFRC, GUSB or PGK1. The normalisation can be performed by substracting the value obtained for the constant gene from the value obtained for the gene under consideration. A threshold may be established by plotting a measure of the expression of the relevant gene for each patient. Generally the responders and the non-responders will be clustered about a different axis/focal point. A threshold can be established in the gap between the clusters by classical statistical methods or simply plotting a “best fit line” to establish the middle ground between the two groups. Values, for example, above the pre-defined threshold can be designated as responders and values, for example below the pre-designated threshold can be designated as non-responders.


In one aspect the invention provides a gene profile for identifying a responder comprising one or more of said genes wherein 50, 60, 70, 75, 80, 85, 90, 95, 99 or 100% of the genes are upregulated.


The genes listed in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 such as Table 1, 2 and/or 3 are generally upregulated in responders.


The robustness of the predictive method of the invention can be further improved for larger sample sizes by employing 2, 3, 4, 5, 6, etc genes from Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 such as Table 1 or 2.


Furthermore, once at least two differential expressed genes are included in the signature then statistical clustering methods can be used to differentiate the responders and non-responders. Methods for statistical clustering and software for the same are discussed below.


One parameter used in quantifying the differential expression of genes is the fold change, which is a metric for comparing a gene's mRNA-expression level between two distinct experimental conditions. Its arithmetic definition differs between investigators. However, the higher the fold change the more likely that the differential expression of the relevant genes will be adequately separated, rendering it easier to decide which category (responder or non-responder) the patient falls into.


The fold change may, for example be at least 10, at least 15, at least 20 or 30.


Another parameter also used to quantify differential expression is the “p” value. It is thought that the lower the p value the more differentially expressed the gene is likely to be, which renders it a good candidate for use in profiles of the invention. P values may for example include 0.1 or less, such as 0.05 or less, in particular 0.01 or less. P values as used herein include corrected “P” values and/or also uncorrected “P” values.


The invention provides a method for the detection of a gene signature in a biological sample, the method comprising the analysis of the expression of at least 5 genes as set forth in Table 1. Alternatively one or more genes may be selected from Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 such as Table 1 or 2.


Thus in one aspect the invention provides a method of identifying whether a cancer patient will be a responder or non-responder to immunotherapy, the method comprising:

    • 1. analysing a sample comprising mRNA or fragments thereof expressed by genes of cancerous cells or DNA or fragments thereof from cancerous cells, for differential expression of one or more genes indicative of T-cell infiltration/activation, for example selected from the group comprising or consisting of genes listed in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 such as Table 1 or 2, and
    • 2. characterising a patient as a responder or a non-responder based on the results of step 1.


Responder in the context of the present invention includes persons where the cancer/tumor(s) is irradiated, reduced or improved (mixed responder or partial responder) or simply stabilised such that the disease is not progressing. In responders where the cancer is stabilised then the period of stabilisation is such that the quality of life and/or patients life expectancy is increased (for example stable disease for more than 6 months) in comparison to a patient that does not receive treatment.


Partial clinical response in respect of cancer is wherein all of the tumors/cancers respond to treatment to some extent, for example where said cancer is reduced by 30, 40, 50, 60% or more. Mixed clinical responder in respect of cancer is defined as wherein some of the tumors/cancers respond to treatment and others remain unchanged or progress.


Standard definitions are available for responders, partial responders and mixed responders to cancer treatment. These standard definitions apply herein unless from the context it is clear that they do not apply.


As used herein, methods to predict a favorable clinical response or to identify subjects more likely to respond to therapy, is not meant to imply a 100% predictive ability, but to indicate that subjects with certain characteristics are more likely to experience a favorable clinical response to a specified therapy than subjects who lack such characteristics. However, as will be apparent to one skilled in the art, some individuals identified as more likely to experience a favorable clinical response may nonetheless fail to demonstrate measurable clinical response to the treatment. Similarly, some individuals predicted as non-responders may nonetheless exhibit a favorable clinical response to the treatment.


As used herein, a ‘favorable response’ (or ‘favorable clinical response’) to, for example, an anticancer treatment refers to a biological or physical response that is recognized by those skilled in the art as indicating a decreased rate of tumor growth, compared to tumor growth that would occur with an alternate treatment or the absence of any treatment. “Favorable clinical response” as used herein is not synonymous with a cure, but includes Partial Response, Mixed Response or Stable Disease. A favorable clinical response to therapy may include a lessening of symptoms experienced by the subject, an increase in the expected or achieved survival time, a decreased rate of tumor growth, cessation of tumor growth (stable disease), regression in the number or mass of metastatic lesions, and/or regression of the overall tumor mass (each as compared to that which would occur in the absence of therapy, or in response to an alternate therapy).


Patients in need of treatment for, for example, a Mage-expressing tumor, whose tumor cells have a gene signature described herein as a “Responder” signature are more likely to have a favorable clinical response, compared to patients whose tumor cells show a gene signature described herein as a “Non-Responder” signature, when treated with Mage specific immunotherapy.


Non-responder in the context of this invention includes persons whose symptoms ie cancers/tumors are not improved or stabilised.


Optionally the characterisation of the patient as a responder or non-responder can be performed by reference to a “standard” or a training set. The standard may be the profile of a person/patient who is known to be a responder or non-responder or alternatively may be a numerical value. Such pre-determined standards may be provided in any suitable form, such as a printed list or diagram, computer software program, or other media.


Training set in the context of the present specification is intended to refer to a group of samples for which the clinical results can be correlated with the gene profile and can be employed for training an appropriate stastical model/programme to identify responders and/or non-responser for new samples. Tables 11A, 11B and 14 contain the training set information relevant to the 41 probe set model described in Example 4.


In one aspect a mathematical model/algorithm/statical method is employed to characterise the patient as responder or non-responder.


In one aspect the invention provides a profile based one or more immune activation genes, such as 5 or more such genes.


In one aspect the invention provides a profile based on the genes in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 such as Table 1 or 2.


In one aspect the invention provides a profile based on 489 probes (listed in Table 4A) and/or approximately 480 genes as listed in Table 4.


According to one aspect the present invention provides a gene signature indicative of improved survival of patients with Mage expressing cancers following treatment with Mage specific immunotherapy. This gene signature, of at least 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, or 31, genes from the genes disclosed in Table 1, is characterised by differential expression compared to the gene signature of MAGE-expressing tumour patients who do not respond to Mage antigen specific cancer immunotherapy. Improved survival in likely to be a corollary of a response to the immunotherapy administered, if the patient is in fact a responder.


Tables with Gene Lists


In one aspect the invention relates to one or more genes listed in Table 1












TABLE 1







Gene Title
Seq Id No


















1.1
chromosome 6 open reading frame 190
1


1.2
hematopoietic cell-specific Lyn substrate 1
2


1.3
interleukin 2 receptor, gamma (severe combined
3



immunodeficiency)


1.4
CD52 antigen (CAMPATH-1 antigen) /// CD52 antigen
4



(CAMPATH-1 antigen)


1.5
CD2 antigen (p50), sheep red blood cell receptor /// CD2 antigen
5



(p50), sheep red blood cell receptor


1.6
ubiquitin D
6


1.7
signal transducer and activator of transcription 4
7


1.8
granzyme K (granzyme 3; tryptase II)///granzyme K (granzyme 3;
8



tryptase II)


1.9
CD3G antigen, gamma polypeptide (TiT3 complex)
9


1.10
G protein-coupled receptor 171
10


1.11
Protein kinase C, beta 1
11


1.12
major histocompatibility complex, class II, DR alpha /// major
12



histocompatibility complex, class II, DR alpha


1.13
Major histocompatibility complex, class II, DQ beta 1 /// Major
13



histocompatibility complex, class II, DQ beta 1


1.14
alcohol dehydrogenase IB (class I), beta polypeptide
14


1.15
T cell receptor alpha constant /// T cell receptor alpha constant
15


1.16
CD69 antigen (p60, early T-cell activation antigen)
16


1.17
protein kinase C, theta
17


1.18
T cell receptor beta variable 19 /// T cell receptor beta constant 1
18


1.19
T cell receptor alpha locus /// T cell receptor delta variable 2 /// T
19



cell receptor alpha variable 20 /// T cell receptor alpha joining 17 ///



T cell receptor alpha constant


1.20
T cell receptor gamma constant 2
20


1.21
T cell receptor beta variable 21-1 /// T cell receptor beta variable 19
21



/// T cell receptor beta variable 5-4 /// T cell receptor beta variable



3-1 /// T cell receptor beta constant 1


1.22
T cell receptor alpha locus
22


1.23
T cell receptor beta variable 19 /// T cell receptor beta variable 19 ///
23



T cell receptor beta constant 1 /// T cell receptor beta constant 1


1.24
CD3D antigen, delta polypeptide (TiT3 complex)
24


1.25
T cell receptor gamma constant 2 /// T cell receptor gamma variable
25



9 /// similar to T-cell receptor gamma chain C region PT-gamma-1/2



/// similar to T-cell receptor gamma chain V region PT-gamma-1/2



precursor /// TCR gamma alternate reading frame protein


1.26
pyrin and HIN domain family, member 1
26


1.27
T cell receptor associated transmembrane adaptor 1
27


1.28
SLAM family member 7
28


1.29
chromosome 4 open reading frame 7
29


1.30
Major histocompatibility complex, class II, DQ alpha 1
30


1.31
Transcribed locus
31


1.32
Amphiphysin (Stiff-Man syndrome with breast cancer 128 kDa
32



autoantigen)


1.33
dendritic cell-associated lectin-1
33









Table 1A at the end of this specification gives the full nucleotide sequence for each of the above genes.


In one aspect the invention provides a profile based on differential expression of 1 or more of 62 genes, identified in the literature, that relate to immune infiltration and activation.


In one aspect the invention provides a profile based on the genes listed in Table 2.













TABLE 2







Gene Symbol
Gene Title
Seq Id No



















2.1
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 1
30


2.2
TRBV3-1
T cell receptor beta variable 3-1
21


2.3
IL2RG
interleukin 2 receptor, gamma (severe combined
3




immunodeficiency


2.4
CD2
CD2 antigen (p50), sheep red blood cell receptor
5


2.5
GPR171
G protein-coupled receptor 171
10


2.6
ADH1B
alcohol dehydrogenase IB (class I), beta polypeptide
14


2.7
CD69
CD69 antigen (p60, early T-cell activation antigen)
16


2.8
TRBV19
T cell receptor beta variable 19
18


2.9
TRAT1
T cell receptor associated transmembrane adaptor 1
27


2.10
C4orf7
chromosome 4 open reading frame 7
29


2.11
PRKCB1
protein kinase C, beta 1
11


2.12
CD3D
CD3D antigen, delta polypeptide (TiT3 complex)
24


2.13
UBD
ubiquitin D
6









In one aspect the invention provides the list of genes in Table 3.












TABLE 3







Gene Symbol
Gene Title


















3.1
CD52
CD52 molecule /// CD52 molecule


3.2
UBD
gamma-aminobutyric acid (GABA) B receptor, 1 /// ubiquitin D


3.3
STAT4
signal transducer and activator of transcription 4


3.4
GZMK
granzyme K (granzyme 3; tryptase II) /// granzyme K (granzyme




3; tryptase II)


3.5
GPR171
G protein-coupled receptor 171


3.6
PRKCQ
protein kinase C, theta


3.7
TRA@ /// TRDV2 ///
T cell receptor alpha locus /// T cell receptor delta variable 2 /// T



TRAV20 /// TRAC
cell receptor alpha variable 20 /// T cell receptor alpha constant


3.8
TRGC2 /// TRGV2 ///
T cell receptor gamma constant 2 /// T cell receptor gamma



TRGV9 /// TARP ///
variable 2 /// T cell receptor gamma variable 9 /// TCR gamma



LOC642083
alternate reading frame protein /// hypothetical protein




LOC642083


3.9
TRBV21-1 ///
T cell receptor beta variable 21-1 /// T cell receptor beta variable



TRBV19 /// TRBV5-4
19 /// T cell receptor beta variable 5-4 /// T cell receptor beta



/// TRBV3-1 ///
variable 3-1 /// T cell receptor beta constant 1 /// similar to T-cell



TRBC1
receptor beta chain V region CTL-L17 precursor


3.10
TRBV19 /// TRBC1
T cell receptor beta variable 19 /// T cell receptor beta variable 19




/// T cell receptor beta constant 1 /// T cell receptor beta constant 1


3.11
CD3D
CD3d molecule, delta (CD3-TCR complex)


3.12
TRAT1
T cell receptor associated transmembrane adaptor 1









In one aspect the invention provides a profile based on one or more genes of Table 4












TABLE 4







Gene Symbol
Gene Title


















4.1
FLJ20647
NA


4.2
NAV1
neuron navigator 1


4.3
GPR171
G protein-coupled receptor 171


4.4
CCL14
chemokine (C-C motif) ligand 14


4.5
C1S
complement component 1, s subcomponent


4.6
CXCL2
chemokine (C—X—C motif) ligand 2


4.7
TRBV3-1
T cell receptor beta variable 3-1


4.8
TRDV2
T cell receptor delta variable 2


4.9
RUFY3
RUN and FYVE domain containing 3


4.10
DOCK8
dedicator of cytokinesis 8


4.11
GCH1
GTP cyclohydrolase 1 (dopa-responsive dystonia)


4.12
CENTD3
centaurin, delta 3


4.13
ACSL5
acyl-CoA synthetase long-chain family member 5


4.14
AMICA1
adhesion molecule, interacts with CXADR antigen 1


4.15
IL2RG
interleukin 2 receptor, gamma (severe combined




immunodeficiency)


4.16
TNFAIP3
tumor necrosis factor, alpha-induced protein 3


4.17
PSCDBP
pleckstrin homology, Sec7 and coiled-coil domains, binding




protein


4.18
ESR1
estrogen receptor 1


4.19
TRBC1
T cell receptor beta constant 1


4.20
CD52
CD52 antigen (CAMPATH-1 antigen)


4.21
LOC442535
NA


4.22
TRBV19
T cell receptor beta variable 19


4.23
IL7R
interleukin 7 receptor


4.24
TRAC
T cell receptor alpha constant


4.25
NCF2
neutrophil cytosolic factor 2 (65 kDa, chronic granulomatous




disease, autosomal 2)


4.26
LOC92689
NA


4.27
GZMK
c(“granzyme K (granzyme 3”, “tryptase II)”)


4.28
NA
NA (gene identified by probe 235831_at)


4.29
RAB34
RAB34, member RAS oncogene family


4.30
DPT
dermatopontin


4.31
PVT1
Pvt1 oncogene homolog, MYC activator (mouse)


4.32
TRGC2
T cell receptor gamma constant 2


4.33
GIMAP5
GTPase, IMAP family member 5


4.34
CD52
CD52 antigen (CAMPATH-1 antigen)


4.35
CD3D
CD3d antigen, delta polypeptide (TiT3 complex)


4.36
TMEM132C
transmembrane protein 132C


4.37
NFKBIA
nuclear factor of kappa light polypeptide gene enhancer in B-




cells inhibitor, alpha


4.38
TRA@
T cell receptor alpha locus


4.39
TRAT1
T cell receptor associated transmembrane adaptor 1


4.40
LOC442535 (NA)
NA (duplicate)


4.41
RAB34
RAB34, member RAS oncogene family


4.42
CD69
CD69 antigen (p60, early T-cell activation antigen)


4.43
DOCK8
dedicator of cytokinesis 8


4.44
GIMAP5 (NA)
GTPase, IMAP family member 5 (NA-duplicate)


4.45
IRF8
interferon regulatory factor 8


4.46
KLRB1
killer cell lectin-like receptor subfamily B, member 1


4.47
NA
NA


4.48
ITGA3
integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3




receptor)


4.49
MAP3K8
mitogen-activated protein kinase kinase kinase 8


4.50
C1orf162
chromosome 1 open reading frame 162


4.51
UBD
ubiquitin D


4.52
TRGV9
T cell receptor gamma variable 9


4.53
NAV1 (NA)
neuron navigator 1 (NA-duplicate)


4.54
ARHGAP9
Rho GTPase activating protein 9


4.55
TIFA
NA


4.56
DPT
dermatopontin


4.57
NA
NA (gene identified by probe 1569942_at)


4.58
GIMAP4
GTPase, IMAP family member 4


4.59
HCLS1
hematopoietic cell-specific Lyn substrate 1


4.60
PRKCH
protein kinase C, eta


4.61
STAT4
signal transducer and activator of transcription 4


4.62
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 1


4.63
ADRB2
adrenergic, beta-2-, receptor, surface


4.64
NA
NA


4.65
CTSW
cathepsin W (lymphopain)


4.66
MYH11
myosin, heavy polypeptide 11, smooth muscle


4.67
GIMAP6
GTPase, IMAP family member 6


4.68
HLA-DQB1
major histocompatibility complex, class II, DQ beta 1


4.69
CD8A
CD8 antigen, alpha polypeptide (p32)


4.70
TNFAIP3
tumor necrosis factor, alpha-induced protein 3


4.71
CP
ceruloplasmin (ferroxidase)


4.72
SMOC2
SPARC related modular calcium binding 2


4.73
C20orf24
chromosome 20 open reading frame 24


4.74
C16orf54
chromosome 16 open reading frame 54


4.75
CD2
CD2 antigen (p50), sheep red blood cell receptor


4.76
SLIT3
slit homolog 3 (Drosophila)


4.77
BAALC
brain and acute leukemia, cytoplasmic


4.78
TRIB3
tribbles homolog 3 (Drosophila)


4.79
LOC440160
NA


4.80
C6orf190
chromosome 6 open reading frame 190


4.81
TAGAP
T-cell activation GTPase activating protein


4.82
FAM92A1
family with sequence similarity 92, member A1


4.83
PSTPIP2
proline-serine-threonine phosphatase interacting protein 2


4.84
PTPRC
protein tyrosine phosphatase, receptor type, C


4.85
HLA-DRA
major histocompatibility complex, class II, DR alpha


4.86
EFCAB2
EF-hand calcium binding domain 2


4.87
TNFAIP8
tumor necrosis factor, alpha-induced protein 8


4.88
SLIC1
NA


4.89
CD1C
CD1c antigen


4.90
TRAF3IP3
TRAF3 interacting protein 3


4.91
HLA-DQA1 (NA)
MHC, class II, DQ α-1 (NA-duplicate)


4.92
NAV1 (NA)
neuron navigator 1 (NA-duplicate)


4.93
HLA-DQB1 (NA)
MHC, class II, DQ beta 1 (NA-duplicate)


4.94
PTPRC (NA)
protein tyrosine phosphatase, receptor type, C (NA-duplicate)


4.95
IGJ
immunoglobulin J polypeptide, linker protein for




immunoglobulin alpha and mu polypeptides


4.96
PLEK
pleckstrin


4.97
TRA@ (NA)
T cell receptor alpha locus (NA-duplicate)


4.98
TMEM44
transmembrane protein 44


4.99
TRA@
T cell receptor alpha locus


4.100
EBI2
Epstein-Barr virus induced gene 2 (lymphocyte-specific G




protein-coupled receptor)


4.101
SAMSN1
SAM domain, SH3 domain and nuclear localisation signals, 1


4.102
KIAA1794
KIAA1794


4.103
ALDH2
aldehyde dehydrogenase 2 family (mitochondrial)


4.104
CDC42SE2
CDC42 small effector 2


4.105
GFRA1
GDNF family receptor alpha 1


4.106
ITK
IL2-inducible T-cell kinase


4.107
HLA-DRA
major histocompatibility complex, class II, DR alpha


4.108
GIMAP7
GTPase, IMAP family member 7


4.109
FLJ20273
NA


4.110
PTPN6
protein tyrosine phosphatase, non-receptor type 6


4.111
PTGER3
prostaglandin E receptor 3 (subtype EP3)


4.112
RAI2
retinoic acid induced 2


4.113
LGALS2
lectin, galactoside-binding, soluble, 2 (galectin 2)


4.114
HMOX1
heme oxygenase (decycling) 1


4.115
NA
NA (gene identified by probe 227995_at)


4.116
ZNFN1A1
zinc finger protein, subfamily 1A, 1 (Ikaros)


4.117
CSF2RB
colony stimulating factor 2 receptor, beta, low-affinity




(granulocyte-macrophage)


4.118
PCSK5
proprotein convertase subtilisin/kexin type 5


4.119
CCDC69
coiled-coil domain containing 69


4.120
CDC42SE2
CDC42 small effector 2


4.121
GZMA
granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated




serine esterase 3)


4.122
C3
complement component 3


4.123
TNFAIP8 (NA)
tumor necrosis factor, alpha-induced protein 8 (NA-duplicate)


4.124
C15orf48
chromosome 15 open reading frame 48


4.125
RARRES3
retinoic acid receptor responder (tazarotene induced) 3


4.126
LOC283537
NA


4.127
CXCL12
chemokine (C—X—C motif) ligand 12 (stromal cell-derived factor




1)


4.128
NAV1 (NA)
neuron navigator 1 (NA-duplicate)


4.129
NA
NA (gene identified by probe set 231882_at)


4.130
SOD2
superoxide dismutase 2, mitochondrial


4.131
CTSS
cathepsin S


4.132
CTBP2
C-terminal binding protein 2


4.133
BCL11B
B-cell CLL/lymphoma 11B (zinc finger protein)


4.134
CCL22
chemokine (C-C motif) ligand 22


4.135
ACSL5
acyl-CoA synthetase long-chain family member 5


4.136
DOC1
NA


4.137
SLC31A2
solute carrier family 31 (copper transporters), member 2


4.138
POPDC3
popeye domain containing 3


4.139
DOC1 (NA)
NA (duplicate)


4.140
SQRDL
sulfide quinone reductase-like (yeast)


4.141
RASGEF1B
RasGEF domain family, member 1B


4.142
FGL2
fibrinogen-like 2


4.143
C10orf128
chromosome 10 open reading frame 128


4.144
IL10RA
interleukin 10 receptor, alpha


4.145
EGFL6
EGF-like-domain, multiple 6


4.146
IL18
interleukin 18 (interferon-gamma-inducing factor)


4.147
ARHGAP30
Rho GTPase activating protein 30


4.148
PALMD
palmdelphin


4.149
RASSF5
Ras association (RalGDS/AF-6) domain family 5


4.150
GATA3
GATA binding protein 3


4.151
DKFZP564O0823
NA


4.152
BCL11B
B-cell CLL/lymphoma 11B (zinc finger protein)


4.153
TXNIP
thioredoxin interacting protein


4.154
DTX4
deltex 4 homolog (Drosophila)


4.155
DARC
Duffy blood group, chemokine receptor


4.156
RNASE6
ribonuclease, RNase A family, k6


4.157
CD86
CD86 antigen (CD28 antigen ligand 2, B7-2 antigen)


4.158
ZFP36
zinc finger protein 36, C3H type, homolog (mouse)


4.159
BASP1
brain abundant, membrane attached signal protein 1


4.160
CKAP1
cytoskeleton associated protein 1


4.161
HCP5
HLA complex P5


4.162
GRB14
growth factor receptor-bound protein 14


4.163
GJA7
gap junction protein, alpha 7, 45 kDa (connexin 45)


4.164
FLJ14054
NA


4.165
VNN1
vanin 1


4.166
ADCY7
adenylate cyclase 7


4.167
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


4.168
CPA3
carboxypeptidase A3 (mast cell)


4.169
PIM1
pim-1 oncogene


4.170
CCL19
chemokine (C-C motif) ligand 19


4.171
SYK
spleen tyrosine kinase


4.172
NAV1 (NA)
neuron navigator 1 (NA-duplicate)


4.173
SIT1
signaling threshold regulating transmembrane adaptor 1


4.174
NA
NA (gene identified by probe set 228812_at)


4.175
NAP1L2
nucleosome assembly protein 1-like 2


4.176
CCL13
chemokine (C-C motif) ligand 13


4.177
SLA
Src-like-adaptor


4.178
NOD3
NA


4.179
PRKCH
protein kinase C, eta


4.180
TRD@
T cell receptor delta locus


4.181
BAALC
brain and acute leukemia, cytoplasmic


4.182
RP1-93H18.5
NA


4.183
FLJ20701
NA


4.184
SH3TC2
SH3 domain and tetratricopeptide repeats 2


4.185
CCR2
chemokine (C-C motif) receptor 2


4.186
CCL5
chemokine (C-C motif) ligand 5


4.187
HLA-DPA1
major histocompatibility complex, class II, DP alpha 1


4.188
MS4A6A (NA)
membrane spanning 4-domains, subfamilyA, member6A (NA-




duplicate)


4.189
PECAM1
platelet/endothelial cell adhesion molecule (CD31 antigen)


4.190
AMIGO2
adhesion molecule with Ig-like domain 2


4.191
CCDC69
coiled-coil domain containing 69


4.192
CLEC7A
C-type lectin domain family 7, member A


4.193
P2RY14
purinergic receptor P2Y, G-protein coupled, 14


4.194
PIK3AP1
phosphoinositide-3-kinase adaptor protein 1


4.195
ADH1B
alcohol dehydrogenase IB (class I), beta polypeptide


4.196
TOP1MT
topoisomerase (DNA) I, mitochondrial


4.197
CD276
CD276 antigen


4.198
HLA-DQB1
major histocompatibility complex, class II, DQ beta I


4.199
JAM2
junctional adhesion molecule 2


4.200
C1S
complement component 1, s subeomponent


4.201
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


4.202
TGFBR3
transforming growth factor, beta receptor III (betaglycan, 300 kDa)


4.203
ITGAL
c(“integrin, alpha L (antigen CD11A (p180), lymphocyte function-




associated antigen 1”, “alpha polypeptide)”)


4.204
IL1R1
interleukin 1 receptor, type I


4.205
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


4.206
HLA-DRB1
major histocompatibility complex, class II, DR beta 1


4.207
GIMAP2
GTPase, IMAP family member 2


4.208
ZC3H12D
zinc finger CCCH-type containing 12D


4.209
PCDH9
protocadherin 9


4.210
SLAMF7
SLAM family member 7


4.211
MGC7036
NA


4.212
RGS18
regulator of G-protein signalling 18


4.213
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 1


4.214
CD53
CD53 antigen


4.215
MPEG1
NA


4.216
SSBP4
single stranded DNA binding protein 4


4.217
NA
NA (gene identified by probe set 231262_at)


4.218
CDH19
cadherin 19, type 2


4.219
CTBP2
C-terminal binding protein 2


4.220
NAV1 (NA)
neuron navigator 1 (NA-duplicate)


4.221
FAM107B
family with sequence similarity 107, member B


4.222
IGKC
immunoglobulin kappa constant


4.223
ITGAM
integrin, alpha M (complement component 3 receptor 3 subunit)


4.224
CKAP1
cytoskeleton associated protein 1


4.225
HLA-DRB1
major histocompatibility complex, class II, DR beta 1


4.226
CDH19
cadherin 19, type 2


4.227
MGC16291
NA


4.228
DDEF2
development and differentiation enhancing factor 2


4.229
TNFAIP2
tumor necrosis factor, alpha-induced protein 2


4.230
CXCL14
chemokine (C—X—C motif) ligand 14


4.231
CD209
CD209 antigen


4.232
COL9A3
collagen, type IX, alpha 3


4.233
ANKRD22
ankyrin repeat domain 22


4.234
NCKAP1L
NCK-associated protein 1-like


4.235
CMKOR1
chemokine orphan receptor 1


4.236
HLA-DRB5
major histocompatibility complex, class II, DR beta 5


4.237
LCP1
lymphocyte cytosolic protein 1 (L-plastin)


4.238
ADH1B
alcohol dehydrogenase IB (class I), beta polypeptide


4.239
CXXC5
CXXC finger 5


4.240
GJA7
gap junction protein, alpha 7, 45 kDa (connexin 45)


4.241
FGD2
FYVE, RhoGEF and PH domain containing 2


4.242
MAN1A1
mannosidase, alpha, class 1A, member 1


4.243
C6orf115
chromosome 6 open reading frame 115


4.244
RP1-93H18.5 (NA)
NA (duplicate)


4.245
CXCL9
chemokine (C—X—C motif) ligand 9


4.246
FAM107B (NA)
family with sequence similarity 107, member B (NA-duplicate)


4.247
NPR3
natriuretic peptide receptor C/guanylate cyclase C (atrionatriuretic




peptide receptor C)


4.248
FYB
FYN binding protein (FYB-120/130)


4.249
VCAM1
vascular cell adhesion molecule 1


4.250
FLI1
Friend leukemia virus integration 1


4.251
CXXC5
CXXC finger 5


4.252
TRAM2
translocation associated membrane protein 2


4.253
IGKC (NA)
immunoglobulin kappa constant (NA-duplicate)


4.254
SHC4
SHC (Src homology 2 domain containing) family, member 4


4.255
SLC9A9
solute carrier family 9 (sodium/hydrogen exchanger), member 9


4.256
PTPRC
protein tyrosine phosphatase, receptor type, C


4.257
PTGER4
prostaglandin E receptor 4 (subtype EP4)


4.258
LILRB1
leukocyte immunoglobulin-like receptor, subfamily B (with TM




and ITIM domains), member 1


4.259
PRDM1
PR domain containing 1, with ZNF domain


4.260
RP1-93H18.5 (NA)
NA (duplicate)


4.261
ARHGAP15
Rho GTPase activating protein 15


4.262
SLC5A3
solute carrier family 5 (inositol transporters), member 3


4.263
DOCK9
dedicator of cytokinesis 9


4.264
GPSM1
G-protein signalling modulator 1 (AGS3-like, C. elegans)


4.265
CCL5
chemokine (C-C motif) ligand 5


4.266
GLIPR1
GLI pathogenesis-related 1 (glioma)


4.267
APOL3
apolipoprotein L, 3


4.268
HLA-DMB
major histocompatibility complex, class II, DM beta


4.269
SYNPO2
synaptopodin 2


4.270
NA
NA (gene identified by probe set 221651_x_at)


4.271
NA
NA (gene identified by probe set 231929_at)


4.272
RP1-93H18.5
NA


4.273
CASP1
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,




convertase)


4.274
PRKCQ
protein kinase C, theta


4.275
IL1R2
interleukin 1 receptor, type II


4.276
CARD15
caspase recruitment domain family, member 15


4.277
ARHGDIB
Rho GDP dissociation inhibitor (GDI) beta


4.278
HLA-DRB4
major histocompatibility complex, class II, DR beta 4


4.279
SART2
squamous cell carcinoma antigen recognized by T cells 2


4.280
LSP1
lymphocyte-specific protein 1


4.281
AMPD3
adenosine monophosphate deaminase (isoform E)


4.282
SEMA4F
sema domain, immunoglobulin domain (Ig), transmembrane




domain (TM) and short cytoplasmic domain, (semaphorin) 4F


4.283
ISOC1
isochorismatase domain containing 1


4.284
CCL5 (NA)
chemokine (C-C motif) ligand 5 (NA-duplicate)


4.285
HPS3
Hermansky-Pudlak syndrome 3


4.286
HLA-DPA1 (NA)
MHC, class II, DP alpha 1 (NA-duplicate)


4.287
HLA-DQB1 (NA)
MHC, class II, DQ beta 1 (NA-duplicate)


4.288
HOXB7
homeobox B7


4.289
FGL2 (NA)
fibrinogen-like 2 (NA-duplicate)


4.290
ZNFN1A1
zinc finger protein, subfamily 1A, 1 (Ikaros)


4.291
ARHGAP9
Rho GTPase activating protein 9


4.292
GATA2
GATA binding protein 2


4.293
AP2B1
adaptor-related protein complex 2, beta 1 subunit


4.294
CTSC
cathepsin C


4.295
PLK2
polo-like kinase 2 (Drosophila)


4.296
CD4
CD4 antigen (p55)


4.297
GGTA1
glycoprotein, alpha-galactosyltransferase 1


4.298
GADD45B
growth arrest and DNA-damage-inducible, beta


4.299
GADD45B (NA)
growth arrest and DNA-damage-inducible, beta (NA-duplicate)


4.300
FLJ10847
NA


4.301
KIF21B
kinesin family member 21B


4.302
CCND2
cyclin D2


4.303
PRG1
proteoglycan 1, secretory granule


4.304
SLC40A1
solute carrier family 40 (iron-regulated transporter), member 1


4.305
HLA-DPA1 (NA)
MHC, class II, DP alpha 1 (NA-duplicate)


4.306
SOD2 (NA)
superoxide dismutase 2, mitochondrial (NA-duplicate)


4.307
CRIP1
cysteine-rich protein 1 (intestinal)


4.308
LOC283070
NA


4.309
SIGLEC1
sialic acid binding Ig-like lectin 1, sialoadhesin


4.310
ZNF11B
zinc finger protein 11B


4.311
CXCR4
chemokine (C—X—C motif) receptor 4


4.312
HLA-DMA
major histocompatibility complex, class II, DM alpha


4.313
MRC1
mannose receptor, C type 1


4.314
CASP1 (NA)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,




convertase) (NA-duplicate)


4.315
LMO2
LIM domain only 2 (rhombotin-like 1)


4.315a
DENND2D
DENN/MADD domain containing 2D


4.316
CCL18
chemokine (C-C motif) ligand 18 (pulmonary and activation-




regulated)


4.317
P2RY13
purinergic receptor P2Y, G-protein coupled, 13


4.318
CCL18 (NA)
chemokine (C-C motif) ligand 18 (pulmonary and activation-




regulated) (NA-duplicate)


4.319
ANGPTL1
angiopoietin-like 1


4.320
NA
NA (gene identified by probe set 230391_at)


4.321
ITGAL (NA)
c(“integrin, alpha L (antigen CD11A (p180), lymphocyte function-




associated antigen 1”, “alpha polypeptide)”) (NA-duplicate)


4.322
C8orf51
chromosome 8 open reading frame 51


4.323
GIMAP8
GTPase, IMAP family member 8


4.324
NA
NA (gene identified by probe set 227780_s_at)


4.325
JAK2
Janus kinase 2 (a protein tyrosine kinase)


4.326
TNFSF10
tumor necrosis factor (ligand) superfamily, member 10


4.327
C1R
complement component 1, r subcomponent


4.328
ACPL2
acid phosphatase-like 2


4.329
TNFRSF19
tumor necrosis factor receptor superfamily, member 19


4.330
PCSK5 (NA)
proprotein convertase subtilisin/kexin type 5 (NA-duplicate)


4.331
LRP12
low density lipoprotein-related protein 12


4.332
NA
NA (gene identified by probe set 1557116_at)


4.333
PECAM1 (NA)
platelet/endothelial cam (CD31 antigen) (NA-duplicate)


4.334
PRKCB1
protein kinase C, beta 1


4.335
IPO11
importin 11


4.336
DLGAP1
discs, large (Drosophila) homolog-associated protein 1


4.337
PRKAR2B
protein kinase, cAMP-dependent, regulatory, type II, beta


4.338
MAP3K8
mitogen-activated protein kinase kinase kinase 8


4.339
EVI2B
ecotropic viral integration site 2B


4.340
GBP1
guanylate binding protein 1, interferon-inducible, 67 kDa


4.341
CXCL10
chemokine (C—X—C motif) ligand 10


4.342
CAMK2N1
calcium/calmodulin-dependent protein kinase II inhibitor 1


4.343
MED12L
mediator of RNA polymerase II transcription, subunit 12 homolog




(yeast)-like


4.344
ID2
inhibitor of DNA binding 2, dominant negative helix-loop-helix




protein


4.345
CTBP2
C-terminal binding protein 2


4.346
IGLJ3
immunoglobulin lambda joining 3


4.347
GBP4
guanylate binding protein 4


4.348
LOC439949
NA


4.349
FBXO16
F-box protein 16


4.350
PRF1
perforin 1 (pore forming protein)


4.351
TRAM2
translocation associated membrane protein 2


4.352
LYN
v-yes-1 Yamaguchi sarcoma viral related oncogene homolog


4.353
CENTD1
centaurin, delta 1


4.354
CASP1 (NA)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,




convertase) (NA-duplicate)


4.355
FLJ20273
NA


4.356
TFEC
transcription factor EC


4.357
PPP1R16B
protein phosphatase 1, regulatory (inhibitor) subunit 16B


4.358
CD48
CD48 antigen (B-cell membrane protein)


4.359
HLA-DPB1
major histocompatibility complex, class II, DP beta 1


4.360
SHC4 (NA)
SHC family, member 4 (NA-duplicate)


4.361
GTPBP5
GTP binding protein 5 (putative)


4.362
GBP5
guanylate binding protein 5


4.363
MAP1B
microtubule-associated protein 1B


4.364
EXTL3
exostoses (multiple)-like 3


4.365
CORO1A
coronin, actin binding protein, 1A


4.366
PDGFRL
platelet-derived growth factor receptor-like


4.367
RP9
retinitis pigmentosa 9 (autosomal dominant)


4.368
RHOU
ras homolog gene family, member U


4.369
MTAC2D1
membrane targeting (tandem) C2 domain containing 1


4.370
CCL8
chemokine (C-C motif) ligand 8


4.371
CECR1
cat eye syndrome chromosome region, candidate 1


4.372
IGKC (NA)
immunoglobulin kappa constant (NA-duplicate)


4.373
SLC40A1
solute carrier family 40 (iron-regulated transporter), member 1


4.374
ADCY6
adenylate cyclase 6


4.375
CP
ceruloplasmin (ferroxidase)


4.376
EDG1
endothelial differentiation, sphingolipid G-protein-coupled




receptor, 1


4.377
RGS3
regulator of G-protein signalling 3


4.378
CD28 (NA)
CD28 antigen (Tp44) (NA-duplicate)


4.379
NA
NA (gene identified by probe set 228339_at)


4.380
ABHD5
abhydrolase domain containing 5


4.381
MS4A7
membrane-spanning 4-domains, subfamily A, member 7


4.382
PRKCH
protein kinase C, eta


4.383
GBP1 (NA)
guanylate binding protein 1, i-inducible, 67 kDa (NA-duplicate)


4.384
LOC286071
NA


4.385
BLNK
B-cell linker


4.386
NA
NA (gene identified by probe set 242546_at)


4.387
PCDHGC3
protocadherin gamma subfamily C, 3


4.388
CCL13 (NA)
chemokine (C-C motif) ligand 13 (NA-duplicate)


4.389
JAK2 (NA)
Janus kinase 2 (a protein tyrosine kinase) (NA-duplicate)


4.390
CAMSAP1L1
calmodulin regulated spectrin-associated protein 1-like 1


4.391
NPY1R
neuropeptide Y receptor Y1


4.392
CD274
CD274 antigen


4.393
PGM5
phosphoglucomutase 5


4.394
PLCG2
phospholipase C, gamma 2 (phosphatidylinositol-specific)


4.395
TNFSF10
tumor necrosis factor (ligand) superfamily, member 10


4.396
SOD2 (NA)
superoxide dismutase 2, mitochondrial (NA-duplicate)


4.397
BTG2
BTG family, member 2


4.398
LAMP3
lysosomal-associated membrane protein 3


4.399
IGLC1
immunoglobulin lambda constant 1 (Mcg marker)


4.400
SIPA1L1
signal-induced proliferation-associated 1 like 1


4.401
AIF1
allograft inflammatory factor 1


4.402
IGLC2
immunoglobulin lambda constant 2 (Kern-Oz-marker)


4.403
B2M
beta-2-microglobulin


4.404
CLEC7A
C-type lectin domain family 7, member A


4.405
MGC17330
NA


4.406
IGF1R
insulin-like growth factor 1 receptor


4.407
HIVEP1
human immunodeficiency virus type I enhancer binding protein 1


4.408
FKBP14
FK506 binding protein 14, 22 kDa


4.409
LAPTM5
lysosomal associated multispanning membrane protein 5


4.410
ABI3BP
ABI gene family, member 3 (NESH) binding protein


4.411
HLA-E
major histocompatibility complex, class I, E


4.412
ARL4C
ADP-ribosylation factor-like 4C


4.413
ASS
argininosuccinate synthetase


4.414
CASP1 (NA)
caspase 1, apoptosis-related cysteine peptidase (interleukin 1, beta,




convertase) (NA-duplicate)


4.415
ITGB3
integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)


4.416
SYK
spleen tyrosine kinase


4.417
RAC2
ras-related C3 botulinum toxin substrate 2 (rho family, small GTP




binding protein Rac2)


4.418
NA
NA (gene identified by probe set 1557222_at)


4.419
CD3G
CD3g antigen, gamma polypeptide (TiT3 complex)


4.420
IGF1
insulin-like growth factor 1 (somatomedin C)


4.421
NA
NA (gene identified by probe set 228858_at)


4.422
CYB5A
cytochrome b5 type A (microsomal)


4.423
TTC25
tetratricopeptide repeat domain 25


4.424
SLAMF6
SLAM family member 6


4.425
ARHGAP21
Rho GTPase activating protein 21


4.426
FLOT1
flotillin 1


4.427
AIF1 (NA)
allograft inflammatory factor 1 (NA-duplicate)


4.428
IBRDC2
IBR domain containing 2


4.429
KIAA1794
KIAA1794


4.430
OLFML1
olfactomedin-like 1


4.431
GMFG
glia maturation factor, gamma


4.432
TNFRSF1B
tumor necrosis factor receptor superfamily, member 1B


4.433
NA
NA (gene identified by probe set 217629_at)


4.434
DEF6
differentially expressed in FDCP 6 homolog (mouse)


4.435
HLA-E (NA)
major histocompatibility complex, class I, E (NA-duplicate)


4.436
MAP4K4
mitogen-activated protein kinase kinase kinase kinase 4


4.437
CMKOR1
chemokine orphan receptor 1


4.438
NA
NA (gene identified by probe set 1563461_at)


4.439
CHKA
choline kinase alpha


4.440
NA
NA (gene identified by probe set 226865_at)


4.441
HS3ST3B1
heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1


4.442
CXorf9
chromosome X open reading frame 9


4.443
EVI2A
ecotropic viral integration site 2A


4.444
GBP1 (NA)
guanylate binding protein 1, i-inducible, 67 kDa (NA-duplicate)


4.445
NFAM1
NFAT activating protein with ITAM motif 1


4.446
NA
NA (gene identified by probe set 242874_at)


4.447
ATP5J
ATP synthase, H+ transporting, mitochondrial F0 complex,




subunit F6


4.448
NAV1 (NA)
neuron navigator 1 (NA-duplicate)


4.449
IGLC2 (NA)
immunoglobulin λ constant 2 (Kern-Oz-marker) (NA-duplicate)


4.450
CYLD
cylindromatosis (turban tumor syndrome)


4.451
GIMAP6
GTPase, IMAP family member 6


4.452
MFAP4
microfibrillar-associated protein 4


4.453
TUBB2B
tubulin, beta 2B


4.454
NELL2
NEL-like 2 (chicken)


4.455
NA
NA


4.456
IL1RN
interleukin 1 receptor antagonist


4.457
KIAA1211 (NA)
NA (duplicate)


4.458
SYK
spleen tyrosine kinase


4.459
ADAMDEC1
ADAM-like, decysin 1


4.460
AOC3
amine oxidase, copper containing 3 (vascular adhesion protein 1)


4.461
SAMHD1
SAM domain and HD domain 1


4.462
CXCL14 (NA)
chemokine (C—X—C motif) ligand 14 (NA-duplicate)


4.463
SLC22A3
solute carrier family 22 (extraneuronal monoamine transporter),




member 3


4.464
IL1R1 (NA)
interleukin 1 receptor, type I (NA-duplicate)


4.465
IGLV3-25
immunoglobulin lambda variable 3-25


4.466
NA
NA (gene identified by probe set 1556185_a_at)


4.467
RAB11FIP1
RAB11 family interacting protein 1 (class I)


4.468
PER2
period homolog 2 (Drosophila)


4.469
TTL
tubulin tyrosine ligase


4.470
SIAHBP1
NA


4.471
LAPTM5
lysosomal associated multispanning membrane protein 5


4.472
FLJ22536
NA


4.473
RP6-213H19.1
NA


4.474
NA
NA (gene identified by probe set 235804_at)


4.475
NCF4
neutrophil cytosolic factor 4, 40 kDa


4.476
EPSTI1
epithelial stromal interaction 1 (breast)


4.477
LOC441212
NA


4.478
ANK3
ankyrin 3, node of Ranvier (ankyrin G)


4.479
PCDH9
protocadherin 9


4.480
C21orf86
chromosome 21 open reading frame 86


4.481
DHRS9
dehydrogenase/reductase (SDR family) member 9


4.482
ARHGAP25
Rho GTPase activating protein 25


4.483
TRAF4
TNF receptor-associated factor 4


4.484
LST1
leukcocyte specific transcript 1


4.485
PALMD
palmdelphin


4.486
TAP1
transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)


4.487
MSX2
msh homeobox homolog 2 (Drosophila)


4.488
SIRPG
signal-regulatory protein gamma





NA = not applicable






In the tables listed herein the given gene may be listed more than once, for example as a specific gene or as a gene cluster. Table 4 above is generated from the probe sets listed in Table 4A below. There are often multiple probe sets for each gene and thus where more than one probe set has been used to identify a particular gene then the gene appears more than once in Table 4. An attempt has been made to remove the duplication by scoring through genes that appear more than once in Table 4.


In one aspect the invention provides across the various embodiments herein one or more genes selected from Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 including combinations thereof. In a further aspect the invention provides all the genes of Table 1, 2, 3, 4, 7, 9, 11, 12 or 13 or indeed combinations thereof.


In a further aspect the invention provides at least 10% of the genes listed in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13, for example at least 40%, 50%, 60% or 70% such as 80%, 90% or 100% thereof.


One or more genes includes 1-5, 6-10, 11-15, 16-20, 21-25, 26-30, 31-35, 36-40, 41-45, 46-50, 51-55, 56-60, 61-65, 66-70, 71-75, 76-80, 81-85, 86-90, 91-95, 96-100, 101-105, 106-110, 111-115, 116-120, 121-125, 126-130, 131-135, 136-140, 141-145, 146-150, 151-155, 156-160, 161-165, 166-170, 171-175, 176-180, 181-185, 186-190, 191-195, 196-200, 201-205, 206-210, 211-215, 216-220, 221-225, 226-230, 231-235, 236-240, 241-245, 246-250, 251-255, 256-260, 261-265, 266-270, 271-275, 276-280, 281-285, 286-290, 291-295, 296-300, 301-305, 306-310, 311-315, 316-320, 321-325, 326-330, 331-335, 336-340, 341-345, 346-350, 351-355, 356-360, 361-365, 366-370, 371-375, 376-380, 381-385, 386-390, 391-395, 396-400, 401-405, 406-410, 411-415, 416-420, 421-425, 426-430, 431-435, 436-440, 441-445, 446-450, 451-455, 456-460, 461-465, 466-470, 471-475, 476-480, as appropriate and combinations thereof.


In one or more aspects the invention provides an embodiment as described in any one of paragraphs 1 to 430 below.


1) Thus the invention may employ one or more genes from Table 4.


2) In another aspect the invention employs one or more genes according to paragraph 1, wherein the gene has the symbol FLJ20647, optionally in combination with one or more genes labeled as 4.2 to 4.488 identified in Table 4.


3) In another aspect the invention employs one or more genes according to paragraph 1 or 2, wherein the gene has the NAV1, optionally in combination with one or more genes labeled as 4.3 to 4.488 identified in Table 4.


4) In another aspect the invention employs one or more genes according to any one of paragraphs 1-3, wherein the gene has the symbol GPR171, optionally in combination with one or more genes labeled as 4.4 to 4.488 identified in Table 4.


5) In another aspect the invention employs one or more genes according to any one of paragraphs 1-4, wherein the gene has the symbol CCL14, optionally in combination with one or more genes labeled as 4.5 to 4.488 identified in Table 4.


6) In another aspect the invention employs one or more genes according to any one of paragraphs 1-5, wherein the gene has the symbol C1S, optionally in combination with one or more genes labeled as 4.6 to 4.488 identified in Table 4.


7) In another aspect the invention employs one or more genes according to any one of paragraphs 1-6, wherein the gene has the symbol CXCL2, optionally in combination with one or more genes labeled as 4.7 to 4.488 identified in Table 4.


8) In another aspect the invention employs one or more genes according to any one of paragraphs 1-7, wherein the gene has the symbol TRBV3-1, optionally in combination with one or more genes labeled as 4.8 to 4.488 identified in Table 4.


9) In another aspect the invention employs one or more genes according to any one of paragraphs 1-8, wherein the gene has the symbol TRDV2, optionally in combination with one or more genes labeled as 4.9 to 4.488 identified in Table 4.


10) In another aspect the invention employs one or more genes according to any one of paragraphs 1-9, wherein the gene has the symbol RUFY3, optionally in combination with one or more genes labeled as 4.10 to 4.488 identified in Table 4.


11) In another aspect the invention employs one or more genes according to any one of paragraphs 1-10, wherein the gene has the symbol DOCK8, optionally in combination with one or more genes labeled as 4.11 to 4.488 identified in Table 4.


12) In another aspect the invention employs one or more genes according to any one of paragraphs 1-11, wherein the gene has the symbol GCH1, optionally in combination with one or more genes labeled as 4.12 to 4.488 identified in Table 4.


13) In another aspect the invention employs one or more genes according to any one of paragraphs 1-12, wherein the gene has the symbol CENTD3, optionally in combination with one or more genes labeled as 4.13 to 4.488 identified in Table 4.


14) In another aspect the invention employs one or more genes according to any one of paragraphs 1-13, wherein the gene has the symbol ACSL5, optionally in combination with one or more genes labeled as 4.14 to 4.488 identified in Table 4.


15) In another aspect the invention employs one or more genes according to any one of paragraphs 1-14, wherein the gene has the symbol AMICA1, optionally in combination with one or more genes labeled as 4.15 to 4.488 identified in Table 4.


16) In another aspect the invention employs one or more genes according to any one of paragraphs 1-15, wherein the gene has the symbol IL2RG, optionally in combination with one or more genes labeled as 4.16 to 4.488 identified in Table 4.


17) In another aspect the invention employs one or more genes according to any one of paragraphs 1-16, wherein the gene has the symbol TNFAIP3, optionally in combination with one or more genes labeled as 4.17 to 4.488 identified in Table 4.


18) In another aspect the invention employs one or more genes according to any one of paragraphs 1-17, wherein the gene has the symbol PSCDBP, optionally in combination with one or more genes labeled as 4.18 to 4.488 identified in Table 4.


19) In another aspect the invention employs one or more genes according to any one of paragraphs 1-18, wherein the gene has the symbol ESR1, optionally in combination with one or more genes labeled as 4.19 to 4.488 identified in Table 4.


20) In another aspect the invention employs one or more genes according to any one of paragraphs 1-19, wherein the gene has the symbol TRBC1, optionally in combination with one or more genes labeled as 4.20 to 4.488 identified in Table 4.


21) In another aspect the invention employs one or more genes according to any one of paragraphs 1-20, wherein the gene has the symbol CD52, optionally in combination with one or more genes labeled as 4.21 to 4.488 identified in Table 4.


22) In another aspect the invention employs one or more genes according to any one of paragraphs 1-21, wherein the gene has the symbol LOC442535, optionally in combination with one or more genes labeled as 4.22 to 4.488 identified in Table 4.


23) In another aspect the invention employs one or more genes according to any one of paragraphs 1-22, wherein the gene has the symbol TRBV19, optionally in combination with one or more genes labeled as 4.23 to 4.488 identified in Table 4.


24) In another aspect the invention employs one or more genes according to any one of paragraphs 1-23, wherein the gene has the symbol IL7R, optionally in combination with one or more genes labeled as 4.24 to 4.488 identified in Table 4.


25) In another aspect the invention employs one or more genes according to any one of paragraphs 1-24, wherein the gene has the symbol TRAC, optionally in combination with one or more genes labeled as 4.25 to 4.488 identified in Table 4.


26) In another aspect the invention employs one or more genes according to any one of paragraphs 1-25, wherein the gene has the symbol NCF2, optionally in combination with one or more genes labeled as 4.26 to 4.488 identified in Table 4.


27) In another aspect the invention employs one or more genes according to any one of paragraphs 1-26, wherein the gene has the symbol LOC92689, optionally in combination with one or more genes labeled as 4.27 to 4.488 identified in Table 4.


28) In another aspect the invention employs one or more genes according to any one of paragraphs 1-27, wherein the gene has the symbol GZMK, optionally in combination with one or more genes labeled as 4.28 to 4.488 identified in Table 4.


29) In another aspect the invention employs one or more genes according to any one of paragraphs 1-28, wherein the gene is the one identified by probe set 235831, optionally in combination with one or more genes labeled as 4.29 to 4.488 identified in Table 4.


30) In another aspect the invention employs one or more genes according to any one of paragraphs 1-29, wherein the gene has the symbol RAB34, optionally in combination with one or more genes labeled as 4.30 to 4.488 identified in Table 4.


31) In another aspect the invention employs one or more genes according to any one of paragraphs 1-30, wherein the gene has the symbol DPT, optionally in combination with one or more genes labeled as 4.31 to 4.488 identified in Table 4.


32) In another aspect the invention employs one or more genes according to any one of paragraphs 1-31, wherein the gene has the symbol PVT1, optionally in combination with one or more genes labeled as 4.32 to 4.488 identified in Table 4.


33) In another aspect the invention employs one or more genes according to any one of paragraphs 1-32, wherein the gene has the symbol TRGC2, optionally in combination with one or more genes labeled as 4.33 to 4.488 identified in Table 4.


34) In another aspect the invention employs one or more genes according to any one of paragraphs 1-33, wherein the gene has the symbol GIMAP5, optionally in combination with one or more genes labeled as 4.34 to 4.488 identified in Table 4.


35) In another aspect the invention employs one or more genes according to any one of paragraphs 1-34, wherein the gene has the symbol CD52, optionally in combination with one or more genes labeled as 4.35 to 4.488 identified in Table 4.


36) In another aspect the invention employs one or more genes according to any one of paragraphs 1-35, wherein the gene has the symbol CD3D, optionally in combination with one or more genes labeled as 4.36 to 4.488 identified in Table 4.


37) In another aspect the invention employs one or more genes according to any one of paragraphs 1-36, wherein the gene has the symbol TMEM132C, optionally in combination with one or more genes labeled as 4.37 to 4.488 identified in Table 4.


38) In another aspect the invention employs one or more genes according to any one of paragraphs 1-37, wherein the gene has the symbol NFKBIA, optionally in combination with one or more genes labeled as 4.38 to 4.488 identified in Table 4.


39) In another aspect the invention employs one or more genes according to any one of paragraphs 1-38, wherein the gene has the symbol TRA@, optionally in combination with one or more genes labeled as 4.39 to 4.488 identified in Table 4.


40) In another aspect the invention employs one or more genes according to any one of paragraphs 1-39, wherein the gene has the symbol TRAT1, optionally in combination with one or more genes labeled as 4.41 to 4.488 identified in Table 4.


41) In another aspect the invention employs one or more genes according to any one of paragraphs 1-40, wherein the gene has the symbol RAB34, optionally in combination with one or more genes labeled as 4.42 to 4.488 identified in Table 4.


42) In another aspect the invention employs one or more genes according to any one of paragraphs 1-41, wherein the gene has the symbol CD69, optionally in combination with one or more genes labeled as 4.43 to 4.488 identified in Table 4.


43) In another aspect the invention employs one or more genes according to any one of paragraphs 1-42, wherein the gene has the symbol DOCK8 optionally in combination with one or more genes labeled as 4.44 to 4.488 identified in Table 4.


44) In another aspect the invention employs one or more genes according to any one of paragraphs 1-43, wherein the gene has the symbol IRF8 optionally in combination with one or more genes labeled as 4.46 to 4.488 identified in Table 4.


45) In another aspect the invention employs one or more genes according to any one of paragraphs 144, wherein the gene has the symbol KLRB1 optionally in combination with one or more genes labeled as 4.47 to 4.488 identified in Table 4.


46) In another aspect the invention employs one or more genes according to any one of paragraphs 1-45, wherein the gene is identifiable by probe set number 236280_at, optionally in combination with one or more genes labeled as 4.48 to 4.488 identified in Table 4.


47) In another aspect the invention employs one or more genes according to any one of paragraphs 1-46, wherein the gene has the symbol ITGA3, optionally in combination with one or more genes labeled as 4.49 to 4.488 identified in Table 4.


48) In another aspect the invention employs one or more genes according to any one of paragraphs 1-47, wherein the gene has the symbol MAP3K8, optionally in combination with one or more genes labeled as 4.50 to 4.488 identified in Table 4.


49) In another aspect the invention employs one or more genes according to any one of paragraphs 1-48, wherein the gene has the symbol Clorf162, optionally in combination with one or more genes labeled as 4.51 to 4.488 identified in Table 4.


50) In another aspect the invention employs one or more genes according to any one of paragraphs 1-49, wherein the gene has the symbol UBD, optionally in combination with one or more genes labeled as 4.52 to 4.488 identified in Table 4.


51) In another aspect the invention employs one or more genes according to any one of paragraphs 1-50, wherein the gene has the symbol TRGV9, optionally in combination with one or more genes labeled as 4.54 to 4.488 identified in Table 4.


52) In another aspect the invention employs one or more genes according to any one of paragraphs 1-51, wherein the gene has the symbol NAV1, optionally in combination with one or more genes labeled as 4.54 to 4.488 identified in Table 4.


53) In another aspect the invention employs one or more genes according to any one of paragraphs 1-51, wherein the gene has the symbol ARHGAP9, optionally in combination with one or more genes labeled as 4.55 to 4.488 identified in Table 4.


54) In another aspect the invention employs one or more genes according to any one of paragraphs 1-53, wherein the gene has the symbol TIFA, optionally in combination with one or more genes labeled as 4.56 to 4.488 identified in Table 4.


55) In another aspect the invention employs one or more genes according to any one of paragraphs 1-54, wherein the gene is identified by probe number 1569942 at, optionally in combination with one or more genes labeled as 4.58 to 4.488 identified in Table 4.


56) In another aspect the invention employs one or more genes according to any one of paragraphs 1-55, wherein the gene has the symbol GIMAP4, optionally in combination with one or more genes labeled as 4.59 to 4.488 identified in Table 4.


57) In another aspect the invention employs one or more genes according to any one of paragraphs 1-56, wherein the gene has the symbol HCLS1, optionally in combination with one or more genes labeled as 4.60 to 4.488 identified in Table 4.


58) In another aspect the invention employs one or more genes according to any one of paragraphs 1-57, wherein the gene has the symbol PRKCH, optionally in combination with one or more genes labeled as 4.61 to 4.488 identified in Table 4.


59) In another aspect the invention employs one or more genes according to any one of paragraphs 1-58, wherein the gene has the symbol STAT4, optionally in combination with one or more genes labeled as 4.62 to 4.488 identified in Table 4.


60) In another aspect the invention employs one or more genes according to any one of paragraphs 1-59, wherein the gene has the symbol HLA-DQA1, optionally in combination with one or more genes labeled as 4.63 to 4.488 identified in Table 4.


61) In another aspect the invention employs one or more genes according to any one of paragraphs 1-60, wherein the gene has the symbol ADRB2, optionally in combination with one or more genes labeled as 4.64 to 4.488 identified in Table 4.


62) In another aspect the invention employs one or more genes according to any one of paragraphs 1-61, wherein the gene is identifiable by probe set number 239237_at, optionally in combination with one or more genes labeled as 4.65 to 4.488 identified in Table 4.


63) In another aspect the invention employs one or more genes according to any one of paragraphs 1-62, wherein the gene has the symbol CTSW, optionally in combination with one or more genes labeled as 4.66 to 4.488 identified in Table 4.


64) In another aspect the invention employs one or more genes according to any one of paragraphs 1-63, wherein the gene has the symbol MYH11, optionally in combination with one or more genes labeled as 4.67 to 4.488 identified in Table 4.


65) In another aspect the invention employs one or more genes according to any one of paragraphs 1-64, wherein the gene has the symbol GIMAP6, optionally in combination with one or more genes labeled as 4.68 to 4.488 identified in Table 4.


66) In another aspect the invention employs one or more genes according to any one of paragraphs 1-65, wherein the gene has the symbol HLA-DQB1, optionally in combination with one or more genes labeled as 4.69 to 4.488 identified in Table 4.


67) In another aspect the invention employs one or more genes according to any one of paragraphs 1-66, wherein the gene has the symbol CD8A, optionally in combination with one or more genes labeled as 4.70 to 4.488 identified in Table 4.


68) In another aspect the invention employs one or more genes according to any one of paragraphs 1-67, wherein the gene has the symbol TNFAIP3, optionally in combination with one or more genes labeled as 4.71 to 4.488 identified in Table 4.


69) In another aspect the invention employs one or more genes according to any one of paragraphs 1-68, wherein the gene has the symbol CP, optionally in combination with one or more genes labeled as 4.72 to 4.488 identified in Table 4.


70) In another aspect the invention employs one or more genes according to any one of paragraphs 1-69, wherein the gene has the symbol SMOC2, optionally in combination with one or more genes labeled as 4.73 to 4.488 identified in Table 4.


71) In another aspect the invention employs one or more genes according to any one of paragraphs 1-70, wherein the gene has the symbol C20orf24, optionally in combination with one or more genes labeled as 4.74 to 4.488 identified in Table 4.


72) In another aspect the invention employs one or more genes according to any one of paragraphs 1-71, wherein the gene has the symbol C16orf54, optionally in combination with one or more genes labeled as 4.75 to 4.488 identified in Table 4.


73) In another aspect the invention employs one or more genes according to any one of paragraphs 1-72, wherein the gene has the symbol CD2, optionally in combination with one or more genes labeled as 4.76 to 4.488 identified in Table 4.


74) In another aspect the invention employs one or more genes according to any one of paragraphs 1-73, wherein the gene has the symbol SLIT3, optionally in combination with one or more genes labeled as 4.77 to 4.488 identified in Table 4.


75) In another aspect the invention employs one or more genes according to any one of paragraphs 1-74, wherein the gene has the symbol BAALC, optionally in combination with one or more genes labeled as 4.78 to 4.488 identified in Table 4.


76) In another aspect the invention employs one or more genes according to any one of paragraphs 1-75, wherein the gene has the symbol TRIB3, optionally in combination with one or more genes labeled as 4.79 to 4.488 identified in Table 4.


77) In another aspect the invention employs one or more genes according to any one of paragraphs 1-76, wherein the gene has the symbol LOC440160, optionally in combination with one or more genes labeled as 4.80 to 4.488 identified in Table 4.


78) In another aspect the invention employs one or more genes according to any one of paragraphs 1-77, wherein the gene has the symbol C6orf190, optionally in combination with one or more genes labeled as 4.81 to 4.488 identified in Table 4.


79) In another aspect the invention employs one or more genes according to any one of paragraphs 1-78, wherein the gene has the symbol TAGAP, optionally in combination with one or more genes labeled as 4.82 to 4.488 identified in Table 4.


80) In another aspect the invention employs one or more genes according to any one of paragraphs 1-79, wherein the gene has the symbol FAM92A1, optionally in combination with one or more genes labeled as 4.83 to 4.488 identified in Table 4.


81) In another aspect the invention employs one or more genes according to any one of paragraphs 1-80, wherein the gene has the symbol PSTPIP2, optionally in combination with one or more genes labeled as 4.84 to 4.488 identified in Table 4.


82) In another aspect the invention employs one or more genes according to any one of paragraphs 1-81, wherein the gene has the symbol PTPRC, optionally in combination with one or more genes labeled as 4.85 to 4.488 identified in Table 4.


83) In another aspect the invention employs one or more genes according to any one of paragraphs 1-82, wherein the gene has the symbol HLA-DRA, optionally in combination with one or more genes labeled as 4.86 to 4.488 identified in Table 4.


84) In another aspect the invention employs one or more genes according to any one of paragraphs 1-83, wherein the gene has the symbol EFCAB2, optionally in combination with one or more genes labeled as 4.87 to 4.488 identified in Table 4.


85) In another aspect the invention employs one or more genes according to any one of paragraphs 1-84, wherein the gene has the symbol TNFAIP8, optionally in combination with one or more genes labeled as 4.88 to 4.488 identified in Table 4.


86) In another aspect the invention employs one or more genes according to any one of paragraphs 1-85, wherein the gene has the symbol SLIC1, optionally in combination with one or more genes labeled as 4.89 to 4.488 identified in Table 4.


87) In another aspect the invention employs one or more genes according to any one of paragraphs 1-86, wherein the gene has the symbol CD1C, optionally in combination with one or more genes labeled as 4.90 to 4.488 identified in Table 4.


88) In another aspect the invention employs one or more genes according to any one of paragraphs 1-87, wherein the gene has the symbol TRAF31P3, optionally in combination with one or more genes labeled as 4.91 to 4.488 identified in Table 4.


89) In another aspect the invention employs one or more genes according to any one of paragraphs 1-88, wherein the gene has the symbol IGJ, optionally in combination with one or more genes labeled as 4.96 to 4.488 identified in Table 4.


90) In another aspect the invention employs one or more genes according to any one of paragraphs 1-89, wherein the gene has the symbol PLEK, optionally in combination with one or more genes labeled as 4.98 to 4.488 identified in Table 4.


91) In another aspect the invention employs one or more genes according to any one of paragraphs 1-90, wherein the gene has the symbol TMEM44, optionally in combination with one or more genes labeled as 4.100 to 4.488 identified in Table 4.


92) In another aspect the invention employs one or more genes according to any one of paragraphs 1-91, wherein the gene has the symbol EBI2, optionally in combination with one or more genes labeled as 4.101 to 4.488 identified in Table 4.


93) In another aspect the invention employs one or more genes according to any one of paragraphs 1-92, wherein the gene has the symbol SAMSN1, optionally in combination with one or more genes labeled as 4.102 to 4.488 identified in Table 4.


94) In another aspect the invention employs one or more genes according to any one of paragraphs 1-93, wherein the gene has the symbol KIAA1794, optionally in combination with one or more genes labeled as 4.103 to 4.488 identified in Table 4.


95) In another aspect the invention employs one or more genes according to any one of paragraphs 1-94, wherein the gene has the symbol ALDH2, optionally in combination with one or more genes labeled as 4.104 to 4.488 identified in Table 4.


96) In another aspect the invention employs one or more genes according to any one of paragraphs 1-95, wherein the gene has the symbol CDC42SE2, optionally in combination with one or more genes labeled as 4.105 to 4.488 identified in Table 4.


97) In another aspect the invention employs one or more genes according to any one of paragraphs 1-96, wherein the gene has the symbol GFRA1, optionally in combination with one or more genes labeled as 4.106 to 4.488 identified in Table 4.


98) In another aspect the invention employs one or more genes according to any one of paragraphs 1-97, wherein the gene has the symbol ITK, optionally in combination with one or more genes labeled as 4.107 to 4.488 identified in Table 4.


99) In another aspect the invention employs one or more genes according to any one of paragraphs 1-98, wherein the gene has the symbol GIMAP7, optionally in combination with one or more genes labeled as 4.109 to 4.488 identified in Table 4.


100) In another aspect the invention employs one or more genes according to any one of paragraphs 1-99, wherein the gene has the symbol FLJ20273, optionally in combination with one or more genes labeled as 4.110 to 4.488 identified in Table 4.


101) In another aspect the invention employs one or more genes according to any one of paragraphs 1-100, wherein the gene has the symbol PTPN6, optionally in combination with one or more genes labeled as 4.111 to 4.488 identified in Table 4.


102) In another aspect the invention employs one or more genes according to any one of paragraphs 1-101, wherein the gene has the symbol PTGER3, optionally in combination with one or more genes labeled as 4.112 to 4.488 identified in Table 4.


103) In another aspect the invention employs one or more genes according to any one of paragraphs 1-102, wherein the gene has the symbol RAI2, optionally in combination with one or more genes labeled as 4.113 to 4.488 identified in Table 4.


104) In another aspect the invention employs one or more genes according to any one of paragraphs 1-103, wherein the gene has the symbol LGALS2, optionally in combination with one or more genes labeled as 4.114 to 4.488 identified in Table 4.


105) In another aspect the invention employs one or more genes according to any one of paragraphs 1-104, wherein the gene has the symbol HMOX1, optionally in combination with one or more genes labeled as 4.115 to 4.488 identified in Table 4.


106) In another aspect the invention employs one or more genes according to any one of paragraphs 1-105, wherein the gene is identifiable by probe set number 227995 at, optionally in combination with one or more genes labeled as 4.116 to 4.488 identified in Table 4.


107) In another aspect the invention employs one or more genes according to any one of paragraphs 1-106, wherein the gene has the symbol ZNFN1A1, optionally in combination with one or more genes labeled as 4.117 to 4.488 identified in Table 4.


108) In another aspect the invention employs one or more genes according to any one of paragraphs 1-107, wherein the gene has the symbol CSF2RB, optionally in combination with one or more genes labeled as 4.118 to 4.488 identified in Table 4.


109) In another aspect the invention employs one or more genes according to any one of paragraphs 1-108, wherein the gene has the symbol PCSK5, optionally in combination with one or more genes labeled as 4.119 to 4.488 identified in Table 4.


110) In another aspect the invention employs one or more genes according to any one of paragraphs 1-109, wherein the gene has the symbol CCDC69, optionally in combination with one or more genes labeled as 4.120 to 4.488 identified in Table 4.


111) In another aspect the invention employs one or more genes according to any one of paragraphs 1-110, wherein the gene has the symbol CDC42SE2, optionally in combination with one or more genes labeled as 4.121 to 4.488 identified in Table 4.


112) In another aspect the invention employs one or more genes according to any one of paragraphs 1-111, wherein the gene has the symbol GZMA, optionally in combination with one or more genes labeled as 4.122 to 4.488 identified in Table 4.


113) In another aspect the invention employs one or more genes according to any one of paragraphs 1-112, wherein the gene has the symbol C3, optionally in combination with one or more genes labeled as 4.123 to 4.488 identified in Table 4.


114) In another aspect the invention employs one or more genes according to any one of paragraphs 1-113, wherein the gene has the symbol C15orf48, optionally in combination with one or more genes labeled as 4.125 to 4.488 identified in Table 4.


115) In another aspect the invention employs one or more genes according to any one of paragraphs 1-114, wherein the gene has the symbol RARRES3, optionally in combination with one or more genes labeled as 4.126 to 4.488 identified in Table 4.


116) In another aspect the invention employs one or more genes according to any one of paragraphs 1-115, wherein the gene has the symbol LOC283537, optionally in combination with one or more genes labeled as 4.127 to 4.488 identified in Table 4.


117) In another aspect the invention employs one or more genes according to any one of paragraphs 1-116, wherein the gene has the symbol CXCL12, optionally in combination with one or more genes labeled as 4.129 to 4.488 identified in Table 4.


118) In another aspect the invention employs one or more genes according to any one of paragraphs 1-117, wherein the gene is identifiable by probe set number 231882_at, optionally in combination with one or more genes labeled as 4.130 to 4.488 identified in Table 4.


119) In another aspect the invention employs one or more genes according to any one of paragraphs 1-118, wherein the gene has the symbol SOD2, optionally in combination with one or more genes labeled as 4.131 to 4.488 identified in Table 4.


120) In another aspect the invention employs one or more genes according to any one of paragraphs 1-119, wherein the gene has the symbol CTSS, optionally in combination with one or more genes labeled as 4.132 to 4.488 identified in Table 4.


121) In another aspect the invention employs one or more genes according to any one of paragraphs 1-120, wherein the gene has the symbol CTBP2, optionally in combination with one or more genes labeled as 4.133 to 4.488 identified in Table 4.


122) In another aspect the invention employs one or more genes according to any one of paragraphs 1-121, wherein the gene has the symbol BCL11B, optionally in combination with one or more genes labeled as 4.134 to 4.488 identified in Table 4.


123) In another aspect the invention employs one or more genes according to any one of paragraphs 1-122, wherein the gene has the symbol CCL22, optionally in combination with one or more genes labeled as 4.135 to 4.488 identified in Table 4.


124) In another aspect the invention employs one or more genes according to any one of paragraphs 1-123, wherein the gene has the symbol ACSL5, optionally in combination with one or more genes labeled as 4.136 to 4.488 identified in Table 4.


125) In another aspect the invention employs one or more genes according to any one of paragraphs 1-124, wherein the gene has the symbol DOC1, optionally in combination with one or more genes labeled as 4.137 to 4.488 identified in Table 4.


126) In another aspect the invention employs one or more genes according to any one of paragraphs 1-125, wherein the gene has the symbol SLC31A2, optionally in combination with one or more genes labeled as 4.138 to 4.488 identified in Table 4.


127) In another aspect the invention employs one or more genes according to any one of paragraphs 1-126, wherein the gene has the symbol POPDC3, optionally in combination with one or more genes labeled as 4.139 to 4.488 identified in Table 4.


128) In another aspect the invention employs one or more genes according to any one of paragraphs 1-127, wherein the gene has the symbol SQRDL, optionally in combination with one or more genes labeled as 4.141 to 4.488 identified in Table 4.


129) In another aspect the invention employs one or more genes according to any one of paragraphs 1-128, wherein the gene has the symbol RASGEF1B, optionally in combination with one or more genes labeled as 4.142 to 4.488 identified in Table 4.


130) In another aspect the invention employs one or more genes according to any one of paragraphs 1-129, wherein the gene has the symbol FGL2, optionally in combination with one or more genes labeled as 4.143 to 4.488 identified in Table 4.


131) In another aspect the invention employs one or more genes according to any one of paragraphs 1-130, wherein the gene has the symbol C10orf128, optionally in combination with one or more genes labeled as 4.144 to 4.488 identified in Table 4.


132) In another aspect the invention employs one or more genes according to any one of paragraphs 1-131, wherein the gene has the symbol IL10RA, optionally in combination with one or more genes labeled as 4.145 to 4.488 identified in Table 4.


133) In another aspect the invention employs one or more genes according to any one of paragraphs 1-132, wherein the gene has the symbol EGFL6, optionally in combination with one or more genes labeled as 4.146 to 4.488 identified in Table 4.


134) In another aspect the invention employs one or more genes according to any one of paragraphs 1-133, wherein the gene has the symbol IL18, optionally in combination with one or more genes labeled as 4.147 to 4.488 identified in Table 4.


135) In another aspect the invention employs one or more genes according to any one of paragraphs 1-134, wherein the gene has the symbol ARHGAP30, optionally in combination with one or more genes labeled as 4.148 to 4.488 identified in Table 4.


136) In another aspect the invention employs one or more genes according to any one of paragraphs 1-135, wherein the gene has the symbol PALMD, optionally in combination with one or more genes labeled as 4.149 to 4.488 identified in Table 4.


137) In another aspect the invention employs one or more genes according to any one of paragraphs 1-136, wherein the gene has the symbol RASSF5, optionally in combination with one or more genes labeled as 4.150 to 4.488 identified in Table 4.


138) In another aspect the invention employs one or more genes according to any one of paragraphs 1-137, wherein the gene has the symbol GATA3, optionally in combination with one or more genes labeled as 4.151 to 4.488 identified in Table 4.


139) In another aspect the invention employs one or more genes according to any one of paragraphs 1-138, wherein the gene has the symbol DKFZP564O0823, optionally in combination with one or more genes labeled as 4.152 to 4.488 identified in Table 4.


140) In another aspect the invention employs one or more genes according to any one of paragraphs 1-139, wherein the gene has the symbol TXNIP, optionally in combination with one or more genes labeled as 4.154 to 4.488 identified in Table 4.


141) In another aspect the invention employs one or more genes according to any one of paragraphs 1-140, wherein the gene has the symbol DTX4, optionally in combination with one or more genes labeled as 4.155 to 4.488 identified in Table 4.


142) In another aspect the invention employs one or more genes according to any one of paragraphs 1-141, wherein the gene has the symbol DARC, optionally in combination with one or more genes labeled as 4.156 to 4.488 identified in Table 4.


143) In another aspect the invention employs one or more genes according to any one of paragraphs 1-142, wherein the gene has the symbol RNASE6, optionally in combination with one or more genes labeled as 4.157 to 4.488 identified in Table 4.


144) In another aspect the invention employs one or more genes according to any one of paragraphs 1-143, wherein the gene has the symbol CD86, optionally in combination with one or more genes labeled as 4.158 to 4.488 identified in Table 4.


145) In another aspect the invention employs one or more genes according to any one of paragraphs 1-144, wherein the gene has the symbol ZFP36, optionally in combination with one or more genes labeled as 4.159 to 4.488 identified in Table 4.


146) In another aspect the invention employs one or more genes according to any one of paragraphs 1-145, wherein the gene has the symbol BASP1, optionally in combination with one or more genes labeled as 4.160 to 4.488 identified in Table 4.


147) In another aspect the invention employs one or more genes according to any one of paragraphs 1-146, wherein the gene has the symbol CKAP1, optionally in combination with one or more genes labeled as 4.161 to 4.488 identified in Table 4.


148) In another aspect the invention employs one or more genes according to any one of paragraphs 1-147, wherein the gene has the symbol HCP5, optionally in combination with one or more genes labeled as 4.162 to 4.488 identified in Table 4.


149) In another aspect the invention employs one or more genes according to any one of paragraphs 1-148, wherein the gene has the symbol GRB14, optionally in combination with one or more genes labeled as 4.163 to 4.488 identified in Table 4.


150) In another aspect the invention employs one or more genes according to any one of paragraphs 1-149, wherein the gene has the symbol GJA7, optionally in combination with one or more genes labeled as 4.164 to 4.488 identified in Table 4.


151) In another aspect the invention employs one or more genes according to any one of paragraphs 1-150, wherein the gene has the symbol FLJ14054, optionally in combination with one or more genes labeled as 4.165 to 4.488 identified in Table 4.


152) In another aspect the invention employs one or more genes according to any one of paragraphs 1-151, wherein the gene has the symbol VNN1, optionally in combination with one or more genes labeled as 4.166 to 4.488 identified in Table 4.


153) In another aspect the invention employs one or more genes according to any one of paragraphs 1-152, wherein the gene has the symbol ADCY7, optionally in combination with one or more genes labeled as 4.167 to 4.488 identified in Table 4.


154) In another aspect the invention employs one or more genes according to any one of paragraphs 1-153, wherein the gene has the symbol MS4A6A, optionally in combination with one or more genes labeled as 4.168 to 4.488 identified in Table 4.


155) In another aspect the invention employs one or more genes according to any one of paragraphs 1-154, wherein the gene has the symbol CPA3, optionally in combination with one or more genes labeled as 4.169 to 4.488 identified in Table 4.


156) In another aspect the invention employs one or more genes according to any one of paragraphs 1-155, wherein the gene has the symbol PIM1, optionally in combination with one or more genes labeled as 4.170 to 4.488 identified in Table 4.


157) In another aspect the invention employs one or more genes according to any one of paragraphs 1-156, wherein the gene has the symbol CCL19, optionally in combination with one or more genes labeled as 4.171 to 4.488 identified in Table 4.


158) In another aspect the invention employs one or more genes according to any one of paragraphs 1-157, wherein the gene has the symbol SYK, optionally in combination with one or more genes labeled as 4.172 to 4.488 identified in Table 4.


159) In another aspect the invention employs one or more genes according to any one of paragraphs 1-158, wherein the gene has the symbol SIT1, optionally in combination with one or more genes labeled as 4.174 to 4.488 identified in Table 4.


160) In another aspect the invention employs one or more genes according to any one of paragraphs 1-159, wherein the gene is identifiable by probe set number 228812_at, optionally in combination with one or more genes labeled as 4.175 to 4.488 identified in Table 4.


161) In another aspect the invention employs one or more genes according to any one of paragraphs 1-160, wherein the gene has the symbol NAP1L2, optionally in combination with one or more genes labeled as 4.176 to 4.488 identified in Table 4.


162) In another aspect the invention employs one or more genes according to any one of paragraphs 1-161, wherein the gene has the symbol CCL13, optionally in combination with one or more genes labeled as 4.177 to 4.488 identified in Table 4.


163) In another aspect the invention employs one or more genes according to any one of paragraphs 1-162, wherein the gene has the symbol SLA, optionally in combination with one or more genes labeled as 4.178 to 4.488 identified in Table 4.


164) In another aspect the invention employs one or more genes according to any one of paragraphs 1-163, wherein the gene has the symbol NOD3, optionally in combination with one or more genes labeled as 4.179 to 4.488 identified in Table 4.


165) In another aspect the invention employs one or more genes according to any one of paragraphs 1-164, wherein the gene has the symbol PRKCH, optionally in combination with one or more genes labeled as 4.180 to 4.488 identified in Table 4.


166) In another aspect the invention employs one or more genes according to any one of paragraphs 1-165, wherein the gene has the symbol TRD@, optionally in combination with one or more genes labeled as 4.181 to 4.488 identified in Table 4.


167) In another aspect the invention employs one or more genes according to any one of paragraphs 1-166, wherein the gene has the symbol BAALC, optionally in combination with one or more genes labeled as 4.182 to 4.488 identified in Table 4.


168) In another aspect the invention employs one or more genes according to any one of paragraphs 1-167, wherein the gene has the symbol RP1-93H18.5, optionally in combination with one or more genes labeled as 4.183 to 4.488 identified in Table 4.


169) In another aspect the invention employs one or more genes according to any one of paragraphs 1-168, wherein the gene has the symbol FLJ20701, optionally in combination with one or more genes labeled as 4.184 to 4.488 identified in Table 4.


170) In another aspect the invention employs one or more genes according to any one of paragraphs 1-169, wherein the gene has the symbol SH3TC2, optionally in combination with one or more genes labeled as 4.185 to 4.488 identified in Table 4.


171) In another aspect the invention employs one or more genes according to any one of paragraphs 1-170, wherein the gene has the symbol CCR2, optionally in combination with one or more genes labeled as 4.186 to 4.488 identified in Table 4.


172) In another aspect the invention employs one or more genes according to any one of paragraphs 1-171, wherein the gene has the symbol CCL5, optionally in combination with one or more genes labeled as 4.187 to 4.488 identified in Table 4.


173) In another aspect the invention employs one or more genes according to any one of paragraphs 1-172, wherein the gene has the symbol HLA-DPA1, optionally in combination with one or more genes labeled as 4.189 to 4.488 identified in Table 4.


174) In another aspect the invention employs one or more genes according to any one of paragraphs 1-173, wherein the gene has the symbol PECAM1, optionally in combination with one or more genes labeled as 4.190 to 4.488 identified in Table 4.


175) In another aspect the invention employs one or more genes according to any one of paragraphs 1-174, wherein the gene has the symbol AMIGO2, optionally in combination with one or more genes labeled as 4.192 to 4.488 identified in Table 4.


176) In another aspect the invention employs one or more genes according to any one of paragraphs 1-175, wherein the gene has the symbol CLEC7A, optionally in combination with one or more genes labeled as 4.193 to 4.488 identified in Table 4.


177) In another aspect the invention employs one or more genes according to any one of paragraphs 1-176, wherein the gene has the symbol P2RY14, optionally in combination with one or more genes labeled as 4.194 to 4.488 identified in Table 4.


178) In another aspect the invention employs one or more genes according to any one of paragraphs 1-177, wherein the gene has the symbol PIK3AP1, optionally in combination with one or more genes labeled as 4.195 to 4.488 identified in Table 4.


179) In another aspect the invention employs one or more genes according to any one of paragraphs 1-178, wherein the gene has the symbol ADH1B, optionally in combination with one or more genes labeled as 4.196 to 4.488 identified in Table 4.


180) In another aspect the invention employs one or more genes according to any one of paragraphs 1-179, wherein the gene has the symbol TOP1MT, optionally in combination with one or more genes labeled as 4.197 to 4.488 identified in Table 4.


181) In another aspect the invention employs one or more genes according to any one of paragraphs 1-180, wherein the gene has the symbol CD276, optionally in combination with one or more genes labeled as 4.199 to 4.488 identified in Table 4.


182) In another aspect the invention employs one or more genes according to any one of paragraphs 1-181, wherein the gene has the symbol JAM2, optionally in combination with one or more genes labeled as 4.200 to 4.488 identified in Table 4.


183) In another aspect the invention employs one or more genes according to any one of paragraphs 1-182, wherein the gene has the symbol C1S, optionally in combination with one or more genes labeled as 4.202 to 4.488 identified in Table 4.


184) In another aspect the invention employs one or more genes according to any one of paragraphs 1-183, wherein the gene has the symbol TGFBR3, optionally in combination with one or more genes labeled as 4.203 to 4.488 identified in Table 4.


185) In another aspect the invention employs one or more genes according to any one of paragraphs 1-184, wherein the gene has the symbol ITGAL, optionally in combination with one or more genes labeled as 4.204 to 4.488 identified in Table 4.


186) In another aspect the invention employs one or more genes according to any one of paragraphs 1-185, wherein the gene has the symbol IL1R1, optionally in combination with one or more genes labeled as 4.206 to 4.488 identified in Table 4.


187) In another aspect the invention employs one or more genes according to any one of paragraphs 1-186, wherein the gene has the symbol HLA-DRB1, optionally in combination with one or more genes labeled as 4.207 to 4.488 identified in Table 4.


188) In another aspect the invention employs one or more genes according to any one of paragraphs 1-187, wherein the gene has the symbol GIMAP2, optionally in combination with one or more genes labeled as 4.208 to 4.488 identified in Table 4.


189) In another aspect the invention employs one or more genes according to any one of paragraphs 1-188, wherein the gene has the symbol ZC3H12D, optionally in combination with one or more genes labeled as 4.209 to 4.488 identified in Table 4.


190) In another aspect the invention employs one or more genes according to any one of paragraphs 1-189, wherein the gene has the symbol PCDH9, optionally in combination with one or more genes labeled as 4.210 to 4.488 identified in Table 4.


191) In another aspect the invention employs one or more genes according to any one of paragraphs 1-190, wherein the gene has the symbol SLAMF7, optionally in combination with one or more genes labeled as 4.211 to 4.488 identified in Table 4.


192) In another aspect the invention employs one or more genes according to any one of paragraphs 1-191, wherein the gene has the symbol MGC7036, optionally in combination with one or more genes labeled as 4.212 to 4.488 identified in Table 4.


193) In another aspect the invention employs one or more genes according to any one of paragraphs 1-192, wherein the gene has the symbol RGS18, optionally in combination with one or more genes labeled as 4.214 to 4.488 identified in Table 4.


194) In another aspect the invention employs one or more genes according to any one of paragraphs 1-193, wherein the gene has the symbol CD53, optionally in combination with one or more genes labeled as 4.215 to 4.488 identified in Table 4.


195) In another aspect the invention employs one or more genes according to any one of paragraphs 1-194, wherein the gene has the symbol MPEG1, optionally in combination with one or more genes labeled as 4.216 to 4.488 identified in Table 4.


196) In another aspect the invention employs one or more genes according to any one of paragraphs 1-195, wherein the gene has the symbol SSBP4, optionally in combination with one or more genes labeled as 4.217 to 4.488 identified in Table 4.


197) In another aspect the invention employs one or more genes according to any one of paragraphs 1-196, wherein the gene is identifiable by probe set number 231262_at, optionally in combination with one or more genes labeled as 4.218 to 4.488 identified in Table 4.


198) In another aspect the invention employs one or more genes according to any one of paragraphs 1-197, wherein the gene has the symbol CDH19, optionally in combination with one or more genes labeled as 4.219 to 4.488 identified in Table 4.


199) In another aspect the invention employs one or more genes according to any one of paragraphs 1-198, wherein the gene has the symbol CTBP2, optionally in combination with one or more genes labeled as 4.221 to 4.488 identified in Table 4.


200) In another aspect the invention employs one or more genes according to any one of paragraphs 1-199, wherein the gene has the symbol FAM107B, optionally in combination with one or more genes labeled as 4.222 to 4.488 identified in Table 4.


201) in another aspect the invention employs one or more genes according to any one of paragraphs 1-200, wherein the gene has the symbol IGKC, optionally in combination with one or more genes labeled as 4.223 to 4.488 identified in Table 4.


202) In another aspect the invention employs one or more genes according to any one of paragraphs 1-201, wherein the gene has the symbol ITGAM, optionally in combination with one or more genes labeled as 4.224 to 4.488 identified in Table 4.


203) In another aspect the invention employs one or more genes according to any one of paragraphs 1-202, wherein the gene has the symbol CKAP1, optionally in combination with one or more genes labeled as 4.227 to 4.488 identified in Table 4.


204) In another aspect the invention employs one or more genes according to any one of paragraphs 1-203, wherein the gene has the symbol MGC16291, optionally in combination with one or more genes labeled as 4.228 to 4.488 identified in Table 4.


205) In another aspect the invention employs one or more genes according to any one of paragraphs 1-204, wherein the gene has the symbol DDEF2, optionally in combination with one or more genes labeled as 4.229 to 4.488 identified in Table 4.


206) In another aspect the invention employs one or more genes according to any one of paragraphs 1-205, wherein the gene has the symbol TNFAIP2, optionally in combination with one or more genes labeled as 4.230 to 4.488 identified in Table 4.


207) In another aspect the invention employs one or more genes according to any one of paragraphs 1-206, wherein the gene has the symbol CXCL14, optionally in combination with one or more genes labeled as 4.231 to 4.488 identified in Table 4.


208) In another aspect the invention employs one or more genes according to any one of paragraphs 1-207, wherein the gene has the symbol CD209, optionally in combination with one or more genes labeled as 4.232 to 4.488 identified in Table 4.


209) In another aspect the invention employs one or more genes according to any one of paragraphs 1-208, wherein the gene has the symbol COL9A3, optionally in combination with one or more genes labeled as 4.233 to 4.488 identified in Table 4.


210) In another aspect the invention employs one or more genes according to any one of paragraphs 1-209, wherein the gene has the symbol ANKRD22, optionally in combination with one or more genes labeled as 4.234 to 4.488 identified in Table 4.


211) In another aspect the invention employs one or more genes according to any one of paragraphs 1-210, wherein the gene has the symbol NCKAP1L, optionally in combination with one or more genes labeled as 4.235 to 4.488 identified in Table 4.


212) In another aspect the invention employs one or more genes according to any one of paragraphs 1-211, wherein the gene has the symbol CMKOR1, optionally in combination with one or more genes labeled as 4.236 to 4.488 identified in Table 4.


213) In another aspect the invention employs one or more genes according to any one of paragraphs 1-212, wherein the gene has the symbol HLA-DRB5, optionally in combination with one or more genes labeled as 4.237 to 4.488 identified in Table 4.


214) In another aspect the invention employs one or more genes according to any one of paragraphs 1-213, wherein the gene has the symbol LCP1, optionally in combination with one or more genes labeled as 4.239 to 4.488 identified in Table 4.


215) In another aspect the invention employs one or more genes according to any one of paragraphs 1-214, wherein the gene has the symbol CXXC5, optionally in combination with one or more genes labeled as 4.240 to 4.488 identified in Table 4.


216) In another aspect the invention employs one or more genes according to any one of paragraphs 1-215, wherein the gene has the symbol GJA7, optionally in combination with one or more genes labeled as 4.241 to 4.488 identified in Table 4.


217) In another aspect the invention employs one or more genes according to any one of paragraphs 1-216, wherein the gene has the symbol FGD2, optionally in combination with one or more genes labeled as 4.242 to 4.488 identified in Table 4.


218) In another aspect the invention employs one or more genes according to any one of paragraphs 1-217, wherein the gene has the symbol MAN1A1, optionally in combination with one or more genes labeled as 4.243 to 4.488 identified in Table 4.


219) In another aspect the invention employs one or more genes according to any one of paragraphs 1-218, wherein the gene has the symbol C6orf115, optionally in combination with one or more genes labeled as 4.245 to 4.488 identified in Table 4.


220) In another aspect the invention employs one or more genes according to any one of paragraphs 1-219, wherein the gene has the symbol CXCL9, optionally in combination with one or more genes labeled as 4.247 to 4.488 identified in Table 4.


221) In another aspect the invention employs one or more genes according to any one of paragraphs 1-220, wherein the gene has the symbol NPR3, optionally in combination with one or more genes labeled as 4.248 to 4.488 identified in Table 4.


222) In another aspect the invention employs one or more genes according to any one of paragraphs 1-221, wherein the gene has the symbol FYB, optionally in combination with one or more genes labeled as 4.249 to 4.488 identified in Table 4.


223) In another aspect the invention employs one or more genes according to any one of paragraphs 1-222, wherein the gene has the symbol VCAM1, optionally in combination with one or more genes labeled as 4.250 to 4.488 identified in Table 4.


224) In another aspect the invention employs one or more genes according to any one of paragraphs 1-223, wherein the gene has the symbol FLI1, optionally in combination with one or more genes labeled as 4.251 to 4.488 identified in Table 4.


225) In another aspect the invention employs one or more genes according to any one of paragraphs 1-224, wherein the gene has the symbol CXXC5, optionally in combination with one or more genes labeled as 4.252 to 4.488 identified in Table 4.


226) In another aspect the invention employs one or more genes according to any one of paragraphs 1-225, wherein the gene has the symbol TRAM2, optionally in combination with one or more genes labeled as 4.254 to 4.488 identified in Table 4.


227) In another aspect the invention employs one or more genes according to any one of paragraphs 1-226, wherein the gene has the symbol SHC4, optionally in combination with one or more genes labeled as 4.255 to 4.488 identified in Table 4.


228) In another aspect the invention employs one or more genes according to any one of paragraphs 1-227, wherein the gene has the symbol SLC9A9, optionally in combination with one or more genes labeled as 4.256 to 4.488 identified in Table 4.


229) In another aspect the invention employs one or more genes according to any one of paragraphs 1-228, wherein the gene has the symbol PTPRC, optionally in combination with one or more genes labeled as 4.257 to 4.488 identified in Table 4.


230) In another aspect the invention employs one or more genes according to any one of paragraphs 1-229, wherein the gene has the symbol PTGER4, optionally in combination with one or more genes labeled as 4.258 to 4.488 identified in Table 4.


231) In another aspect the invention employs one or more genes according to any one of paragraphs 1-230, wherein the gene has the symbol LILRB1, optionally in combination with one or more genes labeled as 4.259 to 4.488 identified in Table 4.


232) In another aspect the invention employs one or more genes according to any one of paragraphs 1-231, wherein the gene has the symbol PRDM1, optionally in combination with one or more genes labeled as 4.261 to 4.488 identified in Table 4.


233) In another aspect the invention employs one or more genes according to any one of paragraphs 1-232, wherein the gene has the symbol ARHGAP15, optionally in combination with one or more genes labeled as 4.262 to 4.488 identified in Table 4.


234) In another aspect the invention employs one or more genes according to any one of paragraphs 1-233, wherein the gene has the symbol SLC5A3, optionally in combination with one or more genes labeled as 4.263 to 4.488 identified in Table 4.


235) In another aspect the invention employs one or more genes according to any one of paragraphs 1-234, wherein the gene has the symbol DOCK9, optionally in combination with one or more genes labeled as 4.264 to 4.488 identified in Table 4.


236) In another aspect the invention employs one or more genes according to any one of paragraphs 1-235, wherein the gene has the symbol GPSM1, optionally in combination with one or more genes labeled as 4.265 to 4.488 identified in Table 4.


237) In another aspect the invention employs one or more genes according to any one of paragraphs 1-236, wherein the gene has the symbol CCL5, optionally in combination with one or more genes labeled as 4.266 to 4.488 identified in Table 4.


238) In another aspect the invention employs one or more genes according to any one of paragraphs 1-237, wherein the gene has the symbol GLIPR1, optionally in combination with one or more genes labeled as 4.267 to 4.488 identified in Table 4.


239) In another aspect the invention employs one or more genes according to any one of paragraphs 1-238, wherein the gene has the symbol APOL3, optionally in combination with one or more genes labeled as 4.268 to 4.488 identified in Table 4.


240) In another aspect the invention employs one or more genes according to any one of paragraphs 1-239, wherein the gene has the symbol HLA-DMB, optionally in combination with one or more genes labeled as 4.269 to 4.488 identified in Table 4.


241) In another aspect the invention employs one or more genes according to any one of paragraphs 1-240, wherein the gene has the symbol SYNPO2, optionally in combination with one or more genes labeled as 4.270 to 4.488 identified in Table 4.


242) In another aspect the invention employs one or more genes according to any one of paragraphs 1-241, wherein the gene is identifiable by probe set number 221651_x_at, optionally in combination with one or more genes labeled as 4.271 to 4.488 identified in Table 4.


243) In another aspect the invention employs one or more genes according to any one of paragraphs 1-242, wherein the gene is identifiable by probe set number 231929_at, optionally in combination with one or more genes labeled as 4.273 to 4.488 identified in Table 4.


244) In another aspect the invention employs one or more genes according to any one of paragraphs 1-243, wherein the gene has the symbol CASP1, optionally in combination with one or more genes labeled as 4.274 to 4.488 identified in Table 4.


245) In another aspect the invention employs one or more genes according to any one of paragraphs 1-244, wherein the gene has the symbol PRKCQ, optionally in combination with one or more genes labeled as 4.275 to 4.488 identified in Table 4.


246) In another aspect the invention employs one or more genes according to any one of paragraphs 1-245, wherein the gene has the symbol IL1R2, optionally in combination with one or more genes labeled as 4.276 to 4.488 identified in Table 4.


247) In another aspect the invention employs one or more genes according to any one of paragraphs 1-246, wherein the gene has the symbol CARD15, optionally in combination with one or more genes labeled as 4.277 to 4.488 identified in Table 4.


248) In another aspect the invention employs one or more genes according to any one of paragraphs 1-247, wherein the gene has the symbol ARHGDIB, optionally in combination with one or more genes labeled as 4.278 to 4.488 identified in Table 4.


249) In another aspect the invention employs one or more genes according to any one of paragraphs 1-248, wherein the gene has the symbol HLA-DRB4, optionally in combination with one or more genes labeled as 4.279 to 4.488 identified in Table 4.


250) In another aspect the invention employs one or more genes according to any one of paragraphs 1-249, wherein the gene has the symbol SART2, optionally in combination with one or more genes labeled as 4.280 to 4.488 identified in Table 4.


251) In another aspect the invention employs one or more genes according to any one of paragraphs 1-250, wherein the gene has the symbol LSP1, optionally in combination with one or more genes labeled as 4.281 to 4.488 identified in Table 4.


252) In another aspect the invention employs one or more genes according to any one of paragraphs 1-251, wherein the gene has the symbol AMPD3, optionally in combination with one or more genes labeled as 4.282 to 4.488 identified in Table 4.


253) In another aspect the invention employs one or more genes according to any one of paragraphs 1-252, wherein the gene has the symbol SEMA4F, optionally in combination with one or more genes labeled as 4.283 to 4.488 identified in Table 4.


254) In another aspect the invention employs one or more genes according to any one of paragraphs 1-253, wherein the gene has the symbol ISOC1, optionally in combination with one or more genes labeled as 4.285 to 4.488 identified in Table 4.


255) In another aspect the invention employs one or more genes according to any one of paragraphs 1-254, wherein the gene has the symbol HPS3, optionally in combination with one or more genes labeled as 4.288 to 4.488 identified in Table 4.


256) In another aspect the invention employs one or more genes according to any one of paragraphs 1-255, wherein the gene has the symbol HOXB7, optionally in combination with one or more genes labeled as 4.290 to 4.488 identified in Table 4.


257) In another aspect the invention employs one or more genes according to any one of paragraphs 1-256, wherein the gene has the symbol ZNFN1A1, optionally in combination with one or more genes labeled as 4.291 to 4.488 identified in Table 4.


258) In another aspect the invention employs one or more genes according to any one of paragraphs 1-257, wherein the gene has the symbol ARHGAP9, optionally in combination with one or more genes labeled as 4.292 to 4.488 identified in Table 4.


259) In another aspect the invention employs one or more genes according to any one of paragraphs 1-258, wherein the gene has the symbol GATA2, optionally in combination with one or more genes labeled as 4.293 to 4.488 identified in Table 4.


260) In another aspect the invention employs one or more genes according to any one of paragraphs 1-259, wherein the gene has the symbol AP2B1, optionally in combination with one or more genes labeled as 4.294 to 4.488 identified in Table 4.


261) In another aspect the invention employs one or more genes according to any one of paragraphs 1-260, wherein the gene has the symbol CTSC, optionally in combination with one or more genes labeled as 4.295 to 4.488 identified in Table 4.


262) In another aspect the invention employs one or more genes according to any one of paragraphs 1-261, wherein the gene has the symbol PLK2, optionally in combination with one or more genes labeled as 4.296 to 4.488 identified in Table 4.


263) In another aspect the invention employs one or more genes according to any one of paragraphs 1-262, wherein the gene has the symbol CD4, optionally in combination with one or more genes labeled as 4.297 to 4.488 identified in Table 4.


264) In another aspect the invention employs one or more genes according to any one of paragraphs 1-263, wherein the gene has the symbol GGTA1, optionally in combination with one or more genes labeled as 4.298 to 4.488 identified in Table 4.


265) In another aspect the invention employs one or more genes according to any one of paragraphs 1-264, wherein the gene has the symbol GADD45B, optionally in combination with one or more genes labeled as 4.300 to 4.488 identified in Table 4.


266) In another aspect the invention employs one or more genes according to any one of paragraphs 1-265, wherein the gene has the symbol FLJ10847, optionally in combination with one or more genes labeled as 4.301 to 4.488 identified in Table 4.


267) In another aspect the invention employs one or more genes according to any one of paragraphs 1-266, wherein the gene has the symbol KIF21B, optionally in combination with one or more genes labeled as 4.302 to 4.488 identified in Table 4.


268) In another aspect the invention employs one or more genes according to any one of paragraphs 1-267, wherein the gene has the symbol CCND2, optionally in combination with one or more genes labeled as 4.303 to 4.488 identified in Table 4.


269) In another aspect the invention employs one or more genes according to any one of paragraphs 1-268, wherein the gene has the symbol PRG1, optionally in combination with one or more genes labeled as 4.304 to 4.488 identified in Table 4.


270) In another aspect the invention employs one or more genes according to any one of paragraphs 1-269, wherein the gene has the symbol SLC40A1, optionally in combination with one or more genes labeled as 4.307 to 4.488 identified in Table 4.


271) In another aspect the invention employs one or more genes according to any one of paragraphs 1-270, wherein the gene has the symbol CRIP1, optionally in combination with one or more genes labeled as 4.308 to 4.488 identified in Table 4.


272) In another aspect the invention employs one or more genes according to any one of paragraphs 1-271, wherein the gene has the symbol LOC283070, optionally in combination with one or more genes labeled as 4.309 to 4.488 identified in Table 4.


273) In another aspect the invention employs one or more genes according to any one of paragraphs 1-272, wherein the gene has the symbol SIGLEC1, optionally in combination with one or more genes labeled as 4.310 to 4.488 identified in Table 4.


274) In another aspect the invention employs one or more genes according to any one of paragraphs 1-273, wherein the gene has the symbol ZNF11B, optionally in combination with one or more genes labeled as 4.311 to 4.488 identified in Table 4.


275) In another aspect the invention employs one or more genes according to any one of paragraphs 1-274, wherein the gene has the symbol CXCR4, optionally in combination with one or more genes labeled as 4.312 to 4.488 identified in Table 4.


276) In another aspect the invention employs one or more genes according to any one of paragraphs 1-275, wherein the gene has the symbol HLA-DMA, optionally in combination with one or more genes labeled as 4.313 to 4.488 identified in Table 4


277) In another aspect the invention employs one or more genes according to any one of paragraphs 1-276, wherein the gene has the symbol MRC1, optionally in combination with one or more genes labeled as 4.315 to 4.488 identified in Table 4.


278) In another aspect the invention employs one or more genes according to any one of paragraphs 1-277, wherein the gene has the symbol LMO2, optionally in combination with one or more genes labeled as 4.315a to 4.488 identified in Table 4.


279) In another aspect the invention employs one or more genes according to any one of paragraphs 1-278, wherein the gene has the symbol DENND2D, optionally in combination with one or more genes labeled as 4.316 to 4.488 identified in Table 4.


280) In another aspect the invention employs one or more genes according to any one of paragraphs 1-279, wherein the gene has the symbol CCL18, optionally in combination with one or more genes labeled as 4.317 to 4.488 identified in Table 4.


281) In another aspect the invention employs one or more genes according to any one of paragraphs 1-280, wherein the gene has the symbol P2RY13, optionally in combination with one or more genes labeled as 4.319 to 4.488 identified in Table 4.


282) In another aspect the invention employs one or more genes according to any one of paragraphs 1-281, wherein the gene has the symbol ANGPTL1, optionally in combination with one or more genes labeled as 4.320 to 4.488 identified in Table 4.


283) In another aspect the invention employs one or more genes according to any one of paragraphs 1-282, wherein the gene is identifiable by probe set number 230391_at, optionally in combination with one or more genes labeled as 4.322 to 4.488 identified in Table 4.


284) In another aspect the invention employs one or more genes according to any one of paragraphs 1-283, wherein the gene has the symbol C8orf51, optionally in combination with one or more genes labeled as 4.323 to 4.488 identified in Table 4.


285) In another aspect the invention employs one or more genes according to any one of paragraphs 1-284, wherein the gene has the symbol GIMAP8, optionally in combination with one or more genes labeled as 4.324 to 4.488 identified in Table 4.


286) In another aspect the invention employs one or more genes according to any one of paragraphs 1-285, wherein the gene is identifiable by probe set number 2277880_at, optionally in combination with one or more genes labeled as 4.325 to 4.488 identified in Table 4.


287) In another aspect the invention employs one or more genes according to any one of paragraphs 1-286, wherein the gene has the symbol JAK2, optionally in combination with one or more genes labeled as 4.326 to 4.488 identified in Table 4.


288) In another aspect the invention employs one or more genes according to any one of paragraphs 1-287, wherein the gene has the symbol TNFSF10, optionally in combination with one or more genes labeled as 4.327 to 4.488 identified in Table 4.


289) In another aspect the invention employs one or more genes according to any one of paragraphs 1-288, wherein the gene has the symbol C1R, optionally in combination with one or more genes labeled as 4.328 to 4.488 identified in Table 4.


290) In another aspect the invention employs one or more genes according to any one of paragraphs 1-289, wherein the gene has the symbol ACPL2, optionally in combination with one or more genes labeled as 4.329 to 4.488 identified in Table 4.


291) In another aspect the invention employs one or more genes according to any one of paragraphs 1-290, wherein the gene has the symbol TNFRSF19, optionally in combination with one or more genes labeled as 4.331 to 4.488 identified in Table 4.


292) In another aspect the invention employs one or more genes according to any one of paragraphs 1-291, wherein the gene has the symbol LRP12, optionally in combination with one or more genes labeled as 4.332 to 4.488 identified in Table 4.


293) In another aspect the invention employs one or more genes according to any one of paragraphs 1-292, wherein the gene is identifiable by probe set number 1557116_at, optionally in combination with one or more genes labeled as 4.334 to 4.488 identified in Table 4.


294) In another aspect the invention employs one or more genes according to any one of paragraphs 1-293, wherein the gene has the symbol PRKCB1, optionally in combination with one or more genes labeled as 4.335 to 4.488 identified in Table 4.


295) In another aspect the invention employs one or more genes according to any one of paragraphs 1-294, wherein the gene has the symbol IPO11, optionally in combination with one or more genes labeled as 4.336 to 4.488 identified in Table 4.


296) In another aspect the invention employs one or more genes according to any one of paragraphs 1-295, wherein the gene has the symbol DLGAP1, optionally in combination with one or more genes labeled as 4.337 to 4.488 identified in Table 4.


297) In another aspect the invention employs one or more genes according to any one of paragraphs 1-296, wherein the gene has the symbol PRKAR2B, optionally in combination with one or more genes labeled as 4.338 to 4.488 identified in Table 4.


298) In another aspect the invention employs one or more genes according to any one of paragraphs 1-297, wherein the gene has the symbol MAP3K8, optionally in combination with one or more genes labeled as 4.339 to 4.488 identified in Table 4.


299) In another aspect the invention employs one or more genes according to any one of paragraphs 1-298, wherein the gene has the symbol EVI2B, optionally in combination with one or more genes labeled as 4.340 to 4.488 identified in Table 4.


300) In another aspect the invention employs one or more genes according to any one of paragraphs 1-299, wherein the gene has the symbol GBP1, optionally in combination with one or more genes labeled as 4.341 to 4.488 identified in Table 4.


301) In another aspect the invention employs one or more genes according to any one of paragraphs 1-300, wherein the gene has the symbol CXCL10, optionally in combination with one or more genes labeled as 4.342 to 4.488 identified in Table 4.


302) In another aspect the invention employs one or more genes according to any one of paragraphs 1-301, wherein the gene has the symbol CAMK2N1, optionally in combination with one or more genes labeled as 4.343 to 4.488 identified in Table 4


303) In another aspect the invention employs one or more genes according to any one of paragraphs 1-302, wherein the gene has the symbol MED12L, optionally in combination with one or more genes labeled as 4.344 to 4.488 identified in Table 4.


304) In another aspect the invention employs one or more genes according to any one of paragraphs 1-303, wherein the gene has the symbol ID2, optionally in combination with one or more genes labeled as 4.345 to 4.488 identified in Table 4.


305) In another aspect the invention employs one or more genes according to any one of paragraphs 1-304, wherein the gene has the symbol CTBP2, optionally in combination with one or more genes labeled as 4.346 to 4.488 identified in Table 4.


306) In another aspect the invention employs one or more genes according to any one of paragraphs 1-305, wherein the gene has the symbol IGLJ3, optionally in combination with one or more genes labeled as 4.347 to 4.488 identified in Table 4.


307) In another aspect the invention employs one or more genes according to any one of paragraphs 1-306, wherein the gene has the symbol GBP4, optionally in combination with one or more genes labeled as 4.348 to 4.488 identified in Table 4.


308) In another aspect the invention employs one or more genes according to any one of paragraphs 1-307, wherein the gene has the symbol LOC439949, optionally in combination with one or more genes labeled as 4.349 to 4.488 identified in Table 4.


309) In another aspect the invention employs one or more genes according to any one of paragraphs 1-308, wherein the gene has the symbol FBXO16, optionally in combination with one or more genes labeled as 4.350 to 4.488 identified in Table 4.


310) In another aspect the invention employs one or more genes according to any one of paragraphs 1-309, wherein the gene has the symbol PRF1, optionally in combination with one or more genes labeled as 4.351 to 4.488 identified in Table 4.


311) In another aspect the invention employs one or more genes according to any one of paragraphs 1-310, wherein the gene has the symbol TRAM2, optionally in combination with one or more genes labeled as 4.352 to 4.488 identified in Table 4.


312) In another aspect the invention employs one or more genes according to any one of paragraphs 1-311, wherein the gene has the symbol LYN, optionally in combination with one or more genes labeled as 4.353 to 4.488 identified in Table 4.


313) In another aspect the invention employs one or more genes according to any one of paragraphs 1-312, wherein the gene has the symbol CENTD1, optionally in combination with one or more genes labeled as 4.355 to 4.488 identified in Table 4.


314) In another aspect the invention employs one or more genes according to any one of paragraphs 1-313, wherein the gene has the symbol FLJ20273, optionally in combination with one or more genes labeled as 4.356 to 4.488 identified in Table 4.


315) In another aspect the invention employs one or more genes according to any one of paragraphs 1-314, wherein the gene has the symbol TFEC, optionally in combination with one or more genes labeled as 4.357 to 4.488 identified in Table 4.


316) In another aspect the invention employs one or more genes according to any one of paragraphs 1-315, wherein the gene has the symbol PPP1R16B, optionally in combination with one or more genes labeled as 4.358 to 4.488 identified in Table 4.


317) In another aspect the invention employs one or more genes according to any one of paragraphs 1-316, wherein the gene has the symbol CD48, optionally in combination with one or more genes labeled as 4.359 to 4.488 identified in Table 4.


318) In another aspect the invention employs one or more genes according to any one of paragraphs 1-317, wherein the gene has the symbol HLA-DPB1, optionally in combination with one or more genes labeled as 4.361 to 4.488 identified in Table 4.


319) In another aspect the invention employs one or more genes according to any one of paragraphs 1-318, wherein the gene has the symbol GTPBP5, optionally in combination with one or more genes labeled as 4.362 to 4.488 identified in Table 4.


320) In another aspect the invention employs one or more genes according to any one of paragraphs 1-319, wherein the gene has the symbol GBP5, optionally in combination with one or more genes labeled as 4.363 to 4.488 identified in Table 4.


321) In another aspect the invention employs one or more genes according to any one of paragraphs 1-320, wherein the gene has the symbol MAP B, optionally in combination with one or more genes labeled as 4.364 to 4.488 identified in Table 4.


322) In another aspect the invention employs one or more genes according to any one of paragraphs 1-321, wherein the gene has the symbol EXTL3, optionally in combination with one or more genes labeled as 4.365 to 4.488 identified in Table 4.


323) In another aspect the invention employs one or more genes according to any one of paragraphs 1-322, wherein the gene has the symbol CORO1A, optionally in combination with one or more genes labeled as 4.366 to 4.488 identified in Table 4.


324) In another aspect the invention employs one or more genes according to any one of paragraphs 1-323, wherein the gene has the symbol PDGFRL, optionally in combination with one or more genes labeled as 4.367 to 4.488 identified in Table 4.


325) In another aspect the invention employs one or more genes according to any one of paragraphs 1-324, wherein the gene has the symbol RP9, optionally in combination with one or more genes labeled as 4.368 to 4.488 identified in Table 4.


326) In another aspect the invention employs one or more genes according to any one of paragraphs 1-325, wherein the gene has the symbol RHOU, optionally in combination with one or more genes labeled as 4.369 to 4.488 identified in Table 4.


327) In another aspect the invention employs one or more genes according to any one of paragraphs 1-326, wherein the gene has the symbol MTAC2D1, optionally in combination with one or more genes labeled as 4.370 to 4.488 identified in Table 4.


328) In another aspect the invention employs one or more genes according to any one of paragraphs 1-327, wherein the gene has the symbol CCL8, optionally in combination with one or more genes labeled as 4.371 to 4.488 identified in Table 4.


329) In another aspect the invention employs one or more genes according to any one of paragraphs 1-328, wherein the gene has the symbol CECR1, optionally in combination with one or more genes labeled as 4.373 to 4.488 identified in Table 4.


330) In another aspect the invention employs one or more genes according to any one of paragraphs 1-329, wherein the gene has the symbol SLC40A1, optionally in combination with one or more genes labeled as 4.374 to 4.488 identified in Table 4.


331) In another aspect the invention employs one or more genes according to any one of paragraphs 1-330, wherein the gene has the symbol ADCY6, optionally in combination with one or more genes labeled as 4.375 to 4.488 identified in Table 4.


332) In another aspect the invention employs one or more genes according to any one of paragraphs 1-331, wherein the gene has the symbol CP, optionally in combination with one or more genes labeled as 4.376 to 4.488 identified in Table 4.


333) In another aspect the invention employs one or more genes according to any one of paragraphs 1-332, wherein the gene has the symbol EDG1, optionally in combination with one or more genes labeled as 4.377 to 4.488 identified in Table 4.


334) In another aspect the invention employs one or more genes according to any one of paragraphs 1-333, wherein the gene has the symbol RGS3, optionally in combination with one or more genes labeled as 4.379 to 4.488 identified in Table 4.


335) In another aspect the invention employs one or more genes according to any one of paragraphs 1-334, wherein the gene is identifiable by probe set number 228339_at, optionally in combination with one or more genes labeled as 4.380 to 4.488 identified in Table 4.


336) In another aspect the invention employs one or more genes according to any one of paragraphs 1-335, wherein the gene has the symbol ABHD5, optionally in combination with one or more genes labeled as 4.381 to 4.488 identified in Table 4.


337) In another aspect the invention employs one or more genes according to any one of paragraphs 1-336, wherein the gene has the symbol MS4A7, optionally in combination with one or more genes labeled as 4.382 to 4.488 identified in Table 4.


338) In another aspect the invention employs one or more genes according to any one of paragraphs 1-337, wherein the gene has the symbol PRKCH, optionally in combination with one or more genes labeled as 4.384 to 4.488 identified in Table 4.


339) In another aspect the invention employs one or more genes according to any one of paragraphs 1-338, wherein the gene has the symbol LOC286071, optionally in combination with one or more genes labeled as 4.385 to 4.488 identified in Table 4.


340) In another aspect the invention employs one or more genes according to any one of paragraphs 1-339, wherein the gene has the symbol BLNK, optionally in combination with one or more genes labeled as 4.386 to 4.488 identified in Table 4.


341) In another aspect the invention employs one or more genes according to any one of paragraphs 1-340, wherein the gene is identifiable by the probe set number 242546 at, optionally in combination with one or more genes labeled as 4.387 to 4.488 identified in Table 4.


342) In another aspect the invention employs one or more genes according to any one of paragraphs 1-341, wherein the gene has the symbol PCDHGC3, optionally in combination with one or more genes labeled as 4.390 to 4.488 identified in Table 4.


343) In another aspect the invention employs one or more genes according to any one of paragraphs 1-342, wherein the gene has the symbol CAMSAP1L1, optionally in combination with one or more genes labeled as 4.391 to 4.488 identified in Table 4.


344) In another aspect the invention employs one or more genes according to any one of paragraphs 1-343, wherein the gene has the symbol NPY1R, optionally in combination with one or more genes labeled as 4.392 to 4.488 identified in Table 4.


345) In another aspect the invention employs one or more genes according to any one of paragraphs 1-344, wherein the gene has the symbol CD274, optionally in combination with one or more genes labeled as 4.393 to 4.488 identified in Table 4.


346) In another aspect the invention employs one or more genes according to any one of paragraphs 1-345, wherein the gene has the symbol PGM5, optionally in combination with one or more genes labeled as 4.394 to 4.488 identified in Table 4.


347) In another aspect the invention employs one or more genes according to any one of paragraphs 1-346, wherein the gene has the symbol PLCG2, optionally in combination with one or more genes labeled as 4.395 to 4.488 identified in Table 4.


348) In another aspect the invention employs one or more genes according to any one of paragraphs 1-347, wherein the gene has the symbol TNFSF10, optionally in combination with one or more genes labeled as 4.397 to 4.488 identified in Table 4.


349) In another aspect the invention employs one or more genes according to any one of paragraphs 1-348, wherein the gene has the symbol BTG2, optionally in combination with one or more genes labeled as 4.398 to 4.488 identified in Table 4.


350) In another aspect the invention employs one or more genes according to any one of paragraphs 1-349, wherein the gene has the symbol LAMP3, optionally in combination with one or more genes labeled as 4.399 to 4.488 identified in Table 4.


351) In another aspect the invention employs one or more genes according to any one of paragraphs 1-350, wherein the gene has the symbol IGLC1, optionally in combination with one or more genes labeled as 4.400 to 4.488 identified in Table 4.


352) In another aspect the invention employs one or more genes according to any one of paragraphs 1-351, wherein the gene has the symbol SIPA1L1, optionally in combination with one or more genes labeled as 4.401 to 4.488 identified in Table 4.


353) In another aspect the invention employs one or more genes according to any one of paragraphs 1-352 wherein the gene has the symbol AIF1, optionally in combination with one or more genes labeled as 4.402 to 4.488 identified in Table 4.


354) In another aspect the invention employs one or more genes according to any one of paragraphs 1-353, wherein the gene has the symbol IGLC2, optionally in combination with one or more genes labeled as 4.403 to 4.488 identified in Table 4.


355) In another aspect the invention employs one or more genes according to any one of paragraphs 1-354, wherein the gene has the symbol B2M, optionally in combination with one or more genes labeled as 4.404 to 4.488 identified in Table 4.


356) In another aspect the invention employs one or more genes according to any one of paragraphs 1-355, wherein the gene has the symbol CLEC7A, optionally in combination with one or more genes labeled as 4.405 to 4.488 identified in Table 4.


357) In another aspect the invention employs one or more genes according to any one of paragraphs 1-356, wherein the gene has the symbol MGC17330, optionally in combination with one or more genes labeled as 4.406 to 4.488 identified in Table 4.


358) In another aspect the invention employs one or more genes according to any one of paragraphs 1-357, wherein the gene has the symbol IGF1R, optionally in combination with one or more genes labeled as 4.407 to 4.488 identified in Table 4.


359) In another aspect the invention employs one or more genes according to any one of paragraphs 1-358, wherein the gene has the symbol HIVEP1, optionally in combination with one or more genes labeled as 4.408 to 4.488 identified in Table 4.


360) In another aspect the invention employs one or more genes according to any one of paragraphs 1-359, wherein the gene has the symbol FKBP14, optionally in combination with one or more genes labeled as 4.409 to 4.488 identified in Table 4.


361) In another aspect the invention employs one or more genes according to any one of paragraphs 1-360, wherein the gene has the symbol LAPTM5, optionally in combination with one or more genes labeled as 4.410 to 4.488 identified in Table 4.


362) In another aspect the invention employs one or more genes according to any one of paragraphs 1-361, wherein the gene has the symbol AB13BP, optionally in combination with one or more genes labeled as 4.411 to 4.488 identified in Table 4.


363) In another aspect the invention employs one or more genes according to any one of paragraphs 1-362, wherein the gene has the symbol HLA-E, optionally in combination with one or more genes labeled as 4.412 to 4.488 identified in Table 4.


364) In another aspect the invention employs one or more genes according to any one of paragraphs 1-363, wherein the gene has the symbol ARLAC, optionally in combination with one or more genes labeled as 4.413 to 4.488 identified in Table 4.


365) In another aspect the invention employs one or more genes according to any one of paragraphs 1-364, wherein the gene has the symbol ASS, optionally in combination with one or more genes labeled as 4.415 to 4.488 identified in Table 4.


366) In another aspect the invention employs one or more genes according to any one of paragraphs 1-365, wherein the gene has the symbol ITGB3, optionally in combination with one or more genes labeled as 4.417 to 4.488 identified in Table 4.


367) In another aspect the invention employs one or more genes according to any one of paragraphs 1-366, wherein the gene has the symbol SYK, optionally in combination with one or more genes labeled as 4.417 to 4.488 identified in Table 4.


368) In another aspect the invention employs one or more genes according to any one of paragraphs 1-366, wherein the gene has the symbol RAC2, optionally in combination with one or more genes labeled as 4.418 to 4.488 identified in Table 4.


369) In another aspect the invention employs one or more genes according to any one of paragraphs 1-368, wherein the gene is identifiable by probe set number 1557222_at, optionally in combination with one or more genes labeled as 4.419 to 4.488 identified in Table 4.


370) In another aspect the invention employs one or more genes according to any one of paragraphs 1-369, wherein the gene has the symbol CD3G, optionally in combination with one or more genes labeled as 4.420 to 4.488 identified in Table 4.


371) In another aspect the invention employs one or more genes according to any one of paragraphs 1-370, wherein the gene has the symbol IGF1, optionally in combination with one or more genes labeled as 4.421 to 4.488 identified in Table 4.


372) In another aspect the invention employs one or more genes according to any one of paragraphs 1-371, wherein the gene is identifiable by probe set number 228858_at, optionally in combination with one or more genes labeled as 4.422 to 4.488 identified in Table 4.


373) In another aspect the invention employs one or more genes according to any one of paragraphs 1-372, wherein the gene is has the symbol CYB5A, optionally in combination with one or more genes labeled as 4.423 to 4.488 identified in Table 4.


374) In another aspect the invention employs one or more genes according to any one of paragraphs 1-373, wherein the gene is has the symbol TTC25, optionally in combination with one or more genes labeled as 4.424 to 4.488 identified in Table 4.


375) In another aspect the invention employs one or more genes according to any one of paragraphs 1-374, wherein the gene is has the symbol SLAMF6, optionally in combination with one or more genes labeled as 4.425 to 4.488 identified in Table 4.


376) In another aspect the invention employs one or more genes according to any one of paragraphs 1-375, wherein the gene is has the symbol ARHGAP21, optionally in combination with one or more genes labeled as 4.426 to 4.488 identified in Table 4.


377) In another aspect the invention employs one or more genes according to any one of paragraphs 1-376, wherein the gene is has the symbol FLOT1, optionally in combination with one or more genes labeled as 4.428 to 4.488 identified in Table 4.


378) In another aspect the invention employs one or more genes according to any one of paragraphs 1-377, wherein the gene is has the symbol IBRDC2 optionally in combination with one or more genes labeled as 4.429 to 4.488 identified in Table 4.


379) In another aspect the invention employs one or more genes according to any one of paragraphs 1-378, wherein the gene is has the symbol KIAA1794, optionally in combination with one or more genes labeled as 4.430 to 4.488 identified in Table 4.


380) In another aspect the invention employs one or more genes according to any one of paragraphs 1-379, wherein the gene is has the symbol OLFML1, optionally in combination with one or more genes labeled as 4.431 to 4.488 identified in Table 4.


381) In another aspect the invention employs one or more genes according to any one of paragraphs 1-380, wherein the gene is has the symbol GMFG, optionally in combination with one or more genes labeled as 4.432 to 4.488 identified in Table 4.


382) In another aspect the invention employs one or more genes according to any one of paragraphs 1-381, wherein the gene is has the symbol TNFRSF1B, optionally in combination with one or more genes labeled as 4.433 to 4.488 identified in Table 4.


383) In another aspect the invention employs one or more genes according to any one of paragraphs 1-382, wherein the gene is identifiable by probe set number 217629_at, optionally in combination with one or more genes labeled as 4.434 to 4.488 identified in Table 4.


384) In another aspect the invention employs one or more genes according to any one of paragraphs 1-383, wherein the gene is has the symbol DEF6, optionally in combination with one or more genes labeled as 4.436 to 4.488 identified in Table 4.


385) In another aspect the invention employs one or more genes according to any one of paragraphs 1-384, wherein the gene is has the symbol MAP4K4, optionally in combination with one or more genes labeled as 4.437 to 4.488 identified in Table 4.


386) In another aspect the invention employs one or more genes according to any one of paragraphs 1-385, wherein the gene is has the symbol CMKOR1, optionally in combination with one or more genes labeled as 4.438 to 4.488 identified in Table 4.


387) In another aspect the invention employs one or more genes according to any one of paragraphs 1-386, wherein the gene is identifiable by probe set number 1563461_at, optionally in combination with one or more genes labeled as 4.439 to 4.488 identified in Table 4.


388) In another aspect the invention employs one or more genes according to any one of paragraphs 1-387, wherein the gene is has the symbol CHKA, optionally in combination with one or more genes labeled as 4.440 to 4.488 identified in Table 4.


389) In another aspect the invention employs one or more genes according to any one of paragraphs 1-388, wherein the gene is identifiable by probe set number 226865_at, optionally in combination with one or more genes labeled as 4.441 to 4.488 identified in Table 4.


390) In another aspect the invention employs one or more genes according to any one of paragraphs 1-389, wherein the gene has the symbol HS3ST3B1, optionally in combination with one or more genes labeled as 4.442 to 4.488 identified in Table 4.


391) In another aspect the invention employs one or more genes according to any one of paragraphs 1-390, wherein the gene has the symbol CXorf9, optionally in combination with one or more genes labeled as 4.443 to 4.488 identified in Table 4.


392) In another aspect the invention employs one or more genes according to any one of paragraphs 1-391, wherein the gene has the symbol EVI2A, optionally in combination with one or more genes labeled as 4.445 to 4.488 identified in Table 4.


393) In another aspect the invention employs one or more genes according to any one of paragraphs 1-392, wherein the gene has the symbol NFAM1, optionally in combination with one or more genes labeled as 4.446 to 4.488 identified in Table 4.


394) In another aspect the invention employs one or more genes according to any one of paragraphs 1-393, wherein the gene is identifiable by probe set number 242874_at, optionally in combination with one or more genes labeled as 4.447 to 4.488 identified in Table 4.


395) In another aspect the invention employs one or more genes according to any one of paragraphs 1-394, wherein the gene has the symbol ATP5J, optionally in combination with one or more genes labeled as 4.450 to 4.488 identified in Table 4.


396) In another aspect the invention employs one or more genes according to any one of paragraphs 1-395, wherein the gene has the symbol CYLD, optionally in combination with one or more genes labeled as 4.451 to 4.488 identified in Table 4.


397) In another aspect the invention employs one or more genes according to any one of paragraphs 1-396, wherein the gene has the symbol GIMAP6, optionally in combination with one or more genes labeled as 4.452 to 4.488 identified in Table 4.


398) In another aspect the invention employs one or more genes according to any one of paragraphs 1-397, wherein the gene has the symbol MFAP4, optionally in combination with one or more genes labeled as 4.453 to 4.488 identified in Table 4.


399) In another aspect the invention employs one or more genes according to any one of paragraphs 1-398, wherein the gene has the symbol TUBB2B, optionally in combination with one or more genes labeled as 4.454 to 4.488 identified in Table 4.


400) In another aspect the invention employs one or more genes according to any one of paragraphs 1-399, wherein the gene has the symbol NELL2, optionally in combination with one or more genes labeled as 4.455 to 4.488 identified in Table 4.


401) In another aspect the invention employs one or more genes according to any one of paragraphs 1-400, wherein the gene is identifiable by probe set number 236583_at, optionally in combination with one or more genes labeled as 4.456 to 4.488 identified in Table 4.


402) In another aspect the invention employs one or more genes according to any one of paragraphs 1-401, wherein the gene has the symbol IL1RN, optionally in combination with one or more genes labeled as 4.457 to 4.488 identified in Table 4.


403) In another aspect the invention employs one or more genes according to any one of paragraphs 1-402, wherein the gene has the symbol KIAA1211, optionally in combination with one or more genes labeled as 4.459 to 4.488 identified in Table 4.


404) In another aspect the invention employs one or more genes according to any one of paragraphs 1-403, wherein the gene has the symbol ADAMDEC1, optionally in combination with one or more genes labeled as 4.460 to 4.488 identified in Table 4.


405) In another aspect the invention employs one or more genes according to any one of paragraphs 1-404, wherein the gene has the symbol AOC3, optionally in combination with one or more genes labeled as 4.461 to 4.488 identified in Table 4.


406) In another aspect the invention employs one or more genes according to any one of paragraphs 1-405, wherein the gene has the symbol SAMHD1, optionally in combination with one or more genes labeled as 4.463 to 4.488 identified in Table 4.


407) In another aspect the invention employs one or more genes according to any one of paragraphs 1-406, wherein the gene has the symbol SLC22A3, optionally in combination with one or more genes labeled as 4.465 to 4.488 identified in Table 4.


408) In another aspect the invention employs one or more genes according to any one of paragraphs 1-407, wherein the gene has the symbol IGLV3-25, optionally in combination with one or more genes labeled as 4.466 to 4.488 identified in Table 4.


409) In another aspect the invention employs one or more genes according to any one of paragraphs 1-408, wherein the gene is identifiable by probe set number 1556185_a_at, optionally in combination with one or more genes labeled as 4.467 to 4.488 identified in Table 4.


410) In another aspect the invention employs one or more genes according to any one of paragraphs 1-409, wherein the gene has the symbol RAB11FIP1, optionally in combination with one or more genes labeled as 4.468- to 4.488 identified in Table 4.


411) In another aspect the invention employs one or more genes according to any one of paragraphs 1-410, wherein the gene has the symbol PER2, optionally in combination with one or more genes labeled as 4.469 to 4.488 identified in Table 4.


412) In another aspect the invention employs one or more genes according to any one of paragraphs 1-411, wherein the gene has the symbol TTL, optionally in combination with one or more genes labeled as 4.470 to 4.488 identified in Table 4.


413) In another aspect the invention employs one or more genes according to any one of paragraphs 1-412, wherein the gene has the symbol SIAHBP1, optionally in combination with one or more genes labeled as 4.472 to 4.488 identified in Table 4.


414) In another aspect the invention employs one or more genes according to any one of paragraphs 1-413, wherein the gene has the symbol FLJ22536, optionally in combination with one or more genes labeled as 4.473 to 4.488 identified in Table 4.


415) In another aspect the invention employs one or more genes according to any one of paragraphs 1-414, wherein the gene has the symbol RP6-213H19.1, optionally in combination with one or more genes labeled as 4.474 to 4.488 identified in Table 4.


416) In another aspect the invention employs one or more genes according to any one of paragraphs 1-415, wherein the gene is identifiable by probe set number 235804_at, optionally in combination with one or more genes labeled as 4.475 to 4.488 identified in Table 4.


417) In another aspect the invention employs one or more genes according to any one of paragraphs 1-416, wherein the gene has the symbol NCF4, optionally in combination with one or more genes labeled as 4.476 to 4.488 identified in Table 4.


418) In another aspect the invention employs one or more genes according to any one of paragraphs 1-417, wherein the gene has the symbol EPSTI1, optionally in combination with one or more genes labeled as 4.477 to 4.488 identified in Table 4.


419) In another aspect the invention employs one or more genes according to any one of paragraphs 1-418, wherein the gene has the symbol LOC441212, optionally in combination with one or more genes labeled as 4.478 to 4.488 identified in Table 4.


420) In another aspect the invention employs one or more genes according to any one of paragraphs 1-419, wherein the gene has the symbol ANK3, optionally in combination with one or more genes labeled as 4.479 to 4.488 identified in Table 4.


421) In another aspect the invention employs one or more genes according to any one of paragraphs 1-420, wherein the gene has the symbol PCDH9, optionally in combination with one or more genes labeled as 4.480 to 4.488 identified in Table 4.


422) In another aspect the invention employs one or more genes according to any one of paragraphs 1-421, wherein the gene has the symbol C21orf86, optionally in combination with one or more genes labeled as 4.481 to 4.488 identified in Table 4.


423) In another aspect the invention employs one or more genes according to any one of paragraphs 1-422, wherein the gene has the symbol DHRS9, optionally in combination with one or more genes labeled as 4.482 to 4.488 identified in Table 4.


424) In another aspect the invention employs one or more genes according to any one of paragraphs 1-423, wherein the gene has the symbol ARHGAP25, optionally in combination with one or more genes labeled as 4.483 to 4.488 identified in Table 4.


425) In another aspect the invention employs one or more genes according to any one of paragraphs 1-424, wherein the gene has the symbol TRAF4, optionally in combination with one or more genes labeled as 4.484 to 4.488 identified in Table 4.


426) In another aspect the invention employs one or more genes according to any one of paragraphs 1-425, wherein the gene has the symbol LST1, optionally in combination with one or more genes labeled as 4.485 to 4.488 identified in Table 4.


427) In another aspect the invention employs one or more genes according to any one of paragraphs 1-426, wherein the gene has the symbol PALMD, optionally in combination with one or more genes labeled as 4.486 to 4.488 identified in Table 4.


428) In another aspect the invention employs one or more genes according to any one of paragraphs 1-427, wherein the gene has the symbol TAP1, optionally in combination with one or more genes labeled as 4.487 to 4.488 identified in Table 4.


429) In another aspect the invention employs one or more genes according to any one of paragraphs 1-428, wherein the gene has the symbol MSX2, optionally in combination with one or more genes labeled as 4.448 identified in Table 4.


430) In another aspect the invention employs one or more genes according to any one of paragraphs 1-429, wherein the gene has the symbol SIRPG.


In one aspect the invention employs a gene listed in Table 7.









TABLE 7





Gene Symbol

















CCL5



FASLG



GNLY



GZMB



PRF1



IFNG



ICOS



TBX21



CD8A



CD3E



CXCL11



CXCL10



CXCR3



CD20



FOXP3



INDO



CD45Ro



CD45R



CD69



TRBV19



TRAT1



TRDV2



STAT4



PRKCQ



GMZK



GPR171



UBD



CD52



CD3D



IL7R



IRF1



TLR7










In one aspect the invention employs one or more genes selected from Table 9.









TABLE 9





Gene Symbol

















PRF1



IRF1



GZMB



GNLY



CD8A



PRKCQ



FOXP3



IFNG



CCL5



GPR171



TRBV19



CD3E



TBX21



FASLG



CXCL10



ICOS



CXCR3



CXCL11










In one aspect the invention employs one or more genes selected from Table 11.










TABLE 11





Gene Symbol
Gene Title







CCL5
chemokine (C-C motif) ligand 5


UCHL1
Ubiquitin carboxyl-terminal esterase L1 (ubiquitin thiolesterase)


PVT1 /// LOC441378
Pvt1 oncogene homolog, MYC activator (mouse) /// LOC441378



CDNA clone IMAGE: 4796388


CD52
CD52 antigen (CAMPATH-1 antigen) /// CD52 antigen (CAMPATH-1



antigen)


UBD
ubiquitin D


STAT4
signal transducer and activator of transcription 4


GZMK
granzyme K (granzyme 3; tryptase II) /// granzyme K (granzyme 3; tryptase



II)


IL18RAP
interleukin 18 receptor accessory protein


GPR171
G protein-coupled receptor 171


PSCDBP
pleckstrin homology, Sec7 and coiled-coil domains, binding protein ///



pleckstrin homology, Sec7 and coiled-coil domains, binding protein


NCF2
neutrophil cytosolic factor 2 (65 kDa, chronic granulomatous disease,



autosomal 2)


PRKCQ
protein kinase C, theta


LST1
leukocyte specific transcript 1


TRA@ /// TRDV2 ///
T cell receptor alpha locus /// T cell receptor delta variable 2 /// T cell receptor


TRAV20 /// TRAJ17
alpha variable 20 /// T cell receptor alpha joining 17 /// T cell receptor alpha


/// TRAC
constant


TRGC2
T cell receptor gamma constant 2


TRBV21-1 ///
T cell receptor beta variable 21-1 /// T cell receptor beta variable 19 /// T cell


TRBV19 /// TRBV5-4
receptor beta variable 5-4 /// T cell receptor beta variable 3-1 /// T cell receptor


/// TRBV3-1 ///
beta constant 1


TRBC1


HLA-DQA1 /// HLA-
major histocompatibility complex, class II, DQ alpha 1 /// major


DQA2
histocompatibility complex, class II, DQ alpha 2


TRBV19 /// TRBC1
T cell receptor beta variable 19 /// T cell receptor beta variable 19 /// T cell



receptor beta constant 1 /// T cell receptor beta constant 1


CD3D
CD3D antigen, delta polypeptide (TiT3 complex)


GADD45B
Growth arrest and DNA-damage-inducible, beta


ITGB3
integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)


TRAT1
T cell receptor associated transmembrane adaptor 1


HLA-DMA
major histocompatibility complex, class II, DM alpha


CENTD3
centaurin, delta 3


SAMSN1
SAM domain, SH3 domain and nuclear localisation signals, 1


CLEC4E
C-type lectin domain family 4, member E


TNFRSF19
tumor necrosis factor receptor superfamily, member 19


NAV1
neuron navigator 1


LOXL4
lysyl oxidase-like 4


TNFRSF19
tumor necrosis factor receptor superfamily, member 19


TAGAP
T-cell activation GTPase activating protein


GIMAP2
GTPase, IMAP family member 2


IGF1R
Insulin-like growth factor 1 receptor


C17orf63
Chromosome 17 open reading frame 63


CD52
CD52 antigen (CAMPATH-1 antigen)









In one aspect the invention employs one or more genes selected from Table 12.










TABLE 12





Gene symbol
Gene title







CCL5
chemokine (C-C motif) ligand 5


TRAT1
T cell receptor associated transmembrane adaptor 1


STAT4
signal transducer and activator of transcription 4


PRKCQ
protein kinase C, theta


GPR171
G protein-coupled receptor 171


UBD
ubiquitin D


CD52
CD52 molecule


CD3D
CD3d molecule, delta (CD3-TCR complex)


PRF1
perforin 1 (pore forming protein)


CD8A
CD8a molecule


CXCL10
chemokine (C—X—C motif) ligand 10


CD69
CD69 molecule


TRBV19
T cell receptor beta variable 19


TRDV2
T cell receptor delta variable 2


IL7R
interleukin 7 receptor


GZMK
granzyme K


CD45R
PROTEIN-TYROSINE PHOSPHATASE, RECEPTOR-



TYPE, C (PTPRC)









In one aspect the invention provides one or more genes selected from Table 13.










TABLE 13





Gene



symbol
Gene title







FASLG
Fas ligand (TNF superfamily, member 6)


GNLY
granulysin


GZMB
granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated



serine esterase 1)


IFNG
interferon, gamma


ICOS
inducible T-cell co-stimulator


TBX21
T-box 21


CD3E
CD3e molecule, epsilon (CD3-TCR complex)


CXCL11
chemokine (C—X—C motif) ligand 11


CXCR3
chemokine (C—X—C motif) receptor 3


CD20
CD20 molecule


FOXP3
forkhead box P3


INDO
indoleamine-pyrrole 2,3 dioxygenase


IRF1
interferon regulatory factor 1


TLR7
toll-like receptor 7









PCR is a more sensitive technique than microarray and therefore can detect lower levels of differentially expressed genes.


In particular the following genes are suitable for PCR analysis: IL7R, CD3D, CD3E, CD52, UBD, GPR171, GMZK, PRKCQ, STAT4, TRDV2, TRAT1, TRBV19, CD69, INDO, CD45R, CD45RO, FOXP3, CD20, CCL5, FASLG, GNLY, GZMB, PRF1, IFNG, ICOS, TBX21, CD8A, CD3E, CXCL10, CXCL11, IRF1, TLR7 and CXCR3.


In one aspect the gene(s) employed are selected from the group comprising or consisting of: CCL5, TRAT1, STAT4, PRKCQ, GPR171, UBD, CD52, CD3D, PRF1, CD8A, CXCL10, CD69, TRBV19, TRDV2, IL7R, GZMK and CD45R.


In one aspect the gene(s) employed are selected from the comprising or consisting of: FASLG, GNLY, GZMB, IFNG, ICOS, TBX21, CD3E, CXCL11, CXCR3, CD20, FOXP3, INDO, IRF1 and TLR7.


The gene(s) FOXP3 and/or PRF1 is/are particularly suitable for PCR analysis according to the invention.


Suitable targets for immunohistochemistry include CD3, CD8, CD86, LAMP, CD20, CD45RO, CXCR3, CXL10/11, CD69, granzyme B, IDO, B cells and gene products from one or more genes from the NK family, HLA family, T cell receptor family and/or activated T cell.


In a further aspect of the invention there is provided a gene signature indicative of a non-responder, for example wherein one or more of immune genes such as those listed herein are NOT differentially expressed and/or are down regulated and/or are NOT upregulated.


In one aspect the gene is NOT FOXP3.


According to a further aspect the present invention provides a gene signature indicative of an increased likelihood of a patients responding favourably to appropriate immunotherapy, which in turn is likely to result in an improved survival of patients, for example with Mage expressing cancers following treatment with Mage specific immunotherapy. This gene signature, of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes from the genes disclosed in Table 1, is characterised by differential expression compared to the gene signature of Mage-expressing tumour patients who do not respond to Mage antigen specific cancer immunotherapy.


In one aspect the invention provides a profile based on differential expression of 1 or more of 62 known genes that relate to immune infiltration and activation.


The predictive genes correspond mainly to expression of and often upregulation of genes related to immune infiltration and activation. These genes include HLA class II, Interleukin-2 receptor gamma, T cell receptor genes (TRBV19, TRAT1, TRGC2), granzyme, and CD69.


In one embodiment there is provided a gene signature, present in patients, for example with or who have had MAGE-expressing tumours, who respond to treatment, in which one or more, for example at least 5, suitably 6, 7, 8, 9, 10 of the genes of Table 2 are differentially expressed:


As shown in FIG. 5a below, characterisation of responders and non-responders may be based on the differential expression on only one or two genes, such as TCR, CD3 and/or IL-7. Other genes that are thought to be particularly suitable in methods employing only one or two genes include: IL7R, CD3D, CD3E, CD52, UBD, GPR171, GMZK, PRKCQ, STAT4, TRDV2, TRAT1, TRBV19, CD69, INDO, CD45R, CD45RO, FOXP3, CD20, CCL5, FASLG, GNLY, GZMB, PRF1, IFNG, ICOS, TBX21, CD8A, CD3E, CXCL10, CXCL11, TRF1, TLR7 and CXCR3, which may require the use of appropriately sensitive analytical techniques.


The invention herein extends to use of all permutations of the genes listed herein for identification of said signature/profile.


The invention also extends to embodiments according to the invention described herein, which comprise, consist essentially of, or consists of the components/elements described.


The invention extends to the functional equivalents of genes listed herein, for example as characterised by hierarchical classification of genes such as described by Hongwei Wu et al 2007 (Hierarchical classification of equivalent genes in prokaryotes-Nucliec Acid Research Advance Access).


Whilst not wishing to be bound by theory, it is thought that is not necessarily the gene per se that is characteristic of the signature but rather it is the gene function which is fundamentally important. Thus a functionally equivalent gene to an immune activation gene such as those listed above, for example in Table 1, 2, 3, 4, 7, 9, 11, 12 or 13 may be employed in the signature, see for example, Journal of the National Cancer Institute Vol 98, No. 7 Apr. 5, 2006.


The genes were identified by specific probes and thus a skilled person will understand that the description of the genes above is a description based on current understanding of what hybridises to the probe. However, regardless of the nomenclature used for the genes by repeating the hybridisation to the relevant probe under the prescribed conditions the requisite gene can be identified.


The invention extends to use of the profile(s) according to the invention for predicting or identifying a patient as a responder or non-responder to immunotherapy, such as cancer immunotherapy, for example cancer testis immunotherapy.


Thus the invention includes a method of analyzing a patient derived sample, based on differential expression of the profile/gene(s) according to the invention for the purpose of characterising the patient from which the sample was derived as a responder or non-responder to immunotherapy. In one aspect the invention provides a method of identifying a profile according to the invention comprising the steps:

    • a) analyzing a patient derived sample for differential expression of one or more immune response genes, and
    • b) characterising the patient from which the sample was derived as a responder or non-responder to appropriate immunotherapy, based on the results of step (a), wherein the characterisation step is optionally performed by reference or comparison to a standard.


Suitable standards are described above.


The present invention therefore, generally relates, in one aspect, to a method for the detection of a gene signature in a biological sample, the method comprising the analysis of the expression of one or more genes of Tables 1, 2, 3, 4, 7, 9, 11, 12 or 13, for example at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 2021, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes (eg for genes set forth in Table 1). In an embodiment, the analysis comprises the expression of at least 5, suitably 6, 7, 8, 9 or 10 genes set forth in Table 2.


In one aspect the invention provides a method for measuring expression levels of polynucleotides from immune activation genes such as one or more genes listed in Tables 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 in a sample for the purpose of identifying if the patient, from whom the sample was derived, is likely to be a responder or non-responder to immunotherapy such a cancer immunotherapy comprising the steps:

    • isolating the RNA from the sample,
    • optionally amplifying the copies of the cDNA from the sample for said genes, and
    • quantifying the levels of cDNA in the sample.


In one embodiment, the diagnostic method comprises determining whether a subject expresses any of the gene products of the genes set forth in Table 1 or any other embodiment of the invention described herein by, for example, detecting the level of the corresponding mRNA and/or protein level of the gene products of the genes set forth in Table 1 etc. For example, by using techniques such as by Northern blot analysis, reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization, immunoprecipitation, Western blot hybridization, or immunohistochemistry. According to the method, cells may be obtained from a subject and the levels of the protein, or mRNA, of the analyzed genes, compared to that of a non-responder patient. Patients who differentially express one or more, for example, 5, 6, 7, 8, 9, 10, 1, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 or another embodiment of the invention are those which can be predicted to benefit from immunotherapy, for example cancer immunotherapy, such as Mage antigen specific cancer immunotherapy. For example, a nucleic acid molecule which hybridizes to a given location on a microarray is said to be differentially expressed if the hybridization signal is, for example, higher than the hybridization signal at the same location on an identical array hybridized with a nucleic acid sample obtained from a subject that does not clinically respond to Mage specific immunotherapy.


The results of 30 patients who have been subjected to gene profiling are shown in FIG. 5. This pictorially demonstrates that the gene signature of the present invention is aligned with clinical response to MAGE-antigen specific cancer immunotherapy.


Alternatively the cancer patient may be characterised as a responder or non-responder to immunotherapy from a visual inspection of a tissue section derived from the cancer or tumour. A responder is likely to be a patient with an infiltration of immune response cells into the cancer/tumour microenvironment.


The invention also provides a method of generating a new gene profile not specifically recited herein, based on differential expression of one or more immune response/activation genes, for indicating whether a patient is likely to be a responder or non-responder to appropriate immunotherapy, for example cancer immunotherapy such as Mage immunotherapy comprising the steps:

    • a) analysing at least two patient derived samples for differential expression of one or more of immune activation genes, where the sample group comprises both responders and non-responders to appropriate immunotherapy, and
    • b) correlating same with clinical outcome, after appropriate treatment, of patients from which the samples were derived, and
    • c) identifying one or more genes which are differentially expressed in responders and/O non-responders.


After the new profile has been identified the invention also extends to analysis of a previously uncharacterised sample, designating same as responders or non-responders (as appropriate) and if desired administering a therapeutically effective amount of an appropriate immunotherapy, for example cancer immunotherapy such as Mage immunotherapy to one or more patients designated as responders.


The invention also provides a method of generating a gene profile based on differential expression of one or more gene sequences recited in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 for indicating whether a patient is likely to be a responder or non-responder to immunotherapy comprising the steps:

    • a) analyzing at least two patient derived samples for differential expression of
      • (i) one or more gene sequences recited in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 and
      • (ii) optionally one or more gene sequences not recited in Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13,
    • where the sample group comprises both responders and non-responders to appropriate immunotherapy;
    • b) correlating differential expression of said one or more gene sequences with clinical outcome, after appropriate treatment, of patients from which the samples were derived, and
    • c) identifying one or more genes which are differentially expressed in responders and non-responders.


After the profile has been identified the invention also extends to analysis of a previously uncharacterised sample, designating same as responders or non-responders (as appropriate) and if desired administering a therapeutically effective amount of an appropriate immunotherapy, for example cancer immunotherapy such as Mage immunotherapy to one or more patients designated as responders.


The invention provides a diagnostic kit comprising at least one component for performing an analysis on a patient derived sample to identify a profile according to the invention, the results of which may be used to designate a patient from which the sample was derived as a responder or non-responder to immunotherapy.


The kit may comprise materials/reagents for PCR (such as QPCR), microarray analysis, immunohistochemistry or other analytical technique that may be used for accessing differential expression of one or more genes.


The invention also provides a diagnostic kit comprising a set of probes capable of hybridising to the mRNA or cDNA of one or more, such as at least 5 genes as set forth in Table 1 or alternatively Tables 2, 3, 4, 7, 9, 11, 12 and/or 13, for example a diagnostic kit comprising a set of probes capable of hybridising to the mRNA or its cDNA of at least 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes as set forth in Table 1.


In another embodiment this invention relates to diagnostic kits. For example, diagnostic kits containing such microarrays comprising a microarray substrate and probes that are capable of hybridising to mRNA or cDNA expressed from, for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes from, for example Table 1 or any other embodiment of the invention that are capable of demonstrating the gene signature of the invention.


In one aspect the invention provides microarrays adapted for identification of a signature according to the invention.


The invention also extends to substrates and probes suitable for hybridising to an mRNA or cDNA moiety expressed from one or more genes employed in the invention, for example from Table 1, 2, 3, 4, 7, 9, 11, 12 or 13.


Commercially available microarrays contain many more probes than are required to characterise the differential expression of the genes under consideration at any one time, to aid the accuracy of the analysis. Thus one or more probe sets may recognise the same gene.


Thus in one embodiment multiple probes or probe sets are used to identify if an immune activation gene is differentially expressed, such as upregulated.


The diagnostic kit may, for example comprise probes, which are arrayed in a microarray. Specifically, prepared microarrays, for example, containing one or more probe sets described herein can readily be prepared by companies such as Affymetrix, thereby providing a specific test and optionally reagents for identifying the profile, according to the invention.


In an embodiment the microarrays or diagnostic kits will additionally be able to test for the presence or absence of the relevant cancer testis antigen expressing gene such as the Mage gene. Thus in one aspect the invention provides a probe and/or probe set suitable for said hybridisation, under appropriate conditions. The invention also extends to use of probes, for example as described herein or functional equivalents thereof, for the identification of a gene profile according to the present invention.


The invention herein described extends to use of all permutations of the probes listed herein (or functional analogues thereof) for identification of the said signature.


In one aspect the invention provides use of a probe for the identification of differential expression of at least one gene product of an immune activation gene for establishing if a gene profile according to the present invention is present in a patient derived sample.


Table 1B discloses probe sets from which probes of typically 25 mer in length may be designed and which are suitable for identifying the mRNA (or its cDNA) expressed from, for example the genes of Table 1 (or alternatively Table 2, 3, 4, 7, 9, 11, 12 or 13). Such probes and probe sets are an aspect of the invention. Typically each probe set may comprise about or exactly 11 individual sequences of about or exactly 25 nucleotides, which correspond precisely to a run of sequences from the probe set.


Accordingly, in one aspect, this invention relates to oligonucleotide probes and primers capable of recognising the mRNA (or its cDNA) expressed from the genes from Table 1, (or alternatively Table 2, 3, 4, 7, 9, 11, 12 or 13) and diagnostic kits based on these probes and primers. Such kits may include probes or kits for the detection of a Mage gene.


In an aspect the invention provides a profile based on the differential expression of one or more of the genes of Table 3 identifiable by one or more of following 13 probes: 204661_at, 205890_at, 206118_at, 206666_at, 207651_at, 210038_at, 210972_x_at, 211144_x_at, 211796_s_at, 213193_x_at, 213539_at, 217147_s_at, 34210_at.


Further details of these probes and the target genes of the same are given in Table 3A below. Hybridisation will generally be preformed under stringent conditions, such as 3×SSC, 0.1% SDS, at 50° C.


Once the target gene(s)/profile has/have been identified then it is well within the skilled person's ability to design alternative probes that hybridise to the same target. Therefore the invention also extends to probes, which under appropriate conditions measure the same differential expression of the gene(s) of the present invention to provide a signature/profile as described.


The invention also extends to use of the relevant probe in analysis of whether a cancer patient will be a responder or non-responder to treatment with an appropriate immunotherapy.


The invention also extends to use (and processes employing same) of known microarrays for identification of said signature.


A nucleic acid probe may be at least 10, 15, 20, 25, 30, 35, 40, 50, 75, 100 or more nucleotides in length and may comprise the full length gene. Probes for use in the invention are those that are able to hybridise specifically to the mRNA (or its cDNA) expressed from the genes listed in Table 1 (or Table 2, 3, 4, 7, 9, 11, 12 or 13) under stringent conditions.


The present invention further relates to a method of screening the effects of a drug on a tissue or cell sample comprising the step of analysing the expression profile of, for example 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 or any other embodiment of the invention described herein before and after drug treatment. The invention therefore provides a method for screening for a drug, which would alter the gene profile to that of a patient having improved survival following treatment with, for example, Mage antigen specific cancer immunotherapy (ie. to alter the gene profile to that of a responder), to enable the patient to benefit from, for example, Mage antigen specific cancer immunotherapy.


The present invention further provides a method of patient diagnosis comprising, for example, the step of analysing the expression profile of, for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 or any other embodiment of the invention described herein and comparing it with a standard to diagnose whether the patient would benefit from Mage specific immunotherapy.


The invention includes a method of patient diagnosis comprising the step of analysing the expression profile of at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 or other embodiment of the invention from a tumour tissue sample given by a patient and assessing whether 5 or more of said genes are expressed.


Thus in clinical applications, tissue samples from a human patient may be screened for the presence and/or absence of the expression of, for example 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 or any other embodiment of the invention described herein.


In the context of the present invention, the sample may be of any biological tissue or fluid derived from a patient potentially in need of treatment. The sample maybe derived from sputum, blood, urine, or from solid tissues such as biopsy from a primary tumour or metastasis, or from sections of previously removed tissues.


Samples could comprise or consist of, for example, needle biopsy cores, surgical resection samples or lymph node tissue. These methods include obtaining a biopsy, which is optionally fractionated by cryostat sectioning to enrich tumour cells to about 80% of the total cell population. In certain embodiments, nucleic acids extracted from these samples may be amplified using techniques well known in the art. The levels of selected markers (eg the gene products of table 1) can be detected and can be compared with statistically valid groups of, for example, Mage positive non responder patients.


For cancer, the biological sample will contain cancer or tumour cells and may, for example, be derived from the cancer or tumour such as a fresh sample (including frozen samples) or a sample that has been preserved in paraffin. Having said this, samples preserved in paraffin can suffer from degradation and the profile observed may be modified. A person working the in field is well able to compensate of these changes observed by recalibrating the parameters of the profile.


Microarrays

A microarray is an array of discrete regions, typically nucleic acids, which are separate from one another and are typically arrayed at a density of between, about 100/cm2 to 1000/cm2, but can be arrayed at greater densities such as 10000/cm2. The principle of a microarray experiment, is that mRNA from a given cell line or tissue is used to generate a labeled sample typically labeled cDNA, termed the ‘target’, which is hybridized in parallel to a large number of, nucleic acid sequences, typically DNA sequences, immobilised on a solid surface in an ordered array. Tens of thousands of transcript species can be detected and quantified simultaneously. Although many different microarray systems have been developed the most commonly used systems today can be divided into two groups, according to the arrayed material: complementary DNA (cDNA) and oligonucleotide microarrays. The arrayed material has generally been termed the probe since it is equivalent to the probe used in a northern blot analysis. Probes for cDNA arrays are usually products of the polymerase chain reaction (PCR) generated from cDNA libraries or clone collections, using either vector-specific or gene-specific primers, and are printed onto glass slides or nylon membranes as spots at defined locations. Spots are typically 10-300 μm in size and are spaced about the same distance apart. Using this technique, arrays consisting of more than 30,000 cDNAs can be fitted onto the surface of a conventional microscope slide. For oligonucleotide arrays, short 20-25mers are synthesized in situ, either by photolithography onto silicon wafers (high-density-oligonucleotide arrays from Affymetrix or by ink-jet technology (developed by Rosetta Inpharmatics, and licensed to Agilent Technologies). Alternatively, presynthesized oligonucleotides can be printed onto glass slides. Methods based on synthetic oligonucleotides offer the advantage that because sequence information alone is sufficient to generate the DNA to be arrayed, no time-consuming handling of cDNA resources is required. Also, probes can be designed to represent the most unique part of a given transcript, making the detection of closely related genes or splice variants possible. Although short oligonucleotides may result in less specific hybridization and reduced sensitivity, the arraying of presynthesized longer oligonucleotides (50-100mers) has recently been developed to counteract these disadvantages. Thus in performing a microarray to ascertain whether a patient presents with a gene signature of the present invention, the following steps are performed: obtain mRNA from the sample and prepare nucleic acids targets, contact the array under conditions, typically as suggested by the manufactures of the microarray (suitably stringent hybridisation conditions such as 3×SSC, 0.1% SDS, at 50° C.) to bind corresponding probes on the array, wash if necessary to remove unbound nucleic acid targets and analyse the results.


It will be appreciated that the mRNA may be enriched for sequences of interest such as those in Table 1 or 2 (or other embodiment of the invention) by methods known in the art, such as primer specific cDNA synthesis. The population may be further amplified, for example, by using PCR technology. The targets or probes are labeled to permit detection of the hybridisation of the target molecule to the microarray. Suitable labels include isotopic or fluorescent labels which can be incorporated into the probe.


In an alternative embodiment, a patient may be diagnosed to ascertain whether his/her tumor expresses the gene signature of the invention utilising a diagnostic kit based on PCR technology, in particular Quantative PCR (For a review see Ginzinger D Experimental haematology 30 (2002) p 503-512 and Giuliette et al Methods, 25 p 386 (2001).


In an alternative aspect the invention provides a method further comprising the steps of analyzing a tumour derived sample to determine which antigen(s) are expressed by the tumour and hence enabling administration of an a therapeutically effective amount of an appropriate antigen specific cancer immunotherapeutic, for example where the tumour is found to be MAGE (such as Mage A3) positive, appropriate treatment may, for example, include administration of Mage A3 antigen specific immunotherapy.


A sample such as tumour tissue of a patient is deemed to present the gene signature of the invention if one or more genes of Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13 are differentially expressed (such as upregulated), for example, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes from for example Table 1 or other embodiment of the invention are expressed and can be detected by microarray analysis or other appropriate analysis for example as described herein. The tumour tissue preferably shows expression of at least 5 genes selected from Table 1, 2, 3, 4, 7, 9, 11, 12 and/or 13, more preferably 10 genes, particularly 5, 6, 7, 8, 9 or 10 genes from Table 1, 2, 3, 4, 7, 9, 11, 12 or 13.


Immunotherapeutics

In a further aspect the invention provides a method of treating a responder patient with an appropriate immunotherapy, for example cancer immunotherapy such as cancer testis immunotherapy, after identification of the same as a responder thereto.


Thus the invention provides a method of treating a patient comprising the step of administering a therapeutically effective amount of an appropriate immunotherapy (for example cancer immunotherapy, such as Mage cancer immunotherapy), after first characterising the patient as a responder based on differential expression of at least one immune activation gene, for example as shown by appropriate analysis of a sample derived from the patient. In particular wherein the patient is characterised as a responder based on one or more embodiments described herein.


In one aspect the immunotherapy comprises an appropriate adjuvant (immunostimulant), see description below.


In yet a further embodiment of the invention there is provided a method of treating a patient suffering from, for example, a Mage expressing tumour, the method comprising determining whether the patient expresses the gene signature of the invention and then administering, for example, a Mage specific immunotherapeutic. In a further embodiment, the patient is treated with, for example, the Mage specific immunotherapy to prevent or ameliorate recurrence of disease, after first receiving treatment such as resection by surgery of any tumour or other chemotherapeutic or radiotherapy treatment.


A further aspect of the invention is a method of treating a patient suffering from a Mage expressing tumour, the method comprising determining whether the patient's tumour expresses at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 2021, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 (or other embodiment of the invention) from a tumour tissue sample given by a patient and then administering a Mage specific immunotherapeutic to said patient.


Also provided is a method of treating a patient susceptible to recurrence of Mage expressing tumour having been treated to remove/treat a Mage expressing tumour, the method comprising determining whether the patient's tumour expresses at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 (or other embodiment of the invention) from a tumour tissue sample given by a patient and then administering a Mage specific immunotherapeutic.


The invention also provides as method of treatment or use employing:

    • MAGE specific immunotherapeutic comprising a MAGE antigen or peptide thereof,
    • MAGE antigen comprising a MAGE-A3 protein or peptide,
    • MAGE antigen comprising the peptide EVDPIGHLY,
    • MAGE antigen or peptide fused or conjugated to a carrier protein, for example in which the carrier protein is selected from protein D, NS1 or CLytA or fragments thereof, and/or
    • MAGE specific immunotherapeutic further comprises an adjuvant, for example in which the adjuvant comprises one or more or combinations of: 3D-MPL; aluminium salts; CpG containing oligonucleotides; saponin-containing adjuvants such as QS21 or ISCOMs; oil-in-water emulsions; and liposomes.


The invention also extends to use of an immunotherapy such as a cancer immunotherapy, in particular Mage immunotherapy in the manufacture of a medicament for the treatment of a patient such as a cancer patient designated as a responder, thereto.


It was observed that one patient initially characterised as a non-responder was subsequently characterised as responder after radiation therapy. Interestingly the inventors also believe that it may be possible to induce a responders profile in at least some non-responders, for example by subjecting the patient to radiation therapy, or administering an inflammatory stimulant such as interferon (for example imiquimod such as administered topically) or a TLR3 (for example as described in WO 2006/054177), 4, 7, 8 or TLR 9 agonist (for example containing a CpG motif, in particular administering a high dose thereof such as 0.1 to 75 mg per Kg adminstered, for example weekly). See for example Krieg, A. M., Efler, S. M., Wittpoth, M., Al Adhami, M. J. & Davis, H. L. Induction of systemic TH 1-like innate immunity in normal volunteers following subcutaneous but not intravenous administration of CPG 7909, a synthetic B-class CpG oligodeoxynucleotide TLR9 agonist. J. Immunother. 27, 460-471 (2004).


The high dose of CpG may, for example be inhaled or given subcutaneously.


Whilst not wishing to be bound by theory, it is hypothesised that the radiation therapy stimulated a systemic inflammatory response/immune response, which once triggered rendered the patient (or tumour tissue therein) more responsive to immunotherapy.


Accordingly, the invention further provides a method of inducing a responders profile by stimulating a systemic immune response, for example by administering an immunostimulant. The invention further provides the use of Mage specific immunotherapy in the manufacture of a medicament for the treatment of patients suffering from Mage expressing tumour or patients who have received treatment (e.g. surgery, chemotherapy or radiotherapy) to remove/treat a Mage expressing tumour, said patient expressing the gene signature of the invention.


The immunotherapy may then be administered once the responders profile has been induced. In one aspect the invention provides use of Mage specific immunotherapy in the manufacture of a medicament for the treatment of patients suffering from Mage expressing tumour, said patient characterised by their tumour expressing at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 21, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1, or alternatively other embodiments of the invention.


The invention also provides use of Mage specific immunotherapy in the manufacture of a medicament for the treatment of patients susceptible to recurrence from Mage expressing tumour said patient characterised by their tumour expressing at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 2021, 22, 23, 24, 25, 26, 27, 28, 29, 30 or 31 genes selected from Table 1 or alternatively other embodiments of the invention.


Advantageously, the invention may allow medics to target those populations of patients that will obtain a clinical benefit from receiving an appropriate immunotherapy. It is expected that after screening that at least 60% of patients such as 70, 75, 80, 85% or more of patients deemed/characterised as responders will receive a clinical benefit from the immunotherapy, which is a significant increase over the current levels observed with therapy such as cancer therapy generally.


Advantageously if the cancer immunotherapy is given concomitantly or subsequent to chemotherapy it may assist in raising the patient's immune responses, which may have been depleted by the chemotherapy.


Antigen Specific Cancer Immunotherapeutics (ASCIs) suitable for use in the invention may, for example include those capable of raising a Mage specific immune response. Such immunotherapeutics may be capable of raising an immune response to a Mage gene product, for example a Mage-A antigen such as Mage-A3. The immunotherapeutic will generally contain at least one epitope from a Mage gene product. Such an epitope may be present as a peptide antigen optionally linked covalently to a carrier and optionally in the presence of an adjuvant. Alternatively larger protein fragments may be used. For example, the immunotherapeutic for use in the invention may comprise an antigen that corresponds to or comprises amino acids 195-279 of MAGE-A1. The fragments and peptides for use must however, when suitably presented be capable of raising a Mage specific immune response. Examples of peptides that may be used in the present invention include the MAGE-3.A1 nonapeptide EVDPIGHLY [Seq. ID No 36] (see Marchand et al., International Journal of Cancer 80(2), 219-230), and the following MAGE-A3 peptides:












FLWGPRALV;
[Seq. ID No 37]







MEVDPIGHLY;
[Seq. ID No 38]







VHFLLLKYRA;
[Seq. ID No 39]







LVHFLLLKYR;
[Seq. ID No 40]







LKYRAREPVT;
[Seq. ID No 41]







ACYEFLWGPRALVETS;
[Seq. ID No 42]



and







TQHFVQENYLEY;
[Seq. ID No 43]






Alternative ASCIs include cancer testis antigens such as PRAME, LAGE 1, LAGE 2, and others, for example details of which can be obtained from www.cancerimmunity.org/CTdatabase. The cancer immunotherapy may be based, for example on one or more of the antigens discussed below.


In one embodiment of the present invention, the antigen to be used may consist or comprise a MAGE tumour antigen, for example, MAGE 1, MAGE 2, MAGE 3, MAGE 4, MAGE 5, MAGE 6, MAGE 7, MAGE 8, MAGE 9, MAGE 10, MAGE 11 or MAGE 12. The genes encoding these MAGE antigens are located on chromosome X and share with each other 64 to 85% homology in their coding sequence (De Plaen, 1994). These antigens are sometimes known as MAGE A1, MAGE A2, MAGE A3, MAGE A4, MAGE A5, MAGE A6, MAGE A7, MAGE A8, MAGE A9, MAGE A 10, MAGE A11 and/or MAGE A12 (The MAGE A family). In one embodiment, the antigen is MAGE A3.


In one embodiment, an antigen from one of two further MAGE families may be used: the MAGE B and MAGE C group. The MAGE B family includes MAGE B1 (also known as MAGE Xp1, and DAM 10), MAGE B2 (also known as MAGE Xp2 and DAM 6) MAGE B3 and MAGE B4—the Mage C family currently includes MAGE C1 and MAGE C2.


In general terms, a MAGE protein can be defined as containing a core sequence signature located towards the C-terminal end of the protein (for example with respect to MAGE A1 a 309 amino acid protein, the core signature corresponds to amino acid 195-279).


The consensus pattern of the core signature is thus described as follows wherein x represents any amino acid, lower case residues are conserved (conservative variants allowed) and upper case residues are perfectly conserved.


Core Sequence Signature





    • LixvL(2×)I(3×)g(2×)apEExiWexl(2×)m(3-4×)Gxe(3-4×)gxp(2×)llt(3×)VqexYLxYxqVPxsxP(2×)yeFLWGprA(2×)Et(3×)kv


      Conservative substitutions are well known and are generally set up as the default scoring matrices in sequence alignment computer programs. These programs include PAM250 (Dayhoft M. O. et al., (1978), “A model of evolutionary changes in proteins”, In “Atlas of Protein sequence and structure” 5(3) M. O. Dayhoft (ed.), 345-352), National Biomedical Research Foundation, Washington, and Blosum 62 (Steven Henikoft and Joija G. Henikoft (1992), “Amino acid substitution matricies from protein blocks”), Proc. Natl. Acad. Sci. USA 89 (Biochemistry): 10915-10919.





In general terms, substitution within the following groups are conservative substitutions, but substitutions between groups are considered non-conserved. The groups are:

    • i) Aspartate/asparagine/glutamate/glutaminc
    • ii) Serine/threonine
    • iii) Lysine/arginine
    • iv) Phenylalanine/tyrosine/tryptophane
    • v) Leucine/isoleucine/valine/methionine
    • vi) Glycine/alanine


In general and in the context of this invention, a MAGE protein will be approximately 50% or more identical, such as 70, 80, 90, 95 or 99% identical, in this core region with amino acids 195 to 279 of MAGE A1.


MAGE protein derivatives are also known in the art, see: WO 99/40188. Such derivatives are suitable for use in therapeutic vaccine formulations (Immunotherapeutic) which are suitable for the treatment of a range of tumour types.


Several CTL epitopes have been identified on the MAGE-3 protein. One such epitope, MAGE-3.A1, is a nonapeptide sequence located between amino acids 168 and 176 of the MAGE-3 protein which constitutes an epitope specific for CTLs when presented in association with the MHC class I molecule HLA.A1. Recently two additional CTL epitopes have been identified on the peptide sequence of the MAGE-3 protein by their ability to mount a CTL response in a mixed culture of melanoma cells and autologous lymphocytes. These two epitopes have specific binding motifs for the HLA.A2 (Van der Bruggen, 1994) and HLA.B44 (Herman, 1996) alleles respectively.


In a further embodiment of the invention, the tumour antigen may comprise or consist of one of the following antigens, or an immunogenic portion thereof which is able to direct an immune response to the antigen:


SSX-2; SSX-4; SSX-5; NA17; MELAN-A; Tyrosinase; LAGE-1; NY-ESO-1; PRAME; P790; P510; P835; B305D; B854; CASB618 (as described in WO00/53748); CASB7439 (as described in WO01/62778); C1491; C1584; and C1585.


In one embodiment, the antigen may comprise or consist of P501S (also known as prostein). The P501S antigen may be a recombinant protein that combines most of the P501S protein with a bacterial fusion protein comprising the C terminal part of protein LytA of Streptococcus pneumoniae in which the P2 universal T helper peptide of tetanus toxoid has been inserted, ie. a fusion comprising CLytA-P2-CLyta (the “CPC” fusion partner), as described in WO03/104272;


In one embodiment, the antigen may comprise or consist of WT-1 expressed by the Wilm's tumor gene, or its N-terminal fragment WT-1F comprising about or approximately amino acids 1-249; the antigen expressed by the Her-2/neu gene, or a fragment thereof. In one embodiment, the Her-2/neu antigen may be one of the following fusion proteins which are described in WO00/44899.


In a further embodiment, the antigen may comprise or consist of “HER-2/neu ECD-ICD fusion protein,” also referred to as “ECD-ICD” or “ECD-ICD fusion protein,” which refers to a fusion protein (or fragments thereof) comprising the extracellular domain (or fragments thereof) and the intracellular domain (or fragments thereof) of the HER-2/neu protein. In one embodiment, this ECD-ICD fusion protein does not include a substantial portion of the HER-2/neu transmembrane domain, or does not include any of the HER-2/neu transmembrane domain.


In a further embodiment, the antigen may comprise or consist of “HER-2/neu ECD-PD fusion protein,” also referred to as “ECD-PD” or “ECD-PD fusion protein,” or the “HER-2/neu ECD-ΔPD fusion protein,” also referred to as “ECD-ΔPD” or “ECD-ΔPD fusion protein,” which refers to fusion proteins (or fragments thereof) comprising the extracellular domain (or fragments thereof) and phosphorylation domain (or fragments thereof, e.g., ΔPD) of the HER-2/neu protein.


In one embodiment, the ECD-PD and ECD-ΔPD fusion proteins do not include a substantial portion of the HER-2/neu transmembrane domain, or does not include any of the HER-2/neu transmembrane domain.


In one embodiment, the antigen may comprise a Mage or other appropriate protein linked to an immunological fusion or expression enhancer partner. Fusion proteins may include a hybrid protein comprising two or more antigens relevant to a given disease or may be a hybrid of an antigen and an expression enhancer partner.


The antigen and partner may be chemically conjugated, or may be expressed as a recombinant fusion protein. In an embodiment in which the antigen and partner are expressed as a recombinant fusion protein, this may allow increased levels to be produced in an expression system compared to non-fused protein. Thus the fusion partner may assist in providing T helper epitopes (immunological fusion partner), preferably T helper epitopes recognised by humans, and/or assist in expressing the protein (expression enhancer) at higher yields than the native recombinant protein. In one embodiment, the fusion partner may be both an immunological fusion partner and expression enhancing partner.


In one embodiment of the invention, the immunological fusion partner that may be used is derived from protein D, a surface protein of the gram-negative bacterium, Haemophilus influenza B (WO 91/18926) or a derivative thereof. The protein D derivative may comprise the first ⅓ of the protein, or approximately or about the first ⅓ of the protein, in particular it may comprise the first N-terminal 100-110 amino acids or approximately the first N-terminal 100-110 amino acids.


In one embodiment the fusion protein comprises the first 109 residues (or 108 residues therefrom) or amino acids 20 to 127 of protein D.


Other fusion partners that may be used include the non-structural protein from influenzae virus, NS1 (hemagglutinin). Typically the N terminal 81 amino acids of NS1 may be utilised, although different fragments may be used provided they include T-helper epitopes.


In another embodiment the immunological fusion partner is the protein known as LytA. LytA is derived from Streptococcus pneumoniae which synthesise an N-acetyl-L-alanine amidase, amidase LytA, (coded by the LytA gene (Gene, 43 (1986) page 265-272) an autolysin that specifically degrades certain bonds in the peptidoglycan backbone. The C-terminal domain of the LytA protein is responsible for the affinity to the choline or to some choline analogues such as DEAE. This property has been exploited for the development of E. coli C-LytA expressing plasmids useful for expression of fusion proteins. Purification of hybrid proteins containing the C-LytA fragment at its amino terminus has been described (Biotechnology: 10, (1992) page 795-798). In one embodiment, the C terminal portion of the molecule may be used. The embodiment may utilise the repeat portion of the LytA molecule found in the C terminal end starting at residue 178. In one embodiment, the LytA portion may incorporate residues 188-305.


In one embodiment of the present invention, the Mage protein may comprise a derivatised free thiol. Such antigens have been described in WO 99/40188. In particular carboxyamidated or carboxymethylated derivatives may be used.


In one embodiment of the present invention, the tumour associated antigen comprises a Mage-A3-protein D molecule. The nucleotide and amino acid sequences for this molecule are shown in seq ID No 35. This antigen and those summarised below are described in more detail in WO 99/40188.


In further embodiments of the present invention, the tumour associated antigen may comprise any of the following fusion proteins:


A fusion protein of Lipoprotein D fragment, MAGE 1 fragment, and histidine tail; fusion protein of NS1-MAGE3, and Histidine tail; fusion protein of CLYTA-MAGE1-Histidine; fusion protein of CLYTA-MAGE3-Histidine.


A further embodiment of the present invention comprises utilising a nucleic acid immunotherapeutic, which comprises a nucleic acid molecule encoding a Mage specific tumour associated antigens as described herein. Such sequences may be inserted into a suitable expression vector and used for DNA/RNA vaccination. Microbial vectors expressing the nucleic acid may also be used as vectored delivered immunotherapeutics. Such vectors include for example, poxvirus, adenovirus, alphavirus and listeria.


Conventional recombinant techniques for obtaining nucleic acid sequences, and production of expression vectors of are described in Maniatis et al., Molecular Cloning—A Laboratory Manual; Cold Spring Harbor, 1982-1989.


For protein based immunotherapeutics the proteins of the present invention are provided either in a liquid form or in a lyophilised form.


It is generally expected that each human dose will comprise 1 to 1000 μg of protein, and preferably 30-300 μg.


The method(s) as described herein may comprise a composition further comprises a vaccine adjuvant, and/or immunostimulatory cytokine or chemokine.


Suitable vaccine adjuvants for use in the present invention are commercially available such as, for example, Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, Mich.); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, N.J.); AS-2 (SmithKline Beecham, Philadelphia, Pa.); aluminium salts such as aluminium hydroxide gel (alum) or aluminium phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatised polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quit A. Cytokines, such as GM-CSF or interleukin-2, -7, or -12, and chemokines may also be used as adjuvants.


In formulations it may be desirable that the adjuvant composition induces an immune response predominantly of the Th1 type. High levels of Th1-type cytokines (e.g., IFN-γ, TNFα, IL-2 and IL-12) tend to favour the induction of cell mediated immune responses to an administered antigen. According to one embodiment, in which a response is predominantly Th1-type, the level of Th1-type cytokines will increase to a greater extent than the level of Th2-type cytokines. The levels of these cytokines may be readily assessed using standard assays. For a review of the families of cytokines, see Mosmann and Coffman, Ann. Rev. Immunol. 7:145-173, 1989. Accordingly, suitable adjuvants that may be used to elicit a predominantly Th1-type response include, for example a combination of monophosphoryl lipid A, such as 3-de-O-acylated monophosphoryl lipid A (3D-MPL) together with an aluminium salt. 3D-MPL or other toll like receptor 4 (TLR4) ligands such as aminoalkyl glucosaminide phosphates as disclosed in WO 98/50399, WO 01/34617 and WO 03/065806 may also be used alone to generate a predominantly Th1-type response.


Other known adjuvants, which may preferentially induce a TH1 type immune response, include TLR9 agonists such as unmethylated CpG containing oligonucleotides. The oligonucleotides are characterised in that the CpG dinucleotide is unmethylated. Such oligonucleotides are well known and are described in, for example WO 96/02555.


Suitable oligionucleotides include:









OLIGO 1:







[Seq ID No 44]







TCC ATG ACG TTC CTG ACG TT (CpG 1826)





OLIGO 2:







[Seq ID No 45]







TCT CCC AGC GTG CGC CAT (CpG 1758)





OLIGO 3:







[Seq ID No 46]







ACC GAT GAC GTC GCC GGT GAC GGC ACC ACG





OLIGO 4







[Seq ID No 47]







TCG TCG TTT TGT CGT TTT GTC GTT (CpG 2006, CpG


7909)





OLIGO 5







[Seq ID No 48]







TCC ATG ACG TTC CTG ATG CT (CpG 1668)






CpG-containing oligonucleotides may also be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a CpG-containing oligonucleotide and a saponin derivative particularly the combination of CpG and QS21 as disclosed in WO 00/09159 and WO 00/62800.


The formulation may additionally comprise an oil in water emulsion and/or tocopherol. Another suitable adjuvant is a saponin, for example QS21 (Aquila Biopharmaceuticals Inc., Framingham, Mass.), that may be used alone or in combination with other adjuvants. For example, an enhanced system involves the combination of a monophosphoryl lipid A and saponin derivative, such as the combination of QS21 and 3D-MPL as described in WO 94/00153, or a less reactogenic composition where the QS21 is quenched with cholesterol, as described in WO 96/33739. Other suitable formulations comprise an oil-in-water emulsion and tocopherol. A particularly potent adjuvant formulation involving QS21, 3D-MPL and tocopherol in, for example, an oil-in-water emulsion is described in WO 95/17210.


In another embodiment, the adjuvants may be formulated in a liposomal composition.


The amount of 3D-MPL used is generally small, but depending on the immunotherapeutic formulation may be in the region of 1-1000 μg per dose, preferably 1-500 μg per dose, and more preferably between 1 to 100 μg per dose.


In an embodiment, the adjuvant system comprises three immunostimulants: a CpG oligonucleotide, 3D-MPL, & QS21 either presented in a liposomal formulation or an oil in water emulsion such as described in WO 95/17210.


The amount of CpG or immunostimulatory oligonucleotides in the adjuvants or immunotherapeutics of the present invention is generally small, but depending on the immunotherapeutic formulation may be in the region of 1-1000 μg per dose, preferably 1-500 μg per dose, and more preferably between 1 to 100 μg per dose.


The amount of saponin for use in the adjuvants of the present invention may be in the region of 1-1000 μg per dose, preferably 1-500 μg per dose, more preferably 1-250 μg per dose, and most preferably between 1 to 100 μg per dose.


Generally, it is expected that each human dose will comprise 0.1-1000 μg of antigen, preferably 0.1-500 μg, preferably 0.1-100 μg, most preferably 0.1 to 50 μg. An optimal amount for a particular immunotherapeutic can be ascertained by standard studies involving observation of appropriate immune responses in vaccinated subjects. Following an initial vaccination, subjects may receive one or several booster immunisation adequately spaced.


Other suitable adjuvants include Montanide ISA 720 (Seppic, France), SAF (Chiron, Calif., United States), ISCOMS (CSL), MF-59 (Chiron), Ribi Detox, RC-529 (GSK, Hamilton, Mont.) and other aminoalkyl glucosaminide 4-phosphates (AGPs).


Accordingly there is provided an immunogenic composition for use in the method of the present invention comprising an antigen as disclosed herein and an adjuvant, wherein the adjuvant comprises one or more of 3D-MPL, QS21, a CpG oligonucleotide, a polyethylene ether or ester or a combination of two or more of these adjuvants. The antigen within the immunogenic composition may be presented in an oil in water or a water in oil emulsion vehicle or in a liposomal formulation.


In one embodiment, the adjuvant may comprise one or more of 3D-MPL, QS21 and an immunostimulatory CpG oligonucleotide. In an embodiment all three immunostimulants are present. In another embodiment 3D-MPL and QS21 are presented in an oil in water emulsion, and in the absence of a CpG oligonucleotide.


A composition for use in the method of the present invention may comprise a pharmaceutical composition comprising tumour associated antigen as described herein, or a fusion protein, in a pharmaceutically acceptable excipient.


EXAMPLES
Example 1
MAGE008 Mage Melanoma Clinical Trial

In this on-going trial, the recMAGE-A3 protein (recombinant mage fusion protein as shown in Seq Id No 35) is combined with two different immunological adjuvants: either AS02B (QS21, MPL) or AS15 (QS21, MPL and CpG7909). The objectives were to discriminate between the adjuvants in terms of safety profile, clinical response and immunological response.


In this experiment two adjuvant compositions are made up of mixtures of two immunostimulants:

    • 1. QS21 (Purified, naturally occurring saponin molecule from the South-American tree Quillaja Saponaria Molina), and
    • 2. MPL (3 de-O-acetylated monophosphoryl lipid A-detoxified derivative of lipid A, derived from S. minnesota LPS).


      AS02B is an oil-in-water emulsion of QS21 and MPL.


In animal models these adjuvants have been successfully shown to induce both humoral and TH1 types of cellular-mediated immune responses, including CD4 and CD8 T-cells producing IFNα (Moore et al., 1999; Gérard et al., 2001). Moreover, the injection of recombinant protein formulated in this type of adjuvant leads to the induction of a systemic anti-tumor response: indeed, vaccinated animals were shown to be protected against challenges with murine tumor cells genetically engineered to express the tumor antigen, and regressing tumors were shown to be highly infiltrated by CD8, CD4 and NK cells and by macrophages.


The second adjuvant system is AS15: it contains a third immunostimulant, namely CpG7909 (otherwise known as CpG 2006 supra), in addition to MPL and QS21, in a liposome formulation. In animal models (mainly mice), it has been shown that the addition of CpG7909 further improves the induced immune and anti-tumor responses (Krieg and Davis, 2001; Ren et al., 2004). CpG oligodeoxynucleotides (ODNs) directly stimulate dendritic-cell activation through TLR9 triggering. In addition, in mice, the systemic application of CpG7909 greatly increases the infiltration of transferred T-cells into tumors (Meidenbauer et al., 2004).


Study Overview

1. Design


The MAGE008 trial is:

    • open
    • randomized
    • two-arm (AS02B vs. AS15)
    • with 68 patients in total.


As described above, the recMAGE-A3 protein is combined with either AS02B or AS15 adjuvant system.


2. Patients Population


The recMAGE-A3 protein is administered to patients with progressive metastatic melanoma with regional or distant skin and/or lymph-node lesions (unresectable stage III and stage IV M1a). The expression of the MAGE-A3 gene by the tumor was assessed by quantitative PCR. The selected patients did not receive previous treatment for melanoma (recMAGE-A3 is given as first-line treatment) and had no visceral disease.


3. Schedule of Immunization


Method of Treatment Schedules
Adjuvant Setting

The method of treatment schedule for use in disease in an adjuvant (post-operative) setting may comprise administration of an antigen as described herein according to the following schedules: Administration of antigen at three week intervals for the first 5 to 8 vaccinations, followed at 3 month intervals for the next 8, 9 or more vaccinations.


The antigen may be administered at the exact time frame indicated, or the antigen may be given 1, 2, 3 or 4 days before or after the exact interval, as required or as practical. An example of this schedule is shown in the table below:

  • Induction: 5 vaccinations at intervals of 3 weeks for example Weeks 0, 3, 6, 9, 12 or Weeks 0, 6, 9, 12
  • Maintenance: 9 vaccinations at intervals of 3 months


    Alternatively, the vaccinations may be given initially at 2 week intervals, for example 6 injections at two week intervals followed by appropriate maintenance therapy.


Active Disease

The method of treatment schedule for use in active or unresectable disease, for example in melanoma cancer, comprising: administration of an antigen as described herein at two or three week intervals for the first six months to one year of treatment. A schedule may comprise the following pattern of injections: the antigen may be given at two week intervals for the first 4 to 10 vaccinations, followed by 3 week intervals for the next 4 to 10 vaccinations, then at 6 week intervals for the next 3 to 7 vaccinations. Long term treatment may then continue with vaccinations at 3 month intervals for 3 to 5 vaccinations, followed by 6 month intervals for the next 3 to 5 vaccinations.


The antigen may be administered at the exact time frame indicated, or the antigen may be given 1, 2, 3 or 4 days before or after the exact interval, as required or as practical.


An example of this schedule is shown in the table below:

  • Cycle 1: 6 vaccinations at intervals of 2 weeks (Weeks 1, 3, 5, 7, 9, 11)
  • Cycle 2: 6 vaccinations at intervals of 3 weeks (Weeks 15, 18, 21, 24, 27, 30)
  • Cycle 3: 4 vaccinations at intervals of 6 weeks (Weeks 34, 40, 46, 52)
  • Long Term Treatment: 4 vaccinations at intervals of 3 months, for example followed by 4 vaccinations at intervals of 6 months


    For both of the above treatment regimes additional vaccinations may be given after treatment, as required.


In order to screen potential participants in the above clinical trial we received biopsies of the tumor, prior to any immunization, as frozen tumor samples. From these samples we extracted RNA for the quantitative PCR. The quality of this purified RNA was extremely high and it was suitable for microarray analysis. We therefore analyzed the tumor samples by microarrays. The goal was to identify a set of genes associated with the clinical response so that patients likely to benefit from this antigen-specific cancer immunotherapeutic are properly identified and selected. Gene profiling has been performed only on biopsies from patients who signed the informed consent for microarray analysis.


Materials and Methods
Tumor Specimens

30 tumor specimens (pre-vaccination) were used from the Mage008 Mage-3 melanoma clinical trial. These were fresh frozen preserved in the RNA stabilizing solution RNAlater.


RNA Purification

Tumoral total RNA was purified using the Tripure method—Tripure extraction (Roche Cat. No. 1 667 165). The protocols provided were followed subsequently by the use of an RNeasy Mini kit—clean-up protocol with DNAse treatment (Qiagen Cat. No. 74106). http://www1.qiagen.com/literature/handbooks/PDF/RNAStabilizationAndPurification/FromAnim alAndPlantTissuesBacteriaYeastAndFungi/RNY_Mini/1035969_HB.pdf. www.roche-applied-science.com/PROD_INF/MANUALS/napi_man/pdf/chapter4/page152-158.pdf


RNA Quality Control

Quantification of RNA was initially completed using optical density at 260 nm and Quant-IT RiboGreen RNA assay kit (Invitrogen—Molecular probes R11490). http://probes.invitrogen.com/media/pis/mp11490.pdf.


The Quality of the 28s and 18s ribosomal RNA peaks were assessed by use of the Agilent bioanalyser.


RNA Labeling and Amplification for Microarray Analysis

Due to the small biopsy size received during the clinical study an amplification method was used in conjunction with the labeling of the RNA for microarray analysis.


The Nugen 3′ ovation biotin kit (Labelling of 50 ng of RNA—Ovation biotin system Cat; 2300-12, 2300-60) http://www.nugeninc.com/html/03_products2.html


A starting input of 50 ng of total RNA was used.


Microarray Chips

The Affymetrix HU-U133.Plus 2.0 gene chips were utilized as these were the most up to date chips (based on the human genome project) available from the supplier. These chips cover about 47,000 potential gene transcripts.


Microarray Hybridization and Scanning

The hybridized chips were washed and scanned according to the standard Affymetrix protocols:


Affymetrix gene chip expression analysis protocols can be downloaded from http://www.affvmetrix.com/support/technical/manual/expression_manual.affx.


The scanner that has to be used with the Affymetrix microarray workstation is http://www.affymetrix.com/products/instruments/specific/scanner3000.affx


Data Normalization

The fluorescent scanned data was then normalized using RMA to allow comparisons between individual chips. The following reference describes this method.


Irizarry R A, Hobbs B, Collin F, Beazer-Barclay Y D, Antonellis K J, Scherf U, Speed T P. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003 April; 4(2):249-64.


Data Analysis

Three independent methods were used to generate gene lists to distinguish responder from non-responding patients. The methods are 1. Spotfire, 2. Baldi B H and 3. Arrayminer. The Baldi analysis method is available from the following website. http://www.igb.uci.edu/˜pfbaldi/software_and_servers.htm.


The spotfire software can be purchased from this site http://www.spotfire.com. The arrayminer software is available for purchase at http://www.optimaldesign.com/ArrayMiner/ArrayMiner.htm.


All data analysis was performed with the use of the R statistics software (available at www.r-project.org) and various Bioconductor packages for R (available at www.bioconductor.org). The raw data were pre-processed for background correction, normalisation and probe summarisation by the RMA (Irizarry R A, Hobbs B, Collin F, Beazer-Barclay Y D, Antonellis K J, Scherf U, Speed T P. Exploration, normalization, and summaries of high density oligonucleotide array probe level data. Biostatistics. 2003 April; 4(2):249-64)


The differential gene expression between any two groups was computed by two different statistical methods, the RankProduct (Breitling, R., Armengaud, P., Amtmann, A., and Herzyk, P. (2004) Rank Products: A simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments, FEBS Letter, 57383-92) and the CyberT (P. Baldi and A. D. Long, “A Bayesian Framework for the Analysis of Microarray Expression Data: Regularized t-Test and Statistical Inferences of Gene Changes”, Bioinformatics, 17, 6, 509-519, (2001)) methods.


In each of them, a correction for multiple testing was done with the method of Benjamini-Hochberg (Y. Benjamini and Y. Hochberg, Controlling the false discovery rate: a practical and powerful approach to multiple testing, J. Roy. Stat. Soc. B 57 (1995)), and the threshold of 5% was chosen for the false discovery rate; thus, the genes had to have a corrected p-value less or equal to 0.05 to be considered as differentially expressed. Baldi-BH is equivalent to CyberT followed by Benjamini-Hochberg correction.


1. Spotfire Analysis

The results of the analysis of patient samples (from the clinical research program named Mage008) are summarized in the FIG. 1.


As a first step, a supervised comparison was performed in order to find a group of genes able to cluster. Two patients that showed clinical response (patient 67 and 59) fell within the cluster of non-repsonders. Two patients who were non-responders (patient 3 and 39) fell within the cluster designated as responders. The responding patients are also found within cross over cluster (ie the areas of overlap in the figure). However, there are two patients who are non-responders that fall within this area of overlap.


In FIG. 1 RESPONDERS were patients 27 and 38 (full/complete clinical responders), patients 2, 10, 20, 26-1, 26-2, 59 & 67 (mixed responders) and patients 19, 23, 65 and 75 (stable disease). NON-RESPONDERS in FIG. 1 were patients 3, 5, 8, 9, 13, 14, 15, 16, 28, 30, 36, 37, 39, 52, 55, 56, 60 and 66.


2. Baldi BH Analysis

This software is designed for statistical supervised gene classification in microarray experiments. A list of 100 most significant genes were identified that define the two groups. See FIG. 2 below. The clustering is a more effective than with spotfire with the majority of the responders found in the responder cluster. However we still see the same patients non responding (patients 3, 39), and the responding patients (67 and 59) that are located within the wrong clusters.


In FIG. 2 RESPONDERS were patients 27 and 38 (full/complete clinical responders), patients 2, 10, 20, 26-1, 26-2, 59 & 67 (mixed responders) and patients 19, 23, 65 and 75 (stable disease). NON-RESPONDERS in FIG. 2 were patients 3, 5, 8, 9, 13, 14, 15, 16, 28, 30, 36, 37, 39, 52, 55, 56, 60 and 66.


3. Arrayminer Analysis

This software is classifies genes by using a “train and test” method. In this method the software first identifies a discriminant set of markers for the training classes, similar to a classical cross-validation study.


Here due to the analysis there is only the responder or non-responder cluster, with no area of overlap. Here again there is mis-classification of samples, in particular patients 59 and 67 who both responded to treatment but in this analysis were in the cluster of non-responders. Patients 3, 14, 39, 52 and 66 were non-responders but were located in the cluster for responders using this analysis.


In FIG. 3 RESPONDERS were patients 27 and 38 (full/complete clinical responders), patients 10, 20, 26-1, 26-2, 59 & 67 (mixed responders and patients) 19, 23, 65 and 75 (stable disease). NON-RESPONDERS in FIG. 3 were patients 3, 5, 8, 9, 13, 14, 15, 16, 28, 30, 36, 37, 39, 52, 55, 56, 60 and 66.


Combination of the Three Methods

The three methods were used together to find a common set of gene probes that will define the signature with high significance. A venn diagram was created comparing all of the results. See FIG. 4. A list of 36 probesets was found that are common with all three programs. (Table 1B). These 36 probesets were then used for a supervised clustering of the responding and non-responding patients. The genes which are identified by the 36 probes sets form a specific aspect of the invention.


Fold Change Definition

In programs such as Arrayminer, Fold change of gene expression can be calculated. This is shown in Table 1B and is the change in average gene expression between two groups, for example responder vs non-responder. The statistical value attached to the fold change is calculated and is the more significant in genes where the level of expression is less variable between patients in each group, and difference between groups is larger.


Gene Expression Shown on a Heat Map


FIG. 5 is a heat map (a diagrammatic respresentation of the expression level of various genes for a given patient), on which can be seen individual expression of genes represented in the Y-Axes by a coloured box and the patients in the X-axes. The expression values of each gene in all samples are normalized to a mean of zero and a standard deviation of 1, and these normalized values are coded into a gradient of colors.


Affymetrix arrays have 11 probe pairs available to interrogate each gene. Ideally, the signal intensity from all of these 11 probes should be equal as they all interrogate the same gene. However, there are enormous differences between individual probes in a probe set. The pattern of the probe signals in a probe set is called a “probe response pattern”. The Robust Multi-array Average” (RMA) software uses, model-based algorithms to incorporate information from multiple microarrays to calculate the expression of a gene. After proper correction for background, and quantile normalisation of the probe intensities, the probe response pattern is fitted over multiple arrays an additive model in RMA software. These algorithms use the fitted models to detect abnormally behaving probes, which are subsequently excluded for calculating gene expression. Therefore, gene expression from these model-based algorithms can be expected to provide more reproducible results. RMA use a stochastic model to estimate gene expression which is potentially a better way of estimating gene expression. Algorithms are implemented in RMA software.



FIG. 4: The predictive 36 probesets correspond mainly to upregulation of genes related to immune infiltration and activation. These genes include HLA class II, Interleukin-2 receptor gamma, T cell receptor genes (TRBV19, TRAT1, TRGC2), granzyme, and CD69.


Increase in Treatment Efficacy

As described herein, gene profiling has allowed the identification of a subset of patients likely to respond to recMAGE-A3 treatment. This subset corresponds to ˜30% of the patient population. Patients having the gene profile show far higher efficacy levels could be obtained. Indeed, with the early identification of patients susceptible for anti-MAGE-A3 immunization, the efficacy of the treatment will probably increase to levels far higher than other current cancer treatments. This may also lead to a better compliance by the patient. For example, in 100 patients with melanoma, 60 will be found to express MAGE-A3. If these patients all receive recMAGE-A3 injections, 10 out of them will respond; leading to a 15% efficacy rate. However, if gene profile is performed on the 60 MAGE-A3-expressing patients, only the 14 out of them who are predicted to be susceptible to this treatment will receive recMAGE-A3 injections. The other 46 patients will receive another treatment. 10 out of these 14 patients will respond to the treatment, leading to a 71% efficacy rate.


Gene Profile in Other Tumour Types

This gene profiling has also been performed in a NSCLC study. However, as this study is blinded, only preliminary data are available. It is thought that the signature observed in melanoma is also present in NSCLC, stages IB and II. Preliminary data suggests approximately 30% of the patients present a gene profile signature characteristic of immune response and immune cell infiltration and that suggests they will respond to ASCI treatment.



FIG. 5 shows and expression profile for 30 individual patients for a number of genes.



FIG. 5
a shows the expression profiles for 31 patients of two genes.


Example 2
Predicting the Clinical Outcome of Patients Using Machine Learning Approaches
Materials & Methods.
Tumor Specimens, RNA Purification, Quality Control, Labeling and Amplification for Microarray Analysis

Tumor specimens (pre-vaccination) were used from a Mage-3 melanoma clinical trial (MAGE008). These were preserved, RNA prepared, labeled and amplified as in Example 1 above. The quality of the RNA samples was checked prior to hybridization to the genechip. Only data from samples that were deemed to adequately hybridize to the genechip were used in this Example (61 samples in total).


Microarray Chips, Hybridizations and Scanning.

As in the material and methods section of the first example above (referred to herein as Example 1), Affymetrix HG-U133.Plus2.0 genechips were employed, and hybridized and scanned as described therein.


Data Processing & Normalization.

The fluorescent scanned data image was processed and normalized using a R 2.3.1 [1] implementation of GCRMA algorithm [2,3].


Unspecific Filtering of Gene Expression Matrix

Prior to calculation of differential expression gene expression matrix was filtered in an unspecific (i.e. independently of experimental groups) manner. 4 processes were used:

  • 1. panp filtering: calls indicating whether a gene is expressed in a given sample (present call, P) or not (absent call, A) were derived for all array measures using the panp method implemented in the panp R package [4]. Only probe sets showing at least one P call throughout experimental samples were kept for subsequent calculations.
  • 2. SD filtering: standard deviation (SD) of each probe sets were calculated throughout samples, were only kept probe sets having SDs above the 75th percentile of all SDs.
  • 3. IQR filtering: interquartile range (IQR) of each probe sets were calculated throughout samples, were only kept probe sets having IQRs above the 7th quantile of all IQRs.
  • 4. SH filtering: SD of each probe sets were calculated throughout samples, the midpoint of the SD shorth (the shortest interval containing all of the data) as calculated using the shorth function of genefilter package [5] under R 2.3.1, were only kept probes sets having SD above the shorth for subsequent calculations.


Calculation of Differential Expression.

The differential expression between the groups of patients showing a clinical benefit after vaccination or not (subsequently called Responder (R) or Non-Responder (NR) groups) was calculated in R 2.3.1 program according to 2 statistical procedures:

  • 1. Regular t-test, as implemented in the genefilter package, and
  • 2. A modified (regularized, moderated) t-test, to account for poor estimates of gene-specific variance under standard t-test, such as the method of Jain et al [6], implemented the LPE R package [7], or the method of Smyth [8], implemented in the limma R package [9], or the method of Baldi and Long [10], also known as Cyber-T [11].


Correction for multiple testing by controlling the false discovery rate (FDR) at 5% was done under R 2.3.1 with Benjamini-Hochberg method [12] implemented in the multitest package [13].


Gene Profile Normalizations

To make the probe sets having low and high levels of expression comparable and to put an emphasis on differential profiles rather than absolute profiles, data was further normalized at the probe set level. Two gene-level normalizations schemes were used:

  • 1. IQR normalization, where each probe set measure is subtracted by its median over samples and divided by its IQR.
  • 2. Z-score normalization, where each probe set measure is subtracted by its mean over samples and divided by its SD.


Machine Learning Algorithms

The 14 machine learning algorithms (or predictive rules) interfaced in MLInterfaces package [14] running under R 2.3.1 program were used to train clinical outcome predictive models and to predict the Mage008 patient clinical outcomes, under the reporter lists calculated by the unspecific filtering, differential expression, gene normalization processes. These algorithms were, knn (k-nearest neighbour, kNN, function of class package), nnet (neural network), gbm (generalized boost regression), lvq1 (learning vector quantization 1), naiveBayes (naïve bayes classifier), svm (support vector machine), lda (linear discriminant algorithm), rpart (recursive partitioning), stat.diag.da (diagonal discriminant analysis), randomforest (random forest), bagging, ipredknn (k-nearest neighbour function form ipred package, equivalent to knn form class package), slda (stabilized linear discriminant analysis), pamr (partition around medoids, also known as nearest shrunken centroid classifier). Default parameters were used for all algorithms except for kNN rule where even values of k ranging from 1 to 7 were tested.


Leave-one-out (LOO) scheme of MLinterfaces coded in the xval function was used for cross-validation when appropriate, without re-calculation of reporter list at each cross-validation loop. The misclassification rate was calculated by averaging the number of wrongly predicted samples to the total number of samples of each patient group or class (either R or NR).


Some of the MLIinterfaces interfaced predictive rules (nnet, Ida, naiveBayes) were used outside of the MLInterfaces package as direct calling to make the related classifiers usable on external data sets independently of the data used to train the models.


The MiPP algorithm [15, 16], implemented in the MiPP R library and ran under R 2.3.1, was employed to reduce the number of probe sets involved in the reporter lists. The best reporters out of the submitted list were selected as optimizing the 10-fold cross-validation of linear discriminant analysis predictions of a training set and further reduced to reporters giving an optimized global misclassification error of linear discriminant analysis predictions of a testing set. Global misclassification error or rate was calculated as the ratio of the total number of misclassified patients to the total of set patients.


Results
Patient Sample Stratification for Training and Testing Section Definitions

A 31 sample subpart of the full 61 sample data set was used to train and test the classifying model in a first attempt; the remaining 30 samples were kept for subsequent model evaluations. Several training and testing sections were defined from the 31 sample data set subpart. The training sections were used to calculate the reporter list (i.e. the differentially expressed genes to be used in clinical outcome prediction of patient samples) and to set the machine learning algorithm weights for clinical outcome prediction. The testing sections allowed evaluation of the model performance independently of the patients used to construct the predictive model. Model evaluations were also undertaken on the training sections according to a cross-validation procedure.


Training and testing sections from the 31 sample data set subpart were defined as follows:

  • 1. A first training section containing 5 Responders and 5 Non-Responders, leaving 21 patients for the testing section;
  • 2. A second training section of 10 Responders and 11 Non-Responders, leaving 10 patients for the testing section;
  • 3. A last training section containing all 31 patients (13 Responders and 18 Non-Responders). In this last stratification there is no patient left for a testing section, classifying model would only be evaluated by a cross-validation procedure.


Identification of the Differential Expression Calculation Process Performing Best for Classification.

Gene expression data was pre-processed and normalized according to Material & Methods taking into account the full data set. Differential expressions (DE) between the Responder and Non-Responder groups were calculated for each training/testing section according to various processes.


The DE calculation framework was constructed as follows:

  • 1. Unspecific filtering of gene expression matrix: panp filtering, or not, followed by either SD, IQR or SH filtering, or none.
  • 2. Calculation of DE: either t-test or a modified (regularized, moderated) t-test, such as the method of Jain et al, implemented the LPE R package, or the method of Smyth, implemented in the limma R package, or the method of Baldi and Long (Cyber-T), followed by multiple testing correction, or not.
  • 3. Gene profile normalizations: Either IQR or Z-score normalizations, or none.


The processes minimizing the overall misclassification rates in both training and testing sections in at least two out of the three available training/testing stratification's were selected. The misclassification rate was obtained by comparing the predicted clinical outcome given by a kNN predictive rule to the given clinical outcome.


Seven DE processes were found as minimizing the overall misclassification rate according to the kNN rule:

    • t-test without correction for multiple testing and irrespective of panp filtering;
    • SH filter, t-test without correction for multiple testing and irrespective of panp filtering;
    • SD filter, t-test without correction for multiple testing;
    • SD filter, t-test without correction for multiple testing, Z-score normalization;
    • IQR filter, t-test without correction for multiple testing, IQR normalization.


The minimized overall misclassification rates for these processes were as follows:

    • 0% in the 5 Responders to 5 Non-Responders stratification, as evaluated by leave-one-out cross-validation, all patients were therefore correctly classified.
    • 20% in the 21 patients testing section, given by the direct prediction of these patients from the model defined from the 5 Responders to 5 Non-Responders training set. 80% of patients were correctly predicted.
    • 12% for the 13 Responders to 18 Non-Responders segregation, as assessed by cross-validation, being 88% of patient correctly predicted.


The performances for the other training/testing stratification was not found to be informative (i.e. no DE process converging to a minimized misclassification rate), hence not mentioned.


The last process, IQR filter, t-test without correction for multiple testing, IQR normalization, was preferred since the minimized misclassification rates were obtained with a higher value of k (k=5) than other six processes (k=3). It was anticipated that working with higher values of k would facilitate the transposition of the predictive model in further settings, since high k values generate simpler models supposed to be less biased towards a training set.


This process generated a reporter list of 489 Affymetrix probe sets. The reporter list is given in Table 4A, as Affymetrix probe set identifications along with gene names and symbols.


External Validation: Independent Evaluation of the Best Clinical Outcome Predicting Model.

The best DE calculation and gene expression treatment process (IQR filter, t-test without correction for multiple testing, IQR normalization) was used to build a kNN predictive model (k=5) from 13 Responders/18 Non-responders training section.


The clinical outcome of the independent patients that were previously left away was then directly predicted from this model. Of these 30 independent patients only 15 were informative (i.e. having a characterized clinical outcome). Misclassification rate was calculated on the basis on these 15 informative patients for the model evaluation.


According to this predictive model, misclassification rate was 34%, hence 66% of independent patients had their clinical outcome correctly predicted.


Improvement of Clinical Outcome Predicting Model Through Other Classification Rules.

On the basis of the best DE (and expression normalization) process as selected with a kNN rule, further classification (predictive) rules were tried to eventually increase the predictive model performance. Beside kNN, 13 other rules were assessed. For each selected DE process that performed for the kNN rule, each further rule was trained on the 13 Responders/18 Non-responders section of the data set, its predictive performance evaluated on the training set by cross-validation and on the independent set of 30 patient samples by direct prediction. Further classification rules did not improve the misclassification rate, as assessed by cross-validation on the training set, the lowest remaining unchanged at 12% of samples miss-predicted (88% of patient assigned to their correct clinical outcome).


However, for the above mentioned preferred DE process, the neural network rule did improve the misclassification rate on the independent set of 15 informative patients out of the 30 available, by reducing it from 34%, as given by KNN rule, to 30% (i.e. one additional patient correctly predicted), while keeping it the lowest on the cross-validation evaluation of the training set. Neural network rule then allows the correct prediction of 70% of patient independently of those used to train the model.


Furthermore, in a further evaluation of the predictive modeling performance, when clinical outcomes were available for all 30 external patient samples, i.e. when all the independent patients were informative for misclassification rate calculation, the lowest misclassification error became 26%, which is 74% of patients were correctly classified. This best performance obtained on a wider data set in terms of informative sample number was given by a Ida rule. A naiveBayes rule was also able to give a 28% misclassification rate, correctly prediction the clinical outcome of 72% of patients. However, the misclassification rate using kNN and nnet rules became 35% and 41%, respectively. This performance is based on the use of the gene list and probes of Table 4A.


Implementation of the Preferred Classifiers, Predicting the Clinical Outcome of Further Patient Biopsies.

To make use on further metastatic melanoma samples of the exemplified neural network classifier, yielding 30% of misclassification on the 15 informative sample external set, the following R code can be used in a R session (a stastical programme):


library(nnet)


set.seed(1234)


predict(nn, data, type=“class”)


where

    • data is a data frame containing the 489 reporter (Table 4A) expression data of the samples to classify (GCRMA sample normalized and IQR gene normalized). Samples are organized in columns and reporters in rows;
    • nn is the R object of class nnet shown in Appendix A.


      the Ida (linear discriminant analysis) classifier would be reproduced by programming the following R code chunk:


      library (MASS)


      predict(lda, data, type=“class”)


      where
    • data is as previously;
    • lda is the R object of class Ida shown in Appendix B.


The naïve Bayes classifier works under the following R coding:


library(e1071)


predict(nb, data, type=“class”)


where

    • data is as previously;
    • nb is the R object of class naiveBayes shown in Appendix C.


Down-Sizing the 489 Probe Set Reporter List While Maintaining an Identical Classification Performance.

The MiPP algorithm was used to determine if it was possible to reduce the number of reporters involved in the IQR filter, t-test without correction for multiple testing, IQR normalization, based predictive model while keeping the same misclassification rate. Indeed, working under a shorter reporter list would be more convenient for classifier follow-up purposes for instance such as transposition from a microarray based format to a quantitative RT-PCR format.


The 489 probe set microarray data was submitted to the MiPP process: 11 classifying probe sets were selected on the 13 R/18 NR training section as being sufficient to achieve a lowest global misclassification error, and 4 probe sets out of these were further identified as minimal on the 30 informative external sample data set to obtain the lowest global misclassification rate for the independent patients.


The 4 probe set reporter list was then used in leave-one-out cross-validation predictions of the 13 R/18 NR stratification of data as training set and direct prediction the 30 informative patient section as external testing set under all 14 predictive rules. LOO performance was increased for most of the rules (being as high as 3% of misclassification rate for Ida and naiveBayes among other), while misclassification rate stayed 28% on the external data set under svm and gbm rules.


The following table depicts the identity of the genes involved in the 4 probe set model:














Probe
Gene
Gene


Set ID
Symbol
Name







207651_at
GPR171
G protein-coupled receptor 171


205392_s_at
CCL14
chemokine (C-C motif) ligand 14


212233_at
MAP1B
microtubule-associated protein 1B


206204_at
GRB14
growth factor receptor-bound protein 14.









Example 3
Predicting the Clinical Outcome of Patients Using Quantitative Polymerase Chain Reaction (Q-PCR)
Material & Methods
Tumor Specimens and RNA Purification.

30 tumor specimens (pre-vaccination) were used from MAGE-A3 melanoma clinical trial (MAGE008). These were preserved and RNA extracted as in Example 1 above.


cDNA Synthesis and Quantitative PCR Amplification


2 μg of total RNA were retro-transcripted into cDNA using M-MLV reverse transcriptase (Invitrogen) and oligo(dT) or random primers.


The different interesting genes were amplified by quantitative PCR using TaqMan chemistry and 7900 sequence detection system (Applied Biosystems).


Genes were amplified using standard 96 well plates or the TaqMan® Immune Profiling Array (TaqMan Low density arrays—TLDA—Applied Biosystems). TLDA are ready to use 384 well plates pre-coated with primers and probes.


The 7900 apparatus is a fully integrated system for real-time detection of PCR including a 96-well or a TLDA thermal cycler, a laser to induce fluorescence, a charge-coupled device detector, a computer and a real-time sequence detection software.


In standard 96 well plates, cDNA corresponding to 50 ng of total RNA was amplified by polymerase-chain-reaction using the TF,TAQMAN,PCR REAGENT CORE KIT (Applied Biosystems). Primers and probes are listed in Table 5.


For the TaqMan® Immune Profiling Array, cDNA corresponding to only 1 ng of RNA was amplified by polymerase-chain-reaction using the TF,TAQMAN,PCR CORE REAGENT KIT (Applied Biosystems). The genes included in the array are listed in Table 6.


Data Processing and Normalization

All PCR data were normalized against H3F3A (standard 96 Well plates) or the geometric mean of GUSB and PGK1 (TLDA) house keeping genes (also referred to as constant genes). Expression values were afterwards log transformed.


Univariate Statistical Analysis

Analyses of variance (ANOVA1) were performed using the SAS software to significantly select the genes able to differentiate responder from non-responder groups. The first group was composed of 14 responder patients, the second one was composed of 15 non-responder patients. Each gene was analyzed independently from the others.


IL7R, CD3D, CD52, UBD, GPR171, GMZK, PRKCQ, STAT4, TRDV2, TRAT1, TRBV19, CD69, INDO1, CD45R, CD45RO, FoxP3, CD20, CCL5, FASLG, GNLY, GZMB, PRF1, IFNG, ICOS, TBX21, CD8A, CD3E, CXCL10, CXCL11, IRF1, TLR7 and CXCR3 genes were selected for their capacity to differentiate both groups. The p-value was <0.00001 for every gene. For every gene, a significant difference was proven between mean (responder/non-responder). The Geomean ratios between both groups were also calculated for all genes (Table 7A) and range from 3.4 to 21.2.


Correlation Analysis

A correlation matrix (Table8) was calculated between 30 genes showing that all these genes are pretty well correlated.


Logistic Regression Model

An analysis by logistic regression was performed using Proc logistic (SAS Sofware). Logistic regression analysis is often used to investigate the relationship between binary responses and a set of explanatory variables.


The number of predictors is too large and the use of all possible regression is not feasible. So, stepwise selection was employed. This procedure gives a model with a good value (high) for a specified criterion: Score Chi-square. This is analogous to the use of SSE or R2 in multiple linear regression.


The model information are:

    • Data: 29 patients and 111 genes.
    • Response variable: clinical status
    • Number of response level: 2 (responder-non responder)
    • Mode: binary logit
    • Optimization technique: Fisher's scoring


The model giving the best value of score Chi-square (Chi-square=16 and pvalue <0.00001) is:


Logit (p)=7.69+5.07 log(PRF1), with p the probability to be responder


Coefficient B0 (7.69) & B1 (5.07) are significant (p<0.005)


Other criterion can be used to test goodness of fit


















Likehood Ratio
23.1429 (chi-square) and <0.001 (p-value)



Wald
 6.9250 (chi-sqaure) and <0.001 (p-value)











Like in linear regression, a R2 is computed: 0.55.


From the 111 genes, 18 (with only one predictor) are listed in the Table 9. Higher the R2(%) and chi-square score are the better the model/gene.


Using the PRF1 model, it is possible to classify correctly 86.6% of patients.


Table 10 gives the percentage of correct classification calculated using the logistic regression model for some other genes.


Combining more than 1 gene didn't improve the classification performance.


Genex Analysis

The 30 patients were also classified using the PCA (Principal Component Analysis) and neural network analysis from Genex software with the genes PRF1, GZMB, GNLY, CD8A, PRKCQ, FOXP3, IFNG, CCL5, GPR171 and TRBV19.


For the neural network analysis, 5 responder patients (Patient ID No.s 27, 53, 65, 119, 127) and 5 non responder patients (Patient ID No.s 8, 60, 66, 81, 160) were used as training set. The remaining 20 patients were used as testing set.



FIG. 6 shows the Principal Component Analysis using PRF1, GZMB, GNLY, CD8A, PRKCQ, FOXP3, IFNG, CCL5, GPR171 and TRBV19 genes.


It can be seen the responders are clustered on the left-hand side of FIG. 6 and the non-responders are clustered on the right-hand side of the figure. Patients labeled 85, 3 and 154 are miss-classified. Therefore, the percentage of “correct” classification is 85% using the PCA.


The neural network approach confirms a correct classification range of 85%.


Comparison: Microarray to Q-PCR data.


17 genes (Table 12) evaluated by the Q-PCR technology were already present in the microarray gene lists. These genes are therefore able to discriminate responder from non responder patients whatever the technology used to detect them. These genes form a specific aspect of the invention.









TABLE 12







Genes present in microarray and Q-PCR list.








Gene symbol
Gene title





CCL5
chemokine (C-C motif) ligand 5


TRAT1
T cell receptor associated transmembrane adaptor 1


STAT4
signal transducer and activator of transcription 4


PRKCQ
protein kinase C, theta


GPR171
G protein-coupled receptor 171


UBD
ubiquitin D


CD52
CD52 molecule


CD3D
CD3d molecule, delta (CD3-TCR complex)


PRF1
perforin 1 (pore forming protein)


CD8A
CD8a molecule


CXCL10
chemokine (C—X—C motif) ligand 10


CD69
CD69 molecule


TRBV19
T cell receptor beta variable 19


TRDV2
T cell receptor delta variable 2


IL7R
interleukin 7 receptor


GZMK
granzyme K



PROTEIN-TYROSINE PHOSPHATASE, RECEPTOR-



TYPE, C


CD45R
(PTPRC)









Fourteen genes (Table 13) were able to discriminate responder from non-responder patients using Q-PCR technology were not present in the microarray gene lists. This may be due to the increased sensitivity of the Q-PCR technology compared to the microarray.









TABLE 13







Gene used to classify patients using Q-PCR technology, absent


in Microarray gene lists.








Gene



symbol
Gene title





FASLG
Fas ligand (TNF superfamily, member 6)


GNLY
granulysin



granzyme B (granzyme 2, cytotoxic T-lymphocyte-associated



serine


GZMB
esterase 1)


IFNG
interferon, gamma


ICOS
inducible T-cell co-stimulator


TBX21
T-box 21


CD3E
CD3e molecule, epsilon (CD3-TCR complex)


CXCL11
chemokine (C—X—C motif) ligand 11


CXCR3
chemokine (C—X—C motif) receptor 3


CD20
CD20 molecule


FOXP3
forkhead box P3


INDO
indoleamine-pyrrole 2,3 dioxygenase


IRF1
interferon regulatory factor 1


TLR7
toll-like receptor 7









Some genes absent in the microarray signature but are known to be expressed by immunological cells and thus are also able to predict the clinical outcome of the patients.


The presence of an immune infiltration into the tumoral tissue seems to be the most important biological event to predict the clinical outcome of the patients rather than only a limited list of genes.


For example, PRF1 and CD8A are present in the microarray gene lists and are expressed by CD8 T lymphocytes. CD8 T lymphocytes express also IFNG that is absent in the microarray gene lists. Nevertheless, a good prediction of the clinical response was achieved using this gene by Q-PCR.


The number of miss-classified patients using the q-PCR data remains in the same range than clustering and KNN approaches using microarray data. Therefore different technologies and softwares can be used to classify the patients.


Example 4
Predicting the Clinical Outcome of Patients Using Hierarchical Clustering Approach
Material & Methods
Tumor Specimens and RNA Purification.

67 tumor specimens (pre-vaccination) were used from MAGE-A3 melanoma clinical trial (MAGE008). These were preserved, RNA prepared, quality controlled, labeled and amplified as in Example 1 above. The quality of the RNA samples was checked prior to hybridization to the genechip.


Microarray Chips, Hybridizations and Scanning

As in the material and methods section of the first example above (referred to herein as Example 1), Affymetrix HG-U133.Plus2.0 genechips were employed, and hybridized and scanned as described in Example 1.


Data Processing & Normalization.

The fluorescent scanned data image was processed and normalized using a R 2.3.1 implementation of GCRMA algorithm as described in Example 2.


Selection of the Gene List

41 Probe Sets were selected to discriminate responder from non responder patients using Arrayminer software described in Example 1.


Analysis parameters were:

    • Train and test evaluation
    • Pre-definition of 2 class
      • a. Responder class: PID2, PID65, PID75, PID20, PID10, PID19, PID23, PID26, PID27, PID38, PID67
      • b. Non Responder class: PID14, PID52, PID66, PID37, PID16, PID13, PID55, PID56, PID5, PID60, PID8
        • wherein PID stands for patient identification No (ie the numerical label given to the patient)
    • Maximum number of markers per class: 25
    • Number of markers per couple: 1
    • Allow multi-class markers: Yes
    • Use KNN classification: No—Proprietary voting method was used.


A list of 50 probe sets was obtained. 9 Probe sets were removed due the Absence status in all samples. The intensities of the 41 probe sets for the 22 patients listed above are listed in Tables 11A and 11B.


Prediction of the Clinical Status

The clinical status of the 67 patients was predicted using the hierarchical clustering approach of Spotfire software.


Data were normalized regarding the genes using a Z-score calculation available in Spotfire before performing the Hierarchical clustering.


Calculation options of the hierarchical clustering were:

    • Clustering method: complete linkage
    • Similarity measure: Euclidean distance
    • Ordering function: average value


This clustering was performed for patients included into the AS15 (FIGS. 7 and 8) or the AS02B (FIGS. 9 and 10) arms.


Using the hierarchical clustering approach, about 58% of patients have the responder signature whatever the adjuvant group.


100% and 87.5% of patients with a clinical benefit are well clustered respectively in AS15 and in AS02b groups.


71% and 52% of patients with a progressive disease are well clustered respectively in AS15 and in AS02b groups.


In the clinical benefit cluster, 28% and 55% of patients have a progressive disease respectively in AS15 and in AS02b groups. The percentage of patients with a responder gene profile according to the invention who achieved a clinical benefit to the MAGE-A3 vaccination when the AS15 adjuvant was used was larger than the percentage who achieved a clinical benefit to the MAGE-A3 vaccination when AS02b adjuvant was employed in the formulation.


Example 5
Inducing a Responder's Profile

Initial biopsy (sampled before irradiation) of patient 59 did not have the responder signature while his second biopsy (sampled after irradiation) had the responder signature (data not shown) suggesting that irradiation of lesions may induce the responder signature.

  • 1. R Development Core Team (2006). R: A language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria. ISBN 3-900051-07-0, URL http://www.R-project.org)
  • 2. Jean (ZHIJIN) Wu and Rafael Irizarry with contributions from James MacDonald Jeff Gentry (2005). germa: Background Adjustment Using Sequence Information. R package version 2.4.1.
  • 3. Wu Z, Irizarry R A, Gentleman R, Martinez-Murillo F, Spencer F: A model-based background adjustment for oligonucleotide expression arrays. Journal of the American Statistical Association 2004, 99:909-917.
  • 4. Peter Warren (2005). panp: Presence-Absence Calls from Negative Strand Matching Probesets. R package version 1.2.0.
  • 5. R. Gentleman, V. Carey and W. Huber (2006). genefilter: genefilter: filter genes. R package version 1.10.1.
  • 6. Jain N, Thatte J, Braciale T, Ley K, O'Connell M, Lee J K. Local-pooled-error test for identifying differentially expressed genes with a small number of replicated microarrays. Bioinformatics. 2003 Oct. 12; 19(15):1945-51.
  • 7. Nitin Jain, Michael O'Connell and Jae K. Lee. Includes R source code contributed by HyungJun Cho <hcho(virginia.edu> (2006). LPE: Methods for analyzing microarray data using Local Pooled Error (LPE) method. R package version 1.6.0. http:/www.r-project.org.
  • 8. Smyth, G. K. Linear models and empirical Bayes methods for assessing differential expression in microarray experiments. Statistical Applications in Genetics and Molecular Biology (2004)3, No. 1, Article 3.
  • 9. Smyth, G. K. (2005). Limma: linear models for microarray data. In: ‘Bioinformatics and Computational Biology Solutions using R and Bioconductor’. R. Gentleman, V. Carey, S. Dudoit, R. Irizarry, W. Huber (eds), Springer, N.Y., pages 397-420.
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TABLE 1A







Gene sequences for and Seq ID No.s for the genes of Table 1










Seq





ID


No.
Gene name
Full gene sequence





 1
chromosome 6 open
>gi|58218985|ref|NM_001010923.1|Homo sapiens chromosome 6 open reading




reading frame 190
frame 190 (C6orf190), mRNA




ATACTTACAATTACGAGATTTATATTTGCATTAGTCTCTTTGGCTGGTGGGTAGGGGTGAGAGGCTCTTC




CTGGATCCCTTATTTTCTACAGGAGAGGAGGAAAACACCTGGGATGCTCCAGTGCTCTTACGCAGATAAT




GATCATTAACATCAGCCTCTCTGATCAAAGAGCTACTCCACCCCACTCTGGCTGTAGTGTGACATTCCTG




CCTGCCTGAGGAAGAAATGGTGAGCAGGGGCTGCAATTGCAGACAAGTGTCACCCAGAAGCCACAAGTTT




CTGTGAGCACCAGGTCTACAAACTACCCAAGGCATAGCAATGGCATTATCACTGGAAGAATTCGTCCACT




CCCTTGACCTCAGGACCCTACCCAGGGTTCTAGAAATCCAGGCAGGCATCTATCTTGAAGGCTCTATTTA




TGAAATGTTTGGAAATGAATGCTGTTTTTCAACAGGAGAAGTGATTAAAATTACTGGTCTCAAAGTTAAG




AAGATCATAGCTGAAATTTGTGAGCAGATTGAAGGTTGTGAGTCTCTACAGCCATTTGAACTGCCTATGA




ATTTTCCAGGTCTTTTTAAGATTGTGGCTGATAAAACTCCATACCTTACTATGGAAGAAATCACAAGGAC




CATTCATATTGGACCAAGTAGACTAGGGCATCCTTGCTTCTATCATCAGAAGGATATAAAACTAGAGAAC




CTCATCATAAAGCAGGGTGAGCAAATCATGCTCAACTCAGTTGAAGAGATTGATGGAGAAATAATGGTGA




GCTGTGCAGTAGCAAGGAATCATCAAACTCACTCATTTAATTTGCCTTTGTCACAAGAAGGAGAATTCTA




CGAGTGTGAAGATGAACGTATTTACACTCTAAAGGAGATTGTTGAATGGAAGATTCCTAAGAACAGAACA




AGAACTGTAAACCTTACAGATTTTTCAAATAAGTGGGACTCAACGAATCCATTTCCTAAAGACTTTTATG




GTACCCTGATTCTCAAGCCTGTTTATGAAATTCAAGGTGTGATGAAATTTCGAAAAGATATAATCCGCAT




CCTCCCCAGTCTAGATGTCGAAGTCAAAGACATCACTGATTCTTACGATGCTAACTGGTTTCTTCAGCTG




TTATCAACAGAAGATCTTTTTGAAATGACTAGTAAAGAGTTCCCCATAGTGACTGAAGTCATAGAAGCAC




CTGAAGGAAACCACCTGCCCCAAAGCATTTTACAGCCTGGGAAAACCATTGTGATCCACAAAAAGTACCA




GGCATCAAGAATCTTAGCTTCAGAAATTAGAAGCAATTTTCCTAAAAGACACTTCTTGATCCCCACTAGC




TATAAAGGCAAGTTCAAGCGGCGACCGAGGGAGTTCCCAACGGCCTATGACCTAGAGATCGCTAAGAGTG




AAAAGGAGCCTCTTCACGTGGTGGCCACCAAAGCGTTTCATTCCCCTCATGACAAGCTGTCATCCGTATC




TGTTGGGGACCAGTTTCTGGTGCATCAGTCAGAGACGACTGAAGTCCTCTGTGAGGGAATAAAAAAAGTG




GTGAATGTTCTGGCCTGTGAAAAAATCCTCAAAAAGTCCTATGAGGCTGCGCTGCTCCCTTTGTACATGG




AAGGAGGTTTTGTAGAGGTGATTCATGATAAGAAACAGTACCCGATTTCTGAGCTCTGTAAACAGTTCCG




TTTGCCCTTCAATGTGAAGGTGTCTGTCAGGGATCTTTCCATTGAAGAGGACGTGTTGGCTGCCACACCA




GGACTGCAGTTGGAGGAGGACATTACAGACTCTTACCTACTCATAAGTGACTTTGCCAACCCCACGGAGT




GCTGGGAAATTCCTGTGGGCCGCTTGAATATGACTGTTCAGTTAGTTAGTAATTTCTCTAGGGATGCAGA




ACCATTTCTAGTCAGGACTCTGGTAGAAGAGATCACTGAAGAGCAATATTACATGATGCGGAGATATGAA




AGCTCAGCCTCACATCCCCCACCTCGCCCTCCGAAACACCCCTCAGTAGAGGAAACAAAGTTAACCCTGC




TAACCTTAGCAGAAGAAAGGACGGTAGACCTGCCCAAGTCTCCCAAGCGTCATCACGTAGACATAACCAA




GAAACTTCACCCAAATCAAGCTGGCCTGGATTCAAAAGTACTGATTGGTAGTCAGAATGATTTGGTGGAT




GAAGAGAAAGAAAGGAGCAACCGTGGGGCCACAGCAATAGCAGAAACATTCAAAAATGAAAAACATCAAA




AATAACAAGATGTGACAGAAGCCACTTAGGCAGCAAACATAAATGTTGCAGTGAAAAAAGAAGCTAGCCT




TCTAGCTGAAAAACGAGTATTCCCCAATGGACTCCAGAAGAAACTTGATTCATCGCTGCAAAGGAAAGAA




CAACCTTAAAACTTTTAACAGATAAAACTTACAGAAACCTATGATATAGAATTCATATAGTCTATTCTGT




TGTGTCTAAATCTGTAGGCATTGTGTTGTTGTTCTTTAGGACGTATTTATTTAACTTGCACATTTTTTCA




GATTCTTATTTCTACTACCAACAACTAAGTAATTGGGAAATAATTCTGTATTTCAGTTTCTGAGTAAAAC




CAGTCTGAAATAGGATAAAAGCCACCAAATATTTTCTTTTTTTTCCAGAATTTGTTTTGCCATTTTTTAG




TGCTATCATCATTCCTAACAAGACTAACTTACAGAAAAATAATTATATCTGACTGATTTAAAATGTTCAG




GTTTCTTATCCAAATCCCTTGGAACTATGGAAAGGAGTTTGATTTCACATTCACAGTGTATTTACAAAAT




ACGCTGTGTCATAAATATGTTTGAATTCCAACAGCCAAAGCCATTGAGAGTCATAGGAGTTTTCCATAAC




CTTCTCTTCTATGACCCAACAACAAGCTCATGACTGAAATTTCACCAGATTTCTGAGACGATGTCTTAAT




ATTCTATGTGCTATGTACCAGATAATTCTTTAGATGAATGTTTCTTAGGATTGTAGGAAAATTATCTAGT




TAATCATAATATTTGATGGAAAGAAAAAGACAATAAAATTGTAATATAATAAATTTGGCTGACAAGAAAC




CAAAGTGATTCTTAATTAGTATACATCAGAATGATGCTCTTATAGTTGTACCATCTATAAAAATTACTTT




AAGGGCTCTCACATTTTAATAATTTATCTTATTATGTATTAAGTATACAGGAACAATATTATTTTTCCTT




TAACAAAATGAAGAGACAGGCTATCTGGTTAATGTTACATAGGAATTTAATAGTAATGCTTGAACTTCAT




CCATAGATCATACTCTGTACAAAATTTGTTAGCTAACATCCTATCTCATAATTATTTTATGTTTTGTGGA




GAAATTTGTTGATTTTGTACCAAAGTGTTTCTGAAGACAATAAATTGTGAGTCAACTTTAGAACAAAAAA




AATTAGAGTTTTTTCAATGTTTATATTCTGATTAAGCTTACTTTACCTTACATTTTTTCTAAGTAACAAT




GAATCCTGATTTCTAGTGTCCTAAAAATTGCTTAGTGATTTGATTGTGGTAATATCATTTCTTATCTACA




ATGTCTAAAGTTTTATGGGACAGTTTTTCTTTTATTTATTTTGCCTGTTTGTGCAGATAAGAACAGAAAC




TTTTCTAAGACCCACATTTGGTTATTGAAGGCCACAGCGAATCTTAACCTAACAGCCTTGACAAACTGCA




CCATAGGTGTTTTTAGACTCATATAATTTGTTATTTTTCAAACAATAGTGAATAATTAATATTTTTGTTT




GGAATTTGAGAACAATTAAATTTGTACTTTTAGTAACTACCATTCTTTGATTAGAAAATTAAGAGAATGC




ATATCTTACTTTGGTTGTAAATTATCAAGGGCTTTCTAATAGAAATCATATATAACATTTCTAAATATAA




GTCCTTTCACATACTGTGTTTCCAGTTGTCTTGATATTGAAAAGTGTAATAAACTTCATGCTCACCTATT




GGAGATTTGGGAAGGTTGAAAATAAACTTCCTAATTTTTAAAAAAAAAA





 2
hematopoietic cell-
>gi|37059786|ref|NM_005335.3|Homo sapiens hematopoietic cell-specific Lyn



specific Lyn
substrate 1 (HCLS1), mRNA



substrate 1
GTGGACGCGAGGAGCCGGGCGCTTAGAACAGAGGCTTGCACAGGTGGAGATGTGGAAGTCTGTAGTGGGC




CATGATGTGTCTGTTTCCGTGGAGACCCAGGGTGATGATTGGGACACAGATCCTGACTTTGTGAATGACA




TCTCTGAAAAGGAGCAACGATGGGGAGCCAAGACCATCGAGGGGTCTGGACGCACAGAACACATCAACAT




CCACCAGCTGAGGAACAAAGTATCAGAGGAGCATGATGTTCTCAGGAAGAAAGAGATGGAGTCAGGGCCC




AAAGCATCCCATGGCTATGGAGGTCGGTTTGGAGTAGAAAGAGACCGAATGGACAAGAGTGCAGTGGGCC




ATGAGTATGTTGCCGAGGTGGAGAAGCACTCTTCTCAGACGGATGCTGCCAAAGGCTTTGGGGGCAAGTA




CGGAGTTGAGAGGGACAGGGCAGACAAGTCAGCAGTCGGCTTTGATTATAAAGGAGAAGTGGAGAAGCAT




ACATCTCAGAAAGATTACTCTCGTGGCTTTGGTGGCCGGTACGGGGTGGAGAAGGATAAATGGGACAAAG




CAGCTCTGGGATATGACTACAAGGGAGAGACGGAGAAACACGAGTCCCAGAGAGATTATGCCAAGGGCTT




TGGTGGCCAGTATGGAATCCAGAAGGACCGAGTGGATAAGAGCGCTGTCGGCTTCAATGAAATGGAGGCC




CCGACCACAGCTTATAAGAAGACGACGCCCATAGAAGCCGCTTCTAGTGGTGCCCGTGGGCTGAAGGCGA




AATTTGAGTCCATGGCTGAGGAGAAGAGGAAGCGAGAGGAAGAGGAGAAGGCACAGCAGGTGGCCAGGAG




GCAACAGGAGCGAAAGGCTGTGACAAAGAGGAGCCCTGAGGCTCCACAGCCAGTGATAGCTATGGAAGAG




CCAGCAGTACCGGCCCCACTGCCCAAGAAAATCTCCTCAGAGGCCTGGCCTCCAGTTGGGACTCCTCCAT




CATCAGAGTCTGAGCCTGTGAGAACCAGCAGGGAACACCCAGTGCCCTTGCTGCCCATTAGGCAGACTCT




CCCGGAGGACAATGAGGAGCCCCCAGCTCTGCCCCCTAGGACTCTGGAAGGCCTCCAGGTGGAGGAAGAG




CCAGTGTACGAAGCAGAGCCTGAGCCTGAGCCCGAGCCTGAGCCCGAGCCTGAGAATGACTATGAGGACG




TTGAGGAGATGGACAGGCATGAGCAGGAGGATGAACCAGAGGGGGACTATGAGGAGGTGCTCGAGCCTGA




AGATTCTTCTTTTTCTTCTGCTCTGGCTGGATCATCAGGCTGCCCGGCTGGGGCTGGGGCTGGGGCTGTG




GCTCTGGGGATCTCAGCTGTGGCTCTATATGATTACCAAGGAGAGGGAAGTGATGAGCTTTCCTTTGATC




CGGACGACGTAATCACTGACATTGAGATGGTGGACGAGGGCTGGTGGCGGGGACGTTGCCATGGCCACTT




TGGACTCTTCCCTGCAAATTATGTCAAGCTTCTGGAGTGACTAGAGCTCACTGTCTACTGCAACTGTGAT




TTCCCATGTCCAAAGTGGCTCTGCCTCCACCCCCTCCCTATTCCTGATGCAAATGTCTAACCAGATGAGT




TTCTGGACAGACTTCCCTCTCCTGCTTCATTAAGGGCTTGCGGCAGAGACAGCATGGGGAAGGAGGTCCC




CTTCCCCAAGAGTCCTCTCTATCCTGGATGAGCTCATGAACATTTCTCTTGTGTTCCTGACTCCTTCCCA




ATGAACACCTCTCTGCCACCCCAAGCTCTGCTCTCCTCCTCTGTGAGCTCTGGGCTTCCCAGTTTGTTTA




CCCGGGAAAGTACGTCTAGATTGTGTGGTTTGCCTCATTGTGCTATTTGCCCACTTTCCTTCCCTGAAGA




AATATCTGTGAACCTTCTTTCTGTTCAGTCCTAAAATTCGAAATAAAGTGAGACTATGGTTCACCTGTAA




AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA





 3
interleukin 2
>gi|4557881|ref|NM_000206.1|Homo sapiens interleukin 2 receptor, gamma



receptor, gamma
(severe combined immunodeficiency) (IL2RG), mRNA



(severe combined
GAAGAGCAAGCGCCATGTTGAAGCCATCATTACCATTCACATCCCTCTTATTCCTGCAGCTGCCCCTGCT



immunodeficiency)
GGGAGTGGGGCTGAACACGACAATTCTGACGCCCAATGGGAATGAAGACACCACAGCTGATTTCTTCCTG




ACCACTATGCCCACTGACTCCCTCAGTGTTTCCACTCTGCCCCTCCCAGAGGTTCAGTGTTTTGTGTTCA




ATGTCGAGTACATGAATTGCACTTGGAACAGCAGCTCTGAGCCCCAGCCTACCAACCTCACTCTGCATTA




TTGGTACAAGAACTCGGATAATGATAAAGTCCAGAAGTGCAGCCACTATCTATTCTCTGAAGAAATCACT




TCTGGCTGTCAGTTGCAAAAAAAGGAGATCCACCTCTACCAAACATTTGTTGTTCAGCTCCAGGACCCAC




GGGAACCCAGGAGACAGGCCACACAGATGCTAAAACTGCAGAATCTGGTGATCCCCTGGGCTCCAGAGAA




CCTAACACTTCACAAACTGAGTGAATCCCAGCTAGAACTGAACTGGAACAACAGATTCTTGAACCACTGT




TTGGAGCACTTGGTGCAGTACCGGACTGACTGGGACCACAGCTGGACTGAACAATCAGTGGATTATAGAC




ATAAGTTCTCCTTGCCTAGTGTGGATGGGCAGAAACGCTACACGTTTCGTGTTCGGAGCCGCTTTAACCC




ACTCTGTGGAAGTGCTCAGCATTGGAGTGAATGGAGCCACCCAATCCACTGGGGGAGCAATACTTCAAAA




GAGAATCCTTTCCTGTTTGCATTGGAAGCCGTGGTTATCTCTGTTGGCTCCATGGGATTGATTATCAGCC




TTCTCTGTGTGTATTTCTGGCTGGAACGGACGATGCCCCGAATTCCCACCCTGAAGAACCTAGAGGATCT




TGTTACTGAATACCACGGGAACTTTTCGGCCTGGAGTGGTGTGTCTAAGGGACTGGCTGAGAGTCTGCAG




CCAGACTACAGTGAACGACTCTGCCTCGTCAGTGAGATTCCCCCAAAAGGAGGGGCCCTTGGGGAGGGGC




CTGGGGCCTCCCCATGCAACCAGCATAGCCCCTACTGGGCCCCCCCATGTTACACCCTAAAGCCTGAAAC




CTGAACCCCAATCCTCTGACAGAAGAACCCCAGGGTCCTGTAGCCCTAAGTGGTACTAACTTTCCTTCAT




TCAACCCACCTGCGTCTCATACTCACCTCACCCCACTGTGGCTGATTTGGAATTTTGTGCCCCCATGTAA




GCACCCCTTCATTTGGCATTCCCCACTTGAGAATTACCCTTTTGCCCCGAACATGTTTTTCTTCTCCCTC




AGTCTGGCCCTTCCTTTTCGCAGGATTCTTCCTCCCTCCCTCTTTCCCTCCCTTCCTCTTTCCATCTACC




CTCCGATTGTTCCTGAACCGATGAGAAATAAAGTTTCTGTTGATAATCATC





 4
CD52 antigen
>gi|68342029|ref|NM_001803.2|Homo sapiens CD52 molecule (CD52), mRNA



(CAMPATH-1
CTCCTGGTTCAAAAGCAGCTAAACCAAAAGAAGCCTCCAGACAGCCCTGAGATCACCTAAAAAGCTGCTA



antigen)///
CCAAGACAGCCACGAAGATCCTACCAAAATGAAGCGCTTCCTCTTCCTCCTACTCACCATCAGCCTCCTG



CD52 antigen
GTTATGGTACAGATACAAACTGGACTCTCAGGACAAAACGACACCAGCCAAACCAGCAGCCCCTCAGCAT



(CAMPATH-1
CCAGCAACATAAGCGGAGGCATTTTCCTTTTCTTCGTGGCCAATGCCATAATCCACCTCTTCTGCTTCAG



antigen)
TTGAGGTGACACGTCTCAGCCTTAGCCCTGTGCCCCCTGAAACAGCTGCCACCATCACTCGCAAGAGAAT




CCCCTCCATCTTTGGGAGGGGTTGATGCCAGACATCACCAGGTTGTAGAAGTTGACAGGCAGTGCCATGG




GGGCAACAGCCAAAATAGGGGGGTAATGATGTAGGGGCCAAGCAGTGCCCAGCTGGGGGTCAATAAAGTT




ACCCTTGTACTTGCAAAAAAAAAAAAAAAAAAA





 5
CD2 antigen (p50),
>gi|31542293|ref|NM_001767.2|Homo sapiens CD2 molecule (CD2), mRNA



sheep red blood
ACCAACCCCTAAGATGAGCTTTCCATGTAAATTTGTAGCCAGCTTCCTTCTGATTTTCAATGTTTCTTCC



cell receptor///
AAAGGTGCAGTCTCCAAAGAGATTACGAATGCCTTGGAAACCTGGGGTGCCTTGGGTCAGGACATCAACT



CD2 antigen (p50),
TGGACATTCCTAGTTTTCAAATGAGTGATGATATTGACGATATAAAATGGGAAAAAACTTCAGACAAGAA



sheep red blood
AAAGATTGCACAATTCAGAAAAGAGAAAGAGACTTTCAAGGAAAAAGATACATATAAGCTATTTAAAAAT



cell receptor
GGAACTCTGAAAATTAAGCATCTGAAGACCGATGATCAGGATATCTACAAGGTATCAATATATGATACAA




AAGGAAAAAATGTGTTGGAAAAAATATTTGATTTGAAGATTCAAGAGAGGGTCTCAAAACCAAAGATCTC




CTGGACTTGTATCAACACAACCCTGACCTGTGAGGTAATGAATGGAACTGACCCCGAATTAAACCTGTAT




CAAGATGGGAAACATCTAAAACTTTCTCAGAGGGTCATCACACACAAGTGGACCACCAGCCTGAGTGCAA




AATTCAAGTGCACAGCAGGGAACAAAGTCAGCAAGGAATCCAGTGTCGAGCCTGTCAGCTGTCCAGAGAA




AGGTCTGGACATCTATCTCATCATTGGCATATGTGGAGGAGGCAGCCTCTTGATGGTCTTTGTGGCACTG




CTCGTTTTCTATATCACCAAAAGGAAAAAACAGAGGAGTCGGAGAAATGATGAGGAGCTGGAGACAAGAG




CCCACAGAGTAGCTACTGAAGAAAGGGGCCGGAAGCCCCAACAAATTCCAGCTTCAACCCCTCAGAATCC




AGCAACTTCCCAACATCCTCCTCCACCACCTGGTCATCGTTCCCAGGCACCTAGTCATCGTCCCCCGCCT




CCTGGACACCGTGTTCAGCACCAGCCTCAGAAGAGGCCTCCTGCTCCGTCGGGCACACAAGTTCACCAGC




AGAAAGGCCCGCCCCTCCCCAGACCTCGAGTTCAGCCAAAACCTCCCCATGGGGCAGCAGAAAACTCATT




GTCCCCTTCCTCTAATTAAAAAAGATAGAAACTGTCTTTTTCAATAAAAAGCACTGTGGATTTCTGCCCT




CCTGATGTGCATATCCGTACTTCCATGAGGTGTTTTCTGTGTGCAGAACATTGTCACCTCCTGAGGCTGT




GGGCCACAGCCACCTCTGCATCTTCGAACTCAGCCATGTGGTCAACATCTGGAGTTTTTGGTCTCCTCAG




AGAGCTCCATCACACCAGTAAGGAGAAGCAATATAAGTGTGATTGCAAGAATGGTAGAGGACCGAGCACA




GAAATCTTAGAGATTTCTTGTCCCCTCTCAGGTCATGTGTAGATGCGATAAATCAAGTGATTGGTGTGCC




TGGGTCTCACTACAAGCAGCCTATCTGCTTAAGAGACTCTGGAGTTTCTTATGTGCCCTGGTGGACACTT




GCCCACCATCCTGTGAGTAAAAGTGAAATAAAAGCTTTGACTAGAAAAAAAAAAAAAAAAAAAAAAAAAA




AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA





 6
ubiquitin D
>gi|50355987|ref|NN_006398.2|Homo sapiens ubiquitin D (UBD), mRNA




GATTGCTTGAGGAGAGAAGTATGTGATCAGAAAGCATTCTTTGTCTATTAACTCCTGCCCAGCAAAAGTG




AAAGAAAATTCATGGGAGCATGCAAGAACAAAGAGCACAGCAAAGCTGGACAAACACAGCAATCCAGGCA




GGGGATTTCCAACTCAACTCTGGTATGTAAGCTGCATGCAAAGTCCTTTTTCTGTCTCTGGTTTCTGGCC




CCTTGTCTGCAGAGATGGCTCCCAATGCTTCCTGCCTCTGTGTGCATGTCCGTTCCGAGGAATGGGATTT




AATGACCTTTGATGCCAACCCATATGACAGCGTGAAAAAAATCAAAGAACATGTCCGGTCTAAGACCAAG




GTTCCTGTGCAGGACCAGGTTCTTTTGCTGGGCTCCAAGATCTTAAAGCCACGGAGAAGCCTCTCATCTT




ACGGCATTGACAAAGAGAAGACCATCCACCTTACCCTGAAAGTGGTGAAGCCCAGTGATGAGGAGCTGCC




CTTGTTTCTTGTGGAGTCAGGTGATGAGGCAAAGAGGCACCTCCTCCAGGTGCGAAGGTCCAGCTCAGTG




GCACAAGTGAAAGCAATGATCGAGACTAAGACGGGTATAATCCCTGAGACCCAGATTGTGACTTGCAATG




GAAAGAGACTGGAAGATGGGAAGATGATGGCAGATTACGGCATCAGAAAGGGCAACTTACTCTTCCTGGC




ATCTTATTGTATTGGAGGGTGACCACCCTGGGCATGGGGTGTTGGCAGGGGTCAAAAAGCTTATTTCTTT




TAATCTCTTACTCAACGAACACATCTTCTGATGATTTCCCAAAATTAATGAGAATGAGATGAGTAGAGTA




AGATTTGGGTGGGATGGGTAGGATGAAGTATATTGCCCAACTCTATGTTTCTTTGATTCTAACACAATTA




ATTAAGTGACATGATTTTTACTAATGTATTACTGAGACTAGTAAATAAATTTTTAAGCCAA





 7
signal transducer
>gi|21618332|ref|NM_003151.2|Homo sapiens signal transducer and activator



and activator of
of transcription 4 (STAT4), mRNA



transcription 4
AGAGGACGCCCGGTGAAGGGGCTCCAGCCTGGCAGTTTCTGCGTGTTAGCATTTCTAGAATAGAGTGGGT




GGGAACTGACCCAAGTAAAGTCCCAGAGACTCGAACACTGACGCACAGGAAAGCCTCAAGTGGGAGGAGA




AATGCAAATCCCCTACTGATGATGGCGTCAGCGGCTTTCTCCTAGGGACTGTGAGGGGCGCTTCTGACTT




TGGACTTGAGCACTGCCTGGGACCTGTGCTGAGAGAGCGCTAGCATGTCTCAGTGGAATCAAGTCCAACA




GTTAGAAATCAAGTTTTTGGAGCAGGTGGATCAATTCTATGATGACAACTTTCCCATGGAAATTCGGCAT




CTGTTGGCCCAATGGATTGAAAATCAAGACTGGGAGGCAGCTTCTAACAATGAAACCATGGCAACGATTC




TTCTTCAAAACTTGTTAATACAACTGGATGAACAGTTAGGTCGTGTTTCCAAAGAGAAAAACCTACTCTT




GATACACAATCTAAAAAGAATTAGGAAGGTCCTTCAGGGAAAATTTCATGGAAATCCAATGCATGTAGCT




GTGGTTATTTCAAACTGTTTAAGGGAAGAGAGGAGAATATTGGCTGCAGCCAACATGCCTGTCCAGGGGC




CTCTAGAGAAATCCTTACAAAGTTCTTCAGTTTCAGAAAGACAGAGGAATGTGGAGCACAAAGTGGCTGC




CATTAAAAACAGTGTGCAGATGACAGAACAAGATACCAAATACTTAGAAGATCTGCAAGACGAATTTGAC




TACAGGTATAAAACAATTCAGACAATGGATCAGAGTGACAAGAATAGTGCCATGGTGAATCAGGAAGTTT




TGACACTGCAGGAAATGCTTAACAGCCTCGATTTCAAGAGAAAGGAGGCTCTCAGTAAAATGACCCAAAT




CATCCATGAGACAGACCTGTTAATGAACACCATGCTCATAGAAGAGCTGCAAGACTGGAAGCGGCGGCAG




CAAATCGCCTGCATCGGGGGTCCACTCCACAATGGGCTCGACCAGCTTCAGAACTGCTTTACACTATTGG




CAGAAAGTCTTTTCCAACTGAGAAGGCAATTGGAGAAACTAGAGGAGCAATCTACCAAAATGACATATGA




AGGTGATCCCATTCCAATGCAAAGAACTCACATGCTAGAAAGAGTCACCTTCTTGATCTACAACCTTTTC




AAGAACTCATTTGTGGTTGAGCGACAGCCATGTATGCCAACCCACCCTCAGAGGCCGTTGGTACTTAAAA




CCCTAATTCAGTTCACTGTAAAACTAAGGCTACTAATAAAATTGCCAGAACTAAACTATCAGGTAAAGGT




TAAGGCATCAATTGACAAGAATGTTTCAACTCTAAGCAACCGAAGATTTGTACTTTGTGGAACTAATGTC




AAAGCCATGTCTATTGAAGAATCTTCCAATGGGAGTCTCTCAGTAGAATTTCGACATTTGCAACCAAAGG




AAATGAAGTCCAGTGCTGGAGGTAAAGGAAATGAGGGCTGTCACATGGTGACTGAAGAACTTCATTCCAT




AACGTTTGAAACACAGATCTGCCTCTATGGCCTGACCATAGATTTGGAGACCAGCTCATTGCCTGTGGTG




ATGATTTCCAATGTCAGTCAGTTACCTAATGCTTGGGCATCCATCATTTGGTACAACGTGTCAACCAACG




ATTCCCAGAACTTGGTTTTCTTTAATAATCCTCCACCTGCCACATTGAGTCAACTACTGGAGGTGATGAG




CTGGCAGTTTTCATCGTACGTTGGTCGTGGTCTTAACTCAGATCAACTCCATATGCTGGCAGAGAAGCTT




ACAGTCCAATCTAGCTACAGTGATGGTCACCTCACCTGGGCCAAGTTCTGCAAGGAACATTTACCTGGTA




AATCATTTACCTTTTGGACATGGCTTGAAGCAATATTGGATCTAATTAAGAAACACATTCTTCCCCTTTG




GATTGATGGGTATGTCATGGGCTTTGTTAGCAAAGAGAAGGAACGGCTGTTGCTAAAGGATAAAATGCCT




GGCACCTTTTTATTAAGATTCAGTGAAAGCCATCTCGGAGGAATAACTTTCACCTGGGTGGACCATTCTG




AAAGTGGGGAAGTGAGATTCCACTCTGTAGAACCCTACAATAAAGGCCGGTTGTCTGCTCTGCCATTCGC




TGACATCCTGCGAGACTACAAAGTTATTATGGCTGAAAACATTCCTGAAAACCCTCTGAAGTACCTATAT




CCTGACATTCCCAAAGACAAAGCCTTCGGTAAACACTACAGCTCTCAGCCTTGCGAAGTTTCAAGACCAA




CAGAAAGGGGTGACAAAGGTTATGTTCCTTCTGTTTTTATCCCCATCTCAACAATCCGAAGTGATTCAAC




AGAGCCACATTCTCCATCAGACCTTCTTCCCATGTCTCCAAGTGTGTATGCGGTGTTGAGAGAAAACCTG




AGTCCCACAACAATTGAAACTGCAATGAAGTCTCCTTATTCTGCTGAATGACAGGATAAACTCTGACGCA




CCAAGAAAGGAAGCAAATGAAAAAGTTTAAAGACTGTTCTTTGCCCAATAACCACATTTTATTTCTTCAG




CTTTGTAAATACCAGGTTCTAGGAAATGTTTGACATCTGAAGCTCTCTTCACACTCCCGTGGCACTCCTC




AATTGGGAGTGTTGTGACTGAAATGCTTGAAACCAAAGCTTCAGATAAACTTGCAAGATAAGACAACTTT




AAGAAACCAGTGTTAATAACAATATTAACAG





 8
granzyme K
>gi|73747815|ref|NM_002104.2|Homo sapiens granzyme K (granzyme 3;



(granzyme 3;
tryptase II) (GZMK), mRNA



tryptase II)///
GATCAACACATTTCATCTGGGCTTCTTAAATCTAAATCTTTAAAATGACTAAGTTTTCTTCCTTTTCTCT



granzyme K
GTTTTTCCTAATAGTTGGGGCTTATATGACTCATGTGTGTTTCAATATGGAAATTATTGGAGGGAAAGAA



(granzyme 3;
GTGTCACCTCATTCCAGGCCATTTATGGCCTCCATCCAGTATGGCGGACATCACGTTTGTGGAGGTGTTC



tryptase II)
TGATTGATCCACAGTGGGTGCTGACAGCAGCCCACTGCCAATATCGGTTTACCAAAGGCCAGTCTCCCAC




TGTGGTTTTAGGCGCACACTCTCTCTCAAAGAATGAGGCCTCCAAACAAACACTGGAGATCAAAAAATTT




ATACCATTCTCAAGAGTTACATCAGATCCTCAATCAAATGATATCATGCTGGTTAAGCTTCAAACAGCCG




CAAAACTCAATAAACATGTCAAGATGCTCCACATAAGATCCAAAACCTCTCTTAGATCTGGAACCAAATG




CAAGGTTACTGGCTGGGGAGCCACCGATCCAGATTCATTAAGACCTTCTGACACCCTGCGAGAAGTCACT




GTTACTGTCCTAAGTCGAAAACTTTGCAACAGCCAAAGTTACTACAACGGCGACCCTTTTATCACCAAAG




ACATGGTCTGTGCAGGAGATGCCAAAGGCCAGAAGGATTCCTGTAAGGGTGACTCAGGGGGCCCCTTGAT




CTGTAAAGGTGTCTTCCACGCTATAGTCTCTGGAGGTCATGAATGTGGTGTTGCCACAAAGCCTGGAATC




TACACCCTGTTAACCAAGAAATACCAGACTTGGATCAAAAGCAACCTTGTCCCGCCTCATACAAATTAAG




TTACAAATAATTTTATTGGATGCACTTGCTTCTTTTTTCCTAATATGCTCGCAGGTTAGAGTTGGGTGTA




AGTAAAGCAGAGCACATATGGGGTCCATTTTTGCACTTGTAAGTCATTTTATTAAGGAATCAAGTTCTTT




TTCACTTGTATCACTGATGTATTTCTACCATGCTGGTTTTATTCTAAATAAAATTTAGAAGACTCAAAAA




AAAAAAAAAAAAAAAAAAAAAAAA





 9
CD3G antigen, gamma
>gi|4557428|ref|NM_000073.1|Homo sapiens CD3g molecule, gamma (CD3-TCR



polypeptide (TiT3
complex) (CD3G), mRNA



complex)
GGGCTGCTCCACGCTTTTGCCGGAGACAGAGACTGACATGGAACAGGGGAAGGGCCTGGCTGTCCTCATC




CTGGCTATCATTCTTCTTCAAGGTACTTTGGCCCAGTCAATCAAAGGAAACCACTTGGTTAAGGTGTATG




ACTATCAAGAAGATGGTTCGGTACTTCTGACTTGTGATGCAGAAGCCAAAAATATCACATGGTTTAAAGA




TGGGAAGATGATCGGCTTCCTAACTGAAGATAAAAAAAAATGGAATCTGGGAAGTAATGCCAAGGACCCT




CGAGGGATGTATCAGTGTAAAGGATCACAGAACAAGTCAAAACCACTCCAAGTGTATTACAGAATGTGTC




AGAACTGCATTGAACTAAATGCAGCCACCATATCTGGCTTTCTCTTTGCTGAAATCGTCAGCATTTTCGT




CCTTGCTGTTGGGGTCTACTTCATTGCTGGACAGGATGGAGTTCGCCAGTCGAGAGCTTCAGACAAGCAG




ACTCTGTTGCCCAATGACCAGCTCTACCAGCCCCTCAAGGATCGAGAAGATGACCAGTACAGCCACCTTC




AAGGAAACCAGTTGAGGAGGAATTGAACTCAGGACTCAGAGTAGTCCAGGTGTTCTCCTCCTATTCAGTT




CCCAGAATCAAAGCAATGCATTTTGGAAAGCTCCTAGCAGAGAGACTTTCAGCCCTAAATCTAGACTCAA




GGTTCCCAGAGATGACAAATGGAGAAGAAAGGCCATCAGAGCAAATTTGGGGGTTTCTCAAATAAAATAA




AAATAAAAACAAATACTGTGTTTCAGAAGCGCCACCTATTGGGGAAAATTGT





10
G protein-coupled
>gi|31377771|ref|NM_013308.2|Homo sapiens G protein-coupled receptor 171



receptor 171
(GPR171), mRNA




GGTTGCTACTGCTGCGGCTAACCAAACAGCTCATGCTTCTCTGAAGACTTGCAGCAAGGTTTGCTGAGGC




TCACAGAAGATAGCCCCAGTGTTTTGGAGTGGTTTTGAATGTGATTCTGAGATCAGACTGACTGAGCTGG




AATCCTGGCTTTATATCTTACCAGCTACACAACCTTGGAGTCTTAGAAATTTTTTCTTTTCAATAAGCAG




TCATCCTTACTTTCCCTCAAGATGACAAACAGTTCGTTCTTCTGCCCAGTTTATAAAGATCTGGAGCCAT




TCACGTATTTTTTTTATTTAGTTTTCCTTGTTGGAATTATTGGAAGTTGTTTTGCAACCTGGGCTTTTAT




ACAGAAGAATACGAATCACAGGTGTGTGAGCATCTACTTAATTAATTTGCTTACAGCCGATTTCCTGCTT




ACTCTGGCATTACCAGTGAAAATTGTTGTTGACTTGGGTGTGGCACCTTGGAAGCTGAAGATATTCCACT




GCCAAGTAACAGCCTGCCTCATCTATATCAATATGTATTTATCAATTATCTTCTTAGCATTTGTCAGCAT




TGACCGCTGTCTTCAGCTGACACACAGCTGCAAGATCTACCGAATACAAGAACCCGGATTTGCCAAAATG




ATATCAACCGTTGTGTGGCTAATGGTCCTTCTTATAATGGTGCCAAATATGATGATTCCCATCAAAGACA




TCAAGGAAAAGTCAAATGTGGGTTGTATGGAGTTTAAAAAGGAATTTGGAAGAAATTGGCATTTGCTGAC




AAATTTCATATGTGTAGCAATATTTTTAAATTTCTCAGCCATCATTTTAATATCCAATTGCCTTGTAATT




CGACAGCTCTACAGAAACAAAGATAATGAAAATTACCCAAATGTGAAAAAGGCTCTCATCAACATACTTT




TAGTGACCACGGGCTACATCATATGCTTTGTTCCTTACCACATTGTCCGAATCCCGTATACCCTCAGCCA




GACAGAAGTCATAACTGATTGCTCAACCAGGATTTCACTCTTCAAAGCCAAAGAGGCTACACTGCTCCTG




GCTGTGTCGAACCTGTGCTTTGATCCTGTCCTGTACTATCACCTCTCAAAAGCATTCCGCTCAAAGGTCA




CTGAGACTTTTGCCTCACCTAAAGAGACCAAGGCTCAGAAAGAAAAATTAAGATGTGAAAATAATGCATA




AAAGACAGGATTTTTGTGCTACCAATTCTGGCCTTACTGGACCATAAAGTTAATTATAGCTTTGAAAGAT




AAAAAAAAAAAAAAAAACAAAAAAAAACTCAGTATGAAAAAATACAGTTAGCTAGCAAATATGGACAGGT




TTACTTAGAAATCCTGTTTCTAAATGCAAGTCAAGCTTTATTGTTAGGCTTGCTGCTACTCATTAACCCA




AATATTTGTACAAAAAACTAAAGAGTCTCATTGAACGAATGTAAAATCCTGCAATATCCTTGAAATCCAA




AAGAGGTCCATGACATAGACCCAAAGGTATTCATGAGTTATTCATTTAAATGCCTGGAACTGACTTCTTG




ATAAAAATATAAAAAATAATTTCCATGTAAGTTACCAGAAAGCCCACCAGCAACATAATTTTAAAGCCTT




TCGGATTACTTTTAAAAAATGCAGCTTACATATAACAACTTGTGCCTATTTTATTTCTAATCTATCACTT




CAAAAGATGGTAATCTTTCAACTCATTATTCCTCCAATTTTTAATGTCGAATTTTTTTCTAACACAATAA




CCAAAAGCTTTTATTTATAAAAAGGCTTGAAAAATATAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA




AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA





11
Protein kinase C,
>gi|89353296|ref|NM_001183.4|Homo sapiens ATPase, H+ transporting,



beta 1
lysosomal accessory protein 1 (ATP6AP1), mRNA




GGGGGCAACGGTCACCTGATCTGCGGCTGTCGAGGCCGCTGAGGCAGTGGAGGCTGAGGCTATGATGGCG




GCCATGGCGACGGCTCGAGTGCGGATGGGGCCGCGATGCGCCCAGGCGCTCTGGCGCATGCCGTGGCTGC




CGGTGTTTTTGTCGTTGGCGGCGGCGGCGGCGGCGGCAGCGGCGGAGCAGCAGGTCCCGCTGGTGCTGTG




GTCGAGTGACCGGGACTTGTGGGCTCCTGCGGCCGACACTCATGAAGGCCACATCACCAGCGACTTGCAG




CTCTCTACCTACTTAGATCCCGCCCTGGAGCTGGGTCCCAGGAATGTGCTGCTGTTCCTGCAGGACAAGC




TGAGCATTGAGGATTTCACAGCATATGGCGGTGTGTTTGGAAACAAGCAGGACAGCGCCTTTTCTAACCT




AGAGAATGCCCTGGACCTGGCCCCCTCCTCACTGGTGCTTCCTGCCGTCGACTGGTATGCAGTCAGCACT




CTGACCACTTACCTGCAGGAGAAGCTCGGGGCCAGCCCCTTGCATGTGGACCTGGCCACCCTGCGGGAGC




TGAAGCTCAATGCCAGCCTCCCTGCTCTGCTGCTCATTCGCCTGCCCTACACAGCCAGCTCTGGTCTGAT




GGCACCCAGGGAAGTCCTCACAGGCAACGATGAGGTCATCGGGCAGGTCCTGAGCACACTCAAGTCCGAA




GATGTCCCATACACAGCGGCCCTCACAGCGGTCCGCCCTTCCAGGGTGGCCCGTGATGTAGCCGTGGTGG




CCGGAGGGCTAGGTCGCCAGCTGCTACAAAAACAGCCAGTATCACCTGTGATCCATCCTCCTGTGAGTTA




CAATGACACCGCTCCCCGGATCCTGTTCTGGGCCCAAAACTTCTCTGTGGCGTACAAGGACCAGTGGGAG




GACCTGACTCCCCTCACCTTTGGGGTGCAGGAACTCAACCTGACTGGCTCCTTCTGGAATGACTCCTTTG




CCAGGCTCTCACTGACCTATGAACGACTCTTTGGTACCACAGTGACATTCAAGTTCATTCTCGCCAACCG




CCTCTACCCAGTGTCTGCCCGGCACTGGTTTACCATGGAGCGCCTCGAAGTCCACAGCAATGGCTCCGTC




GCCTACTTCAATGCTTCCCAGGTCACAGGGCCCAGCATCTACTCCTTCCACTGCGAGTATGTCAGCAGCC




TGAGCAAGAAGGGTAGTCTCCTCGTGGCCCGCACGCAGCCCTCTCCCTGGCAGATGATGCTTCAGGACTT




CCAGATCCAGGCTTTCAACGTAATGGGGGAGCAGTTCTCCTACGCCAGCGACTGTGCCAGCTTCTTCTCC




CCCGGCATCTGGATGGGGCTGCTCACCTCCCTGTTCATGCTCTTCATCTTCACCTATGGCCTGCACATGA




TCCTCAGCCTCAAGACCATGGATCGCTTTGATGACCACAAGGGCCCCACTATTTCTTTGACCCAGATTGT




GTGACCCTGTGCCAGTGGGGGGGTTGAGGGTGGGACGGTGTCCGTGTTGTTGCTTTCCCACCCTGCAGCG




CACTGGACTGAAGAGCTTCCCTCTTCCTACTGCAGCATGAACTGCAAGCTCCCCTCAGCCCATCTTGCTC




CCTCTTCAGCCCGCTGAGGAGCTTTCTTGGGCTGCCCCCATCTCTCCCAACAAGGTGTACATATTCTGCG




TAGATGCTAGACCAACCAGCTTCCCAGGGTTCGTCGCTGTGAGGCGTAAGGGACATGAATTCTAGGGTCT




CCTTTCTCCTTATTTATTCTTGTGGCTACATCATCCCTGGCTGTGGATAGTGCTTTTGTGTAGCAAATGC




TCCCTCCTTAAGGTTATAGGGCTCCCTGAGTTTGGGAGTGTGGAAGTACTACTTAACTGTCTGTCCTGCT




TGGCTGTCGTTATCGTTTTCTGGTGATGTTGTGCTAACAATAAGAAGTACACGGGTTTATTTCTGTGGCC




TGAGAAGGAAGGGACCTCCACGACAGGTGGGCTGGGTGCGATCGCCGGCTGTTTGGCATGTTCCCACCGG




GAGTGCCGGGCAGGAGCATGGGGTGCTTGGTTGTTTCCTTCCTAATAAAATAAACGCGGGTCGCCATGCA




AAAAAAAAA





12
major histo-
>gi|52426773|ref|NM_019111.3|Homo sapiens major histocompatibility



compatibility
complex, class II, DR alpha (HLA-DRA), mRNA



complex, class
ACATTCTCTTTTCTTTTATTCTTGTCTGTTCTGCCTCACTCCCGAGCTCTACTGACTCCCAACAGAGCGC



II, DR alpha///
CCAAGAAGAAAATGGCCATAAGTGGAGTCCCTGTGCTAGGATTTTTCATCATAGCTGTGCTGATGAGCGC



major histo-
TCAGGAATCATGGGCTATCAAAGAAGAACATGTGATCATCCAGGCCGAGTTCTATCTGAATCCTGACCAA



compatibility
TCAGGCGAGTTTATGTTTGACTTTGATGGTGATGAGATTTTCCATGTGGATATGGCAAAGAAGGAGACGG



complex, class
TCTGGCGGCTTGAAGAATTTGGACGATTTGCCAGCTTTGAGGCTCAAGGTGCATTGGCCAACATAGCTGT



II, DR alpha
GGACAAAGCCAACCTGGAAATCATGACAAAGCGCTCCAACTATACTCCGATCACCAATGTACCTCCAGAG




GTAACTGTGCTCACGAACAGCCCTGTGGAACTGAGAGAGCCCAACGTCCTCATCTGTTTCATAGACAAGT




TCACCCCACCAGTGGTCAATGTCACGTGGCTTCGAAATGGAAAACCTGTCACCACAGGAGTGTCAGAGAC




AGTCTTCCTGCCCAGGGAAGACCACCTTTTCCGCAAGTTCCACTATCTCCCCTTCCTGCCCTCAACTGAG




GACGTTTACGACTGCAGGGTGGAGCACTGGGGCTTGGATGAGCCTCTTCTCAAGCACTGGGAGTTTGATG




CTCCAAGCCCTCTCCCAGAGACTACAGAGAACGTGGTGTGTGCCCTGGGCCTGACTGTGGGTCTGGTGGG




CATCATTATTGGGACCATCTTCATCATCAAGGGATTGCGCAAAAGCAATGCAGCAGAACGCAGGGGGCCT




CTGTAAGGCACATGGAGGTGATGGTGTTTCTTAGAGAGAAGATCACTGAAGAAACTTCTGCTTTAATGGC




TTTACAAAGCTGGCAATATTACAATCCTTGACCTCAGTGAAAGCAGTCATCTTCAGCATTTTCCAGCCCT




ATAGCCACCCCAAGTGTGGATATGCCTCTTCGATTGCTCCGTACTCTAACATCTAGCTGGCTTCCCTGTC




TATTGCCTTTTCCTGTATCTATTTTCCTCTATTTCCTATCATTTTATTATCACCATGCAATGCCTCTGGA




ATAAAACATACAGGAGTCTGTCTCTGCTATGGAATGCCCCATGGGGCATCTCTTGTGTACTTATTGTTTA




AGGTTTCCTCAAACTGTGATTTTTCTGAACACAATAAACTATTTTGATGATCTTGGGTGGAAAAAAAAAA




AAAAAAA





Sequence
Major histo-
>gi|24797068|ref|NM_002123.2|Homo sapiens major histocompatibility


13
compatibility
complex, class II, DQ beta 1 (HLA-DQB1), mRNA



complex, class
CAGATCCATCAGGTCCGAGCTGTGTTGACTACCACTTTTCCCTTCGTCTCAATTATGTCTTGGAAAAAGG



II, DQ beta 1///
CTTTGCGGATCCCCGGAGGCCTTCGGGCAGCAACTGTGACCTTGATGCTGTCGATGCTGAGCACCCCAGT



Major histo-
GGCTGAGGGCAGAGACTCTCCCGAGGATTTCGTGTACCAGTTTAAGGGCATGTGCTACTTCACCAACGGG



compatibility
ACAGAGCGCGTGCGTCTTGTGAGCAGAAGCATCTATAACCGAGAAGAGATCGTGCGCTTCGACAGCGACG



complex, class
TGGGGGAGTTCCGGGCGGTGACGCTGCTGGGGCTGCCTGCCGCCGAGTACTGGAACAGCCAGAAGGACAT



II, DQ beta 1
CCTGGAGAGGAAACGGGCGGCGGTGGACAGGGTGTGCAGACACAACTACCAGTTGGAGCTCCGCACGACC




TTGCAGCGGCGAGTGGAGCCCACAGTGACCATCTCCCCATCCAGGACAGAGGCCCTCAACCACCACAACC




TGCTGGTCTGCTCGGTGACAGATTTCTATCCAGCCCAGATCAAAGTCCGGTGGTTTCGGAATGACCAGGA




GGAGACAGCTGGCGTTGTGTCCACCCCCCTTATTAGGAATGGTGACTGGACCTTCCAGATCCTGGTGATG




CTGGAAATGACTCCCCAGCGTGGAGACGTCTACACCTGCCACGTGGAGCACCCCAGCCTCCAGAGCCCCA




TCACCGTGGAGTGGCGGGCTCAATCTGAATCTGCCCAGAGCAAGATGCTGAGTGGCATTGGAGGCTTCGT




GCTGGGGCTGATCTTCCTCGGGCTGGGCCTTATCATCCATCACAGGAGTCAGAAAGGGCTCCTGCACTGA




CTCCTGAGACTATTTTAACTGGGATTGGTTATCACTTTTCTGTAACGCCTGCTTGTCCCTGCCCAGAATT




CCCAGCTGTCTGTGTCAGCCTGTCCCCCTGAGATCAGAGTCCTACAGTGGCTGTCACGCAGCCACCAGGT




CATCTCCTTTCATCCCCACCTTGAGGCGGATGGCTGTGACCCTACTTCCTGCACTGACCCACAGCCTCTG




CCTGTGCACGGCCAGCTGCATCTACTCAGGCCCCAAGGGGTTTCTGTTTCTATTCTCTCCTCAGACTGCT




CAAGAGAAGCACATGAAAACCATTACCTGACTTTAGAGCTTTTTTACATAATTAAACATGATCCTGAGTT





14
alcohol
>gi|34577060|ref|NM_000668.3|Homo sapiens alcohol dehydrogenase IB (class



dehydrogenase
I), beta polypeptide (ADH1B), mRNA



IB (class I),
ATGCACTCAAGCAGAGAAGAAATCCACAAAGACTCACAGTCTGCTGGTGGGCAGAGAAGACAGAAACGAC



beta
ATGAGCACAGCAGGAAAAGTAATCAAATGCAAAGCAGCTGTGCTATGGGAGGTAAAGAAACCCTTTTCCA



polypeptide
TTGAGGATGTGGAGGTTGCACCTCCTAAGGCTTATGAAGTTCGCATTAAGATGGTGGCTGTAGGAATCTG




TCACACAGATGACCACGTGGTTAGTGGCAACCTGGTGACCCCCCTTCCTGTGATTTTAGGCCATGAGGCA




GCCGGCATCGTGGAGAGTGTTGGAGAAGGGGTGACTACAGTCAAACCAGGTGATAAAGTCATCCCGCTCT




TTACTCCTCAGTGTGGAAAATGCAGAGTTTGTAAAAACCCGGAGAGCAACTACTGCTTGAAAAATGATCT




AGGCAATCCTCGGGGGACCCTGCAGGATGGCACCAGGAGGTTCACCTGCAGGGGGAAGCCCATTCACCAC




TTCCTTGGCACCAGCACCTTCTCCCAGTACACGGTGGTGGATGAGAATGCAGTGGCCAAAATTGATGCAG




CCTCGCCCCTGGAGAAAGTCTGCCTCATTGGCTGTGGATTCTCGACTGGTTATGGGTCTGCAGTTAACGT




TGCCAAGGTCACCCCAGGCTCTACCTGTGCTGTGTTTGGCCTGGGAGGGGTCGGCCTATCTGCTGTTATG




GGCTGTAAAGCAGCTGGAGCAGCCAGAATCATTGCGGTGGACATCAACAAGGACAAATTTGCAAAGGCCA




AAGAGTTGGGTGCCACTGAATGCATCAACCCTCAAGACTACAAGAAACCCATCCAGGAAGTGCTAAAGGA




AATGACTGATGGAGGTGTGGATTTTTCGTTTGAAGTCATCGGTCGGCTTGACACCATGATGGCTTCCCTG




TTATGTTGTCATGAGGCATGTGGCACAAGCGTCATCGTAGGGGTACCTCCTGCTTCCCAGAACCTCTCAA




TAAACCCTATGCTGCTACTGACTGGACGCACCTGGAAGGGGGCTGTTTATGGTGGCTTTAAGAGTAAAGA




AGGTATCCCAAAACTTGTGGCTGATTTTATGGCTAAGAAGTTTTCACTGGATGCGTTAATAACCCATGTT




TTACCTTTTGAAAAAATAAATGAAGGATTTGACCTGCTTCACTCTGGGAAAAGTATCCGTACCGTCCTGA




CGTTTTGAGGCAATAGAGATGCCTTCCCCTGTAGCAGTCTTCAGCCTCCTCTACCCTACAAGATCTGGAG




CAACAGCTAGGAAATATCATTAATTCAGCTCTTCAGAGATGTTATCAATAAATTACACATGGGGGCTTTC




CAAAGAAATGGAAATTGATGGGAAATTATTTTTCAGGAAAATTTAAAATTCAAGTGAGAAGTAAATAAAG




TGTTGAACATCAGCTGGGGAATTGAAGCCAACAAACCTTCCTTCTTAACCATTCTACTGTGTCACCTTTG




CCATTGAGGAAAAATATTCCTGTGACTTCTTGCATTTTTGGTATCTTCATAATCTTTAGTCATCGAATCC




CAGTGGAGGGGACCCTTTTACTTGCCCTGAACATACACATGCTGGGCCATTGTGATTGAAGTCTTCTAAC




TCTGTCTCAGTTTTCACTGTCGACATTTTCCTTTTTCTAATAAAAATGTACCAAATCCCTGGGGTAAAAG




CTAGGGTAAGGTAAAGGATAGACTCACATTTACAAGTAGTGAAGGTCCAAGAGTTCTAAATACAGGAAAT




TTCTTAGGAACTCAAATAAAATGCCCCACATTTTACTACAGTAAATGGCAGTGTTTTTATGACTTTTATA




CTATTTCTTTATGGTCGATATACAATTGATTTTTTAAAATAATAGCAGATTTCTTGCTTCATATGACAAA




GCCTCAATTACTAATTGTAAAAACTGAACTATTCCCAGAATCATGTTCAAAAAATCTGTAATTTTTGCTG




ATGAAAGTGCTTCATTGACTAAACAGTATTAGTTTGTGGCTATAAATGATTATTTAGATGATGACTGAAA




ATGTGTATAAAGTAATTAAAAGTAATATGGTGGCTTTAAGTGTAGAGATGGGATGGCAAATGCTGTGAAT




GCAGAATGTAAAATTGGTAACTAAGAAATGGCACAAACACCTTAAGCAATATATTTTCCTAGTAGATATA




TATATACACATACATATATACACATATACAAATGTATATTTTTGCAAAATTGTTTTCAATCTAGAACTTT




TCTATTAACTACCATGTCTTAAAATCAAGTCTATAATCCTAGCATTAGTTTAATATTTTGAATATGTAAA




GACCTGTGTTAATGCTTTGTTAATGCTTTTCCCACTCTCATTTGTTAATGCTTTCCCACTCTCAGGGGAA




GGATTTGCATTTTGAGCTTTATCTCTAAATGTGACATGCAAAGATTATTCCTGGTAAAGGAGGTAGCTGT




CTCCAAAAATGCTATTGTTGCAATATCTACATTCTATTTCATATTATGAAAGACCTTAGACATAAAGTAA




AATAGTTTATCATTTACTGTGTGATCTTCAGTAAGTCTCTCAGGCTCTCTGAGCTTGTTCATCCTTTGTT




TTGAAAAAATTACTCAACCAATCCATTACAGCTTAACCAAGATTAAATGGGATGATGTTAATGAAAGAGC




TTCGCC





15
T cell receptor
>gi|36944|emb|X02592.1|HSTCRAR Human mRNA for T-cell receptor alpha chain



alpha constant///
(TCR-alpha)



T cell receptor
TTTTGAAACCCTTCAAAGGCAGAGACTTGTCCAGCCTAACCTGCCTGCTGCTCCTAGCTCCTGAGGCTCA



alpha constant
GGGCCCTTGGCTTCTGTCCGCTCTGCTCAGGGCCCTCCAGCGTGGCCACTGCTCAGCCATGCTCCTGCTG




CTCGTCCCAGTGCTCGAGGTGATTTTTACCCTGGGAGGAACCAGAGCCCAGTCGGTGACCCAGCTTGGCA




GCCACGTCTCTGTCTCTGAAGGAGCCCTGGTTCTGCTGAGGTGCAACTACTCATCGTCTGTTCCACCATA




TCTCTTCTGGTATGTGCAATACCCCAACCAAGGACTCCAGCTTCTCCTGAAGTACACATCAGCGGCCACC




CTGGTTAAAGGCATCAACGGTTTTGAGGCTGAATTTAAGAAGAGTGAAACCTCCTTCCACCTGACGAAAC




CCTCAGCCCATATGAGCGACGCGGCTGAGTACTTCTGTGCTGTGAGTGATCTCGAACCGAACAGCAGTGC




TTCCAAGATAATCTTTGGATCAGGGACCAGACTCAGCATCCGGCCAAATATCCAGAACCCTGACCCTGCC




GTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTATTCACCGATTTTGATTCTCAAA




CAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGACAAAACTGTGCTAGACATGAGGTCTAT




GGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAAC




AACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGAAAGTTCCTGTGATGTCAAGCTGGTCGAGA




AAAGCTTTGAAACAGATACGAACCTAAACTTTCAAAACCTGTCAGTGATTGGGTTCCGAATCCTCCTCCT




GAAAGTGGCCGGGTTTAATCTGCTCATGACGCTGCGGCTGTGGTCCAGCTGAGATCTGCAAGATTGTAAG




ACAGCCTGTGCTCCCTCGCTCCTTCCTCTGCATTGCCCCTCTTCTCCCTCTCCAAACAGAGGGAACTCTC




CTACCCCCAAGGAGGTGAAAGCTGCTACCACCTCTGTGCCCCCCCGGTAATGCCACCAACTGGATCCTAC




CCGAATTTATGATTAAGATTGCTGAAGAGCTGCCAAACACTGCTGCCACCCCCTCTGTTCCCTTATTGCT




GCTTGTCACTGCCTGACATTCACGGCAGAGGCAAGGCTGCTGCAGCCTCCCCTGGCTGTGCACATTCCCT




CCTGCTCCCCAGAGACTGCCTCCGCCATCCCACAGATGATGGATCTTCAGTGGGTTCTCTTGGGCTCTAG




GTCCTGGAGAATGTTGTGAGGGGTTTATTTTTTTTTAATAGTGTTCATAAAGAAATACATAGTATTCTTC




TTCTCAAGACGTGGGGGGAAATTATCTCATTATCGAGGCCCTGCTATGCTGTGTGTCTGGGCGTGTTGTA




TGTCCTGCTGCCGATGCCTTCATTAAAATGATTTGGAA





16
CD69 antigen
>gi|4502680|ref|NM_001781.1|Homo sapiens CD69 molecule (CD69), mRNA



(p60, early
AGACTCAACAAGAGCTCCAGCAAAGACTTTCACTGTAGCTTGACTTGACCTGAGATTAACTAGGGAATCT



T-cell
TGAGAATAAAGATGAGCTCTGAAAATTGTTTCGTAGCAGAGAACAGCTCTTTGCATCCGGAGAGTGGACA



activation
AGAAAATGATGCCACCAGTCCCCATTTCTCAACACGTCATGAAGGGTCCTTCCAAGTTCCTGTCCTGTGT



antigen)
GCTGTAATGAATGTGGTCTTCATCACCATTTTAATCATAGCTCTCATTGCCTTATCAGTGGGCCAATACA




ATTGTCCAGGCCAATACACATTCTCAATGCCATCAGACAGCCATGTTTCTTCATGCTCTGAGGACTGGGT




TGGCTACCAGAGGAAATGCTACTTTATTTCTACTGTGAAGAGGAGCTGGACTTCAGCCCAAAATGCTTGT




TCTGAACATGGTGCTACTCTTGCTGTCATTGATTCTGAAAAGGACATGAACTTTCTAAAACGATACGCAG




GTAGAGAGGAACACTGGGTTGGACTGAAAAAGGAACCTGGTCACCCATGGAAGTGGTCAAATGGCAAAGA




ATTTAACAACTGGTTCAACGTTACAGGGTCTGACAAGTGTGTTTTTCTGAAAAACACAGAGGTCAGCAGC




ATGGAATGTGAGAAGAATTTATACTGGATATGTAACAAACCTTACAAATAATAAGGAAACATGTTCACTT




ATTGACTATTATAGAATGGAACTCAAGGAAATCTGTGTCAGTGGATGCTGCTCTGTGGTCCGAAGTCTTC




CATAGAGACTTTGTGAAAAAAAATTTTATAGTGTCTTGGGAATTTTCTTCCAAACAGAACTATGGAAAAA




AAGGAAGAAATTCCAGGAAAATCTGCACTGTGGGCTTTTATTGCCATGAGCTAGAAGCATCACAGGTTGA




CCAATAACCATGCCCAAGAATGAGAAGAATGACTATGCAACCTTTGGATGCACTTTATATTATTTTGAAT




CCAGAAATAATGAAATAACTAGGCGTGGACTTACTATTTATTGCTGAATGACTACCAACAGTGAGAGCCC




TTCATGCATTTGCACTACTGGAAGGAGTTAGATGTTGGTACTAGATACTGAATGTAAACAAAGGAATTAT




GGCTGGTAACATAGGTTTTTAGTCTAATTGAATCCCTTAAACTCAGGGAGCATTTATAAATGGACAAATG




CTTATGAAACTAAGATTTGTAATATTTCTCTCTTTTTAGAGAAATTTGCCAATTTACTTTGTTATTTTTC




CCCAAAAAGAATGGGATGATCGTGTATTTATTTTTTTACTTCCTCAGCTGTAGACAGGTCCTTTTCGATG




GTACATATTTCTTTGCCTTTATAATCTTTTATACAGTGTCTTACAGAGAAAAGACATAAGCAAAGACTAT




GAGGAATATTTGCAAGACATAGAATAGTGTTGGAAAATGTGCAATATGTGATGTGGCAAATCTCTATTAG




GAAATATTCTGTAATCTTCAGACCTAGAATAATACTAGTCTTATAATAGGTTTGTGACTTTCCTAAATCA




ATTCTATTACGTGCAATACTTCAATACTTCATTTAAAATATTTTTATGTGCAATAAAATGTATTTGTTTG




TATTTTGTGTTCAGTACAATTATAAGCTGTTTTTATATATGTGAAATAAAAGTAGAATAAACACAAAAAA




AAAAAAAAAAAAAAAAAAAAAA





17
protein kinase
>gi|48255887|ref|NM_006257.2|Homo sapiens protein kinase C, theta



C, theta
(PRKCQ), mRNA




AGTCCCCGCGCAGTCCCCGCGCAGTCCCAGCGCCACCGGGCAGCAGCGGCGCCGTGCTCGCTCCAGGGCG




CAACCATGTCGCCATTTCTTCGGATTGGCTTGTCCAACTTTGACTGCGGGTCCTGCCAGTCTTGTCAGGG




CGAGGCTGTTAACCCTTACTGTGCTGTGCTCGTCAAAGAGTATGTCGAATCAGAGAACGGGCAGATGTAT




ATCCAGAAAAAGCCTACCATGTACCCACCCTGGGACAGCACTTTTGATGCCCATATCAACAAGGGAAGAG




TCATGCAGATCATTGTGAAAGGCAAAAACGTGGACCTCATCTCTGAAACCACCGTGGAGCTCTACTCGCT




GGCTGAGAGGTGCAGGAAGAACAACGGGAAGACAGAAATATGGTTAGAGCTGAAACCTCAAGGCCGAATG




CTAATGAATGCAAGATACTTTCTGGAAATGAGTGACACAAAGGACATGAATGAATTTGAGACGGAAGGCT




TCTTTGCTTTGCATCAGCGCCGGGGTGCCATCAAGCAGGCAAAGGTCCACCACGTCAAGTGCCACGAGTT




CACTGCCACCTTCTTCCCACAGCCCACATTTTGCTCTGTCTGCCACGAGTTTGTCTGGGGCCTGAACAAA




CAGGGCTACCAGTGCCGACAATGCAATGCAGCAATTCACAAGAAGTGTATTGATAAAGTTATAGCAAAGT




GCACAGGATCAGCTATCAATAGCCGAGAAACCATGTTCCACAAGGAGAGATTCAAAATTGACATGCCACA




CAGATTTAAAGTCTACAATTACAAGAGCCCGACCTTCTGTGAACACTGTGGGACCCTGCTGTGGGGACTG




GCACGGCAAGGACTCAAGTGTGATGCATGTGGCATGAATGTGCATCATAGATGCCAGACAAAGGTGGCCA




ACCTTTGTGGCATAAACCAGAAGCTAATGGCTGAAGCGCTGGCCATGATTGAGAGCACTCAACAGGCTCG




CTGCTTAAGAGATACTGAACAGATCTTCAGAGAAGGTCCGGTTGAAATTGGTCTCCCATGCTCCATCAAA




AATGAAGCAAGGCCGCCATGTTTACCGACACCGGGAAAAAGAGAGCCTCAGGGCATTTCCTGGGAGTCTC




CGTTGGATGAGGTGGATAAAATGTGCCATCTTCCAGAACCTGAACTGAACAAAGAAAGACCATCTCTGCA




GATTAAACTAAAAATTGAGGATTTTATCTTGCACAAAATGTTGGGGAAAGGAAGTTTTGGCAAGGTCTTC




CTGGCAGAATTCAAGAAAACCAATCAATTTTTCGCAATAAAGGCCTTAAAGAAAGATGTGGTCTTGATGG




ACGATGATGTTGAGTGCACGATGGTAGAGAAGAGAGTTCTTTCCTTGGCCTGGGAGCATCCGTTTCTGAC




GCACATGTTTTGTACATTCCAGACCAAGGAAAACCTCTTTTTTGTGATGGAGTACCTCAACGGAGGGGAC




TTAATGTACCACATCCAAAGCTGCCACAAGTTCGACCTTTCCAGAGCGACGTTTTATGCTGCTGAAATCA




TTCTTGGTCTGCAGTTCCTTCATTCCAAAGGAATAGTCTACAGGGACCTGAAGCTAGATAACATCCTGTT




AGACAAAGATGGACATATCAAGATCGCGGATTTTGGAATGTGCAAGGAGAACATGTTAGGAGATGCCAAG




ACGAATACCTTCTGTGGGACACCTGACTACATCGCCCCAGAGATCTTGCTGGGTCAGAAATACAACCACT




CTGTGGACTGGTGGTCCTTCGGGGTTCTCCTTTATGAAATGCTGATTGGTCAGTCGCCTTTCCACGGGCA




GGATGAGGAGGAGCTCTTCCACTCCATCCGCATGGACAATCCCTTTTACCCACGGTGGCTGGAGAAGGAA




GCAAAGGACCTTCTGGTGAAGCTCTTCGTGCGAGAACCTGAGAAGAGGCTGGGCGTGAGGGGAGACATCC




GCCAGCACCCTTTGTTTCGGGAGATCAACTGGGAGGAACTTGAACGGAAGGAGATTGACCCACCGTTCCG




GCCGAAAGTGAAATCACCATTTGACTGCAGCAATTTCGACAAAGAATTCTTAAACGAGAAGCCCCGGCTG




TCATTTGCCGACAGAGCACTGATCAACAGCATGGACCAGAATATGTTCAGGAACTTTTCCTTCATGAACC




CCGGGATGGAGCGGCTGATATCCTGAATCTTGCCCCTCCAGAGACAGGAAAGAATTTGCCTTCTCCCTGG




GAACTGGTTCAAGAGACACTGCTTGGGTTCCTTTTTCAACTTGGAAAAAGAAAGAAACACTCAACAATAA




AGACTGAGACCCGTTCGCCCCCATGTGACTTTTATCTGTAGCAGAAACCAAGTCTACTTCACTAATGACG




ATGCCGTGTGTCTCGTCTCCTGACATGTCTCACAGACGCTCCTGAAGTTAGGTCATTACTAACCATAGTT




ATTTACTTGAAAGATGGGTCTCCGCACTTGGAAAGGTTTCAAGACTTGATACTGCAATAAATTATGGCTC




TTCACCTGGGCGCCAACTGCTGATCAATGAAATGCTTGTTGAATCAGGGGCAAACGGAGTACAGACGTCT




CAAGACTGAAACGGCCCCATTGCCTGGTCTAGTAGCGGATCTCACTCAGCCGCAGACAAGTAATCACTAA




CCCGTTTTATTCTATTCCTATCTGTGGATGTGTAAATGGCTGGGGGGCCAGCCCTGGATAGGTTTTTATG




GGAATTCTTTACAATAAACATAGCTTGTAACTTGAGATCTACAAATCCATTCATCCTGATTGGGCATGAA




ATCCATGGTCAAGAGGACAAGTGGAAAGTGAGAGGGAAGGTTTGCTAGACACCTTCGCTTGTTATCTTGT




CAAGATAGAAAAGATAGTATCATTTCACCCTTGCCAGTAAAAACCTTTCCATCCACCCATTCTCAGCAGA




CTCCAGTATTGGCACAGTCACTCACTGCCATTCTCACACTATAACAAGAAAAGAAATGAAGTGCATAAGT




CTCCTGGGAAAAGAACCTTAACCCCTTCTCGTGCCATGACTGGTGATTTCATGACTCATAAGCCCCTCCG




TAGGCATCATTCAAGATCAATGGCCCATGCATGCTGTTTGCAGCAGTCAATTGAGTTGAATTAGAATTCC




AACCATACATTTTAAAGGTATTTGTGCTGTGTGTATATTTTGATAAAATGTTGTGACTTCATGGCAAACA




GGTGGATGTGTAAAAATGGAATAAAAAAAAAAAAAGAGTCAAAAAAAAAAAAA





18
T cell receptor
>gi|339011|gb|M15564.1|HUMTCBYZ Human T-cell receptor rearranged beta-



beta variable
chain V-region (V-D-J) mRNA, complete cds



19///T cell
GTAAAGCTCCCATCCTGCCCTGACCCTGCCATGGGCACCAGCCTCCTCTGCTGGATGGCCCTGTGTCTCC



receptor beta
TGGGGGCAGATCACGCAGATACTCGAGTCTCCCAGAACCCCAGACACAACATCACAAAGAGGGGACAGAA



constant 1
TGTAACTTTCAGGTGTGATCCAATTTCTGAACACAACCGCCTTTATTGGTACCGACAGACCCTGGGGCAG




GGCCCAGAGTTTCTGACTTACTTCCAGAATGAAGCTCAACTAGAAAAATCAAGGCTGCTCAGTGATCGGT




TCTCTGCAGAGAGGCCTAAGGGATCTTTCTCCACCTTGGAGATCCAGCGCACAGAGCAGGGGGACTCGGC




CATGTATCTCTGTGCCAGCAGCTTAGCAGGGTTGAATCAGCCCCAGCATTTTGGTGATGGGACTCGACTC




TCCATCCTAGAGGACCTGAACAAGGTGTTCCCACCCGAGGTCGCTGTGTTTGAGCCATCAGAAGCAGAGA




TCTCCCACACCCAAAAGGCCACACTGGTGTGCCTGGCCACAGGTATCTTCCCTGACCACGTGGAGCTGAG




CTGGTGGGTGAATGGGAAGGAGGTGCACAGTGGGGTCAGCACGGACCCGCAGCCCCTCAAGGAGCAGCCC




GCCCTCAATGACTCCAGATACTGCCTGAGCAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCC




GCAACCACTTCCGCTGTCAAGTCCAGTTCTACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGC




CAAACCCGTCACCCAGATCGTCAGCGCCGAGGCCTGGGGTAGAGCAGACTGTGGCTTTACCTCGGTGTCC




TACCAGCAAGGGGTCCTGTCTGCCACCATCCTCTATGAGATCCTGCTAGGGAAGGCCACCATGTATGCTG




TGCTGGTCAGCGCCCTTGTGTTGATGGCCATGGTCAAGAGAAAGGATTTCTGAAGGCAGCCCTGGAAGTG




GAGTTAGGAGCTTCTAACCCGTCATGGTTTCAATACACATTCTTCTTTTGCCAGCGCTTCTGAAGAGCTG




CTCTCACCTCTCTGCATCCCAATA





19
T cell receptor
>gi|338765|gb|M15565.1|HUMTCAYE Human T-cell receptor rearranged alpha-



alpha locus///T
chain V-region (V-D-J) mRNA, complete cds



cell receptor
TCCAAAATGAAGGGTCTGTGGAAGGACATGAATAAAGCACAGGAGGTTGAAGTCAGATTTGCAGCTTTCT



delta variable
AGGCAGGAGACAAGACAATCTGCATCTTCACAGGAGGGATGGCCATGCTCCTGGGGGCATCAGTGCTGAT



2///T cell
TCTGTGGCTTCAGCCAGACTGGGTAAACAGTCAACAGAAGAATGATGACCAGCAAGTTAAGCAAAATTCA



receptor alpha
CCATCCCTGAGCGTCCAGGAAGGAAGAATTTCTATTCTGAACTGTGACTATACTAACAGCATGTTTGATT



variable 20///T
ATTTCCTATGGTACAAAAAATACCCTGCTGAAGGTCCTACATTCCTGATATCTATAAGTTCCATTAAGGA



cell receptor
TAAAAATGAAGATGGAAGATTCACTGTCTTCTTAAACAAAAGTGCCAAGCACCTCTCTCTGCACATTGTG



alpha joining
CCCTCCCAGCCTGGAGACTCTGCAGTGTACTTCTGTGCAGCAAACGGGGCCGGCACTGCCAGTAAACTCA



17///T cell
CCTTTGGGACTGGAACAAGACTTCAGGTCACGCTCGATATCCAGAACCCTGACCCTGCCGTGTACCAGCT



receptor alpha
GAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTATTCACCGATTTTGATTCTCAAACAAATGTGTCA



constant
CAAAGTAAGGATTCTGATGTGTATATCACAGACAAAACTGTGCTAGACATGAGGTCTATGGACTTCAAGA




GCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACTTTGCATGTGCAAACGCCTTCAACAACAGCATTAT




TCCAGAAGACACCTTCTTCCCCAGCCCAGAAAGTTCCTGTGATGTCAAGCTGGTCGAGAAAAGCTTTGAA




ACAGATACGAACCTAAACTTTCAAAACCTGTCAGTGATTGGGTTCCGAATCCTCCTCCTGAAAGTGGCCG




GGTTTAATCTGCTCATGACGCTGCGGCTGTGGTCCAGCTGAGATCTGCAAGATTGTAAGACAGCCTGTGC




TCCCTCGCTCCTTCCTCTGCATTGCCCCTCTTCTCCCTCTCCAAACAGAGGGAACTCTCCCACCCCCAAG




GAGGTGAAAGCTGCTACCACCCTGTGTGCC





20
T cell receptor
>gi|339406|gb|M30894.1|HUMTCRGAD Human T-cell receptor Ti rearranged



gamma constant 2
gamma-chain mRNA V-J-C region, complete cds




GAATCAGGAAGACCAGCTCCTCCTACTGTCTTCTGTGTTACGGGATCAGCGTTCCTTGTTGAGTGGGACC




TGAGTTTTGAGAGGGTCTTCTGCTCCTCTTGGTCTGGTCCCTTACTTCCAAGAGCCCCAGAGAGGAAGGC




ATGCTGTTGGCTCTAGCTCTGCTTCTAGCTTTCCTGCCTCCTGCCAGTCAGAAATCTTCCAACTTGGAAG




GGAGAACAAAGTCAGTCACCAGGCCAACTGGGTCATCAGCTGTAATCACTTGTGATCTTCCTGTAGAAAA




TGCCGTCTACACCCACTGGTACCTACACCAGGAGGGGAAGGCCCCACAGCGTCTTCTGTACTATGACTCC




TACAACTCCAGGGTTGTGTTGGAATCAGGAATCAGTCGAGAAAAGTATCATACTTATGCAAGCACAGGGA




AGAGCCTTAAATTTATACTGGAAAATCTAATTGAACGTGACTCTGGGGTCTATTACTGTGCCACCTGGAA




GGATTATTATAAGAAACTCTTTGGCAGTGGAACAACACTTGTTGTCACAGATAAACAACTTGATGCAGAT




GTTTCCCCCAAGCCCACTATTTTTCTTCCTTCGATTGCTGAAACAAAACTCCAGAAGGCTGGAACATATC




TTTGTCTTCTTGAGAAATTTTTCCCAGATATTATTAAGATACATTGGCAAGAAAAGAAGAGCAACACGAT




TCTGGGATCCCAGGAGGGGAACACCATGAAGACTAACGACACATACATGAAATTTAGCTGGTTAACGGTG




CCAGAAGAGTCACTGGACAAAGAACACAGATGTATCGTCAGACATGAGAATAATAAAAACGGAATTGATC




AAGAAATTATCTTTCCTCCAATAAAGACAGATGTCACCACAGTGGATCCCAAAGACAGTTATTCAAAAGA




TGCAAATGATGTCACCACAGTGGATCCCAAATACAATTATTCAAAGGATGCAAATGATGTCATCACAATG




GATCCCAAAGACAATTGGTCAAAAGATGCAAATGATACACTACTGCTGCAGCTCACAAACACCTCTGCAT




ATTACATGTACCTCCTCCTGCTCCTCAAGAGTGTGGTCTATTTTGCCATCATCACCTGCTGTCTGCTTGG




AAGAACGGCTTTCTGCTGCAATGGAGAGAAATCATAACAGACGGTGGCACAAGGAGGCCATCTTTTCCTC




ATCGGTTATTGTCCCTAGAAGCGTCTTCTGAGGATCTAGTTGGGCTTTCTTTCTGGGTTTGGGCCATTTC




AGTTCTCATGTGTGtACTATTCTATCATTATTGTATAATGGTTTTCAAACCAGTGGGCACACAGAGAACC




TCAGTCTGTAATAACAATGAGGAATAGCCATGGCGATCTCCAGCACCAATCTCTCCATGTTTTCCACAGC




TCCTCCAGCCAACCCAAATAGCGCCTGCTATAGTGTAGACAGCCTGCGGCTTCTAGCCTTGTCCCTCTCT




TAGTGTTCTTTAATCAGATAACTGCCTGGAAGCCTTTCATTTTACACGCCCTGAAGCAGTCTTCTTTGCT




AGTTGAATTATGTGGTGTGTTTTTCCGTAATAAGCAAAATAAATTT





21
T cell receptor
>gi|3002924|gb|AF043179.1|AF043179 Homo sapiens T cell receptor beta



beta variable
chain (TCRBV13S1-TCRBJ2S1) mRNA, complete cds



21-1///T cell
ATGAGCATCGGCCTCCTGTGCTGTGCAGCCTTGTCTCTCCTGTGGGCAGGTCCAGTGAATGCTGGTGTCA



receptor beta
CTCAGACCCCAAAATTCCAGGTCCTGAAGACAGGACAGAGCATGACACTGCAGTGTGCCCAGGATATGAA



variable 19///
CCATGAATACATGTCCTGGTATCGACAAGACCCAGGCATGGGGCTGAGGCTGATTCATTACTCAGTTGGT



T cell receptor
GCTGGTATCACTGACCAAGGAGAAGTCCCCAATGGCTACAATGTCTCCAGATCAACCACAGAGGATTTCC



beta variable
CGCTCAGGCTGCTGTCGGCTGCTCCCTCCCAGACATCTGTGTACTTCTGTGCCAGCAGTTTCCCCCGGCA



5-4///T cell
GCCGTCCTACAATGAGCAGTTCTTCGGGCCAGGGACACGGCTCACCGTGCTAGAGGACCTGAAAAACGTG



receptor beta
TTCCCACCCGAGGTCGCTGTGTTTGAGCCATCAGAAGCAGAGATCTCCCACACCCAAAAGGCCACACTGG



variable 3-1///
TGTGCCTGGCCACAGGTTTCTACCCCGACCACGTGGAGCTGAGCTGGTGGGTGAATGGGAAGGAGGTGCA



T cell receptor
CAGTGGGGTCAGCACAGACCCGCAGCCCCTCAAGGAGCAGCCCGCCCTCAATGACTCCAGATACTGCCTG



beta constant 1
AGCAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGCAACCACTTCCGCTGTCAAGTCCAGT




TCTACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGCCAAACCTGTCACCCAGATCGTCAGCGC




CGAGGCCTGGGGTAGAGCAGACTGTGGCTTCACCTCCGAGTCTTACCAGCAAGGGGTCCTGTCTGCCACC




ATCCTCTATGAGATCTTGCTAGGGAAGGCCACCTTGTATGCTGTGCTGGTCAGTGCCCTCGTGCTGATGG




CCATGGTCAAGAGAAAGGATTCCAGAGGCTGA





22
T cell receptor
>gi|1100165|gb|L34703.1|HUMTCRAZ Homo sapiens T-cell receptor alpha chain



alpha locus
(TCRA) mRNA (HLA-A1, 24; B7, 8; DR 1, 3), complete cds




ATGGCATGCCCTGGCTTCCTGTGGGCACTTGTGATCTCCACCTGTCTTGAATTTAGCATGGCTCAGACAG




TCACTCAGTCTCAACCAGAGATGTCTGTGCAGGAGGCAGAGACCGTGACCCTGAGCTGCACATATGACAC




CAGTGAGAGTGATTATTATTTATTCTGGTACAAGCAGCCTCCCAGCAGGCAGATGATTCTCGTTATTCGC




CAAGAAGCTTATAAGCAACAGAATGCAACAGAGAATCGTTTCTCTGTGAACTTCCAGAAAGCAGCCAAAT




CCTTCAGTCTCAAGATCTCAGACTCACAGCTGGGGGATGCCGCGATGTATTTCTGTGCTTATAGGAGTGC




ATACTCTGGGGCTGGGAGTTACCAACTCACTTTCGGGAAGGGGACCAAACTCTCGGTCATACCAAATATC




CAGAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTATTCA




CCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGACAAAACTGT




GCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACTTTGCA




TGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGAAAGTTCCTGTG




ATGTCAAGCTGGTCGAGAAAAGCTTTGAAACAGATACGAACCTAAACTTTCAAAACCTGTCAGTGATTGG




GTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTGCTCATGACGCTGCGGTTGTGGTCCAGCTGA





23
T cell receptor
>gi|46184507|gb|AL559122.3|AL559122 AL559122 Homo sapiens T CELLS (JURKAT



beta variable
CELL LINE) COT 10-NORMALIZED Homo sapiens cDNA clone CS0DJ014YE01 5-PRIME,



19///T cell
mRNA sequence



receptor beta
TGCCTGGCCACAGGCTTCTTCCCCGACCACGTGGAGCTGAGCTGGTGGGTGAATGGGAAGGAGGTGCACA



variable 19///
ATGGGGTCAACACAGACCCGCAGCCCCTCAAAGAACAGCCCGCCCTCAATGACTCCAAATAMTGCCTGAG



T cell receptor
CAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGCAACCACTTCCGCTGTCAAGTCCAGTTC



beta constant
TACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGCCAAACCCGTCACCCAAATCGTCAGCGCCG



1///T cell
AGGCCTGGGGTAPAGCARAMTGTGGCTTTACCTCGGTGTCCTACCAACAAGGGGTCCTGTCTGCCACCAT



receptor beta
CCTCTATGARATCCTGCTAGGGAAGGCCACCCTGTATGCTGTGCTGGTCAGCGCCCTTGTGTTGATGGCC



constant 1
ATGGTCAAGAGAAAGGATTTCTGAAGGCAGCCCTGGAAGTGGAATTAAGAACTTCTAACCCGTCATGGTT




TCAATACACATTCTTCTTTTGCCAGCGCTTCTGAAGAGCTGCTCTCACCTCTCTGCATCCCAATAGATAT




CCCCCTATGTGCATGCACACCTGCACACTCACGGCTGAAATCTCCCTAACCCAGGCGGACCTTAGCATGC




CTAAGTGACTAAACCAATAAAAATGTTCTGGTCTGGCCTGA





24
CD3D antigen,
>gi|98985799|ref|NM_000732.41|Homo sapiens CD3d molecule, delta (CD3-TCR



delta polypep-
complex) (CD3D), transcript variant 1, mRNA



tide (TiT3)
AGAGAAGCAGACATCTTCTAGTTCCTCCCCCACTCTCCTCTTTCCGGTACCTGTGAGTCAGCTAGGGGAG



complex)
GGCAGCTCTCACCCAGGCTGATAGTTCGGTGACCTGGCTTTATCTACTGGATGAGTTCCGCTGGGAGATG




GAACATAGCACGTTTCTCTCTGGCCTGGTACTGGCTACCCTTCTCTCGCAAGTGAGCCCCTTCAAGATAC




CTATAGAGGAACTTGAGGACAGAGTGTTTGTGAATTGCAATACCAGCATCACATGGGTAGAGGGAACGGT




GGGAACACTGCTCTCAGACATTACAAGACTGGACCTGGGAAAACGCATCCTGGACCCACGAGGAATATAT




AGGTGTAATGGGACAGATATATACAAGGACAAAGAATCTACCGTGCAAGTTCATTATCGAATGTGCCAGA




GCTGTGTGGAGCTGGATCCAGCCACCGTGGCTGGCATCATTGTCACTGATGTCATTGCCACTCTGCTCCT




TGCTTTGGGAGTCTTCTGCTTTGCTGGACATGAGACTGGAAGGCTGTCTGGGGCTGCCGACACACAAGCT




CTGTTGAGGAATGACCAGGTCTATCAGCCCCTCCGAGATCGAGATGATGCTCAGTACAGCCACCTTGGAG




GAAACTGGGCTCGGAACAAGTGAACCTGAGACTGGTGGCTTCTAGAAGCAGCCATTACCAACTGTACCTT




CCCTTCTTGCTCAGCCAATAAATATATCCTCTTTCACTCAGAAAAAAAAAAAAAAAAAAAAAAAAAAAAA




A





25
T cell receptor
>gi|339168|gb|M13231.1|HUMTCGXH Human T-cell receptor aberrantly



gamma constant
rearranged gamma-chain mRNA from cell line HPB-MLT



2///T cell
GGCATGCGGTGGGCCCTACTGGTGCTTCTAGCTTTCCTGTCTCCTGCCAGTCAGAAATCTTCCAACTTGG



receptor gamma
AAGGGAGAACGAAGTCAGTCACCAGGCAGACTGGGTCATCTGCTGAAATCACTTGCGATCTTACTGTAAC



variable 9///
AAATACCTTCTACATCCACTGGTACCTACACCAGGAGGGGAAGGCCCCACAGCGTCTTCTGTACTATGAC



similar to T-
GTCTCCACTGCAAGGGATGTGTTGGAATCAGGACTCAGTCCAGGAAAGTATTATACTCATACACCCAGGA



cell receptor
GGTGGAGCTGGATATTGAGACTGCAAAATCTAATTGAAAATGATTCTGGGGTCTATTACTGTGCCACCTG



gamma chain C
GGACAGGCAAAAATTATTATAAGAAACTCTTTGGCAGTGGAACAACACTTGTTGTCACAGATAAACAACT



region PT-
TGATGCAGATGTTTCCCCCAAGCCCACTATTTTTCTTCCTTCAATTGCTGAAACAAAACTCCAGAAGGCT



gamma-½///
GGAACATACCTTTGTCTTCTTGAGAAATTTTTCCCAGATATTATTAAGATACATTCGCAAGAAAAGAAGA



similar to T-
GCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAAGACTAACGACACATACATGAAATTTAGCTG



cell receptor
GTTAACGGTGCCAGAAGAGTCACTGGACAAAGAACACAGATGTATCGTCAGACATGAGAATAATAAAAAC



gamma chain V
GGAATTGATCAAGAAATTATCTTTCCTCCAATAAAGACAGATGTCACCACAGTGGATCCCAAAGACAGTT



region PT-
ATTCAAAAGATGCAAATGATGTCATCACAATGGATCCCAAAGACAATTGGTCAAAAGATGCAAATGATAC



gamma-½
ACTACTGCTGCAGCTCACAAACACCTCTGCATATTACATGTACCTCCTCCTGCTCCTCAAGAGTGTGGTC



precursor///
TATTTTGCCATCATCACCTGCTGTCTGCTTGGAAGAACGGCTTTGTGCTGCAATGGAGAGAAATCATAAC



TCR gamma
AGACGGTGGCACAAGGAGGCCATCTTTTCCTCATCGGTTATTGTCCCTAGAAGCGTCTTCTGAGGATCTA



alternate
GTTGGGCTTTCTTTCTGGGTTTGGGCCATTTCAGTTCTCATGTGTGTAGTATTCTATCATTATTGTATAA



reading frame
TGGTTTTCAAACCAGTGGGCACACAGAGAACCTCAGTCTGTAATAACAATGAGGAATAGCCATGGCGATC



protein
TCCAGCACCAATCTCTCCATGTTTTCCACAGCTCCTCCAGCCAACCCAAATAGCGCCTGCTATAGTGTAG




ACAGCCTGCGGCTTCTAGCCTTGTCCCTCTCTTAGTGTTCTTTAATCAGATAACTGCCTCGAAGCCTTTC




ATTTTACACGCCCTGAAGCAGTCTTCTTTGCTAGTTGAATTATGTGGTGTGTTTTTCCGTAATAAGCAAA




ATAAATTTAAAAAAATGAAAA





26
pyrin and HIN
>gi|10437303|dbj|AK024890.1|Homo sapiens cDNA: FLJ21237 fis, clone



domain family,
COL01114



member 1
GTCAAAGGAATAATCCCATCTAAAAAGACGAAACAGAAAGAAGTGTATCCTGCTACACCTGCATGCACCC




CAAGCAACCGTCTCACAGCTAAAGGAGCAGAGGAGACTCTTGGACCTCAGGTAAGCTTCAGGAAGAGGAG




CAGGCTTCAAGTCTCACAGTGGAAGCTCTGCTGTGGCTGTTCCACTCAATCTGTCCAGCAGGCAGTTATT




TCTTCATATGTTTCCCATCAAGTTTCAGATTTATCAAATTACATAATAATTGATCATCTTTCTGCAAGGC




AACAAGTTAAACGCTTTAGTAAACATAATGTAAATATACATAAAATAAATATAATATTTTCATCTCCAAT




AGAGAAGGATGTTAACTTGAGAGTCAGATAAAAAAACGTTTGCCTATGTTTACAAAAGCCTAGTTTCTTA




ACTGCAAGTCAGCATATCCCAAAACACAAGTAATTAAGGAATGATGTGTGTTACTTTCTCTGCTCCCTTT




TTAAAAATGAAACCATCTATGCCATGTTCTTTCAATTGGCCTGGGGATGTACTTAAGTTTCCAAGAAAAA




CAATTTATATACAATAAATATATTACCTTGTAATGAAAATGTGCTCTGCTTCATTTGACACTGAAAGTAA




TTAACAAGAAAAATAAACTACTTGTAGAAAAGAAAAAAACCATCTGAAGAAGAGACTGGAACCAAAAGGA




GTAAGATGTCCAAAGAGCAGACTCGGCCTTCCTGCTCTGCAGGAGCCAGCACGTCCACAGCCATGGGCCG




TTCCCCACCTCCCCAGACCTCATCATCAGCTCCACCCAACACTTCCTCAACTGAGGTACACTCTTCCTGG




TCCCCTTTTGATTCATTTTCTTCAACCCAAAATGTAGGAATCTGATTTCATCTTCTACTGAAAAATGACA




TCAATCATCAGCCAGTAAATCAAATGTATAGACTGAGAATTAACTGCATTTTAATCTTTTGCTTCCACAG




GCATATTTGATGAACTTGACATTATCTCTGACTGCAGGAAGTTTTCTGTCCTGTGCTGTTTGGGGAAGAG




ACAGAGAACTGCGGAATCTGGAACTTTCAGCAACAGACTCACTGTCTACTGCCCCCATCTATTATACACC




CATTCCCTTTGCTCACTAATTTGTTCAAGTTTCTCTGACATACACCATGCTCCTTTTTCCTTTAGGATTT




TCACACACCATATTTCTTTCACCTTTAAACTCTTACCTGGCCAACCCTATCCACCCTCTGGATCCCAATA




TTGAGATCTTATCCTCAGGGAATCCTCACTTAGACCCCTGTAACAGGTTAAATCTTCATGGTGTTCTGTT




TCCTAGGAACTTCTTTCTTTTCTACTGTTTATGACAACTGAAGTTAATAAGTGTTTATCTTTCCCACCTA




CTCAAAGTAGTTCCAAGATTAGGGCTAGTTTGTAATTCTGTGGACCACTGTAAACGAGGGCCTAGTTCAG




TGTCTGCCTCATGGGAAGCTTCCAATAAATACCTTTGCTCAACGAAAAAATGAAAACCCAGTGGCTCACG




CCTGTAATCCCAGCACTTTGGGAGGCCGAGGCAGGTGGATTGCCTGAGGTCAGGAGTTTGAGACTAGTCT




GGCCAACATGGTGAAACACTATCTCTACTAAAAATACAAAAAAATTAGCTGGGTATGGTGGCTTACGCCT




ATAATCCCAGCTACTCAGGAGGCTGAGGCAGGGGAATTGCTTGAACCAGGGAGGTGGAGGTTGCAGTGAG




CTGAGATCGCACCACTGCACTCCAGCCTGGGTGACAGAGCGAGACTCCATCTCAAAATAAAAAAGTAAAA




AAAAAAAAAAAAAA





27
T cell receptor
>gi|54607136|ref|NM_016388.2|Homo sapiens T cell receptor associated



associated
transmembrane adaptor 1 (TRAT1), mRNA



transmembrane
GAGGCACAGATAAAGATAAGTTTTACTGTCATGCTGCTTTTAACATAACAGAGCAACATCACCTAGGAAA



adaptor 1
AAAGTTTGTAGGAGGATTTTTAATCCATATATTTGTCTTATGGCTAGATAAAGATTTCTCTGAAAAAAAG




AAGCATGTCAGGAATCTCTGGGTGCCCCTTTTTCCTCTGGGGACTTCTAGCATTGTTGGGCTTGGCTTTG




GTTATATCACTGATCTTCAATATTrCCCACTATGTCGAAAAGCAACGACAAGATAAAATGTACAGCTACT




CCAGTGACCACACCAGGGTTGATGAGTATTATATTGAAGACACACCAATTTATGGTAACTTAGATGATAT




GATTTCAGAACCAATGGATGAAAATTGCTATGAACAAATGAAAGCCCGACCAGAGAAATCTGTAAATAAG




ATGCAGGAAGCCACCCCATCTGCACAGGCAACCAATGAAACACAGATGTGCTACGCCTCACTTGATCACA




GCGTTAAGGGGAAGCGTAGAAAGCCCAGGAAACAGAATACTCATTTCTCAGACAAGGATGGAGATGAGCA




ACTACATGCAATAGATGCCAGCGITTCTAAGACCACCTTAGTAGACAGTTTCTCCCCAGAAAGCCAGGCA




GTAGAGGAAAACATTCATGATGATCCCATCAGACTGTTTGGATTGATCCGTGCTAAGAGAGAACCTATAA




ACTAGCTGGACCATGATCTAGTTCAATGATTTGGCTCCTATTGAAGATGGCTTCTAAGAAAACAAGATGC




ACAGAGGACACAGAAGGACTTGGCAGCAGGGTGATGACCTGATCATTTGTTGATGGGATGGTGGCTTACC




TCTTATTCACAGCTTACACTTATGCATGCCAAATGTAAGGCCATGAAAATCAGTATTTCAAATAACTTAA




AAAATGCTTTACTACTAAAATGTAAAAAATTAATGTGCTCACCTCGGCAGCACATATACTAAAAATTAAT




AAGACCCAGCTTGAAAATTGAGCCTGATAACAAGATTACAAATTCACAATACCTAATACTTAGGGAAATA




TAAAAATTTAAGCATGAATGCGTTCTGGAACACGTTAGAAGAAAAATAAAAGCCAATGAGTTTTTTTTTA




ATTCTCCTTTCTCACCAATGGGCAATAGCCCATAATTGAIATAAATTTCTGATTGAAAGGTATAGGAAAC




ATTAAAATGCATTACTAAGAGAAGTAATATAATTTTCTTACAAAGTATTTTTCCCAAAGATAGCTTTACT




ATTTCAAAAATTGTCAAATTAATGCATGCTCCTTACAACAAACAAATATCAAAAAGAGTTTAGGAATTCT




ACTAGCCAGAGATAGTCACTTGGAGAAACTTTCTATATATCCTTCTAAATATTTTTCTGGGCATGCTTAT




GTATGTACATCAGTTGTTTCTTTTTATTTTGAACCAAAAATGTGGTTTCTTTTGTACACATTACTTAAAC




TTTCTTTCCAGTCAACAATATATTGTGGATTTATTTTCACTGTTATATTTAACTATATATAAATACGCAT




ATATTGTAATTTTAATGTCTGCTTAGCACCCCACTGATAACCAAATCACAGTTTATTTAAATAATTTTAA




TGACTTTTCAAAAACAATTTATTGATGCAAAAAGCAAGGTTGAGATGACAATGTTTCTTTCAATAATTAA




AAAATACTGCTTCAC





28
SLAM family
>gi|19923571|ref|NN_021181.3|Homo sapiens SLAM family member 7 (SLAMF7),



member 7
mRNA




CTTCCAGAGAGCAATATGGCTGGTTCCCCAACATGCCTCACCCTCATCTATATCCTTTGGCAGCTCACAG




GGTCAGCAGCCTCTGGACCCGTGAAAGAGCTGGTCGGTTCCGTTGGTGGGGCCGTGACTTTCCCCCTGAA




GTCCAAAGTAAAGCAAGTTGACTCTATTGTCTGGACCTTCAACACAACCCCTCTTGTCACCATACAGCCA




GAAGGGGGCACTATCATAGTGACCCAAAATCGTAATAGGGAGAGAGTAGACTTCCCAGATGGAGGCTACT




CCCTGAAGCTCAGCAAACTGAAGAAGAATGACTCAGGGATCTACTATGTGGGGATATACAGCTCATCACT




CCAGCAGCCCTCCACCCAGGAGTACGTGCTGCATGTCTACGAGCACCTGTCAAAGCCTAAAGTCACCATG




GGTCTGCAGAGCAATAAGAATGGCACCTGTGTGACCAATCTGACATGCTGCATGGAACATGGGGAAGAGG




ATGTGATTTATACCTGGAAGGCCcTGGGGCAAGCAGCCAATGAGTCCCATAATGGGTCCATCCTCCCCAT




CTCCTGGAGATGGGGAGAAAGTGATATGACCTTCATCTGCGTTGCCAGGAACCCTGTCAGCAGAAACTTC




TCAAGCCCCATCCTTGCCAGGAAGCTCTGTGAAGGTGCTGCTGATGACCCAGATTCCTCCATGGTCcTCC




TGTGTCTCcTGTTGGTGCCCCTCCTGCTCAGTCTCTTTGTACTGGGGCTATTTCTTTGGTTTCTGAAGAG




AGAGAGACAAGAAGAGTACATTGAAGAGAAGAAGAGAGTGGACATTTGTCGGGAAACTCCTAACATATGC




CCCCATTCTGGAGAGAACACAGAGTACGACACAATCCCTCACACTAATAGAACAATCCTAAAGGAAGATC




CAGCAAATACGGTTTACTCCACTGTGGAAATACCGAAAAAGATGGAAAATCCCCACTCACTGCTCACGAT




GCCAGACACACCAAGGCTATTTGCCTATGAGAATGTTATCTAGACAGCAGTGCACTCCCCTAAGTCTCTG




CTCAAAAAAAAAACAATTCTCGGCCCAAAGAAAACAATCAGAAGAATTCACTGATTTGACTAGAAACATC




AAGGAAGAATGAAGAACGTTGACTTTTTTCCAGGATAAATTATCTCTGATGCTTCTTTAGATTTAAGAGT




TCATAATTCCATCCACTGCTGAGAAATCTCCTCAAACCCAGAAGGTTTAATCACTTCATCCCAAAAATGG




GATTGTGAATGTCAGCAAACCATAAAAAAAGTGCTTAGAAGTATTCCTATAGAAATGTAAATGCAAGGTC




ACACATATTAATGACAGCCTGTTGTATTAATGATGGCTCCAGGTCAGTGTCTGGAGTTTCATTCCATCCC




AGGGCTTGGATGTAAGGATTATACCAAGAGTCTTGCTACCAGGAGGGCAAGAAGACCAAAACAGACAGAC




AAGTCCAGCAGAAGCAGATGCACCTGACAAAAATGGATGTATTAATTGGCTCTATAAACTATGTGCCCAG




CACTATGCTGAGCTTACACTAATTGGTCAGACGTGCTGTCTGCCCTCATGAAATTGGCTCCAAATGAATG




AACTACTTTCATGAGCAGTTGTAGCAGGCCTGACCACAGATTCCCAGAGGGCCAGGTGTGGATCCACACG




ACTTGAAGGTCAAAGTTCACAAAGATGAAGAATCAGGGTAGCTGACCATGTTTGGCAGATACTATAATGG




AGACACAGAAGTGTGCATGGCCCAAGGACAAGGACCTCCAGCCAGGCTTCATTTATGCACTTGTGCTGCA




AAAGAAAAGTCTAGGTTTTAAGGCTGTGCCAGAACCCATCCCAATAAAGAGACCGAGTCTGAAGTCACAT




TGTAAATCTAGTGTAGGAGACTTGGAGTCAGGCAGTGAGACTGGTGGGGCACGGGGGGCAGTGGGTACTT




GTAAACCTTTAAAGATGGTTAATTCATTCAATAGATATTTATTAAGAACCTATGCGGCCCGGCATGGTGG




CTCACACCTGTAATCCCAGCACTTTGGGAGGCCAAGGTGGGTGGGTCATCTGAGGTCAGGAGTTCAAGAC




CAGCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAGATACAAAAATTTGCTGAGCGTGGTGGTGTGC




ACCTGTAATCCCAGCTACTCGAGAGGCCAAGGCATGAGAATCGCTTGAACCTGGGAGGTGGAGGTTGCAG




TGAGCTGAGATGGCACCACTGCACTCCGGCCTAGGCAACGAGAGCAAAACTCCAATACAAACAAACAAAC




AAACACCTGTGCTAGGTCAGTCTGGCACGTAAGATGAACATCCCTACCAACACAGAGCTCACCATCTCTT




ATACTTAAGTGAAAAACATGGGGAAGGGGAAAGGGGAATGGCTGCTTTTGATATGTTCCCTGACACATAT




CTTGAATGGAGACCTCCCTACCAAGTGATGAAAGTGTTGAAAAACTTAATAACAAATGCTTGTTGGGCAA




GAATGGGATTGAGGATTATCTTCTCTCAGAAAGGCATTGTGAAGGAATTGAGCCAGATCTCTCTCCCTAC




TGCAAAACCCTATTGTAGTAAAAAAGTCTTCTTTACTATCTTAATAAAACAGATATTGTGAGATTCAAAA




AAAAAAAAAAAA





29
chromosome 4 open
>gi|50428928|ref|NM_152997.2|Homo sapiens chromosome 4 open reading frame



reading frame 7
7 (C4orf7), mRNA




TAAAACAGCTACAATATTCCAGGGCCAGTCACTTGCCATTTCTCATAACAGCGTCAGAGAGAAAGAACTG




ACTGAAACGTTTGAGATGAAGAAAGTTCTCCTCCTGATCACAGCCATCTTGGCAGTGGCTGTTGGTTTCC




CAGTCTCTCAAGACCAGGAACGAGAAAAAAGAAGTATCAGTGACAGCGATGAATTAGCTTCAGGGTTTTT




TGTGTTCCCTTACCCATATCCATTTCGCCCACTTCCACCAATTCCATTTCCAAGATTTCCATGGTTTAGA




CGTAATTTTCCTATTCCAATACCTGAATCTGCCCCTACAACTCCCCTTCCTAGCGAAAAGTAAACAAGAA




GGAAAAGTCACGATAAACCTGGTCACCTGAAATTGAAATTGAGCCACTTCCTTGAAGAATCAAAATTCCT




GTTAATAAAAGAAAAACAAATGTAATTGAAATAGCACACAGCATTCTCTAGTCAATATCTTTAGTGATCT




TCTTTAATAAACTTGAAAGCAAAGATTTTGGTTTCTTAATTTCCACAAA





30
Major histo-
>gi|52426772|ref|NM_002122.3|Homo sapiens major histocompatibility



compatibility
complex, class II, DQ alpha 1 (HLA-DQA1), mRNA



complex, class
ACAATTACTCTACAGCTCAGAACACCAACTGCTGAGGCTGCCTTGGGAAGAGGATGATCCTAAACAAAGC



II, DQ alpha 1
TCTGCTGCTGGGGGCCCTCGCTCTGACCACCGTGATGAGCCCCTGTGGAGGTGAAGACATTGTGGCTGAC




CACGTTGCCTCTTGTGGTGTAAACTTGTACCACTTTTACGGTCCCTCTGGCCAGTACACCCATGAATTTG




ATGGAGATGAGCAGTTCTACGTGGACCTGGAGAGGAAGGAGACTGCCTGOCGGTGGCCTGAGTTCAGCAA




ATTTGGAGGTTTTGACCCGCAGGGTGCACTGAGAAACATGGCTGTGGCAAAACACAACTTGAACATCATG




ATTAAACGCTACAACTCTACCGCTGCTACCAATGAGGTTCCTGAGGTCACAGTGTTTTCCAAGTCTCCCG




TGACACTGGGTCAGCCCAACACCCTCATTTGTCTTGTGGACAACATCTTTCcTCCTGTGGTCAACATCAC




ATGGCTGAGCAATGGGCAGTCAGTCACAGAAGGTGTTTCTGAGACCAGCTTCCTCTCCAAGAGTGATCAT




TCCTTCTTCAAGATCAGTTACCTCACCTTCCTCCCTTCTGCTGATGAGATTTATGACTGCAAGGTGGAGC




ACTGGGGCCTGGACCAGCCTCTTGTGAAACACTGGGAGCCTGAGATTCCAGCCCCTATGTCAGAGCTCAC




AGAGACTGTGGTCTGTGCCCTGGGGTTGTCTGTGGGCCTCATGGGCATTGTGGTGGGCACTGTCTTCATC




ATCCAAGGCCTGCGTTCAGTTGGTGCTTCCAGACACCAAGGGCCATTGTGAATCCCATCCTGGAAGGGAA




GGTGCATCGCCATCTACAGGAGCAGAAGAATGGACTTGCTAAATGACCTAGCACTATTCTCTGGCCCGAT




TTATCATATCCCTTTTCTCCTCCAAATATTTCTCCTCTCACCTTTTCTCTGGGACTTAAGCTGCTATATC




CCCTCAGAGCTCACAAATGCCTTTACATTCTTTCCCTGACCTCCTGATTTTTTTTTTCTTTTCTCAAATG




TTACCTACAAAGACATGCCTGGGGTAAGCCACCCGGCTACCTAATTCCTCAGTAACCTCCATCTAAAATC




TCCAAGGAAGCAATAAATTCCTTTTATGAGATCTATGTCAAATTTTTCCATCTTTCATCCAGGGCTGACT




GAAACTATGGCTAATAATTGGGGTACTCTTATGTTTCAATCCAATTTAACCTCATTTCCCAGATCATTTT




TCATGTCCAGTAACACAGAAGCCACCAAGTACAGTATAGCCTGATAATATGTTGATTTCTTAGCTGACAT




TAATATTTCTTGCTTCCTTGTGTTCCCACCCTTGGCACTGCCACCCACCCCTCAATTCAGGCAACAATGA




AATTAATGGATACCGTCTGCCCTTGGCCCAGAATTGTTATAGCAAAAATTTTAGAACCAAAAAATAAGTC




TGTACTAATTTCAATGTGGCTTTTAAAAGTATGACAGAGAAATAAGTTAGGATAAAGGAAATTTGAATCT




CA





31
Transcribed locus
>gi|3807951|gb|AI225238.1|AI225238 qx12c04.x1 NCI_CGAP_Lym12 Homo sapiens




cDNA clone IMAGE: 2001126 3′, mRNA sequence




AGCGGCCGCCCTTTTTTTTTTTTTTTGAATGTTTTTATATTTTTATGTTTTTCTCTCTCACCACATTAGA




GATTCACATGTCAAAAAAAAAGTTCAAAGATTCCACTTAAATGGTAGTCAAAATTAAAAGCATGTTGTTT




AATTTGCCAACTATTCCATAAATCCTGTGCTTGAAGCACTACCTTTTATCAACCACTTGAAAGGAAGGAA




TATGAAGTGTGACTCTTGAGGATTGCAGTTCCATTTCTCCACAGACATAGCAGGGTGTGTAGTTCCAAAT




GGGTTTCTTCCAAAGTCATCTCCTCAGAGTAGGACTGTCTGAGTAGTCATTCTGATAATGTTGCCATTAA




CTACAAGCACATCTGAGAACCCTCGTAAGGAAGTGCCATTAGATTCAGA





32
Amphiphysin (Stiff-
>gi|51466133|ref|XM_499518.1|PREDICTED: Homo sapiens LOC442534



Man syndrome with
(LOC442534), mRNA



breast cancer
GGCCCAGCCCTAGGAGGGGGCAGTCCCACAGCAGGCTCACACCCTGCCCTTCAGAGTTGCAGCAGCTAAT



128 kDa autoantigen)
GCTGATGCCAGGACCTTGTCCTGCCAGGAAGCCTCTGATTAGGGCTGTGAACCAACTTCCTTTTCACATC




TGCAAGGACTCTGCTCTAAGCTCAAATTTTGCAGTTTCTGCTGTCATCACAGCTGGGAATGAGAAAGGGA




AGGGGCTCCAGTTGGTCTCCCTCTGCCTCTGGAGCACACGTGGAGGACATGAGGCTTCCGCAGGAACAGC




TCTGAAAGCTGAGTTCTCGGGTCCCTGTGAAGGAGGGAAGCTTGCCTGCCTTGGAGCGTGAAAAAGTCTT




GCTGGACAGAAGTCTCACGGTTTAAAACTGGGAAGGGAGAGGATTGAGATCACACTAGAATGCACAGAAA




ATTCTT





33
dendritic cell-
>gi|40548404|ref|NM_172004.2|Homo sapiens dendritic cell-associated



associated lectin-1
lectin-1 (DCAL1), mRNA




ATGGTTAGTAATTTCTTCCATGTCATACAAGTATTCGAGAAATCTGCTACCTTGATTAGTAAGACTGAAC




ACATTGGTTTTGTCATTTATTCATGGAGGAAGTCCACCACCCACTTGGGGAGCAGAAGGAAATTTGCCAT




CTCAATTTACTTATCAGAAGTTTCTTTGCAGAAATATGATTGTCCCTTCAGTGGGACATCATTTGTGGTC




TTCTCTCTCTTTTTGATCTGTGCAATGGCTGGAGATGTAGTCTACGCTGACATCAAAACTGTTCGGACTT




CCCCGTTAGAACTCGCGTTTCCACTTCAGAGATCTGTTTCTTTCAACTTTTCTACTGTCCATAAATCATG




TCCTGCCAAAGACTGGAAGGTGCATAAGGGAAAATGTTACTGGATTGCTGAAACTAAGAAATCTTGGAAC




AAAAGTCAAAATGACTGTGCCATAAACAATTCATATCTCATGGTGATTCAAGACATTACTGCTATGGTGA




GATTTAACATTTAGAGGTGACAGCATCCCCCACACTGGCAGTGAATTTTTTGTGCTACAAACTTGGCAAA




AGTCTGTGAAAAGAAGTTTCAACTTCATGTGTTATTAACTATACAAATATTAGTTGAATGAATTGTTGAA




TTACAAAAAAAAAAAAAAA
















TABLE 1B







Probes for identifying genes of Table 1 (and their fold upregulation in Mage cancer patients)












Probe



Fold



set ID
Gene name
Probeset sequence
Full gene sequence
change















1558972_
chromosome
ttctaagacccacatttggttatt
>gi|58218985|ref|NM_001010923.1|Homo sapiens
44.93



s_at
6 open
gaaggccacagcgaatcttaacct
chromosome 6 open reading frame 190 (C6orf190),



reading
aacagccttgac
mRNA



frame 190
aaactgcaccataggtgtttttag
ATACTTACAATTACGAGATTTATATTTGCATTAGTCTCTTTGGCTGG




actcatataatttgttatttttca
TGGGTAGGGGTGAGAGGCTCTTC




aacaatagtgaa
CTGGATCCCTTATTTTCTACAGGAGAGGAGGAAAACACCTGGGATGC




taattaatattnttgtttggaatt
TCCAGTGCTCTTACGCAGATAAT




tgagnacaattaaatttgtacttt
GATCATTAACATCAGCCTCTCTGATCAAAGAGCTACTCCACCCCACT




tagtaactacca
CTGGCTGTAGTGTGACATTCCTG




ttctttgattagaaaattaagaga
CCTGCCTGAGGAAGAAATGGTGAGCAGGGGCTGCAATTGCAGACAAG




atgcatatcttactttggttgtaa
TGTCACCCAGAAGCCACAAGTTT




attatcaagggc
CTGTGAGCACCAGGTCTACAAACTACCCAAGGCATAGCAATGGCATT




tttctaatagaaatcatatataac
ATCACTGGAAGAATTCGTCCACT




atttctaaatataagtcctttcac
CCCTTGACCTCAGGACCCTACCCAGGGTTCTAGAAATCCAGGCAGGC




atactgtgtttc
ATCTATCTTGAAGGCTCTATTTA




cagttgtcttgatattgaaaagtg
TGAAATGTTTGGAAATGAATGCTGTTTTTCAACAGGAGAAGTGATTA




taataaacttcatgctcacctat
AAATTACTGGTCTCAAAGTTAAG




[Seq ID No 49]
AAGATCATAGCTGAAATTTGTGAGCAGATTGAAGGTTGTGAGTCTCT





ACAGCCATTTGAACTGCCTATGA





ATTTTCCAGGTCTTTTTAAGATTGTGGCTGATAAAACTCCATACCTT





ACTATGGAAGAAATCACAAGGAC





CATTCATATTGGACCAAGTAGACTAGGGCATCCTTGCTTCTATCATC





AGAAGGATATAAAACTAGAGAAC





CTCATCATAAAGCAGGGTGAGCAAATCATGCTCAACTCAGTTGAAGA





GATTGATGGAGAAATAATGGTGA





GCTGTGCAGTAGCAAGGAATCATCAAACTCACTCATTTAATTTGCCT





TTGTCACAAGAAGGAGAATTCTA





CGAGTGTGAAGATGAACGTATTTACACTCTAAAGGAGATTGTTGAAT





GGAAGATTCCTAAGAACAGAACA





AGAACTGTAAACCTTACAGATTTTTCAAATAAGTGGGACTCAACGAA





TCCATTTCCTAAAGACTTTTATG





GTACCCTGATTCTCAAGCCTGTTTATGAAATTCAAGGTGTGATGAAA





TTTCGAAAAGATATAATCCGCAT





CCTCCCCAGTCTAGATGTCGAAGTCAAAGACATCACTGATTCTTACG





ATGCTAACTGGTTTCTTCAGCTG





TTATCAACAGAAGATCTTTTTGAAATGACTAGTAAAGAGTTCCCCAT





AGTGACTGAAGTCATAGAAGCAC





CTGAAGGAAACCACCTGCCCCAAAGCATTTTACAGCCTGGGAAAACC





ATTGTGATCCACAAAAAGTACCA





GGCATCAAGAATCTTAGCTTCAGAAATTAGAAGCAATTTTCCTAAAA





GACACTTCTTGATCCCCACTAGC





TATAAAGGCAAGTTCAAGCGGCGACCGAGGGAGTTCCCAACGGCCTA





TGACCTAGAGATCGCTAAGAGTG





AAAAGGAGCCTCTTCACGTGGTGGCCACCAAAGCGTTTCATTCCCCT





CATGACAAGCTGTCATCCGTATC





TGTTGGGGACCAGTTTCTGGTGCATCAGTCAGAGACGACTGAAGTCC





TCTGTGAGGGAATAAAAAAAGTG





GTGAATGTTCTGGCCTGTGAAAAAATCCTCAAAAAGTCCTATGAGGC





TGCGCTGCTCCCTTTGTACATGG





AAGGAGGTTTTGTAGAGGTGATTCATGATAAGAAACAGTACCCGATT





TCTGAGCTCTGTAAACAGTTCCG





TTTGCCCTTCAATGTGAAGGTGTCTGTCAGGGATCTTTCCATTGAAG





AGGACGTGTTGGCTGCCACACCA





GGACTGCAGTTGGAGGAGGACATTACAGACTCTTACCTACTCATAAG





TGACTTTGCCAACCCCACGGAGT





GCTGGGAAATTCCTGTGGGCCGCTTGAATATGACTGTTCAGTTAGTT





AGTAATTTCTCTAGGGATGCAGA





ACCATTTCTAGTCAGGACTCTGGTAGAAGAGATCACTGAAGAGCAAT





ATTACATGATGCGGAGATATGAA





AGCTCAGCCTCACATCCCCCACCTCGCCCTCCGAAACACCCCTCAGT





AGAGGAAACAAAGTTAACCCTGC





TAACCTTAGCAGAAGAAAGGACGGTAGACCTGCCCAAGTCTCCCAAG





CGTCATCACGTAGACATAACCAA





GAAACTTCACCCAAATCAAGCTGGCCTGGATTCAAAAGTACTGATTG





GTAGTCAGAATGATTTGGTGGAT





GAAGAGAAAGAAAGGAGCAACCGTGGGGCCACAGCAATAGCAGAAAC





ATTCAAAAATGAAAAACATCAAA





AATAACAAGATGTGACAGAAGCCACTTAGGCAGCAAACATAAATGTT





GCAGTGAAAAAAGAAGCTAGCCT





TCTAGCTGAAAAACGAGTATTCCCCAATGGACTCCAGAAGAAACTTG





ATTCATCGCTGCAAAGGAAAGAA





CAACCTTAAAACTTTTAACAGATAAAACTTACAGAAACCTATGATAT





AGAATTCATATAGTCTATTCTGT





TGTGTCTAAATCTGTAGGCATTGTGTTGTTGTTCTTTAGGACGTATT





TATTTAACTTGCACATTTTTTCA





GATTCTTATTTCTACTACCAACAACTAAGTAATTGGGAAATAATTCT





GTATTTCAGTTTCTGAGTAAAAC





CAGTCTGAAATAGGATAAAAGCCACCAAATATTTTCTTTTTTTTCCA





GAATTTGTTTTGCCATTTTTTAG





TGCTATCATCATTCCTAACAAGACTAACTTACAGAAAAATAATTATA





TCTGACTGATTTAAAATGTTCAG





GTTTCTTATCCAAATCCCTTGGAACTATGGAAAGGAGTTTGATTTCA





CATTCACAGTGTATTTACAAAAT





ACGCTGTGTCATAAATATGTTTGAATTCCAACAGCCAAAGCCATTGA





GAGTCATAGGAGTTTTCCATAAC





CTTCTCTTCTATGACCCAACAACAAGCTCATGACTGAAATTTCACCA





GATTTCTGAGACGATGTCTTAAT





ATTCTATGTGCTATGTACCAGATAATTCTTTAGATGAATGTTTCTTA





GGATTGTAGGAAAATTATCTAGT





TAATCATAATATTTGATGGAAAGAAAAAGACAATAAAATTGTAATAT





AATAAATTTGGCTGACAAGAAAC





CAAAGTGATTCTTAATTAGTATACATCAGAATGATGCTCTTATAGTT





GTACCATCTATAAAAATTACTTT





AAGGGCTCTCACATTTTAATAATTTATCTTATTATGTATTAAGTATA





CAGGAACAATATTATTTTTCCTT





TAACAAAATGAAGAGACAGGCTATCTGGTTAATGTTACATAGGAATT





TAATAGTAATGCTTGAACTTCAT





CCATAGATCATACTCTGTACAAAATTTGTTAGCTAACATCCTATCTC





ATAATTATTTTATGTTTTGTGGA





GAAATTTGTTGATTTTGTACCAAAGTGTTTCTGAAGACAATAAATTG





TGAGTCAACTTTAGAACAAAAAA





AATTAGAGTTTTTTCAATGTTTATATTCTGATTAAGCTTACTTTACC





TTACATTTTTTCTAAGTAACAAT





GAATCCTGATTTCTAGTGTCCTAAAAATTGCTTAGTGATTTGATTGT





GGTAATATCATTTCTTATCTACA





ATGTCTAAAGTTTTATGGGACAGTTTTTCTTTTATTTATTTTGCCTG





TTTGTGCAGATAAGAACAGAAAC





TTTTCTAAGACCCACATTTGGTTATTGAAGGCCACAGCGAATCTTAA





CCTAACAGCCTTGACAAACTGCA





CCATAGGTGTTTTTAGACTCATATAATTTGTTATTTTTCAAACAATA





GTGAATAATTAATATTTTTGTTT





GGAATTTGAGAACAATTAAATTTGTACTTTTAGTAACTACCATTCTT





TGATTAGAAAATTAAGAGAATGC





ATATCTTACTTTGGTTGTAAATTATCAAGGGCTTTCTAATAGAAATC





ATATATAACATTTCTAAATATAA





GTCCTTTCACATACTGTGTTTCCAGTTGTCTTGATATTGAAAAGTGT





AATAAACTTCATGCTCACCTATT





GGAGATTTGGGAAGGTTGAAAATAAACTTCCTAATTTTTAAAAAAAA





AA





202957_
hematopoietic
ttgctggcttctcttatactaacc
>gi|37059786|ref|NM_005335.3|Homo sapiens
19.09


_at
cell-
cagagtttgtcattaatgtgtagg
hematopoietic cell-specific Lyn substrate 1



specific
tgaatgcaaact
(HCLS1), mRNA



Lyn
ccatcgttgagcctggggtgtaag
GTGGACGCGAGGAGCCGGGCGCTTAGAACAGAGGCTTGCACAGGTGG



substrate 1
acttcaagccaagcgtatgtatca
AGATGTGGAAGTCTGTAGTGGGC




attctagtcttc
CATGATGTGTCTGTTTCCGTGGAGACCCAGGGTGATGATTGGGACAC




caggattcacggtgcacatgctgg
AGATCCTGACTTTGTGAATGACA




cattcaacatgtggaaagcttgtc
TCTCTGAAAAGGAGCAACGATGGGGAGCCAAGACCATCGAGGGGTCT




ttagaggccttt
GGACGCACAGAACACATCAACAT




cttgtatgtgtagcttgctagttt
CCACCAGCTGAGGAACAAAGTATCAGAGGAGCATGATGTTCTCAGGA




gttttctacatttgaaaatgttta
AGAAAGAGATGGAGTCAGGGCCC




gtttagaataag
AAAGCATCCCATGGCTATGGAGGTCGGTTTGGAGTAGAAAGAGACCG




cgcattatccaattatagaggtac
AATGGACAAGAGTGCAGTGGGCC




aattttccaaacttccagaaactc
ATGAGTATGTTGCCGAGGTGGAGAAGCACTCTTCTCAGACGGATGCT




atcaaatgaaca
GCCAAAGGCTTTGGGGGCAAGTA




gacaatgtcaaaactactgtgtct
CGGAGTTGAGAGGGACAGGGCAGACAAGTCAGCAGTCGGCTTTGATT




gataccaaaatgcttcagtatttg
ATAAAGGAGAAGTGGAGAAGCAT




taatttttcaag
ACATCTCAGAAAGATTACTCTCGTGGCTTTGGTGGCCGGTACGGGGT




tcagaagctgatgttcctggtaaa
GGAGAAGGATAAATGGGACAAAG




agtt
CAGCTCTGGGATATGACTACAAGGGAGAGACGGAGAAACACGAGTCC




[Seq ID No 50]
CAGAGAGATTATGCCAAGGGCTT





TGGTGGCCAGTATGGAATCCAGAAGGACCGAGTGGATAAGAGCGCTG





TCGGCTTCAATGAAATGGAGGCC





CCGACCACAGCTTATAAGAAGACGACGCCCATAGAAGCCGCTTCTAG





TGGTGCCCGTGGGCTGAAGGCGA





AATTTGAGTCCATGGCTGAGGAGAAGAGGAAGCGAGAGGAAGAGGAG





AAGGCACAGCAGGTGGCCAGGAG





GCAACAGGAGCGAAAGGCTGTGACAAAGAGGAGCCCTGAGGCTCCAC





AGCCAGTGATAGCTATGGAAGAG





CCAGCAGTACCGGCCCCACTGCCCAAGAAAATCTCCTCAGAGGCCTG





GCCTCCAGTTGGGACTCCTCCAT





CATCAGAGTCTGAGCCTGTGAGAACCAGCAGGGAACACCCAGTGCCC





TTGCTGCCCATTAGGCAGACTCT





CCCGGAGGACAATGAGGAGCCCCCAGCTCTGCCCCCTAGGACTCTGG





AAGGCCTCCAGGTGGAGGAAGAG





CCAGTGTACGAAGCAGAGCCTGAGCCTGAGCCCGAGCCTGAGCCCGA





GCCTGAGAATGACTATGAGGACG





TTGAGGAGATGGACAGGCATGAGCAGGAGGATGAACCAGAGGGGGAC





TATGAGGAGGTGCTCGAGCCTGA





AGATTCTTCTTTTTCTTCTGCTCTGGCTGGATCATCAGGCTGCCCGG





CTGGGGCTGGGGCTGGGGCTGTG





GCTCTGGGGATCTCAGCTGTGGCTCTATATGATTACCAAGGAGAGGG





AAGTGATGAGCTTTCCTTTGATC





CGGACGACGTAATCACTGACATTGAGATGGTGGACGAGGGCTGGTGG





CGGGGACGTTGCCATGGCCACTT





TGGACTCTTCCCTGCAAATTATGTCAAGCTTCTGGAGTGACTAGAGC





TCACTGTCTACTGCAACTGTGAT





TTCCCATGTCCAAAGTGGCTCTGCCTCCACCCCCTCCCTATTCCTGA





TGCAAATGTCTAACCAGATGAGT





TTCTGGACAGACTTCCCTCTCCTGCTTCATTAAGGGCTTGGGGCAGA





GACAGCATGGGGAAGGAGGTCCC





CTTCCCCAAGAGTCCTCTCTATCCTGGATGAGCTCATGAACATTTCT





CTTGTGTTCCTGACTCCTTCCCA





ATGAACACCTCTCTGCCACCCCAAGCTCTGCTCTCCTCCTCTGTGAG





CTCTGGGCTTCCCAGTTTGTTTA





CCCGGGAAAGTACGTCTAGATTGTGTGGTTTGCCTCATTGTGCTATT





TGCCCACTTTCCTTCCCTGAAGA





AATATCTGTGAACCTTCTTTCTGTTCAGTCCTAAAATTCGAAATAAA





GTGAGACTATGGTTCACCTGTAA





AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA





AAAAAAAAAAAAAAAAAAAAAA





204116_
interleukin
ttctggctggaacggacgatgccc
>gi|4557881|ref|NM_00206.1|Homo sapiens
61.98


at
2 receptor,
cgaattcccaccctgaagaaccta
interleukin 2 receptor, gamma (severe combined



gamma
gaggatcttgtt
immunodeficiency) (IL2RG), mRNA



(severe
actgaataccacgggaacttttcg
GAAGAGCAAGCGCCATGTTGAAGCCATCATTACCATTCACATCCCTC



combined
gcctggagtggtgtgtctaaggga
TTATTCCTGCAGCTGCCCCTGCT



immuno-
ctggctgagagtctgcagccagac
GGGAGTGGGGCTGAACACGACAATTCTGACGCCCAATGGGAATGAAG



deficiency)
tacagtgaacgactctgcctcgtc
ACACCACAGCTGATTTCTTCCTG




agtgagattcccccaaaaggaggg
ACCACTATGCCCACTGACTCCCTCAGTGTTTCCACTCTGCCCCTCCC




gcccttggggaggggcctggggcc
AGAGGTTCAGTGTTTTGTGTTCA




tccccatgcaaccagcatagcccc
ATGTCGAGTACATGAATTGCACTTGGAACAGCAGCTCTGAGCCCCAG




tactgggcccccccatgttacacc
CCTACCAACCTCACTCTGCATTA




ctaaagcctgaaacctgaacccca
TTGGTACAAGAACTCGGATAATGATAAAGTCCAGAAGTGCAGCCACT




atcctctgacagaagaaccccagg
ATCTATTCTCTGAAGAAATCACT




gtcctgtagccctaagtggtacta
TCTGGCTGTCAGTTGCAAAAAAAGGAGATCCACCTCTACCAAACATT




actttccttcattcaacccacctg
TGTTGTTCAGCTCCAGGACCCAC




cgtctcatactcacctcaccccac
GGGAACCCAGGAGACAGGCCACACAGATGCTAAAACTGCAGAATCTG




tgtggctgatttggaattttgtgc
GTGATCCCCTGGGCTCCAGAGAA




ccccatgtaagcacc
CCTAACACTTCACAAACTGAGTGAATCCCAGCTAGAACTGAACTGGA




[Seq ID No 51]
ACAACAGATTCTTGAACCACTGT





TTGGAGCACTTGGTGCAGTACCGGACTGACTGGGACCACAGCTGGAC





TGAACAATCAGTGGATTATAGAC





ATAAGTTCTCCTTGCCTAGTGTGGATGGGCAGAAACGCTACACGTTT





CGTGTTCGGAGCCGCTTTAACCC





ACTCTGTGGAAGTGCTCAGCATTGGAGTGAATGGAGCCACCCAATCC





ACTGGGGGAGCAATACTTCAAAA





GAGAATCCTTTCCTGTTTGCATTGGAAGCCGTGGTTATCTCTGTTGG





CTCCATGGGATTGATTATCAGCC





TTCTCTGTGTGTATTTCTGGCTGGAACGGACGATGCCCCGAATTCCC





ACCCTGAAGAACCTAGAGGATCT





TGTTACTGAATACCACGGGAACTTTTCGGCCTGGAGTGGTGTGTCTA





AGGGACTGGCTGAGAGTCTGCAG





CCAGACTACAGTGAACGACTCTGCCTCGTCAGTGAGATTCCCCCAAA





AGGAGGGGCCCTTGGGGAGGGGC





CTGGGGCCTCCCCATGCAACCAGCATAGCCCCTACTGGGCCCCCCCA





TGTTACACCCTAAAGCCTGAAAC





CTGAACCCCAATCCTCTGACAGAAGAACCCCAGGGTCCTGTAGCCCT





AAGTGGTACTAACTTTCCTTCAT





TCAACCCACCTGCGTCTCATACTCACCTCACCCCACTGTGGCTGATT





TGGAATTTTGTGCCCCCATGTAA





GCACCCCTTCATTTGGCATTCCCCACTTGAGAATTACCCTTTTGCCC





CGAACATGTTTTTCTTCTCCCTC





AGTCTGGCCCTTCCTTTTCGCAGGATTCTTCCTCCCTCCCTCTTTCC





CTCCCTTCCTCTTTCCATCTACC





CTCCGATTGTTCCTGAACCGATGAGAAATAAAGTTTCTGTTGATAAT





CATC





204661_
CD52
acagccacgaagatcctaccaaaa
>gi|68342029|ref|NM_001803.2|Homo sapiens CD52
30.71


at
antigen
tgaagcgcttcctcttcctcctac
molecule (CD52), mRNA



(CAMPATH-1
tcaccatcagcc
CTCCTGGTTCAAAAGCAGCTAAACCAAAAGAAGCCTCCAGACAGCCC



antigen)///
tcctggttatggtacagatacaaa
TGAGATCACCTAAAAAGCTGCAT



CD52
ctggactctcaggacaaaacgaca
CCAAGACAGCCACGAAGATCCTACCAAAATGAAGCGCTTCCTCTTCC



antigen
ccagccaaaccagcagcccctcag
TCCTACTCACCATCAGCCTCCTG



(CAMPATH-1
catccagcagcatgagcggaggca
GTTATGGTACAGATACAAACTGGACTCTCAGGACAAAACGACACCAG



antigen)
ttttccttttcttcgtggccaatg
CCAAACCAGCAGCCCCTCAGCAT




ccataatccacctcttctgcttca
CCAGCAACATAAGCGGAGGCATTTTCCTTTTCTTCGTGGCCAATGCC




gttgaggtgacacgtctcagcctt
ATAATCCACCTCTTCTGCTTCAG




agccctgtgccc
TTGAGGTGACACGTCTCAGCCTTAGCCCTGTGCCCCCTGAAACAGCT




cctgaaacagctgccaccatcact
GCCACCATCACTCGCAAGAGAAT




cgcaagagaatcccctccatcttt
CCCCTCCATCTTTGGGAGGGGTTGATGCCAGACATCACCAGGTTGTA




gggaggggttgatgccagacatca
GAAGTTGACAGGCAGTGCCATGG




ccaggttgtagaagttgacaggca
GGGCAACAGCCAAAATAGGGGGGTAATGATGTAGGGGCCAAGCAGTG




gtgccatgggggcaacagccaaaa
CCCAGCTGGGGGTCAATAAAGTT




taggggggtaatgatgtaggggcc
ACCCTTGTACTTGCAAAAAAAAAAAAAAAAAAA




aagc




[Seq ID No 52]





205831_
CD2
agacctcgagttcagccaaaacct
>gi|31542293|ref|NM_001767.2|Homo sapiens CD2
22.66


at
antigen
ccccatggggcagcagaaaactca
molecule (CD2), mRNA



(p50),
ttgtccccttcctctaattaaaaa
ACCAACCCCTAAGATGAGCTTTCCATGTAAATTTGTAGCCAGCTTCC



sheep red
agatagaaactgtctttttcaata
TTCTGATTTTCAATGTTTCTTCC



blood cell
aaaagcactgtggatttctgccct
AAAGGTGCAGTCTCCAAAGAGATTACGAATGCCTTGGAAACCTGGGG



receptor///
cctgatgtgcatatccgtacttcc
TGCCTTGGGTCAGGACATCAACT



CD2
atgaggtgttttctgtgtgcagaa
TGGACATTCCTAGTTTTCAAATGAGTGATGATATTGACGATATAAAA



antigen
cattgtcacctc
TGGGAAAAAACTTCAGACAAGAA



(p50),
ctgaggctgtgggccacagccacc
AAAGATTGCACAATTCAGAAAAGAGAAAGAGACTTTCAAGGAAAAAG



sheep red
tctgcatcttcgaactcagccatg
ATACATATAAGCTATTTAAAAAT



blood cell
tggtcaacatct
GGAACTCTGAAAATTAAGCATCTGAAGACCGATGATCAGGATATCTA



receptor
ggagtttttggtctcctcagagag
CAAGGTATCAATATATGATACAA




ctccatcacaccagtaaggagaag
AAGGAAAAAATGTGTTGGAAAAAATATTTGATTTGAAGATTCAAGAG




caatataagtgt
AGGGTCTCAAAACCAAAGATCTC




gattgcaagaatggtagaggaccg
CTGGACTTGTATCAACACAACCCTGACCTGTGAGGTAATGAATGGAA




agcacagaaatcttagagatttct
CTGACCCCGAATTAAACCTGTAT




tgtcccctctca
CAAGATGGGAAACATCTAAAACTTTCTCAGAGGGTCATCACACACAA




ggtcatgtgtagatgcgataaatc
GTGGACCACCAGCCTGAGTGCAA




aagtgattggtgtgcctgggtctc
AATTCAAGTGCACAGCAGGGAACAAAGTCAGCAAGGAATCCAGTGTC




actacaagcagc
GAGCCTGTCAGCTGTCCAGAGAA




ctatctgc
AGGTCTGGACATCTATCTCATCATTGGCATATGTGGAGGAGGCAGCC




[Seq ID No 53]
TCTTGATGGTCTTTGTGGCACTG





CTCGTTTTCTATATCACCAAAAGGAAAAAACAGAGGAGTCGGAGAAA





TGATGAGGAGCTGGAGACAAGAG





CCCACAGAGTAGCTACTGAAGAAAGGGGCCGGAAGCCCCAACAAATT





CCAGCTTCAACCCCTCAGAATCC





AGCAACTTCCCAACATCCTCCTCCACCACCTGGTCATCGTTCCCAGG





CACCTAGTCATCGTCCCCCGCCT





CCTGGACACCGTGTTCAGCACCAGCCTCAGAAGAGGCCTCCTGCTCC





GTCGGGCACACAAGTTCACCAGC





AGAAAGGCCCGCCCCTCCCCAGACCTCGAGTTCAGCCAAAACCTCCC





CATGGGGCAGCAGAAAACTCATT





GTCCCCTTCCTCTAATTAAAAAAGATAGAAACTGTCTTTTTCAATAA





AAAGCACTGTGGATTTCTGCCCT





CCTGATGTGCATATCCGTACTTCCATGAGGTGTTTTCTGTGTGCAGA





ACATTGTCACCTCCTGAGGCTGT





GGGCCACAGCCACCTCTGCATCTTCGAACTCAGCCATGTGGTCAACA





TCTGGAGTTTTTGGTCTCCTCAG





AGAGCTCCATCACACCAGTAAGGAGAAGCAATATAAGTGTGATTGCA





AGAATGGTAGAGGACCGAGCACA





GAAATCTTAGAGATTTCTTGTCCCCTCTCAGGTCATGTGTAGATGCG





ATAAATCAAGTGATTGGTGTGCC





TGGGTCTCACTACAAGCAGCCTATCTGCTTAAGAGACTCTGGAGTTT





CTTATGTGCCCTGGTGGACACTT





GCCCACCATCCTGTGAGTAAAAGTGAAATAAAAGCTTTGACTAGAAA





AAAAAAAAAAAAAAAAAAAAAAA





AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA





205890_
ubiquitin D
Gatcttaaagccacggagaagcct
>gi|50355987|ref|NM_006398.2|Homo sapiens
30.29


s_at

ctcatcttatggcattgacaaaga
ubiquitin D (UBD), mRNA




gaagaccatccaccttaccctgaa
GATTGCTTGAGGAGAGAAGTATGTGATCAGAAAGCATTCTTTGTCTA




agtggtgaagcccagtgatgagga
TTAACTCCTGCCCAGCAAAAGTG




gctgcccttgtttcttgtggagtc
AAAGAAAATTCATGGGAGCATGCAAGAACAAAGAGCACAGCAAAGCT




aggtgatgaggcaaagaggcacct
GGACAAACACAGCAATCCAGGCA




cctccaggtgcgaaggtccagctc
GGGGATTTCCAACTCAACTCTGGTATGTAAGCTGCATGCAAAGTCCT




agtggcacaagtgaaagcaatgat
TTTTCTGTCTCTGGTTTCTGGCC




cgagactaagacgggtataatccc
CCTTGTCTGCAGAGATGGCTCCCAATGCTTCCTGCCTCTGTGTGCAT




tgagacccagattgtgacttgcaa
GTCCGTTCCGAGGAATGGGATTT




tggaaagagactggaagatgggaa
AATGACCTTTGATGCCAACCCATATGACAGCGTGAAAAAAATCAAAG




gatgatggcagattacggcatcag
AACATGTCCGGTCTAAGACCAAG




aaagggcaacttactcttcctggc
GTTCCTGTGCAGGACCAGGTTCTTTTGCTGGGCTCCAAGATCTTAAA




atcttattgtattggagggtgacc
GCCACGGAGAAGCCTCTCATCTT




accctggggatggggtgttggcag
ACGGCATTGACAAAGAGAAGACCATCCACCTTACCCTGAAAGTGGTG




gggtcaaaaagcttatttctttta
AAGCCCAGTGATGAGGAGCTGCC




atctcttactcaacgaacacatct
CTTGTTTCTTGTGGAGTCAGGTGATGAGGCAAAGAGGCACCTCCTCC




tctgatgatttcccaaaattaatg
AGGTGCGAAGGTCCAGCTCAGTG




agaatgagatgagtagagtaagat
GCACAAGTGAAAGCAATGATCGAGACTAAGACGGGTATAATCCCTGA




ttgggtgggatgggtaggatgaag
GACCCAGATTGTGACTTGCAATG




tatattgcccaactctatgtttct
GAAAGAGACTGGAAGATGGGAAGATGATGGCAGATTACGGCATCAGA




ttga
AAGGGCAACTTACTCTTCCTGGC




[Seq ID No 54]
ATCTTATTGTATTGGAGGGTGACCACCCTGGGCATGGGGTGTTGGCA





GGGGTCAAAAAGCTTATTTCTTT





TAATCTCTTACTCAACGAACACATCTTCTGATGATTTCCCAAAATTA





ATGAGAATGAGATGAGTAGAGTA





AGATTTGGGTGGGATGGGTAGGATGAAGTATATTGCCCAACTCTATG





TTTCTTTGATTCTAACACAATTA





ATTAAGTGACATGATTTTTACTAATGTATTACTGAGACTAGTAAATA





AATTTTTAAGCCAA





206118_
signal
gctgacatcctgcgagactacaaa
>gi|21618332|ref|NM_003151.2|Homo sapiens
13.56


at
transducer
gttattatggctgaaaacattcct
signal transducer and activator of



and
gaaaaccctctg
transcription 4 (STAT4), mRNA



activator
aagtacctatatcctgacattccc
AGAGGACGCCCGGTGAAGGGGCTCCAGCCTGGCAGTTTCTGCGTGTT



of tran-
aaagacaaagccttcggtaaacac
AGCATTTCTAGAATAGAGTGGGT



scription 4
tacagct ctcag
GGGAACTGACCCAAGTAAAGTCCCAGAGACTCGAACACTGACGCACA




ccttgcgaagtttcaagaccaaca
GGAAAGCCTCAAGTGGGAGGAGA




gaaaggggtgacaaaggttatgtt
AATGCAAATCCCCTACTGATGATGGCGTCAGCGGCTTTCTCCTAGGG




ccttctgttttt
ACTGTGAGGGGCGCTTCTGACTT




atccccatctcaacaatccgaagt
TGGACTTGAGCACTGCCTGGGACCTGTGCTGAGAGAGCGCTAGCATG




gattcaacagagccacattctcca
TCTCAGTGGAATCAAGTCCAACA




tcagaccttctt
GTTAGAAATCAAGTTTTTGGAGCAGGTGGATCAATTCTATGATGACA




cccatgtctccaagtgtgtatgcg
ACTTTCCCATGGAAATTCGGCAT




gtgttgagagaaaacctgagtccc
CTGTTGGCCCAATGGATTGAAAATCAAGACTGGGAGGCAGCTTCTAA




acaacaattgaa
CAATGAAACCATGGCAACGATTC




actgcaatgaagtctccttattct
TTCTTCAAAACTTGTTAATACAACTGGATGAACAGTTAGGTCGTGTT




gctgaatgacaggataaactctga
TCCAAAGAGAAAAACCTACTCTT




cgcaccaagaaa
GATACACAATCTAAAAAGAATTAGGAAGGTCCTTCAGGGAAAATTTC




ggaagcaaatgaaaaagtttaaag
ATGGAAATCCAATGCATGTAGCT




actgttctttgcccaataaccaca
GTGGTTATTTCAAACTGTTTAAGGGAAGAGAGGAGAATATTGGCTGC




ttttatttcttc
AGCCAACATGCCTGTCCAGGGGC




agctttgtaaataccaggttctag
CTCTAGAGAAATCCTTACAAAGTTCTTCAGTTTCAGAAAGACAGAGG




gaaatgtttgacatctgaagctct
AATGTGGAGCACAAAGTGGCTGC




cttcacactccc
CATTAAAAACAGTGTGCAGATGACAGAACAAGATACCAAATACTTAG




gtggcactcctcaattgggag
AAGATCTGCAAGACGAATTTGAC




[Seq ID No 55]
TACAGGTATAAAACAATTCAGACAATGGATCAGAGTGACAAGAATAG





TGCCATGGTGAATCAGGAAGTTT





TGACACTGCAGGAAATGCTTAACAGCCTCGATTTCAAGAGAAAGGAG





GCTCTCAGTAAAATGACCCAAAT





CATCCATGAGACAGACCTGTTAATGAACACCATGCTCATAGAAGAGC





TGCAAGACTGGAAGCGGCGGCAG





CAAATCGCCTGCATCGGGGGTCCACTCCACAATGGGCTCGACCAGCT





TCAGAACTGCTTTACACTATTGG





CAGAAAGTCTTTTCCAACTGAGAAGGCAATTGGAGAAACTAGAGGAG





CAATCTACCAAAATGACATATGA





AGGTGATCCCATTCCAATGCAAAGAACTCACATGCTAGAAAGAGTCA





CCTTCTTGATCTACAACCTTTTC





AAGAACTCATTTGTGGTTGAGCGACAGCCATGTATGCCAACCCACCC





TCAGAGGCCGTTGGTACTTAAAA





CCCTAATTCAGTTCACTGTAAAACTAAGGCTACTAATAAAATTGCCA





GAACTAAACTATCAGGTAAAGGT





TAAGGCATCAATTGACAAGAATGTTTCAACTCTAAGCAACCGAAGAT





TTGTACTTTGTGGAACTAATGTC





AAAGCCATGTCTATTGAAGAATCTTCCAATGGGAGTCTCTCAGTAGA





ATTTCGACATTTGCAACCAAAGG





AAATGAAGTCCAGTGCTGGAGGTAAAGGAAATGAGGGCTGTCACATG





GTGACTGAAGAACTTCATTCCAT





AACGTTTGAAACACAGATCTGCCTCTATGGCCTGACCATAGATTTGG





AGACCAGCTCATTGCCTGTGGTG





ATGATTTCCAATGTCAGTCAGTTACCTAATGCTTGGGCATCCATCAT





TTGGTACAACGTGTCAACCAACG





ATTCCCAGAACTTGGTTTTCTTTAATAATCCTCCACCTGCCACATTG





AGTCAACTACTGGAGGTGATGAG





CTGGCAGTTTTCATCGTACGTTGGTCGTGGTCTTAACTCAGATCAAC





TCCATATGCTGGCAGAGAAGCTT





ACAGTCCAATCTAGCTACAGTGATGGTCACCTCACCTGGGCCAAGTT





CTGCAAGGAACATTTACCTGGTA





AATCATTTACCTTTTGGACATGGCTTGAAGCAATATTGGATCTAATT





AAGAAACACATTCTTCCCCTTTG





GATTGATGGGTATGTCATGGGCTTTGTTAGCAAAGAGAAGGAACGGC





TGTTGCTAAAGGATAAAATGCCT





GGCACCTTTTTATTAAGATTCAGTGAAAGCCATCTCGGAGGAATAAC





TTTCACCTGGGTGGACCATTCTG





AAAGTGGGGAAGTGAGATTCCACTCTGTAGAACCCTACAATAAAGGC





CGGTTGTCTGCTCTGCCATTCGC





TGACATCCTGCGAGACTACAAAGTTATTATGGCTGAAAACATTCCTG





AAAACCCTCTGAAGTACCTATAT





CCTGACATTCCCAAAGACAAAGCCTTCGGTAAACACTACAGCTCTCA





GCCTTGCGAAGTTTCAAGACCAA





CAGAAAGGGGTGACAAAGGTTATGTTCCTTCTGTTTTTATCCCCATC





TCAACAATCCGAAGTGATTCAAC





AGAGCCACATTCTCCATCAGACCTTCTTCCCATGTCTCCAAGTGTGT





ATGCGGTGTTGAGAGAAAACCTG





AGTCCCACAACAATTGAAACTGCAATGAAGTCTCCTTATTCTGCTGA





ATGACAGGATAAACTCTGACGCA





CCAAGAAAGGAAGCAAATGAAAAAGTTTAAAGACTGTTCTTTGCCCA





ATAACCACATTTTATTTCTTCAG





CTTTGTAAATACCAGGTTCTAGGAAATGTTTGACATCTGAAGCTCTC





TTCACACTCCCGTGGCACTCCTC





AATTGGGAGTGTTGTGACTGAAATGCTTGAAACCAAAGCTTCAGATA





AACTTGCAAGATAAGACAACTTT





AAGAAACCAGTGTTAATAACAATATTAACAG





206666_
granzyme K
aaacctctcttagatctggaacca
>gi|73747815|ref|NM_002104.2|Homo sapiens
18.25


at
(granzyme
aatgcaaggttactggctggggag
granzyme K (granzyme 3; tryptase II) (GZMK),



3; tryptase
ccaccgatccagattcattaagac
mRNA



II)///
cttctgacaccctgcgagaagtca
GATCAACACATTTCATGTGGGCTTCTTAAATCTAAATCTTTAAAATG



granzyme K
ctgttactgtcctaagtcgaaaac
ACTAAGTTTTCTTCCTTTTCTCT



(granzyme
tttgcaacagccaaagttactaca
GTTTTTCCTAATAGTTGGGGCTTATATGACTCATGTGTGTTTCAATA



3; tryptase
acggcgacccttttatcaccaaag
TGGAAATTATTGGAGGGAAAGAA



II)
acatggtctgtg
GTGTCACCTCATTCCAGGCCATTTATGGCCTCCATCCAGTATGGCGG




caggagatgccaaaggccagaagg
ACATCACGTTTGTGGAGGTGTTC




attcctgtaagggtgactcagggg
TGATTGATCCACAGTGGGTGCTGACAGCAGCCCACTGCCAATATCGG




gccccttgatctgtaaaggtgtct
TTTACCAAAGGCCAGTCTCCCAC




tccacgctatagtctctggaggtc
TGTGGTTTTAGGCGCACACTCTCTCTCAAAGAATGAGGCCTCCAAAC




atgaatgtggtgttgccacaaagc
AAACACTGGAGATCAAAAAATTT




ctggaatctacaccctgttaacca
ATACCATTCTCAAGAGTTACATCAGATCCTCAATCAAATGATATCAT




agaaataccagacttggatcaaaa
GCTGGTTAAGCTTCAAACAGCCG




gcaaccttgtcccgcctcatacaa
CAAAACTCAATAAACATGTCAAGATGCTCCACATAAGATCCAAAACC




attaagttacaaataattttattg
TCTCTTAGATCTGGAACCAAATG




gatgcacttgcttcttttttccta
CAAGGTTACTGGCTGGGGAGCCACCGATCCAGATTCATTAAGACCTT




atatgctcgcaggttagagttggg
CTGACACCCTGCGAGAAGTCACT




tgtaagtaaagcagagcacatatg
GTTACTGTCCTAAGTCGAAAACTTTGCAACAGCCAAAGTTACTACAA




gggtccattttt
CGGCGACCCTTTTATCACCAAAG




gcacttgta
ACATGGTCTGTGCAGGAGATGCCAAAGGCCAGAAGGATTCCTGTAAG




[Seq ID No 56]
GGTGACTCAGGGGGCCCCTTGAT





CTGTAAAGGTGTCTTCCACGCTATAGTCTCTGGAGGTCATGAATGTG





GTGTTGCCACAAAGCCTGGAATC





TACACCCTGTTAACCAAGAAATACCAGACTTGGATCAAAAGCAACCT





TGTCCCGCCTCATACAAATTAAG





TTACAAATAATTTTATTGGATGCACTTGCTTTTTTTTTCCTAATATG





CTCGCAGGTTAGAGTTGGGTGTA





AGTAAAGCAGAGCACATATGGGGTCCATTTTTGCACTTGTAAGTCAT





TTTATTAAGGAATCAAGTTCTTT





TTCACTTGTATCACTGATGTATTTCTACCATGCTGGTTTTATTCTAA





ATAAAATTTAGAAGACTCAAAAA





AAAAAAAAAAAAAAAAAAAAAAAA





206804_
CD3G
gtaatgccaaggaccctcgaggga
>gi|4557428|ref|NM_000073.1|Homo sapiens CD3g
23.86


at
antigen
tgtatcagtgtaaaggatcacaga
molecule, gamma (CD3-TCR complex) (CD3G), mRNA



gamma
acaagtcaaaaccactccaagtgt
GGGCTGCTCCACGCTTTTGCCGGAGACAGAGACTGACATGGAACAGG



polypeptide
attacagaatgtgtcagaactgca
GGAAGGGCCTGGCTGTCCTCATC



(TiT3
ttgaactaaatgcagccaccatat
CTGGCTATCATTCTTCTTCAAGGTACTTTGGCCCAGTCAATCAAAGG



complex)
ctggctttctctttgctgaaatcg
AAACCACTTGGTTAAGGTGTATG




tcagcattttcgtccttgctgttg
ACTATCAAGAAGATGGTTCGGTACTTCTGACTTGTGATGCAGAAGCC




gggtctacttca
AAAAATATCACATGGTTTAAAGA




ttgctggacaggatggagttcgcc
TGGGAAGATGATCGGCTTCCTAACTGAAGATAAAAAAAAATGGAATC




agtcgagagcttcagacaagcaga
TGGGAAGTAATGCCAAGGACCCT




ctctgttgcccaatgaccagctct
CGAGGGATGTATCAGTGTAAAGGATCACAGAACAAGTCAAAACCACT




accagcccctcaaggatcgagaag
CCAAGTGTATTACAGAATGTGTC




atgaccagtacagccaccttcaag
AGAACTGCATTGAACTAAATGCAGCCACCATATCTGGCTTTCTCTTT




gaaaccagttgaggaggaattgaa
GCTGAAATCGTCAGCATTTTCGT




ctcaggactcagagtagtccaggt
CCTTGCTGTTGGGGTCTACTTCATTGCTGGACAGGATGGAGTTCGCC




gttctcctcctattcagttcccag
AGTCGAGAGCTTCAGACAAGCAG




aatcaaagcaatgcattttggaaa
ACTCTGTTGCCCAATGACCAGCTCTACCAGCCCCTCAAGGATCGAGA




gctcctagcagagagactttcagc
AGATGACCAGTACAGCCACCTTC




cctaaatctagactcaaggttccc
AAGGAAACCAGTTGAGGAGGAATTGAACTCAGGACTCAGAGTAGTCC




agagatgac
AGGTGTTCTCCTCCTATTCAGTT




[Seq ID No 57]
CCCAGAATGAAAGCAATGCATTTTGGAAAGCTCCTAGCAGAGAGACT





TTCAGCCCTAAATCTAGACTCAA





GGTTCCCAGAGATGACAAATGGAGAAGAAAGGCCATCAGAGCAAATT





TGGGGGTTTCTCAAATAAAATAA





AAATAAAAACAAATACTCTGTTTCAGAAGCGCCACCTATTGGGGAAA





ATTGT





207651_
G protein-
ttgccttgtaattcgacagctcta
>gi|31377771|ref|NM_013308.2|Homo sapiens G
46.65


at
coupled
cagaaacaaagataatgaaaatta
protein-coupled receptor 171 (GPR171), mRNA



receptor
cccaaatgtgaa
GGTTGCTACTGCTGCGGCTAACCAAACAGCTCATGCTTCTCTGAAGA



171
aaaggctctcatcaacatactttt
CTTGCAGCAAGGTTTGCTGAGGC




agtgaccacgggctacatcatatg
TCACAGAAGATAGCCCCAGTGTTTTGGAGTGGTTTTGAATGTGATTC




ctttgttcctta
TGAGATCAGACTGACTGAGCTGG




ccacattgtccgaatcccgtatac
AATCCTGGCTTTATATCTTACCAGCTACACAACCTTGGAGTCTTAGA




cctcagccagacagaagtcataac
AATTTTTTCTTTTCAATAAGCAG




tgattgctcaac
TCATCCTTACTTTCCCTCAAGATGACAAACAGTTCGTTCTTCTGCCC




caggatttcactcttcaaagccaa
AGTTTATAAAGATCTGGAGCCAT




agaggctacactgctcctggctgt
TCACGTATTTTTTTTTTTTAGTTTTCCTTGTTGGAATTATTGGAAGT




gtcgaacctgtg
TGTTTTGCAACCTGGGCTTTTAT




ctttgatcctatcctgtactatca
ACAGAAGAATACGAATCACAGGTGTGTGAGCATCTACTTAATTAATT




cctctcaaaagcattccgctcaaa
TGCTTACAGCCGATTTCCTGCTT




ggtcactgagac
ACTCTGGCATTACCAGTGAAAATTGTTGTTGACTTGGGTGTGGCACC




ttttgcctcacctaaagagaccaa
TTGGAAGCTGAAGATATTCCACT




ggctcagaaagaaaaattaagatg
GCCAAGTAACAGCCTGCCTCATCTATATCAATATGTATTTATCAATT




tgaaaataatgc
ATCTTCTTAGCATTTGTCAGCAT




ataaaagacaggattttttgtgct
TGACCGCTGTCTTCAGCTGACACACAGCTGCAAGATCTACCGAATAC




accaattctggccttactgga
AAGAACCCGGATTTGCCAAAATG




[Seq ID No 58]
ATATCAACCGTTGTGTGGCTAATGGTCCTTCTTATAATGGTGCCAAA





TATGATGATTCCCATCAAAGACA





TCAAGGAAAAGTCAAATGTGGGTTGTATGGAGTTTAAAAAGGAATTT





GGAAGAAATTGGCATTTGCTGAC





AAATTTCATATGTGTAGCAATATTTTTAAATTTCTCAGCCATCATTT





TAATATCCAATTGCCTTGTAATT





CGACAGCTCTACAGAAACAAAGATAATGAAAATTACCCAAATGTGAA





AAAGGCTCTCATCAACATACTTT





TAGTGACCACGGGCTACATCATATGCTTTGTTCCTTACCACATTGTC





CGAATCCCGTATACCCTCAGCCA





GACAGAAGTCATAACTGATTGCTCAACCAGGATTTCACTCTTCAAAG





CCAAAGAGGCTACACTGCTCCTG





GCTGTGTCGAACCTGTGCTTTGATCCTGTCCTGTACTATCACCTCTC





AAAAGCATTCCGCTCAAAGGTCA





CTGAGACTTTTGCCTCACCTAAAGAGACCAAGGCTCAGAAAGAAAAA





TTAAGATGTGAAAATAATGCATA





AAAGACAGGATTTTTGTGCTACCAATTCTGGCCTTACTGGACCATAA





AGTTAATTATAGCTTTGAAAGAT





AAAAAAAAAAAAAAAAACAAAAAAAAACTCAGTATGAAAAAATACAG





TTAGCTAGCAAATATGGACAGGT





TTACTTAGAAATCCTGTTTCTAAATGCAAGTCAAGCTTTATTGTTAG





GCTTGCTGCTACTCATTAACCCA





AATATTTGTACAAAAAACTAAAGAGTCTCATTGAACGAATGTAAAAT





CCTGCAATATCCTTGAAATCCAA





AAGAGGTCCATGACATAGACCCAAAGGTATTCATGAGTTATTCATTT





AAATGCCTGGAACTGACTTCTTG





ATAAAAATATAAAAAATAATTTCCATGTAAGTTACCAGAAAGCCCAC





CAGCAACATAATTTTAAAGCCTT





TCGGATTACTTTTAAAAAATGCAGCTTACATATAACAACTTGTGCCT





ATTTTATTTCTAATCTATCACTT





CAAAAGATGGTAATCTTTCAACTCATTATTCCTCCAATTTTTAATGT





CGAATTTTTTTCTAACACAATAA





CCAAAAGCTTTTATTTATAAAAAGGCTTGAAAAATATAAAAAAAAAA





AAAAAAAAAAAAAAAAAAAAAAA





AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA





207957_
Protein
tgatgagctttcctttgatccgga
>gi|89353296|ref|NM_001183.4|Homo sapiens
34.17


s_at
kinase C,
cgacgtaatcactgacattgagat
ATPase, H+ transporting, lysosomal accessory



beta 1
ggtggacgaggg
protein 1 (ATP6AP1), mRNA




ctggtggcggggacgttgccatgg
GGGGGCAACGGTCACCTGATCTGCGGCTGTCGAGGCCGCTGAGGCAG




ccactttggactcttccctgcaaa
TGGAGGCTGAGGCTATGATGGCG




ttatgtcaagct
GCCATGGCGACGGCTCGAGTGCGGATGGGGCCGCGATGCGCCCAGGC




tctggagtgactagagctcactgt
GCTCTGGCGCATGCCGTGGCTGC




ctactgcaactgtgatttcccatg
CGGTGTTTTTGTCGTTGGCGGCGGCGGCGGCGGCGGCAGCGGCGGAG




tccaaagtggct
CAGCAGGTCCCGCTGGTGCTGTG




ctgctccaccccctccctattcct
GTCGAGTGACCGGGACTTGTGGGCTCCTGCGGCCGACACTCATGAAG




gatgcaaatgtctaaccagatgag
GCCACATCACCAGCGACTTGCAG




tttctggacaga
CTCTCTACCTACTTAGATCCCGCCCTGGAGCTGGGTCCCAGGAATGT




cttccctctcctgcttcattaagg
GCTGCTGTTCCTGCAGGACAAGC




gcttggggcagagacagcatgggg
TGAGCATTGAGGATTTCACAGCATATGGCGGTGTGTTTGGAAACAAG




aaggaggtccccttccccaagagt
CAGGACAGCGCCTTTTCTAACCT




cctctctatcctggatgagctcat
AGAGAATGCCCTGGACCTGGCCCCCTCCTCACTGGTGCTTCCTGCCG




gaacatttctcttgtgttcctgac
TCGACTGGTATGCAGTCAGCACT




tccttcccaatgaacacctctctg
CTGACCACTTACCTGCAGGAGAAGCTCGGGGCCAGCCCCTTGCATGT




ccaccccaagctctgctctcctcc
GGACCTGGCCACCCTGCGGGAGC




tctgtgagctct
TGAAGCTCAATGCCAGCCTCCCTGCTCTGCTGCTCATTCGCCTGCCC




gggcttcccagtttgtttacccgg
TACACAGCCAGCTCTGGTCTGAT




gaaagtacgtctagattgtgtggt
GGCACCCAGGGAAGTCCTCACAGGCAACGATGAGGTCATCGGGCAGG




ttgcctcattgt
TCCTGAGCACACTCAAGTCCGAA




gctatttgcccactttccttccct
GATGTCCCATACACAGCGGCCCTCACAGCGGTCCGCCCTTCCAGGGT




gaagaaatatctgtgaaccttctt
GGCCCGTGATGTAGCCGTGGTGG




tctgttcagtcc
CCGGAGGGCTAGGTCGCCAGCTGCTACAAAAACAGCCAGTATCACCT




ta
GTGATCCATCCTCCTGTGAGTTA




[Seq Id No 59]
CAATGACACCGCTCCCCGGATCCTGTTCTGGGCCCAAAACTTCTCTG





TGGCGTACAAGGACCAGTGGGAG





GACCTGACTCCCCTCACCTTTGGGGTGCAGGAACTCAACCTGACTGG





CTCCTTCTGGAATGACTCCTTTG





CCAGGCTCTCACTGACCTATGAACGACTCTTTGGTACCACAGTGACA





TTCAAGTTCATTCTGGCCAACCG





CCTCTACCCAGTGTCTGCCCGGCACTGGTTTACCATGGAGCGCCTCG





AAGTCCACAGCAATGGCTCCGTC





GCCTACTTCAATGCTTCCCAGGTCACAGGGCCCAGCATCTACTCCTT





CCACTGCGAGTATGTCAGCAGCC





TGAGCAAGAAGGGTAGTCTCCTCGTGGCCCGCACGCAGCCCTCTCCC





TGGCAGATGATGCTTCAGGACTT





CCAGATCCAGGCTTTCAACGTAATGGGGGAGCAGTTCTCCTACGCCA





GCGACTGTGCCAGCTTCTTCTCC





CCCGGCATCTGGATGGGGCTGCTCACCTCCCTGTTCATGCTCTTCAT





CTTCACCTATGGCCTGCACATGA





TCCTCAGCCTCAAGACCATGGATCGCTTTGATGACCACAAGGGCCCC





AGTATTTCTTTGACCCAGATTGT





GTGACCCTGTGCCAGTGGGGGGGTTGAGGGTGGGACGGTGTCCGTGT





TGTTGCTTTCCCACCCTGCAGCG





CACTGGACTGAAGAGCTTCCCTCTTCCTACTGCAGCATGAACTGCAA





GCTCCCCTCAGCCCATCTTGCTC





CCTCTTCAGCCCGCTGAGGAGCTTTCTTGGGCTGCCCCCATCTCTCC





CAACAAGGTGTACATATTCTGCG





TAGATGCTAGACCAACCAGCTTCCCAGGGTTCGTCGCTGTGAGGCGT





AAGGGACATGAATTCTAGGGTCT





CCTTTCTCCTTATTTATTCTTGTGGCTACATCATCCCTGGCTGTGGA





TAGTGCTTTTGTGTAGCAAATGC





TCCCTCCTTAAGGTTATAGGGCTCCCTGAGTTTGGGAGTGTGGAAGT





ACTACTTAACTGTCTGTCCTGCT





TGGCTGTCGTTATCGTTTTCTGGTGATGTTGTGCTAACAATAAGAAG





TACACGGGTTTATTTCTGTGGCC





TGAGAAGGAAGGGACCTCCACGACAGGTGGGCTGGGTGCGATCGCCG





GCTGTTTGGCATGTTCCCACCGG





GAGTGCCGGGCAGGAGCATGGGGTGCTTGGTTGTTTCCTTCCTAATA





AAATAAACGCGGGTCGCCATGCA





AAAAAAAAA





208894_
major histo-
cgatcaccaatgtacctccagagg
>gi|52426773|ref|NM_09111.3|Homo sapiens
6.11


at
compatibility
taactgtgctcacgaacagccctg
major histocompatibility complex, class II, DR



complex,
tggaactgagagagcccaacgtcc
alpha (HLA-DRA), mRNA



class II,
tcatctgtttcatagacaagttca
ACATTCTCTTTTCTTTTATTCTTGTCTGTTCTGCCTCACTCCCGAGC



DR alpha///
cccca
TCTACTGACTCCCAACAGAGCGC



major histo-
[Seq Id No 60]
CCAAGAAGAAAATGGCCATAAGTGGAGTCCCTGTGCTAGGATTTTTC



compatibility

ATCATAGCTGTGCTGATGAGCGC



complex,

TCAGGAATCATGGGCTATCAAAGAAGAACATGTGATCATCCAGGCCG



class II,

AGTTCTATCTGAATCCTGACCAA



DR alpha

TCAGGCGAGTTTATGTTTGACTTTGATGGTGATGAGATTTTCCATGT





GGATATGGCAAAGAAGGAGACGG





TCTGGCGGCTTGAAGAATTTGGACGATTTGCCAGCTTTGAGGCTCAA





GGTGCATTGGCCAACATAGCTGT





GGACAAAGCCAACCTGGAAATCATGACAAAGCGCTCCAACTATACTC





CGATCACCAATGTACCTCCAGAG





GTAACTGTGCTCACGAACAGCCCTGTGGAACTGAGAGAGCCCAACGT





CCTCATCTGTTTCATAGACAAGT





TCACCCCACCAGTGGTCAATGTCACGTGGCTTCGAAATGGAAAACCT





GTCACCACAGGAGTGTCAGAGAC





AGTCTTCCTGCCCAGGGAAGACCACCTTTTCCGCAAGTTCCACTATC





TCCCCTTCCTGCCCTCAACTGAG





GACGTTTACGACTGCAGGGTGGAGCACTGGGGCTTGGATGAGCCTCT





TCTCAAGCACTGGGAGTTTGATG





CTCCAAGCCCTCTCCCAGAGACTACAGAGAACGTGGTGTGTGCCCTG





GGCCTGACTGTGGGTCTGGTGGG





CATCATTATTGGGACCATCTTCATCATCAAGGGATTGCGCAAAAGCA





ATGCAGCAGAACGCAGGGGGCCT





CTGTAAGGCACATGGAGGTGATGGTGTTTCTTAGAGAGAAGATCACT





GAAGAAACTTCTGCTTTAATGGC





TTTACAAAGCTGGCAATATTACAATCCTTGACCTCAGTGAAAGCAGT





CATCTTCAGCATTTTCCAGCCCT





ATAGCCACCCCAAGTGTGGATATGCCTCTTCGATTGCTCCGTACTCT





AACATCTAGCTGGCTTCCCTGTC





TATTGCCTTTTCCTGTATCTATTTTCCTCTATTTCCTATCATTTTAT





TATCACCATGCAATGCCTCTGGA





ATAAAACATACAGGAGTCTGTCTCTGCTATGGAATGCCCCATGGGGC





ATCTCTTGTGTACTTATTGTTTA





AGGTTTCCTCAAACTGTGATTTTTCTGAACACAATAAACTATTTTGA





TGATCTTGGGTGGAAAAAAAAAA





AAAAAAA





209480_
Major histo-
aaaaaaggaaatcgctgcagaatg
>gi|24797068|ref|NM_002123.2|Homo sapiens
12.55


at
compatibility
aaggaatatcccttgaggtgaccc
major histocompatibility complex, class II, DQ



complex,
agccaacctgtggccagaaggagg
beta 1 (HLA-DQB1), mRNA



class II,
gttgtacct:gaaaagaccactga
CAGATCCATCAGGTCCGAGCTGTGTTGACTACCACTTTTCCCTTCGT



DQ beta 1///
aagcattttggggtgtcaagtaag
CTCAATTATGTCTTGGAAAAAGG



Major histo-
ggtgggcagaggaggtagaaaatc
CTTTGCGGATCCCCGGAGGCCTTCGGGCAGCAACTGTGACCTTGATG



compatibility
aattcaattgtcgcatcattcatg
CTGTCGATGCTGAGCACCCCAGT



complex,
gttctttaatattgatgctcagtg
GGCTGAGGGCAGAGACTCTCCCGAGGATTTCGTGTACCAGTTTAAGG



class II,
cattggccttagaatatcccagcc
GCATGTGCTACTTCACCAACGGG



DQ beta 1
tctcttctggtttggtgagtgctg
ACAGAGCGCGTGCGTCTTGTGAGCAGAAGCATCTATAACCGAGAAGA




tgtaagtaagcatggtagaattgt
GATCGTGCGCTTCGACAGCGACG




ttggagacatatatagtgatcctt
TGGGGGAGTTCCGGGCGGTGACGCTGCTGGGGCTGCCTGCCGCCGAG




ggtcactggtgt
TACTGGAACAGCCAGAAGGACAT




ttcaaacattctggaaagtcacat
CCTGGAGAGGAAACGGGCGGCGGTGGACAGGGTGTGCAGACACAACT




cgatcaagaatatttttt
ACCAGTTGGAGCTCCGCACGACC




[Seq Id No 61]
TTGCAGCGGCGAGTGGAGCCCACAGTGACCATCTCCCCATCCAGGAC





AGAGGCCCTCAACCACCACAACC





TGCTGGTCTGCTCGGTGACAGATTTCTATCCAGCCCAGATCAAAGTC





CGGTGGTTTCGGAATGACCAGGA





GGAGACAGCTGGCGTTGTGTCCACCCCCCTTATTAGGAATGGTGACT





GGACCTTCCAGATCCTGGTGATG





CTGGAAATGACTCCCCAGCGTGGAGACGTCTACACCTGCCACGTGGA





GCACCCCAGCCTCCAGAGCCCCA





TCACCGTGGAGTGGCGGGCTCAATCTGAATCTGCCCAGAGCAAGATG





CTGAGTGGCATTGGAGGCTTCGT





GCTGGGGCTGATCTTCCTCGGGCTGGGCCTTATCATCCATCACAGGA





GTCAGAAAGGGCTCCTGCACTGA





CTCCTGAGACTATTTTAACTGGGATTGGTTATCACTTTTCTGTAACG





CCTGCTTGTCCCTGCCCAGAATT





CCCAGCTGTCTGTGTCAGCCTGTCCCCCTGAGATCAGAGTCCTACAG





TGGCTGTCACGCAGCCACCAGGT





CATCTCCTTTCATCCCCACCTTGAGGCGGATGGCTGTGACCCTACTT





CCTGCACTGACCCACAGCCTCTG





CCTGTGCACGGCCAGCTGCATCTACTCAGGCCCCAAGGGGTTTCTGT





TTCTATTCTCTCCTCAGACTGCT





CAAGAGAAGCACATGAAAACCATTACCTGACTTTAGAGCTTTTTTAC





ATAATTAAACATGATCCTGAGTT





209613_
alcohol
gcagatttcttgcttcatatgaca
>gi|34577060|ref|NM_000668.3|Homo sapiens
58.89


s_at
dehydrogenase
aagcctcaattactaattgtaaaa
alcohol dehydrogenase IB (class I), beta



IB
actgaactattc
polypeptide (ADH1B), mRNA



(class I),
ccagaatcatgttcaaaaaatctg
ATGCACTCAAGCAGAGAAGAAATCCACAAAGACTCACAGTCTGCTGG



beta poly-
taatttttgctgatcgaaagtgct
TGGGCAGAGAAGACAGAAACGAC



peptide
tcattgactaaa
ATGAGCACAGCAGGAAAAGTAATCAAATGCAAAGCAGCTGTGCTATG




cagtattagtttgtggctataaat
GGAGGTAAAGAAACCCTTTTCCA




gattatttagatgatgactgaaaa
TTGAGGATGTGGAGGTTGCACCTCCTAAGGCTTATGAAGTTCGCATT




tgtgtataaagt
AAGATGGTGGCTGTAGGAATCTG




aattaaaagtaatatggtggcttt
TCACACAGATGACCACGTGGTTAGTGGCAACCTGGTGACCCCCCTTC




aagtgtagagatgggatggcaaat
CTGTGATTTTAGGCCATGAGGCA




gctgtgaatgca
GCCGGCATCGTGGAGAGTGTTGGAGAAGGGGTGACTACAGTCAAACC




gaatgtaaaattggtaactaagaa
AGGTGATAAAGTCATCCCGCTCT




atggcacaaacaccttaagcaata
TTACTCCTCAGTGTGGAAAATGCAGAGTTTGTAAAAACCCGGAGAGC




tattttcctagt
AACTACTGCTTGAAAAATGATCT




agatatatatatacacatacatat
AGGCAATCCTCGGGGGACCCTGCAGGATGGCACCAGGAGGTTCACCT




atacacatatacaaatgtatattt
GCAGGGGGAAGCCCATTCACCAC




ttgcaaaattgt
TTCCTTGGCACCAGCACCTTCTCCCAGTACACGGTGGTGGATGAGAA




tttcaatctagaacttttctatta
TGCAGTGGCCAAAATTGATGCAG




actaccatgtcttaaaatcaagtc
CCTCGCCCCTGGAGAAAGTCTGCCTCATTGGCTGTGGATTCTCGACT




tataatcctagc
GGTTATGGGTCTGCAGTTAACGT




attagtttaatattttgaatatgt
TGCCAAGGTCACCCCAGGCTCTACCTGTGCTGTGTTTGGCCTGGGAG




aaacacctgtgttaatgctttgtt
GGGTCGGCCTATCTGCTGTTATG




aatgcttttccc
GGCTGTAAAGCAGCTGGAGCAGCCAGAATCATTGCGGTGGACATCAA




actctcatttgttaatgctttccc
CAAGGACAAATTTGCAAAGGCCA




actctcgggaaggatttgcatttt
AAGAGTTGGGTGCCACTGAATGCATCAACCCTCAAGACTACAAGAAA




gagctttatctc
CCCATCCAGGAAGTGCTAAAGGA




taaatgtgacatgca
AATGACTGATGGAGGTGTGGATTTTTCGTTTGAAGTCATCGGTCGGC




[Seq Id No 62]
TTGACACCATGATGGCTTCCCTG





TTATGTTGTCATGAGGCATGTGGCACAAGCGTCATCGTAGGGGTACC





TCCTGCTTCCCAGAACCTCTCAA





TAAACCCTATGCTGCTACTGACTGGACGCACCTGGAAGGGGGCTGTT





TATGGTGGCTTTAAGAGTAAAGA





AGGTATCCCAAAACTTGTGGCTGATTTTATGGCTAAGAAGTTTTCAC





TGGATGCGTTAATAACCCATGTT





TTACCTTTTGAAAAAATAAATGAAGGATTTGACCTGCTTCACTCTGG





GAAAAGTATCCGTACCGTCCTGA





CGTTTTGAGGCAATAGAGATGCCTTCCCCTGTAGCAGTCTTCAGCCT





CCTCTACCCTACAAGATCTGGAG





CAACAGCTAGGAAATATCATTAATTCAGCTCTTCAGAGATGTTATCA





ATAAATTACACATGGGGGCTTTC





CAAAGAAATGGAAATTGATGGGAAATTATTTTTCAGGAAAATTTAAA





ATTCAAGTGAGAAGTAAATAAAG





TGTTGAACATCAGCTGGGGAATTGAAGCCAACAAACCTTCCTTCTTA





ACCATTCTACTGTGTCACCTTTG





CCATTGAGGAAAAATATTCCTGTGACTTCTTGCATTTTTGGTATCTT





CATAATCTTTAGTCATCGAATCC





CAGTGGAGGGGACCCTTTTACTTGCCCTGAACATACACATGCTGGGC





CATTGTGATTGAAGTCTTCTAAC





TCTGTCTCAGTTTTCACTGTCGACATTTTCCTTTTTCTAATAAAAAT





GTACCAAATCCCTGGGGTAAAAG





CTAGGGTAAGGTAAAGGATAGACTCACATTTACAAGTAGTGAAGGTC





CAAGAGTTCTAAATACAGGAAAT





TTCTTAGGAACTCAAATAAAATGCCCCACATTTTACTACAGTAAATG





GCAGTGTTTTTATGACTTTTATA





CTATTTCTTTATGGTCGATATACAATTGATTTTTTAAATAATAGCA





GATTTCTTGCTTCATATGACAAA





GCCTCAATTACTAATTGTAAAAACTGAACTATTCCCAGAATCATGTT





CAAAAAATCTGTAATTTTTGCTG





ATGAAAGTGCTTCATTGACTAAACAGTATTAGTTTGTGGCTATAAAT





GATTATTTAGATGATGACTGAAA





ATGTGTATAAAGTAATTAAAAGTAATATGGTGGCTTTAAGTGTAGAG





ATGGGATGGCAAATGCTGTGAAT





GCAGAATGTAAAATTGGTAACTAAGAAATGGCACAAACACCTTAAGC





AATATATTTTCCTAGTAGATATA





TATATACACATACATATATACACATATACAAATGTATATTTTTGCAA





AATTGTTTTCAATCTAGAACTTT





TCTATTAACTACCATGTCTTAAAATCAAGTCTATAATCCTAGCATTA





GTTTAATATTTTGAATATGTAAA





GACCTGTGTTAATGCTTTGTTAATGCTTTTCCCACTCTCATTTGTTA





ATGCTTTCCCACTCTCAGGGGAA





GGATTTGCATTTTGAGCTTTATCTCTAAATGTGACATGCAAAGATTA





TTCCTGGTAAAGGAGGTAGCTGT





CTCCAAAAATGCTATTGTTGCAATATCTACATTCTATTTCATATTAT





GAAAGACCTTAGACATAAAGTAA





AATAGTTTATCATTTACTGTGTGATCTTCAGTAAGTCTCTCAGGCTC





TCTGAGCTTGTTCATCCTTTGTT





TTGAAAAAATTACTCAACCAATCCATTACAGCTTAACCAAGATTAAA





TGGGATGATGTTAATGAAAGAGC





TTCGCC





209670_
T cell
caactggatcctacccgaatttat
>gi|36944|emb|X02592.1|HSTCRAR Human mRNA for
24.26


at
receptor
gattaagattgctgaagagctgcc
receptor alpha chain (TCR-alpha)



alpha
aaacactgctgc
TTTTGAAACCCTTCAAAGGCAGAGACTTGTCCAGCCTAACCTGCCTG



constant///
caccccctctgttcccttattgct
CTGCTCCTAGCTCCTGAGGCTCA



T cell
gcttgtcactgcctgacattcacg
GGGCCCTTGGCTTCTGTCCGCTCTGCTCAGGGCCCTCCAGCGTGGCC



receptor
gcagaggcaagg
ACTGCTCAGCCATGCTCCTGCTG



alpha
ctgctgcagcctcccctggctgtg
CTCGTCCCAGTGCTCGAGGTGATTTTTACCCTGGGAGGAACCAGAGC



constant
cacattccctcctgctccccagag
CCAGTCGGTGACCCAGCTTGGCA




actgcctccgcc
GCCACGTCTCTGTCTCTGAAGGAGCCCTGGTTCTGCTGAGGTGCAAC




atcccacagatgatggatcttcag
TACTCATCGTCTGTTCCACCATA




tgggttctcttgggctctaggtcc
TCTCTTCTGGTATGTGCAATACCCCAACCAAGGACTCCAGCTTCTCC




tggagaatgttg
TGAAGTACACATCAGCGGCCACC




tgaggggtttatttttttttaata
CTGGTTAAAGGCATCAACGGTTTTGAGGCTGAATTTAAGAAGAGTGA




gtgttcataaagaaatacatagta
AACCTCCTTCCACCTGACGAAAC




ttcttcttctca
CCTCAGCCCATATGAGCGACGCGGCTGAGTACTTCTGTGCTGTGAGT




agacgtggggggaaattatctcat
GATCTCGAACCGAACAGCAGTGC




tatcgaggccctgctatgctgtgt
TTCCAAGATAATCTTTGGATCAGGGACCAGACTCAGCATCCGGCCAA




gtctgggcgtgt
ATATCCAGAACCCTGACCCTGCC




tgtatgtcctgc
GTGTACCAGCTGAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCT




[Seq Id No 63]
ATTCACCGATTTTGATTCTCAAA





CAAATGTGTCACAAAGTAAGGATTCTGATGTGTATATCACAGACAAA





ACTGTGCTAGACATGAGGTCTAT





GGACTTCAAGAGCAACAGTGCTGTGGCCTGGAGCAACAAATCTGACT





TTGCATGTGCAAACGCCTTCAAC





AACAGCATTATTCCAGAAGACACCTTCTTCCCCAGCCCAGAAAGTTC





CTGTGATGTCAAGCTGGTCGAGA





AAAGCTTTGAAACAGATACGAACCTAAACTTTCAAAACCTGTCAGTG





ATTGGGTTCCGAATCCTCCTCCT





GAAAGTGGCCGGGTTTAATCTGCTCATGACGCTGCGGCTGTGGTCCA





GCTGAGATCTGCAAGATTGTAAG





ACAGCCTGTGCTCCCTCGCTCCTTCCTCTGCATTGCCCCTCTTCTCC





CTCTCCAAACAGAGGGAACTCTC





CTACCCCCAAGGAGGTGAAAGCTGCTACCACCTCTGTGCCCCCCCGG





TAATGCCACCAACTGGATCCTAC





CCGAATTTATGATTAAGATTGCTGAAGAGCTGCCAAACACTGCTGCC





ACCCCCTCTGTTCCCTTATTGCT





GCTTGTCACTGCCTGACATTCACGGCAGAGGCAAGGCTGCTGCAGCC





TCCCCTGGCTGTGCACATTCCCT





CCTGCTCCCCAGAGACTGCCTCCGCCATCCCACAGATGATGGATCTT





CAGTGGGTTCTCTTGGGCTCTAG





GTCCTGGAGAATGTTGTGAGGGGTTTATTTTTTTTTAATAGTGTTCA





TAAAGAAATACATAGTATTCTTC





TTCTCAAGACGTGGGGGGAAATTATCTCATTATCGAGGCCCTGCTAT





GCTGTGTGTCTGGGCGTGTTGTA





TGTCCTGCTGCCGATGCCTTCATTAAAATGATTTGGAA





209795_
CD69
tagtctaattgaatcccttaaact
>gi|4502680|ref|NM_001781.1|Homo sapiens CD69
30.48


at
antigen
cagggagcatttataaatggcaaa
molecule (CD69), mRNA



(p60, early
tgcttatgaaac
AGACTCAACAAGAGCTCCAGCAAAGACTTTCACTGTAGCTTGACTTG



T-cell
taagatttgtaatatttctctctt
ACCTGAGATTAACTAGGGAATCT



activation
tttagagaaatttgccaatttact
TGAGAATAAAGATGAGCTCTGAAAATTGTTTCGTAGCAGAGAACAGC



antigen)
ttgttatttttc
TCTTTGCATCCGGAGAGTGGACA




cccaaaaagaatgggatgatcgtg
AGAAAATGATGCCACCAGTCCCCATTTCTCAACACGTCATGAAGGGT




tatttatttttttacttcctcagc
CCTTCCAAGTTCCTGTCCTGTGT




tgtagacaggtc
GCTGTAATGAATGTGGTCTTCATCACCATTTTAATCATAGCTCTCAT




cttttcgatggtacatatttcttt
TGCCTTATCAGTGGGCCAATACA




gcctttataatcttttatacagtg
ATTGTCCAGGCCAATACACATTCTCAATGCCATCAGACAGCCATGTT




tcttacagagaa
TCTTCATGCTCTGAGGACTGGGT




aagacataagcaaagactatgagg
TGGCTACCAGAGGAAATGCTACTTTATTTCTACTGTGAAGAGGAGCT




aatatttgcaagacatagaatagt
GGACTTCAGCCCAAAATGCTTGT




gttggaaaatgt
TCTGAACATGGTGCTACTCTTGCTGTCATTGATTCTGAAAAGGACAT




gcaatatgtgatgtggcaaatctc
GAACTTTCTAAAACGATACGCAG




tattaggaaatattctgtaatctt
GTAGAGAGGAACACTGGGTTGGACTGAAAAAGGAACCTGGTCACCCA




cagacatagaat
TGGAAGTGGTCAAATGGCAAAGA




aatactagtcttataataggtttg
ATTTAACAACTGGTTCAACGTTACAGGGTCTGACAAGTGTGTTTTTC




tgactttcctaaatcaattctatt
TGAAAAACACAGAGGTCAGCAGC




acgtgcaatact
ATGGAATGTGAGAAGAATTTATACTGGATATGTAACAAACCTTACAA




tcaatacttcat
ATAATAAGGAAACATGTTCACTT




[Seq Id No 64]
ATTGACTATTATAGAATGGAACTCAAGGAAATCTGTGTCAGTGGATG





CTGCTCTGTGGTCCGAAGTCTTC





CATAGAGACTTTGTGAAAAAAAATTTTATAGTGTCTTGGGAATTTTC





TTCCAAACAGAACTATGGAAAAA





AAGGAAGAAATTCCAGGAAAATCTGCACTGTGGGCTTTTATTGCCAT





GAGCTAGAAGCATCACAGGTTGA





CCAATAACCATGCCCAAGAATGAGAAGAATGACTATGCAACCTTTGG





ATGCACTTTATATTATTTTGAAT





CCAGAAATAATGAAATAACTAGGCGTGGACTTACTATTTATTGCTGA





ATGACTACCAACAGTGAGAGCCC





TTCATGCATTTGCACTACTGGAAGGAGTTAGATGTTGGTACTAGATA





CTGAATGTAAACAAAGGAATTAT





GGCTGGTAACATAGGTTTTTAGTCTAATTGAATCCCTTAAACTCAGG





GAGCATTTATAAATGGACAAATG





CTTATGAAACTAAGATTTGTAATATTTCTCTCTTTTTAGAGAAATTT





GCCAATTTACTTTGTTATTTTTC





CCCAAAAAGAATGGGATGATCGTGTATTTATTTTTTTACTTCCTCAG





CTGTAGACAGGTCCTTTTCGATG





GTACATATTTCTTTGCCTTTATAATCTTTTATACAGTGTCTTACAGA





GAAAAGACATAAGCAAAGACTAT





GAGGAATATTTGCAAGACATAGAATAGTGTTGGAAAATGTGCAATAT





GTGATGTGGCAAATCTCTATTAG





GAAATATTCTGTAATCTTCAGACCTAGAATAATACTAGTCTTATAAT





AGGTTTGTGACTTTCCTAAATCA





ATTCTATTACGTGCAATACTTCAATACTTCATTTAAAATATTTTTAT





GTGCAATAAAATGTATTTGTTTG





TATTTTGTGTTCAGTACAATTATAAGCTGTTTTTATATATGTGAAAT





AAAAGTAGAATAAACACAAAAAA





AAAAAAAAAAAAAAAAAAAAAA





210038_
protein
aatccattcatcctgattgggcat
>gi|48255887|ref|NM_006257.2|Homo sapiens
19.42


at
kinase C,
gaaatccatggtcaagaggacaag
protein kinase C, theta (PRKCQ), mRNA



theta
tggaaagtgagagggaaggtttgc
AGTCCCCGCGCAGTCCCCGCGCAcTCCCAGCGCCACCGGGCAGCAGC




tagacaccttcgcttgttatcttg
GGCGCCGTGCTCGCTCCAGGGCG




tcaagatagaaaagatagtatcat
CAACCATGTCGCCATTTCTTCGGATTGGCTTGTCCAACTTTGACTGC




ttcacccttgccagtaaaaacctt
GCGTCCTGCCAGTCTTGTCAGGG




tccatccacccattctcagcagac
CGAGGCTGTTAACCCTTACTGTGCTGTGCTCGTCAAAGAGTATGTCG




tccagtattggc
AATCAGAGAACGGGCAGATGTAT




acagtcactcactgccattctcac
ATCCAGAAAAAGCCTACCATGTACCCACCCTGGGACAGCACTTTTGA




actataacaagaaaagaaatgaag
TGCCCATATCAACAAGGGAAGAG




tgcataagtctc
TCATGCAGATCATTGTGAAAGGCAAAAACGTGGACCTCATCTCTGAA




ctgggaaaagaaccttaacccctt
ACCACCGTGGAGCTCTACTCGCT




ctcgtgccatgactggtgatttca
GGCTGAGAGGTGCAGGAAGAACAACGGGAAGACAGAAATATGGTTAG




tgactcataagc
AGCTGAAACCTCAAGGCCGAATG




ccctccgtaggcatcattcaagat
CTAATGAATGCAAGATACTTTCTGGAAATGAGTGACACAAAGGACAT




caatggcccatgcatgctgtttgc
GAATGAATTTGAGACGGAAGGCT




agca
TCTTTGCTTTGCATCAGCGCCGGGGTGCCATCAAGCAGGCAAAGGTC




[Seq Id No 65]
CACCACGTCAAGTGCCACGAGTT





CACTGCCACCTTCTTCCCACAGCCCACATTTTGCTCTGTCTGCCACG





AGTTTGTCTGGGGCCTGAACAAA





CAGGGCTACCAGTGCCGACAATGCAATGCAGCAATTCACAAGAAGTG





TATTGATAAAGTTATAGCAAAGT





GCACAGGATCAGCTATCAATAGCCGAGAAACCATGTTCCACAAGGAG





AGATTCAAAATTGACATGCCACA





CAGATTTAAAGTCTACAATTACAAGAGCCCGACCTTCTGTGAACACT





GTGGGACCCTGCTGTGGGGACTG





GCACGGCAAGGACTCAAGTGTGATGCATGTGGCATGAATGTGCATCA





TAGATGCCAGACAAAGGTGGCCA





ACCTTTGTGGCATAAACCAGAAGCTAATGGCTGAAGCGCTGGCCATG





ATTGAGAGCACTCAACAGGCTCG





CTGCTTAAGAGATACTGAACAGATCTTCAGAGAAGGTCCGGTTGAAA





TTGGTCTCCCATGCTCCATCAAA





AATGAAGCAAGGCCGCCATGTTTACCGACACCGGGAAAAAGAGAGCC





TCAGGGCATTTCCTGGGAGTCTC





CGTTGGATGAGGTGGATAAAATGTGCCATCTTCCAGAACCTGAACTG





AACAAAGAAAGACCATCTCTGCA





GATTAAACTAAAAATTGAGGATTTTATCTTGCACAAAATGTTGGGGA





AAGGAAGTTTTGGCAAGGTCTTC





CTGGCAGAATTCAAGAAAACCAATCAATTTTTCGCAATAAAGGCCTT





AAAGAAAGATGTGGTCTTGATGG





ACGATGATGTTGAGTGCACGATGGTAGAGAAGAGAGTTCTTTCCTTG





GCCTGGGAGCATCCGTTTCTGAC





GCACATGTTTTGTACATTCCAGACCAAGGAAAACCTCTTTTTTGTGA





TGGAGTACCTCAACGGAGGGGAC





TTAATGTACCACATCCAAAGCTGCCACAAGTTCGACCTTTCCAGAGC





GACGTTTTATGCTGCTGAAATCA





TTCTTGGTCTGCAGTTCCTTCATTCCAAAGGAATAGTCTACAGGGAC





CTGAAGCTAGATAACATCCTGTT





AGACAAAGATGGACATATCAAGATCGCGGATTTTGGAATGTGCAAGG





AGAACATGTTAGGAGATGCCAAG





ACGAATACCTTCTGTGGGACACCTGACTACATCGCCCCAGAGATCTT





GCTGGGTCAGAAATACAACCACT





CTGTGGACTGGTGGTCCTTCGGGGTTCTCCTTTATGAAATGCTGATT





GGTCAGTCGCCTTTCCACGGGCA





GGATGAGGAGGAGCTCTTCCACTCCATCCGCATGGACAATCCCTTTT





ACCCACGGTGGCTGGAGAAGGAA





GCAAAGGACCTTCTGGTGAAGCTCTTCGTGCGAGAACCTGAGAAGAG





GCTGGGCGTGAGGGGAGACATCC





GCCAGCACCCTTTGTTTCGGGAGATCAACTGGGAGGAACTTGAACGG





AAGGAGATTGACCCACCGTTCCG





GCCGAAAGTGAAATCACCATTTGACTGCAGCAATTTCGACAAAGAAT





TCTTAAACGAGAAGCCCCGGCTG





TCATTTGCCGACAGAGCACTGATCAACAGCATGGACCAGAATATGTT





CAGGAACTTTTCCTTCATGAACC





CCGGGATGGAGCGGCTGATATCCTGAATCTTGCCCCTCCAGAGACAG





GAAAGAATTTGCCTTCTCCCTGG





GAACTGGTTCAAGAGACACTGCTTGGGTTCCTTTTTCAACTTGGAAA





AAGAAAGAAACACTCAACAATAA





AGACTGAGACCCGTTCGCCCCCATGTGACTTTTATCTGTAGCAGAAA





CCAAGTCTACTTCACTAATGACG





ATGCCGTGTGTCTCGTCTCCTGACATGTCTCACAGACGCTCCTGAAG





TTAGGTCATTACTAACCATAGTT





ATTTACTTGAAAGATGGGTCTCCGCACTTGGAAAGGTTTCAAGACTT





GATACTGCAATAAATTATGGCTC





TTCACCTGGGCGCCAACTGCTGATCAATGAAATGCTTGTTGAATCAG





GGGCAAACGGAGTACAGACGTCT





CAAGACTGAAACGGCCCCATTGCCTGGTCTAGTAGCGGATCTCACTC





AGCCGCAGACAAGTAATCACTAA





CCCGTTTTATTCTATTCCTATCTGTGGATGTGTAAATGGCTGGGGGG





CCAGCCCTGGATAGGTFTTTATG





GGAATTCTTTACAATAAACATAGCTTGTAACTTGAGATCTACAAATC





CATTCATCCTGATTGGGCATGAA





ATCCATGGTCAAGAGGACAAGTGGAAAGTGAGAGGGAAGGTTTGCTA





GACACCTTCGCTTGTTATCTTGT





CAAGATAGAAAAGATAGTATCATTTCACCCTTGCCAGTAAAAACCTT





TCCATCCACCCATTCTCAGCAGA





CTCCAGTATTGGCACAGTCACTCACTGCCATTCTCACACTATAACAA





GAAAAGAAATGAAGTGCATAAGT





CTCCTGGGAAAAGAACCTTAACCCCTTCTCGTGCCATGACTGGTGAT





TTCATGACTCATAAGCCCCTCCG





TAGGCATCATTCAAGATCAATGGCCCATGCATGCTGTTTGCAGCAGT





CAATTGAGTTGAATTAGAATTCC





AACCATACATTTTAAAGGTATTTGTGCTGTGTGTATATTTTGATAAA





ATGTTGTGACTTCATGGCAAACA





GGTGGATGTGTAAAAATGGAATAAAAAAAAAAAAAGAGTCAAAAAAA





AAAAAA





210915_
T cell
Aaaggccacactggtgtgcctggc
>gi|339011|gb|M15564.1|HUMTCBYZ Human T-cell
48.45


x_at
receptor
cacaggtatcttccctgaccacgt
receptor rearranged beta-chain V-region (V-D-J)



beta
ggagctgagctggtgggtgaatgg
mRNA, complete cds



variable
gaaggaggtgcacagtggggtcag
GTAAAGCTCCCATCCTGCCCTGACCCTGCCATGGGCACCAGCCTCCT



19///T
cacggacccgcagcccctcaagga
CTGCTGGATGGCCCTGTGTCTCC



cell
gcagcccgccctcaatgactccag
TGGGGGCAGATCACGCAGATACTGGAGTCTCCCAGAACCCCAGACAC



receptor
atactgcctgagcagccgcctgag
AACATCACAAAGAGGGGACAGAA



beta
ggtctcggccaccttctggcagaa
TGTAACTTTCAGGTGTGATCCAATTTCTGAACACAACCGCCTTTATT



constant 1
cccccgcaaccacttccgctgtca
GGTACCGACAGACCCTGGGGCAG




agtccagttctacgggctctcgga
GGCCCAGAGTTTCTGACTTACTTCCAGAATGAAGCTCAACTAGAAAA




gaatgacgagtggacccaggatag
ATCAAGGCTGCTCAGTGATCGGT




ggccaaacccgtcacccagatcgt
TCTCTGCAGAGAGGCCTAAGGGATCTTTCTCCACCTTGGAGATCCAG




cagcgccgaggcctggggtagagc
CGCACAGAGCAGGGGGACTCGGC




agactgtggctttacctcggtgtc
CATGTATCTCTGTGCCAGCAGCTTAGCAGGGTTGAATCAGCCCCAGC




ctaccagcaaggggtcctgtctgc
ATTTTGGTGATGGGACTCGACTC




caccatcctctatgagatcctgct
TCCATCCTAGAGGACCTGAACAAGGTGTTCCCACCCGAGGTCGCTGT




agggaaggccaccatgtatgctgt
GTTTGAGCCATCAGAAGCAGAGA




gctggtcagcgcccttgtgttgat
TCTCCCACACCCAAAAGGCCACACTGGTGTGCCTGGCCACAGGTATC




ggccatggtcaagagaaaggattt
TTCCCTGACCACGTGGAGCTGAG




ctgaaggcagccctggaagtggag
CTGGTGGGTGAATGGGAAGGAGGTGCACAGTGGGGTCAGCACGGACC




ttaggagcttctaacccgtcatgg
CGCAGCCCCTCAAGGAGCAGCCC




tttcaatacacattcttcttttgc
GCCCTCAATGACTCCAGATACTGCCTGAGCAGCCGCCTGAGGGTCTC




cagc
GGCCACCTTCTGGCAGAACCCCC




[Seq Id No 66]
GCAACCACTTCCGCTGTCAAGTCCAGTTCTACGGGCTCTCGGAGAAT





GACGAGTGGACCCAGGATAGGGC





CAAACCCGTCACCCAGATCGTCAGCGCCGAGGCCTGGGGTAGAGCAG





ACTGTGGCTTTACCTCGGTGTCC





TACCAGCAAGGGGTCCTGTCTGCCACCATCCTCTATGAGATCCTGCT





AGGGAAGGCCACCATGTATGCTG





TGCTGGTCAGCGCCCTTGTGTTGATGGCCATGGTCAAGAGAAAGGAT





TTCTGAAGGCAGCCCTGGAAGTG





GAGTTAGGAGCTTCTAACCCGTCATGGTTTCAATACACATTCTTCTT





TTGCCAGCGCTTCTGAAGAGCTG





CTCTCACCTCTCTGCATCCCAATA





210972_
T cell
ggaacaagacttcaggtcacgctc
>gi|338765|gb|M15565.1|HUMTCAYE Human T-cell
26.45


x_at
receptor
gatatccagaaccctgaccctgcc
receptor rearranged alpha-chain V-region (V-D-



alpha
gtgtaccagctgagagactctaaa
J) mRNA, complete cds



locus///
tccagtgacaagtctgtctgccta
TCCAAAATGAACGGTCTGTGGAAGGACATGAATAAAGCACAGGAGGT



T cell
ttcaccgattttgattctcaaaca
TGAAGTCAGATTTGCAGCTTTCT



receptor
aatgtgtcacaaagtaaggattct
AGGCAGGAGACAAGACAATCTGCATCITcACAGGAGGGATGGCCATG



delta
gatgtgtatatcacagacaaaact
CTCCTGGGGGCATcAGTGCTGAT



variable
gtgctagacatg
TCTGTGGCTTCAGCCAGACTGGGTAAACAGTCAACAGAAGAATGATG



2///T cell
aggtctatggacttcaagagcaac
ACCAGCAAGTTAAGCAAAATTCA



receptor
agtgctgtggcctggagcaacaaa
CCATCCCTGAGCGTCCAGGAAGGAAGAATTTcTATTCTGAACTGTGA



alpha
tctgactttgcatgtgcaaacgcc
CTATACTAACAGCATGTTTGATT



variable
ttcaacaacagcattattccagaa
ATTTCCTATGGTACAAAAAATACCCTGCTGAAGGTCCTACATTCCTG



20///T
gacaccttcttccccagcccagaa
ATATCTATAAGTTCCATTAAGGA



cell
agttcctgtgatgtcaagctggtc
TAAAAATGAAGATGGAAGATTCACTGTCTTCTTAAACAAAAGTGCCA



receptor
gagaaaagctttgaaacagatacg
AGCACCTCTCTCTGCACATTGTG



alpha
aacctaaacttt
CCCTCCCAGCCTGGAGACTCTGCAGTGTACTTCTGTGCAGCAAAGGG



joining
caaaacctgtcagtgattgggttc
GGCCGGCACTGCCAGTAAACTCA



17///T
cgaatcctcctcctgaaagtggcc
CCTTTGGGACTGGAACAAGACTTCAGGTCACGCTCGATATCCAGAAC



cell
gggtttaatctg
CCTGACCCTGCCGTGTACCAGCT



receptor
ctcatgacgctgcggctgtggtcc
GAGAGACTCTAAATCCAGTGACAAGTCTGTCTGCCTATTCACCGATT



alpha
agctgagatctgcaagattgtaag
TTGATTCTCAAACAAATGTGTCA



constant
acagcctgtgct
CAAAGTAAGGATTCTGATGTGTATATCACAGACAAAACTGTGCTAGA




ccct
CATGAGGTCTATGCACTTCAAGA




[Seq Id No 67]
GCAACAGTGCTGTGGCCTGOAGCAACAAATCTGACTTTGCATGTGCA





AACGCCTTCAACAACAGCATTAT





TCCAGAAGACACCTTCTTCCCCAGCCCAGAAAGTTCCTGTGATGTCA





AGCTGGTCGAGAAAAGGTTTGAA





ACAGATACGAACCTAAACTTTCAAAACCTGTCAGTGATTGGGTTCCG





AATCCTCCTCCTGAAAGTGGCCG





GGTTTAATCTGCTCATGACGCTGCGGCTGTGGTCCAGCTGAGATCTG





CAAGATTGTAAGACAGCCTGTGC





TCCCTCGCTCCTTCCTCTGCATTGCCCCTCTTCTCCCTCTCcAJAACA





GAGGGAACTCTCCCACCCCCAAG





GAGGTGAAAGCTGCTACCACCCTCTGTGCC





211144_
T cell
aaatgatacactactgctgcagct
>gi|339406|gb|M30894.1|HUMTCRGAD Human T-cell
17.38


x_at
receptor
cacaaacacctctgcatattacat
receptor Ti rearranged gamma-chain mRNA V-J-C



gamma
gtacctcctcct
region, complete cds



constant 2
gctcctcaagagtgtggtctattt
GAATCAGGAAGACCAGCTCCTCCTACTGTCTTCTGTGTTACGGGATC




tgccatcatcacctgctgtctgct
AGCGTTCCTTGTTGAGTGGGACC




tggaagaacggc
TGAGTTTTGAGAGGGTCTTCTGCTCCTCTTGGTCTGGTCCCTTACTT




tttctgctgcaatggagagaaatc
CCAAGAGCCCCAGAGAGGAAGGC




ataacagacggtggcacaaggagg
ATGCTGTTGGCTCTAGCICTGCTTCTAGCTTTCCTGCCTCCTGCCAG




ccatcttttcct
TCAGAAATCTTCCAACTTGGAAG




catcggttattgtccctagaagcg
GGAGAACAAAGTCAGTCACCAGGCCAACTGGGTCATCAGCTGTAATC




tcttctgaggatctagttgggctt
ACTTGTGATCTTCCTGTAGAAAA




tctttctgggtt
TGCCGTCTACACCCACTGGTACCTACACCAGGAGGGGAAGGCCCCAC




tgggccatttcagttctcatgtgt
AGCGTCTTCTGTACTATGACTCC




gtactattctatcattattgtata
TACAACTCCAGGGTTGTGTTGGAATCAGGAATCAGTCGAGAAAAGTA




atggttttcaaa
TCATACTTATGCAAGCACAGGGA




ccagtgggcacacagagaacctca
AGAGCCTTAAATTTATACTGGAAAATCTAATTGAACGTGACTCTGGG




gtctgtaataacaatgaggaatag
GTCTATTACTGTGCCACCTGGAA




ccatggcgatctccagcaccaatc
GGATTATTATAAGAAAGTCTTTGGCAGTGGAACAACACTTGTTGTCA




tctccatgttttccacagctcctc
CAGATAAACAACTTGATGCAGAT




cagccaacccaaatagcgcctgct
GTTTCCCCCAAGCCCAcTATTTTTCTTCCTTCGATTGCTGAAACAAA




atagtgtagacagcctgcggcttc
ACTCCAGAAGGCTGGAACATATC




tagccttgtccctctcttagtgtt
TTTGTCTTCTTGAGAAATTTTTCCCAGATATTATTAAGATACATTGG




ctttaatcagat
CAAGAAAAGAAGAGCAACACGAT




aactgcctggaagcctttcatttt
TCTGGGATCCCAGGAGGGGAACACCATGAAGACTAACGACACATACA




acacgccc
TGAAATTTAGCTGGTTAACGGTG




[Seq Id No 68]
CCAGAAGAGTCACTGGACAAAGAACACAGATGTATCGTCAGACATGA





GAATAATAAAAACGGAATTGATC





AAGAAATTATCTTTCCTCCAATAAAGACAGATGTCACCACAGTGGAT





CCCAAAGACAGTTATTCAAAAGA





TGCAAATGATGTCACCACAGTGGATCCCAAATACAATTATTCAAAGG





ATGCAAATGATGTCATCACAATG





GATCCCAAAGACAATTGGTCAAAAGATGCAAATGATACACTACTGCT





GCAGCTCACAAACACCTCTGCAT





ATTACATGTACCTCCTCCTGCTCCTCAAGAGTGTGGTCTATTTTGCC





ATCATCACCTGCTGTCTGCTTGG





AAGAACGGCTTTCTGCTGCAATGGAGAGAAATCATAACAGACGGTGG





CACAAGGAGGCCATCTTTTCCTC





ATCGGTTATTGTCCCTAGAAGCGTCTTCTGAGGATCTAGTTGGGCTT





TCTTTCTGGGTTTGGGCCATTTC





AGTTCTCATGTGTGTACTATTCTATCATTATTGTATAATGGTTTTCA





AACCAGTGGGCACACAGAGAACC





TCAGTCTGTAATAACAATGAGGAATAGCCATGGCGATCTCCAGCACC





AATCTCTCCATGTTTTCCACAGC





TCCTCCAGCCAACCCAAATAGCGCCTGCTATAGTGTAGACAGCCTGC





GGCTTCTAGCCTTGTCCCTCTCT





TAGTGTTCTTTAATCAGATAACTGCCTGGAAGCCTTTCATTTTACAC





GCCCTGAAGCAGTCTTCTTTGCT





AGTTGAATTATGTGGTGTGTTTTTCCGTAATAAGCAAAATAAATTT





211796_
T cell
gccatcagaagcagagatctccca
>gi|3002924|gb|AF043179.1|AF043179 Homo sapiens
63.34


s_at
receptor
cacccaaaaggccacactggtgtg
T cell receptor beta chain (TCRBV13S1-TCRBJ2S1)



beta
cctggccacaggtttctaccccga
mRNA, complete cds



variable
ccacgtggagctgagctggtgggt
ATGAGCATCGGCCTCCTGTGCTGTGCAGCCTTGTCTCTCCTGTGGGC



21-1///T
gaatgggaaggaggtgcacagtgg
AGGTCCAGTGAATGCTGGTGTCA



cell
ggtcagcacagacccgcagcccct
CTCAGACCCCAAAATTCCAGGTCCTGAAGACAGGACAGAGCATGACA



receptor
caaggagcagcccgccctcaatga
CTGCAGTGTGCCCAGGATATGAA



beta
ctccagatactgcctgagcagccg
CCATGAATACATGTCCTGGTATCGACAAGACCCAGGCATGGGGCTGA



variable
cctgagggtctcggccaccttctg
GGCTGATTCATTACTCAGTTCGT



19///T
gcagaacccccgcaaccacttccg
GCTGGTATCACTGACCAAGGAGAAGTCCCCAATGGCTACAATGTCTC



cell
ctgtcaagtccagttctacgggct
CAGATCAACCACAGAGGATTTCC



receptor
ctcggagaatgacgagtggaccca
CGCTCAGGCTGCTGTCGGCTGCTCCCTCCCAGACATCTGTGTACTTC



beta
ggatagggccaaacctgtcaccca
TGTGCCAGCAGTTTCCCCCGGCA



variable
gatcgtcagcgccgaggcctgggg
GCCGTCCTACAATGAGCAGTTCTTCGGGCCAGGGACACGGCTCACCG



5-4///T
tagagcagactgtggcttcacctc
TGCTAGAGGACCTGAAAAACGTG



cell
cgagtcttaccagcaaggggtcct
TTCCCACCCGAGGTCGCTGTGTTTGAGCCATCAGAAGCAGAGATCTC



receptor
gtctgccaccatcctctatgagat
CCACACCCAAAAGGCCACACTGG



beta
cttgctagggaaggccaccttgta
TGTGCCTGGCCACAGGTTTCTACCCCGACCACGTGGAGCTGAGCTGG



variable
tgctgtgctggtcagtgccctcgt
TGGGTGAATGGGAAGGAGGTGCA



3-1///T
gctgatggccatggtcaagagaaa
CAGTGGGGTCAGCACAGACCCGCAGCCCCTCAAGGAGCAGCCCGCCC



cell
gga
TCAATGACTCCAGATACTGCCTG



receptor
[Seq Id No 69]
AGCAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGCAA



beta

CCACTTCCGCTGTCAAGTCCAGT



constant 1

TCTACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGCCAAA





CCTGTCACCCAGATCGTCAGCGC





CGAGGCCTGGGGTAGAGCAGACTGTGGCTTCACCTCCGAGTCTTACC





AGCAAGGGGTCCTGTCTGCCACC





ATCCTCTATGAGATCTTGCTAGGGAAGGCCACCTTGTATGCTGTGCT





GGTCAGTGCCCTCGTGCTGATGG





CCATGGTCAAGAGAAAGGATTCCAGAGGCTGA





211902_
T cell
gaatcgtttctctgtgaacttcca
>gi|1100165|gb|L34703.1|HUMTCRAZ Homo sapiens
20.68


x_at
receptor
gaaagcagccaaatccttcagtct
T-cell receptor alpha chain (TCRA) mRNA (HLA



alpha
caagatctcaga
A1, 24; B7, 8; DR 1, 3), complete cds



locus
ctcacagctgggggatgccgcgat
ATGGCATGCCCTGGCTTCCTGTGGGCACTTGTGATCTCCACCTGTCT




gtatttctgtgcttataggagtgc
TGAATTTAGCATGGCTCAGACAG




atactctggggc
TCACTCAGTCTCAACCAGAGATGTCTGTGCAGGAGGCAGAGACCGTG




tgggagttaccaactcactttcgg
ACCCTGAGCTGCACATATGACAC




gaaggggaccaaactctcggtcat
CAGTGAGAGTGATTATTATTTATTCTGGTACAAGCAGCCTCCCAGCA




accaaatatccagaaccctgaccc
GGCAGATGATTCTCGTTATTCGC




tgccgtgtaccagctgagagactc
CAAGAAGCTTATAAGCAACAGAATGCAACAGAGAATCGTTTCTCTGT




taaatccagtgacaagtctgtctg
GAACTTCCAGAAAGCAGCCAAAT




cctattcaccgattttgattctca
CCTTCAGTCTCAAGATCTCAGACTCACAGCTGGGGGATGCCGCGATG




aacaaatgtgtcacaaagtaagga
TATTTCTGTGCTTATAGGAGTGC




ttctgatgtgta
ATACTCTGGGGCTGGGAGTTACCAACTCACTTTCGGGAAGGGGACCA




tatcacagacaaaactgtgctaga
AACTCTCGGTCATACCAAATATC




catgaggtctatggacttcaagag
CAGAACCCTGACCCTGCCGTGTACCAGCTGAGAGACTCTAAATCCAG




caacagtgctgt
TGACAAGTCTGTCTGCCTATTCA




ggcctggagcaacaaatctgactt
CCGATTTTGATTCTCAAACAAATGTGTCACAAAGTAAGGATTCTGAT




tgcatgtgcaaacgccttcaacaa
GTGTATATCACAGACAAAACTGT




cagcattattcc
GCTAGACATGAGGTCTATGGACTTCAAGAGCAACAGTGCTGTGGCCT




agaagacaccttcttccccagccc
GGAGCAACAAATCTGACTTTGCA




agaaagttcctgtgatgtcaagct
TGTGCAAACGCCTTCAACAACAGCATTATTCCAGAAGACACCTTCTT




ggtcgagaaaagctttgaaacaga
CCCCAGCCCAGAAAGTTCCTGTG




tacgaacctaaactttcaaaacct
ATGTCAAGCTGGTCGAGAAAAGCTTTGAAACAGATACGAACCTAAAC




gtcagtgattgggttccgaatcct
TTTCAAAACCTGTCAGTGATTGG




cctcctgaaagtggccgggtttaa
GTTCCGAATCCTCCTCCTGAAAGTGGCCGGGTTTAATCTGCTCATGA




tctgctcatgacgctgcggttgtg
CGCTGCGGTTGTGGTCCAGCTGA




gtcc




[Seq Id No 70]





212999_
Major histo-
cactgcagaatgaaggaacatccc
>gi|24797068|ref|NM_002123.2|Homo sapiens
15.79


x_at
compatibility
ttgaggtgacccagccaacctgtg
major histocompatibility complex, class II, DQ



complex,
gccagaaggagqnttgtaccttga
beta 1 (HLA-DQB1), mRNA



class II,
aaagacactgaaagcattttggng
CAGATCCATCAGGTCCGAGCTGTGTTGACTACCACTTTTCCCTTCGT



DQ beta 1///
tgtnaagtaagggtgggcagagga
CTCAATTATGTCTTGGAAAAAGG



Major histo-
ggtagaaaatcaattcaattgtcg
CTTTGCGGATCCCCGGAGGCCTTCGGGCAGCAACTGTGACCTTGATG



compatibility
catcattcatggttctttaatatt
CTGTCGATGCTGAGCACCCCAGT



complex,
gatgctcagtgcantggcctnaga
GGCTGAGGGCAGAGACTCTCCCGAGGATTTCGTGTACCAGTTTAAGG



class II,
atatcccagcctctcttctggttt
GCATGTGCTACTTCACCAACGGG



DQ beta 1
gntgagtgctntntaagtaagcat
ACAGAGCGCGTGCGTCTTGTGAGCAGAAGCATCTATAACCGAGAAGA




ggtngaattgtttggggncanata
GATCGTGCGCTTCGACAGCGACG




tagtganccttggtcactggtgtt
TGGGGGAGTTCCGGGCGGTGACGCTGCTGGGGCTGCCTGCCGCCGAG




tcaaacattctg
TACTGGAACAGCCAGAAGGACAT




gnaagtcacatcnatcaagaatan
CCTGGAGAGGAAACGGGCGGCGGTGGACAGGGTGTGCAGACACAACT




tttttanttttaagaaagcataac
ACCAGTTGGAGCTCCGCACGACC




cagcaataaa
TTGCAGCGGCGAGTGGAGCCCACAGTGACCATCTCCCCATCCAGGAC




[Seq Id No 71]
AGAGGCCCTCAACCACCACAACC





TGCTGGTCTGCTCGGTGACAGATTTCTATCCAGCCCAGATCAAAGTC





CGGTGGTTTCGGAATGACCAGGA





GGAGACAGCTGGCGTTGTGTCCACCCCCCTTATTAGGAATGGTGACT





GGACCTTCCAGATCCTGGTGATG





CTGGAAATGACTCCCCAGCGTGGAGACGTCTACACCTGCCACGTGGA





GCACCCCAGCCTCCAGAGCCCCA





TCACCGTGGAGTGGCGGGCTCAATCTGAATCTGCCCAGAGCAAGATG





CTGAGTGGCATTGGAGGCTTCGT





GCTGGGGCTGATCTTCCTCGGGCTGGGCCTTATCATCCATCACAGGA





GTCAGAAAGGGCTCCTGCACTGA





CTCCTGAGACTATTTTAACTGGGATTGGTTATCACTTTTCTGTAACG





CCTGCTTGTCCCTGCCCAGAATT





CCCAGCTGTCTGTGTCAGCCTGTCCCCCTGAGATCAGAGTCCTACAG





TGGCTGTCACGCAGCCACCAGGT





CATCTCCTTTCATCCCCACCTTGAGGCGGATGGCTGTGACCCTACTT





CCTGCACTGACCCACAGCCTCTG





CCTGTGCACGGCCAGCTGCATCTACTCAGGCCCCAAGGGGTTTCTGT





TTCTATTCTCTCCTCAGACTGCT





CAAGAGAAGCACATGAAAACCATTACCTGACTTTAGAGCTTTTTTAC





ATAATTAAACATGATCCTGAGTT





213193_
T cell
Tgactccagatactgcctgagcag
>gi|46184507|gb|AL559122.3|AL559122 AL559122
44.75


x_at
receptor
ccgcctgagggtctcggccacctt

Homo sapiens T CELLS (JURKAT CELL LINE) COT 10-




beta
ctggcagaacccccgcaaccactt
NORMALIZED Homo sapiens cDNA clone CS0DJ014YE01



variable
ccgctgtcaagtccagttctacgg
5-PRIME, mRNA sequence



19///T
gctctcggagaatgacgagtggac
TGCCTGGCCACAGGCTTCTTCCCCGACCACGTGGAGCTGAGCTGGTG



cell
ccaggatagggccaaacccgtcac
GGTGAATGGGAAGGAGGTGCACA



receptor
ccagatcqtcagcgccgaggcctg
ATGGGGTCAACACAGACCCGCAGCCCCTCAAAGAACAGCCCGCCCTC



beta
gggtagagcagactgtggctttac
AATGACTCCAAATAMTGCCTGAG



variable
ctcggtgtcctaccagcaaggggt
CAGCCGCCTGAGGGTCTCGGCCACCTTCTGGCAGAACCCCCGCAACC



19///T
cctgtctgccaccatcctctatga
ACTTCCGCTGTCAAGTCCAGTTC



cell
gatcctgctagggaaggccaccct
TACGGGCTCTCGGAGAATGACGAGTGGACCCAGGATAGGGCCAAACC



receptor
gtatgctgtgctggtcagcnccct
CGTCACCCAAATCGTCAGCGCCG



beta
tgtgttgatggccatggtcaagag
AGGCCTGGGGTARAGCARAMTGTGGCTTTACCTCGGTGTCCTACCAA



constant
aaaggatttctgaaggcagccctg
CAAGGGGTCCTGTCTGCCACCAT



1///T
gaagtggagttaggagcttctaac
CCTCTATGARATCCTGcTAGGGAAGGCCACCcTGTATGCTGTGCTGG



cell
ccgtcatggtttcaatacacattc
TCAGCGCCCTTGTGTTGATGGCC



receptor
ttcttttgccagcgcttctgaaga
ATGGTCAAGAGAAAGGATTTCTGAAGGCAGCCCTGGAAGTGGAATTA



beta
gctgctctcacctctctgcatccc
AGAACTTCTAACCCGTCATGGTT



constant 1
aatagatatccccctatgtgcatg
TCAATACACATTCTTCTTTTGCCAGCGCTTCTGAAGAGCTGCTCTCA




cacacctgcacactcacggctgaa
CCTCTCTGCATCCCAATAGATAT




atctccctaacccagggggacctt
CCCCCTATGTGCATGCACACCTGCACACTCACGGCTGAAATCTCCCT




agcatgcctaagtga
AACCCAGGOGGACCTTACCATGC




[Seq Id No 72]
CTAAGTGACTAAACCAATAAAAATGTTCTGGTCTGGCCTGA





213539_
CD3D
gggaacactgctctcagacattac
>gi|98985799|ref|NM_000732.4|Homo sapiens CD3d
34.66


at
antigen,
aagactggacctgggaaaacgcat
molecule, delta (CD3-TCR complex) (CD3D),



delta poly-
cctggacccacgaggaatatatag
transcript variant 1, mRNA



peptide
gtgtaatgggacagatatatacaa
AGAGAAGCAGACATCTTCTAGTTCCTCCCCCACTCTCCTCTTTCCGG



(TiT3
ggacaaagaatctaccgtgcaagt
TACCTGTGAGTCAGCTAGGGGAG



complex)
tcattatcgaatgtgccagagctg
GGCAGCTCTCACCCAGGCTGATAGTTCGGTGACCTGGCTTTATCTAC




tgtggagctggatccagccaccgt
TGGATGAGTTCCGCTGGGAGATG




ggctggcatcattgtcactgatgt
GAACATAGCACGTTTCTCTCTGCCCTGGTACTGGCTACCCTTCTCTC




cattgccactctgctccttgcttt
GCAAGTGAGCCCCTTCAAGATAC




gggagtcttctgctttgctggaca
CTATAGAGGAACTTGAGGACAGAGTGTTTGTGAATTGCAATACCAGC




tgagactggaaggctgtctggggc
ATCACATGGGTAGAGGGAACGGT




tgccgacacacaagctctgttgag
GGGAACACTGCTCTCAGACATTACAAGACTGGACCTGGGAAAACGCA




gaatgaccaggtctatcagcccct
TCCTGGACCCACGAGGAATATAT




ccgagatcgagatgatgctcagta
AGGTGTAATGGGACAGATATATACAAGGACAAAGAATCTACCGTGCA




cagccaccttggaggaaactgggc
AGTTCATTATCGAATGTGCCAGA




tcggaacaagtgaacctgagactg
GCTGTGTGAGCTGGATCCAGCCACCGTGGCTGGCATCATTGTCACT




gtggcttctagaagcagccattac
GATGTCATTGCCACTCTGCTCCT




caactgtacct
TGCTTTGGGAGTCTTCTGCTTTGCTGGACATGAGACTGGAAGGCTGT




[Seq Id No 73]
CTGGGGCTGCCGACACACAAGCT





CTGTTGAGGAATGACCAGGTCTATCAGCCCCTCCGAGATCGAGATGA





TGCTCAGTACAGCCACCTTGGAG





GAAACTGGGCTCGGAACAAGTGAACCTGAGACTGGTGGCTTCTAGAA





GCAGCCATTACCAACTGTACCTT





CCCTTCTTGCTCAGCCAATAAATATATCCTCTTTCACTCAGAAAAAA





AAAAAAAAAAAAAAAAAAAAAAA





A





215806_
T cell
aaatgatacactactgctgcagct
>gi|339168|gb|M13231.1|HUMTCGXH Human T-cell
19.96


x_at
receptor
cacaaacacctctgcatattacat
receptor aberrantly rearranged gamma-chain mRNA



gamma
gtacctcctcct
from cell line HPB-MLT



constant
gctcctcaagagtgtggtctattt
GGCATGCGGTGGGCCCTACTGGTGCTTCTAGCTTTCCTGTCTCCTGC



2///T cell
tgccatcatcacctgctgtctgcn
CAGTCAGAAATCTTCCAACTTGG



receptor
tgnaagaacggc
AAGCGAGAACGAAGTCAGTCACCAGGCAGACTGGGTCATCTGCTGAA



gamma
nnnctgctgcaatggagagaantc
ATCACTTGCGATCTTACTGTAAC



variable
ataacagacggtggcacaaggagg
AAATACCTTCTACATCCACTGGTACCTACACCAGGAGGGGAAGGCCC



9///
ccnncntntcctcatcggnnattg
CACAGCGTCTTCTGTACTATGAC



similar to
tccctagaagcgtcttctgaggat
GTCTCCACTGCAAGGGATGTGTTGGAATCAGGACTCAGTCCAGGAAA



T-cell
ctagttgggctttctttctgggtt
GTATTATACTCATACACCCAGGA



receptor
tgggccatttcagttctcatgtgt
GGTGGAGCTGGATATTGAGACTGCAAAATCTAATTGAAAATGATTCT



gamma
gtactattctatcattattgtata
GGGGTCTATTACTGTGCCACCTG



chain C
atggttttcaaa
GGACAGGCAAAAATTATTATAAGAAACTCTTTGGCAGTGGAACAACA



region PT-
ccagtgggcacacagagaacctca
CTTGTTGTCACAGATAAACAACT



gamma-
gtctgtaataacaatgaggaatag
TGATGCAGATGTTTCCCCCAAGCCCACTATTTTTCTTCCTTCAATTG



½///
ccatggcgatctccagcaccaatc
CTGAAACAAAACTCCAGAAGGCT



similar to
tctccatgttttccacagctcctc
GGAACATACCTTTGTCTTCTTGAGAAATTTTTCCCAGATATTATTAA



T-cell
cagccaacccaaatagcgcctgct
GATACATTGGCAAGAAAAGAAGA



receptor
atagtgtaganannctgcggcttc
GCAACACGATTCTGGGATCCCAGGAGGGGAACACCATGAAGACTAAC



gamma
tagccttgtccctctcttagtgtt
GACACATACATGAAATTTAGCTG



chain V
ctttaatcagat
GTTAACGGTGCCAGAAGAGTCACTGGACAAAGAACACAGATGTATCG



region PT-
aactgcctggaagcctttcatttt
TCAGACATGAGAATAATAAAAAC



gamma-
acacgccctgaagcagtcttcttt
GGAATTGATCAAGAAATTATCTTTCCTCCAATAAAGACAGATGTCAC



½ pre-
gcta
CACAGTGGATCCCAAAGACAGTT



cursor///
[Seq Id No 74]
ATTCAAAAGATGCAAATGATGTCATCACAATGGATCCCAAAGACAAT



TCR gamma

TGGTCAAAAGATGCAAATGATAC



alternate

ACTACTGCTGCAGCTCACAAACACCTCTGCATATTACATGTACCTCC



reading

TCCTGCTCCTCAAGAGTGTGGTC



frame

TATTTTGCCATCATCACCTGCTGTCTGCTTGGAAGAACGGCTTTCTG



protein

CTGCAATGGAGAGAAATCATAAC





AGACGGTGGCACAAGGAGGCCATCTTTTCCTCATCGGTTATTGTCCC





TAGTAGAAGCGTCTTCTGAGGATCTA





GTTGGGCTTTCTTTCTGGGTTTGGGCCATTTCAGTTCTCATGTGTGT





ACTATTCTATCATTATTGTATAA





TGGTTTTCAAACCAGTGGGCACACAGAGAACCTCAGTCTGTAATAAC





AATGAGGAATAGCCATGCCGATC





TCCAGCACCAATCTCTCCATGTTTTCCACAGCTCCTCCAGCCAACCC





AAATAGCGCCTGCTATAGTGTAG





ACAGCCTGCGGCTTCTAGCCTTGTCCCTCTCTTAGTGTTCTTTAATC





AGATAACTGCCTGGAAGCCTTTC





ATTTTACACGCCCTGAAGCAGTCTTCTTTGCTAGTTGAATTATGTGG





TGTGTTTTTCCGTAATAAGCAAA





ATAAATTTAAAAAAATGAAAA





216748_
pyrin and
ccaccctctggatcccaatattga
>gi|10437303|dbj|AK024890.1|Homo sapiens cDNA:
10.74


at
HIN domain
gatcttatcctcagggaatcctca
FLJ21237 fis, clone COL01114



family
cttagacccctg
GTCAAAGGAATAATCCCATCTAAAAAGACGAAACAGAAAGAAGTGTA



member 1
taacaggttaaatcttcatggtgt
TCCTGCTACACCTGCATGCACCC




tctgtttcctaggaacttctttct
CAAGCAACCGTCTCACAGCTAAAGGAGCAGAGGAGACTCTTGGACCT




tttctactgttt
CAGGTAAGCTTCAGGAAGAGGAG




atgacaactgaagttaataagtgt
CAGGCTTCAAGTCTCACAGTGGAAGCTCTGCTGTGGCTGTTCCACTC




ttatctttcccacctactcaaagt
AATCTGTCCAGCAGGCAGTTATT




agttccaagatt
TCTTCATATGTTTCCCATCAAGTTTCAGATTTATCAAATTACATAAT




agggctagtttgtaattctgtgga
AATTGATCATCTTTCTGCAAGGC




ccactgtaaacgagggcctagttc
AACAAGTTAAACGCTTTAGTAAACATAATGTAAATATACATAAAATA




agtgtctgcctc
AATATAATATTTTCATCTCCAAT




atgggaagcttccaataaatacct
AGAGAAGGATGTTAACTTGAGAGTCAGATAAAAAAACGTTTGCCTAT




ttg
GTTTACAAAAGCCTAGTTTCTTA




[Seq Id No 75]
ACTGCAAGTCAGCATATCCCAAAACACAAGTAATTAAGGAATGATGT





GTGTTACTTTCTCTGCTCCCTTT





TTAAAAATGAAACCATCTATGCCATGTTCTTTCAATTGGCCTGGGGA





TGTACTTAAGTTTCCAAGAAAAA





CAATTTATATACAATAAATATATTACCTTGTAATGAAAATGTGCTCT





GCTTCATTTGACACTGAAAGTAA





TTAACAAGAAAAATAAACTACTTGTAGAAAAGAAAAAAACCATCTGA





AGAAGAGACTGGAACCAAAAGGA





GTAAGATGTCCAAAGAGCAGACTCGGCCTTCCTGCTCTGCAGGAGCC





AGCACGTCCACAGCCATGGGCCG





TTCCCCACCTCCCCAGACCTCATCATCAGCTCCACCCAACACTTCCT





CAACTGAGGTACACTCTTCCTGG





TCCCCTTTTGATTCATTTTCTTCAACCCAAAATGTAGGAATCTGATT





TCATCTTCTACTGAAAAATGACA





TCAATCATCAGCCAGTAAATCAAATGTATAGACTGAGAATTAACTGC





ATTTTAATCTTTTGCTTCCACAG





GCATATTTGATGAACTTGACATTATCTCTGACTGCAGGAAGTTTTCT





GTCCTGTGCTGTTTGGGGAAGAG





ACAGAGAACTGCGGAATCTGGAACTTTCAGCAACAGACTCACTGTCT





ACTGCCCCCATCTATTATACACC





CATTCCCTTTGCTCACTAATTTGTTCAAGTTTCTCTGACATACACCA





TGCTCCTTTTTCCTTTAGGATTT





TCACACACCATATTTCTTTCACCTTTAAACTCTTACCTGGCCAACCC





TATCCACCCTCTGGATCCCAATA





TTGAGATCTTATCCTCAGGGAATCCTCACTTAGACCCCTGTAACAGG





TTAAATCTTCATGGTGTTCTGTT





TCCTAGGAACTTCTTTCTTTTCTACTGTTTATGACAACTGAAGTTAA





TAAGTGTTTATCTTTCCCACCTA





CTCAAAGTAGTTCCAAGATTAGGGCTAGTTTGTAATTCTGTGGACCA





CTGTAAACGAGGGCCTAGTTCAG





TGTCTGCCTCATGGGAAGCTTCCAATAAATACCTTTGCTCAACGAAA





AAATGAAAACCCAGTGGCTCACG





CCTGTAATCCCAGCACTTTGGGAGGCCGAGGCAGGTGGATTGCCTGA





GGTCAGGAGTTTGAGACTAGTCT





GGCCAACATGGTGAAACACTATCTCTACTAAAAATACAAAAAAATTA





GCTGGGTATGGTGGCTTACGCCT





ATAATCCCAGCTACTCAGGAGGCTGAGGCAGGGGAATTGCTTGAACC





AGGGAGGTGGAGGTTGCAGTGAG





CTGAGATCGCACCACTGCACTCCAGCCTGGGTGACAGAGCGAGACTC





CATCTCAAAATAAAAAAGTAAAA





AAAAAAAAAAAAAA





217147_
T cell
tctcctttctcaccaatgggcaat
>gi|54607136|ref|NM_016388.2|Homo sapiens T
24.16


s_at
receptor
agcccataattgaaataaatttct
cell receptor associated transmembrane adaptor



associated
gattgaaaggta
1 (TRAT1), mRNA



transmembrane
taggaaacattaaaatgcattact
GAGGCACAGATAAAGATAAGTTTTACTGTCATGCTGCTTTTAACATA



adaptor 1
aagagaagtaatataattttctta
ACAGAGCAACATCACCTAGGAAA




caaagtattttt
AAAGTTTGTAGGAGGATTTTTAATCCATATATTTGTCTTATGGCTAG




cccaaagatagctttactatttca
ATAAAGATTTCTCTGAAAAAAAG




aaaattgtcaaattaatgcatgct
AAGCATGTCAGGAATCTCTGGGTGCCCCTTTTTCCTCTGGGGACTTC




ccttacaacaaa
TAGCATTGTTGGGCTTGGCTTTG




caaatatcaaaaagagtttaggaa
GTTATATCACTGATCTTCAATATTTCCCACTATGTGGAAAAGCAACG




ttctactagccagagatagtcact
ACAAGATAAAATGTACAGCTACT




tggagaaacttt
CCAGTGACCACACCAGGGTTGATGAGTATTATATTGAAGACACACCA




ctatatatccttctaaatattttt
ATTTATGGTAACTTAGATGATAT




ctgggcatgctcatgtatgtacat
GATTTCAGAACCAATGGATGAAAATTGCTATGAACAAATGAAAGCCC




cagttgtttctt
GACCAGAGAAATCTGTAAATAAG




tttattttgaaccaaaaatgtggt
ATGCAGGAAGCCACCCCATCTGCACACGCAACCAATGAAACACAGAT




ttcttttgtacacattacttaaac
GTGCTACGCCTCACTTGATCACA




tttctttccagt
GCGTTAACGGGAAGCGTAGAAAGCCCAGGAAACAGAATACTCATTTC




caacaatatattgtggatttattt
TCAGACAAGGATGGAGATGAGCA




tcactgttatatttaactatatat
ACTACATGCAATAGATGCCAGCGTTTCTAAGACCACCTTAGTAGACA




aaatacgcatat
GTTTCTCCCCAGAAAGCCAGGCA




attgtaattttaatgtctgcttag
GTAGAGGAAAACATTCATGATGATCCCATCAGACTGTTTGGATTGAT




caccccactgataaccaaatcaca
CCGTGCTAAGAGAGAACCTATAA




g
ACTAGCTGGACCATGATCTAGTTCAATGATTTGGCTCCTATTGAAGA




[Seq Id No 76]
TGGCTTCTAAGAAAACAAGATGC





ACAGAGGACACAGAAGGACTTGGCAGCAGGGTGATGACCTGATCATT





TGTTGATGGGATGGTGGCTTACC





TCTTATTCACAGCTTACACTTATGCATGCCAAATGTAAGGCCATGAA





AATCAGTATTTCAAATAACTTAA





AAAATGCTTTACTACTAAAATGTAAAAAATTAATGTGCTCACCTCGG





CAGCACATATACTAAAAATTAAT





AAGACCCAGCTTGAAAATTGAGCCTGATAACAAGATTACAAATTCAC





AATACCTAATACTTAGGCAAATA





TAAAAATTTAAGCATGAATGCGTTCTGGAACACGTTAGAAGAAAAAT





AAAAGCCAATGAGTTTTTTTTTA





ATTCTCCTTTCTCACCAATGGGCAATAGCCCATAATTGAAATAAATT





TCTGATTGAAAGGTATAGGAAAC





ATTAAAATGCATTACTAAGAGAAGTAATATAATTTTCTTACAAAGTA





TTTTTCCCAAAGATAGCTTTACT





ATTTCAAAAATTGTCAAATTAATGCATGCTCCTTACAACAAACAAAT





ATCAAAAAGAGTTTAGGAATTCT





ACTAGCCAGAGATAGTCACTTGGAGAAACTTTCTATATATCCTTCTA





AATATTTTTCTGGGCATGCTTAT





GTATGTACATCAGTTGTTTCTTTTTATTTTGAACCAAAAATGTGGTT





TCTTTTGTACACATTACTTAAAC





TTTCTTTCCAGTCAACAATATATTGTGGATTTATTTTCACTGTTATA





TTTAACTATATATAAATACGCAT





ATATTGTAATTTTAATGTCTGCTTAGCACCCCACTGATAACCAAATC





ACAGTTTATTTAAATAATTTTAA





TGACTTTTCAAAAACAATTTATTGATGCAAAAAGCAAGGTTGAGATG





ACAATGTTTCTTTCAATAATTAA





AAAATACTGCTTCAC





219159_
SLAM
Gagagtggacatttgtcgggaaac
>gi|19923571|ref|NM_021181.3|Homo sapiens SLAM
15.84


s_at
family
tcctaacatatgcccccattctgg
family member 7 (SLAMF7), mRNA



member 7
agagaacacagagtacgacacaat
CTTCCAGAGAGCAATATGGCTGGTTCCCCAACATGCCTCACCCTCAT




ccctcacactaatagaacaatcct
CTATATCCTTTGGCAGCTCACAG




a
GGTCAGCAGCCTCTGGACCCGTGAAAGAGCTGGTCGGTTCCGTTGGT




[Seq Id No 77]
GGGGCCGTGACTTTCCCCCTGAA





GTCCAAAGTAAAGCAAGTTGACTCTATTGTCTGGACCTTCAACACAA





CCCCTCTTGTCACCATACAGCCA





GAAGGGGGCACTATCATAGTGACCCAAAATCGTAATAGGGAGAGAGT





AGACTTCCCAGATGGAGGCTACT





CCCTGAAGCTCAGCAAACTGAAGAAGAATGACTCAGGGATCTACTAT





GTGGGGATATACAGCTCATCACT





CCAGCAGCCCTCCACCCAGGAGTACGTGCTGCATGTCTACGAGCACC





TGTCAAAGCCTAAAGTCACCATG





GGTCTGCAGAGCAATAAGAATGGCACCTGTGTGACCAATCTGACATG





CTGCATGGAACATGGGGAAGAGG





ATGTGATTTATACCTGGAAGGCCCTGGGGCAAGCAGCCAATGAGTCC





CATAATGGGTCCATCCTCCCCAT





CTCCTGGAGATGGGGAGAAAGTGATATGACCTTCATCTGCGTTGCCA





GCAACCCTGTCAGCAGAAACTTC





TCAAGCCCCATCCTTGCCAGGAAGCTCTGTGAAGGTGCTGCTGATGA





CCCAGATTCCTCCATGGTCCTCC





TGTGTCTCCTGTTGGTGCCCCTCCTGCTCAGTCTCTTTGTACTGGGG





CTATTTCTTTGGTTTCTGAAGAG





AGAGAGACAAGAAGAGTACATTGAAGAGAAGAAGAGAGTGGACATTT





GTCGGGAAACTCCTAACATATGC





CCCCATTCTGGAGAGAACACAGAGTACGACACAATCCCTCACACTAA





TAGAACAATCCTAAAGGAAGATC





CAGCAAATACGGTTTACTCCACTGTGGAAATACCGAAAAAGATGGAA





AATCCCCACTCACTGCTCACGAT





GCCAGACACACCAAGGCTATTTGCCTATGAGAATGTTATCTAGACAG





CAGTGCACTCCCCTAAGTCTCTG





CTCAAAAAAAAAACAATTCTCGGCCCAAAGAAAACAATCAGAAGAAT





TCACTGATTTGACTAGAAACATC





AAGGAAGAATGAAGAACGTTGACTTTTTTCCAGGATAAATTATCTCT





GATGCTTCTTTAGATTTAAGAGT





TCATAATTCCATCCACTGCTGAGAAATCTCCTCAAACCCAGAAGGTT





TAATCACTTCATCCCAAAAATGG





GATTGTGAATGTCAGCAAACCATAAAAAAAGTGCTTAGAAGTATTCC





TATAGAAATGTAAATGCAAGGTC





ACACATATTAATGACAGCCTGTTGTATTAATGATGGCTCCAGGTCAG





TGTCTGGAGTTTCATTCCATCCC





AGGGCTTGGATGTAAGGATTATACCAAGAGTCTTGCTACCAGGAGGG





CAAGAAGACCAAAACAGACAGAC





AAGTCCAGCAGAAGCAGATGCACCTGACAAAAATGGATGTATTAATT





GGCTCTATAAACTATGTGCCCAG





CACTATGCTGAGCTTACACTAATTGGTCAGACGTGCTGTCTGCCCTC





ATGAAATTGGCTCCAAATGAATG





AACTACTTTCATGAGCAGTTGTAGCAGGCCTGACCACAGATTCCCAG





AGGGCCAGGTGTGGATCCACAGG





ACTTGAAGGTCAAAGTTCACAAAGATGAAGAATCAGGGTAGCTGACC





ATGTTTGGCAGATACTATAATGG





AGACACAGAAGTGTGCATGGCCCAAGGACAAGGACCTCCAGCCAGGC





TTCATTTATGCACTTGTGCTGCA





AAAGAAAAGTCTAGGTTTTAAGGCTGTGCCAGAACCCATCCCAATAA





AGAGACCGAGTCTGAAGTCACAT





TGTAAATCTAGTGTAGGAGACTTGGAGTCAGGCAGTGAGACTGGTGG





GGCACGGGGGGCAGTGGGTACTT





GTAAACCTTTAAAGATGGTTAATTCATTCAATAGATATTTATTAAGA





ACCTATGCGGCCCGGCATGGTGG





CTCACACCTGTAATCCCAGCACTTTGGGAGGCCAAGGTGGGTGGGTC





ATCTGAGGTCAGGAGTTCAAGAC





CAGCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAGATACAAAA





ATTTGCTGAGCGTGGTGGTGTGC





ACCTGTAATCCCAGCTACTCGAGAGGCCAAGGCATGAGAATCGCTTG





AACCTGGGAGGTGGAGGTTGCAG





TGAGCTGAGATGGCACCACTGCACTCCGGCCTAGGCAACGAGAGCAA





AACTCCAATACAAACAAACAAAC





AAACACCTGTGCTAGGTCAGTCTGGCACGTAAGATGAACATCCCTAC





CAACACAGAGCTCACCATCTCTT





ATACTTAAGTGAAAAACATGGGGAAGGGGAAAGGGGAATGGCTGCTT





TTGATATGTTCCCTGACACATAT





CTTGAATGGAGACCTCCCTACCAAGTGATGAAAGTGTTGAAAAACTT





AATAACAAATGCTTGTTGGGCAA





GAATGGGATTGAGGATTATCTTCTCTCAGAAAGGCATTGTGAAGGAA





TTGAGCCAGATCTCTCTCCCTAC





TGCAAAACCCTATTGTAGTAAAAAAGTCTTCTTTACTATCTTAATAA





AACAGATATTGTGAGATTCAAAA





AAAAAAAAAAAA





222838_
SLAM
aacacctgtgctaggtcagtctgg
>gi|19923571|ref|NM_021181.3|Homo sapiens SLAM
22.54


at
family
cacgtaagatgaacatccctacca
family member 7 (SLAMF7), mRNA



member 7
acacagagctcaccatctcttata
CTTCCAGAGAGCAATATGGCTGGTTCCCCAACATGCCTCACCCTCAT




cttaagtgaaaaacatggggaagg
CTATATCCTTTGGCAGCTCACAG




ggaaaggggaatggctgcttttga
GGTCAGCAGCCTCTGGACCCGTGAAAGAGCTGGTCGGTTCCGTTGGT




tatgttccctgacacatatcttga
GGGGCCGTGACTTTCCCCCTGAA




atggagacctccctaccaagtgat
GTCCAAAGTAAAGCAAGTTGACTCTATTGTCTGGACCTTCAACACAA




gaaagtgttgaa
CCCCTCTTGTCACCATACAGCCA




aaacttaataacaaatgcttgttg
GAAGGGGGCACTATCATAGTGACCCAAAATCGTAATAGGGAGAGAGT




ggcaagaatgggattgaggattat
AGACTTCCCAGATGGAGGCTACT




cttctctcagaa
CCCTGAAGCTCAGCAAACTGAAGAAGAATGACTCAGGGATCTACTAT




aggcattgtgaagaattgagcca
GTGGGGATATACAGCTCATCACT




gatctctctccctactgcaaaacc
CCAGCAGCCCTCCACCCAGGAGTACGTGCTGCATGTCTACGAGCACC




ctattgtagta
TGTCAAAGCCTAAAGTCACCATG




[Seq Id No 78]
GGTCTGCAGAGCAATAAGAATGGCACCTGTGTGACCAATCTGACATG





CTGCATGGAACATGGGGAAGAGG





ATGTGATTTATACCTGGAAGGCCCTGGGGCAAGCAGCCAATGAGTCC





CATAATGGGTCCATCCTCCCCAT





CTCCTGGAGATGGGGAGAAAGTCATATGACCTTCATCTGCGTTGCCA





GGAACCCTGTCAGCAGAAACTTC





TCAAGCCCCATCCTTGCCAGGAAGCTCTGTGAAGGTGCTGCTGATGA





CCCAGATTCCTCCATGGTCCTCC





TGTGTCTCCTGTTGGTGCCCCTCCTGCTCAGTCTCTTTGTACTGGGG





CTATTTCTTTGGTTTCTGAAGAG





AGAGACACAAGAAGAGTACATTGAAGAGAAGAAGAGAGTGGACATTT





GTCGGGAAACTCCTAACATATGC





CCCCATTCTGGAGAGAACACAGAGTACGACACAATCCCTCACACTAA





TAGAACAATCCTAAAGGAAGATC





CAGCAAATACGGTTTACTCCACTGTGGAAATACCGAAAAAGATGGAA





AATCCCCACTCACTGCTCACGAT





GCCAGACACACCAAGGCTATTTGCCTATGAGAATGTTATCTAGACAG





CAGTGCACTCCCCTAAGTCTCTG





CTCAAAAAAAAAACAATTCTCGGCCCAAAGAAAACAATCAGAAGAAT





TCACTGATTTGACTAGAAACATC





AAGGAAGAATGAAGAACGTTGACTTTTTTCCAGGATAAATTATCTCT





GATGCTTCTTTAGATTTAAGAGT





TCATAATTCCATCCACTGCTGAGAAATCTCCTCAAACCCAGAAGGTT





TAATCACTTCATCCCAAAAATGG





GATTGTGAATGTCAGCAAACCATAAAAAAAGTGCTTAGAAGTATTCC





TATAGAAATGTAAATGCAAGGTC





ACACATATTAATGACAGCCTGTTGTATTAATGATGGCTCCAGGTCAG





TGTCTGGAGTTTCATTCCATCCC





AGGGCTTGGATGTAAGGATTATACCAAGAGTCTTGCTACCAGGAGGG





CAAGAAGACCAAAACAGACAGAC





AAGTCCAGCAGAAGCAGATGCACCTGACAAAAATGGATGTATTAATT





GGCTCTATAAACTATGTGCCCAG





CACTATGCTGAGCTTACACTAATTGGTCAGACGTGCTGTCTGCCCTC





ATGAAATTGGCTCCAAATGAATG





AACTACTTTCATGAGCAGTTGTAGCAGGCCTGACCACAGATTCCCAG





AGGGCCAGGTGTGGATCCACAGG





ACTTGAGGTCAAAGTTCACAAAGATGAAGAATCAGGGTAGCTGACC





ATGTTTGGCAGATACTATAATGG





AGACACAGAAGTGTGCATGGCCCAAGGACAAGGACCTCCAGCCAGGC





TTCATTTATGCACTTGTGCTGCA





AAAGAAAAGTCTAGGTTTTAAGGCTGTGCCAGAACCCATCCCAATAA





AGAGACCGAGTCTGAAGTCACAT





TGTAAATCTAGTGTAGGAGACTTGGAGTCAGGCAGTGAGACTGGTGG





GGCACGGGGGGCAGTGGGTACTT





GTAAACCTTTAAAGATGGTTAATTCATTCAATAGATATTTATTAAGA





ACCTATGCGGCCCGGCATGGTGG





CTCACACCTGTAATCCCAGCACTTTGGGAGGCCAAGGTGGGTGGGTC





ATCTGAGGTCAGGAGTTCAAGAC





CAGCCTGGCCAACATGGTGAAACCCCATCTCTACTAAAGATACAAAA





ATTTGCTGAGCGTCGTGGTGTGC





ACCTGTAATCCCAGCTACTCGAGAGGCCAAGGCATGAGAATCGCTTG





AACCTGGGAGGTGGAGGTTGCAG





TGAGCTGAGATGGCACCACTGCACTCCGGCCTAGGCAACGAGAGCAA





AACTCCAATACAAACAAACAAAC





AAACACCTGTGCTAGGTCAGTCTGGCACGTAAGATGAACATCCCTAC





CAACACAGAGCTCACCATCTCTT





ATACTTAAGTGAAAAACATGGGGAAGGGGAAAGGGGAATGGCTGCTT





TTGATATGTTCCCTGACACATAT





CTTGAATGGAGACCTCCCTACCAAGTGATGAAAGTGTTGAAAAACTT





AATAACAAATGCTTGTTGGGCAA





GAATGGGATTGAGGATTATCTTGTCTCAGAAAGGCATTGTGAAGGAA





TTGAGCCAGATCTCTCTCCCTAC





TGCAAAACCCTATTGTAGTAAAAAAGTCTTCTTTACTATCTTAATAA





AACAGATATTGTGAGATTCAAAA





AAAAAAAAAAAA





229152_
chromosome
tgaagaaagttctcctcctgatca
>gi|50428928|ref|NM_152997.2|Homo sapiens
154.05


at
4 open
cagccatcttggcagtggctgttg
chromosome 4 open reading frame 7 (C4orf7),



reading
gtttcccagtct
mRNA



frame 7
ctcaagaccaggaacgagaaaaaa
TAAAACAGCTACAATATTCCAGGGCCAGTCACTTGCCATTTCTCATA




gaagtatcagtgacagcgatgaat
ACAGCGTCAGAGAGAAAGAACTG




tagcttcagggttttttgtgttcc
ACTGAAACGTTTGAGATGAAGAAAGTTCTCCTCCTGATCACAGCCAT




cttacccatatccatttcgcccac
CTTGGCAGTGGCTGTTGGTTTCC




ttccaccaattccatttccaagat
CAGTCTCTCAAGACCAGGAACGAGAAAAAAGAAGTATCAGTGACAGC




ttccatggtttagacgtaattttc
GATGAATTAGCTTCAGGGTTTTT




ctattccaatacctgaatctgccc
TGTGTTCCCTTACCCATATCCATTTCGCCCACTTCCACCAATTCCAT




ctacaactcccc
TTCCAAGATTTCCATGGTTTAGA




ttcctagcgaaaagtaaacaagaa
CGTAATTTTCCTATTCCAATACCTGAATCTGCCCCTACAACTCCCCT




ggaaaagtcacgataaacctggtc
TCCTAGCGAAAAGTAAACAAGAA




acctgaaattgaaattgagccact
GGAAAAGTCACGATAAACCTGGTCACCTGAAATTGAAATTGAGCCAC




tccttgaagaatcaaaattcctgt
TTCCTTGAAGAATCAAAATTCCT




taataaaagaaaaacaaatgtaat
GTTAATAAAAGAAAAACAAATGTAATTGAAATAGCACACAGCATTCT




tgaaatagcacacagcattctcta
CTAGTCAATATCTTTAGTGATCT




gtcaatatctttagtgatcttctt
TCTTTAATAAACTTGAAAGCAAAGATTTTGGTTTCTTAATTTCCACA




taata
AA




[Seq Id No 79]





236203_
Major histo-
atgtcaggtttgtacctaccacat
>gi|52426772|ref|NM_002122.3|Homo sapiens
38.77


at
compatibility
ttaaaatagggacttgaagaatta
major histocompatibility complex, class II, DQ



complex,
aacattttatta
alpha 1 (HLA-DQA1), mRNA



class II,
caaatgaagcacttcatgcacaga
ACAATTACTCTACAGCTCAGAACACCAACTGCTGAGGCTGCCTTGGG



DQ alpha 1
ctggcacatagtaagtagtcgata
AAGAGGATGATCCTAAACAAAGC




ggtgttaacaat
TCTGCTGCTGGGGGCCCTCGCTCTGACCACCGTGATGAGCCCCTGTG




ttgtgttattgttattttctggag
GAGGTGAAGACATTGTGGCTGAC




tccaactaacaaatcccacagtga
CACGTTGCCTCTTGTGGTGTAAACTTGTACCAGTTTTACGGTCCCTC




atgacatcacag
TGGCCAGTACACCCATGAATTTG




ggatgcaaccaacaagatccagaa
ATGGAGATGAGCAGTTCTACGTGGACCTGGAGAGGAAGGAGACTGCC




tatggaaacttctactagataaac
TGGCGGTGGCCTGAGTTCAGCAA




aactccatttct
ATTTGGAGGTTTTGACCCGCAGGGTGCACTGAGAAACATGGCTGTGG




tcagcaacaattcaagagagagag
CAAAACACAACTTGAACATCATG




agaagagaagctatacattttaaa
ATTAAACGCTACAACTCTACCGCTGCTACCAATGAGGTTCCTGAGGT




aggctgaagaaatatatgaaccaa
CACAGTGTTTTCCAAGTCTCCCG




atttgtatgaggcaatcagaaaaa
TGACACTGGGTCAGCCCAACACCCTCATTTGTCTTGTGGACAACATC




ctgacaccgactgtattaaggaat
TTTCCTCCTGTGGTCAACATCAC




tatctaattttagtgtggtaatga
ATGGCTGAGCAATGGGCAGTCAGTCACAGAAGGTGTTTCTGAGACCA




gattgctgttatgttttctaa
GCTTCCTCTCCAAGAGTGATCAT




[Seq Id No 80]
TCCTTCTTCAAGATCAGTTACCTCACCTTCCTCCCTTCTGCTGATGA





GATTTATGACTGCAAGGTGGAGC





ACTGGGGCCTGGACCAGCCTCTTCTGAAACACTGGGAGCCTGAGATT





CCAGCCCCTATGTCAGAGCTCAC





AGAGACTGTGGTCTGTGCCCTGGGGTTGTCTGTGGGCCTCATGGGCA





TTGTGGTGGGCACTGTCTTCATC





ATCCAAGGCCTGCGTTCAGTTGGTGCTTCCAGACACCAAGGGCCATT





GTGAATCCCATCCTGGAAGGGAA





GGTGCATCGCCATCTACAGGAGCAGAAGAATGGACTTGCTAAATGAC





CTAGCACTATTCTGTGGCCCGAT





TTATCATATCCCTTTTCTCCTCCAAATATTTCTCCTCTCACCTTTTC





TCTGGGACTTAAGCTGCTATATC





CCCTCAGAGCTCACAAATGCCTTTACATTCTTTCCCTGACCTCCTGA





TTTTTTTTTTCTTTTCTCAAATG





TTACCTACAAAGACATGCCTGGGGTAAGCCACCCGGCTACCTAATTC





CTCAGTAACCTCCATCTAAAATC





TCCAAGGAAGCAATAAATTCCTTTTATGAGATCTATGTCAAATTTTT





CCATCTTTCATCCAGGGCTGACT





GAAACTATGGCTAATAATTGGGGTACTCTTATGTTTCAATCCAATTT





AACCTCATTTCCCAGATCATTTT





TCATGTCCAGTAACACAGAAGCCACCAAGTACAGTATAGCCTGATAA





TATGTTGATTTCTTAGCTGACAT





TAATATTTCTTGCTTCCTTGTGTTCCCACCCTTGGCACTGCCACCCA





CCCCTCAATTCAGGCAACAATGA





AATTAATGGATACCGTCTGCCCTTGGCCCAGAATTGTTATAGCAAAA





ATTTTAGAACCAAAAAATAAGTC





TGTACTAATTTCAATGTGGCTTTTAAAAGTATGACAGAGAAATAAGT





TAGGATAAAGGAAATTTGAATCT





CA





236280_
Transcribe
aaaagatctctcactgggaaaaga
>gi|3807951|gb|AI225238.1|AI225238 qx12c04.x1
77.63


at
d locus
aaaagttatgcatttataaagtaa
NCI_CGAP_Lym12 Homo sapiens cDNA clone




ttaaactggttt
IMAGE: 2001126 3′, mRNA sequence




tccttgtactttattaatctgaat
AGCGGCCGCCCTTTTTTTTTTTTTTTGAATGTTTTTATATTTTTATG




ctaatggcacttccttacgagggt
TTTTTCTCTCTCACCACATTAGA




tttcagatgtgc
GATTCACATGTCAAAAAAAAAGTTCAAAGATTCCACTTAAATGGTAG




ttgtagttaatggcaacattatca
TCAAAATTAAAAGCATGTTGTTT




gaatgactacacagacagtcctac
AATTTGCCAACTATTCCATAAATCCTGTGCTTGAAGCACTACCTTTT




tctgaggagatg
ATCAACCACTTGAAAGGAAGGAA




actttggaagaaacccatttggaa
TATGAAGTGTGACTCTTGAGGATTGCAGTTCCATTTCTCCACAGACA




ctacacaccctgctatgtctgtgg
TAGCAGGGTGTGTAGTTCCAAAT




agaaatggaact
GGGTTTCTTCCAAAGTCATCTCCTCAGAGTAGGACTGTCTGAGTAGT




gcaatcctcaagagtcacacttca
CATTCTGATAATGTTGCCATTAA




tattccttcctttcaagtggttga
CTACAAGCACATCTGAGAACCCTCGTAAGGAAGTGCCATTAGATTCA




taaaaggtagtg
GA




cttcaagcacaggatttatggaat




agttggcaaattaaacaacatgct




ttttattttgac




tacca




[Seq Id No 81]





239237_
Amphiphysin
ttatcaccattaatccatgccagt
>gi|51466133|ref|XM_A99518.1|PREDICTED: Homo
25.87


at
(Stiff-Man
tatgtacagttttgcatgtttgtt

sapiens LOC442534 (LOC442534), mRNA




syndrome
ttttattttact
GGCCCAGCCCTAGGAGGGGGCAGTCCCACAGCAGGCTCACACCCTGC



with
cttttctctccttcattccctatt
CCTTCAGAGTTGCAGCAGCTAAT



breast
cctgttcccccataggtgcccagt
GCTGATGCCAGGACCTTGTCCTGCCAGGAAGCCTCTGATTAGGGCTG



cancer
ctaatgtatttg
TGAACCAACTTCCTTTTCACATC



128 kDa
atatctgtccttagagcctccgta
TGCAAGGACTCTGCTCTAAGCTCAAATTTTGCAGTTTCTGCTGTCAT



autoantigen)
tctgtgaagactagagtcatgcac
CACAGCTGGGAATGAGAAAGGGA




ttcatcacattt
AGGGGCTCCAGTTGGTCTCCCTCTGCCTCTGGAGCACACGTGGAGGA




cagtaacgatgggccgcatgtacc
CATGAGGCTTCCGCAGGAACAGC




acagtcccatgagatgatagaggt
TCTGAAAGCTGAGTTCTCGGGTCCCTGTGAAGGAGGGAAGCTTGCCT




gcagaaaaattcctgtcatctagt
GCCTTGGAGCGTGAAAAAGTCTT




gacatcgtagccatcataacatnn
GCTGGACAGAAGTCTCACGGTTTAAAACTGGGAAGGGAGAGGATTGA




caacacgactctcatttgtggtga
GATCACACTAGAATGCACAGAAA




ccctggtgtacacaaacctac
ATTCTT




[Seq Id No 82]





244413_
dendritic
atggctggagatgtagtctacgct
>gi|40548404|ref|NM_172004.2|Homo sapiens
12.75


at
cell-
gacatcaaaactgttcggacttcc
dendritic cell-associated lectin-1 (DCAL1),



associated
ccgttagaactc
mRNA



lectin-1
gcgtttccacttcagagatctgtt
ATGGTTAGTAATTTCTTCCATGTCATACAAGTATTCGAGAAATCTGC




tctttcaacttttctactgtccat
TACCTTGATTAGTAAGACTGAAC




aaatcatgtcct
ACATTGGTTTTGTCATTTATTCATGGAGGAAGTCCACCACCCACTTG




gccaaagactggaaggtgcataag
GGGAGCAGAAGGAAATTTGCCAT




ggaaaatgttactggattgctgaa
CTCAATTTACTTATCAGAAGTTTCTTTGCAGAAATATGATTGTCCCT




actaagaaatcttggaacaaaagt
TCAGTGGGACATCATTTGTGGTC




caaaatgactgtgccataaacaat
TTCTCTCTCTTTTTGATCTGTGCAATGGCTGGAGATGTAGTCTACGC




tcatatctcatggtgattcaagac
TGACATCAAAACTGTTCGGACTT




attactgctatggtgagatttaac
CCCCGTTAGAACTCGCGTTTCCACTTCAGAGATCTGTTTCTTTCAAC




atttagaggtgacagcatccccca
TTTTCTACTGTCCATAAATCATG




cactggcagtga
TCCTGCCAAAGACTGGAAGGTGCATAAGGGAAAATGTTACTGGATTG




attttttgtgctacaaacttggca
CTGAAACTAAGAAATCTTGGAAC




aaagtctgtgaaaagaagtttcaa
AAAAGTCAAAATGACTGTGCCATAAACAATTCATATCTCATGGTGAT




cttcatgtgtta
TCAAGACATTACTGCTATGGTGA




ttaact
GATTTAACATTTAGAGGTGACAGCATCCCCCACACTGGCAGTGAATT




[Seq Id No 83]
TTTTGTGCTACAAACTTGGCAAA





AGTCTGTGAAAAGAAGTTTCAACTTCATGTGTTATTAACTATACAAA





TATTAGTTGAATGAATTGTTGAA





TTACAAAAAAAAAAAAAAA





34210_
CD52
Taatcggctcactataggaatttg
>gi|68342029|ref|NM_001803.2|Homo sapiens CD52
31.41


at
antigen
cntcgaggccaagattcgnacgag
molecule (CD52), mRNA



(CAMPATH-1
aagaagcctccagacagccctgag
CTCCTGGTTCAAAAGCAGCTAAACCAAAAGAAGCCTCCAGACAGCCC



antigen)
atcacctaaaaagctgctaccaag
TGAGATCACCTAAAAAGCTGCTA




acagccacgaagatcctaccaaaa
CCAAGACAGCCACGAAGATCCTACCAAAATGAAGCGCTTCCTCTTCC




tgaagcgcttcctcttcctcctac
TCCTACTCACCATCAGCCTCCTG




tcaccatcagcctcctggttatgg
GTTATGGTACAGATACAAACTGGACTCTCAGGACAAAACGACACCAG




tacagatacaaactggactctcag
CCAAACCAGCAGCCCCTCAGCAT




gacaaaacgacaccagccaaacca
CCAGCAACATAAGCGGAGGCATITTCCTTTTCTTCGTGGCCAATGCC




gcagcccctcagcatacagcagca
ATAATCCACCTCTTCTGCTTCAG




tgagcggaggcattttccttttct
TTGAGGTGACACGTCTCAGCCTTAGCCCTGTGCCCCCTGAAACAGCT




tcgtggccaatgccataatccacc
GCCACCATCACTCGCAAGAGAAT




tcttctgcttcagttgaggtgaca
CCCCTCCATCTTTGGGAGGGGTTGATGCCAGACATCACCAGGTTGTA




cgtctcagccttagccctgtgccc
GAAGTTGACAGGCAGTGCCATGG




cctgaaacannnnnnnnnnnnnnn
GGGCAACAGCCAAAATAGGGGGGTAATGATGTAGGGGCCAAGCAGTG




nnnnagagaatcccctccatcttt
CCCAGCTGGGGGTCAATAAAGTT




gggaggggttgatgccagacatca
ACCCTTGTACTTGAAAAAAAAAAAAAAAAAAAA




ccaggttgtagaagttgacaggca




gtgccatggggncaacagccaaaa




taggggggtaatgatgtaggggcc




aagcagtgcccagctgggggtcaa




taaagttacccttgtacttg




[Seq Id No 84]
















TABLE 3A







List of 13 probe sets suitable for identify the genes listed in Table 3











Probe
Gene





Set ID
Symbol
Gene Title
Gene Sequences





204661_at
CD52
CD52 molecule ///
Acagccacgaagatcctaccaaaatgaagcgcttcctcttcctcctactcaccatcagcctcc





CD52 molecule
tggttatggtacagatacaaactggactctcaggacaaaacgacaccagccaaaccagcagcc





cctcagcatccagcagcatgagcggaggcattttccttttcttcgtggccaatgccataatcc





acctcttctgcttcagttgaggtgacacgtctcagccttagccctgtgccccctgaaacagct





gccaccatcactcgcaagagaatcccctccatctttgggaggggttgatgccagacatcacca





ggttgtagaagttgacaggcagtgccatgggggcaacagccaaaataggggggtaatgatgta





ggggccaagc





[Seq Id No 85]





205890_s_at
UBD
gamma-
Gatcttaaagccacggagaagcctctcatcttatggcattgacaaagagaagaccatccacct




aminobutyric acid
taccctgaaagtggtgaagcccagtgatgaggagctgcccttgtttcttgtggagtcaggtga




(GABA) B
tgaggcaaagaggcacctcctccaggtgcgaaggtccagctcagtggcacaagtgaaagcaat




receptor, 1 ///
gatcgagactaagacgggtataatccctgagacccagattgtgacttgcaatggaaagagact




ubiquitin D
ggaagatgggaagatgatggcagattacggcatcagaaagggcaacttactcttcctggcatc





ttattgtattggagggtgaccaccctggggatggggtgttggcaggggtcaaaaagcttattt





cttttaatctcttactcaacgaacacatcttctgatgatttcccaaaattaatgagaatgaga





tgagtagagtaagatttgggtgggatgggtaggatgaagtatattgcccaactctatgtttct





ttga





[Seq Id No 86]





206118_at
STAT4
signal transducer
Gctgacatcctgcgagactacaaagttattatggctgaaaacattcctgaaaaccctctgaag




and activator of
tacctatatcctgacattcccaaagacaaagccttcggtaaacactacagctctcagccttgc




transcription 4
gaagtttcaagaccaacagaaaggggtgacaaaggttatgttccttctgtttttatccccatc





tcaacaatccgaagtgattcaacagagccacattctccatcagaccttcttcccatgtctcca





agtgtgtatgcggtgttgagagaaaacctgagtcccacaacaattgaaactgcaatgaagtct





ccttattctgctgaatgacaggataaactctgacgcaccaagaaaggaagcaaatgaaaaagt





ttaaagactgttctttgcccaataaccacattttatttcttcagctttgtaaataccaggttc





taggaaatgtttgacatctgaagctctcttcacactcccgtggcactcctcaattgggag





[Seq Id No 87]





206666_at
GZMK
granzyme K
aaacctctcttagatctggaaccaaatgcaaggttactggctggggagccaccgatccagatt




(granzyme 3;
cattaagaccttctgacaccctgcgagaagtcactgttactgtcctaagtcgaaaactttgca




tryptase II) ///
acagccaaagttactacaacggcgacccttttatcaccaaagacatggtctgtgcaggagatg




granzyme K
ccaaaggccagaaggattcctgtaagggtgactcagggggccccttgatctgtaaaggtgtct




(granzyme 3;
tccacgctatagtctctggaggtcatgaatgtggtgttgccacaaagcctggaatctacaccct




tryptase II)
gttaaccaagaaataccagacttggatcaaaagcaaccttgtcccgcctcatacaaattaagtt





acaaataattttattggatgcacttgcttcttttttcctaatatgctcgcaggttagagttggg





tgtaagtaaagcagagcacatatggggtccatttttgcacttgta





[Seq Id No 88]





207651_at
GPR171
G protein-coupled
Ttgccttgtaattcgacagctctacagaaacaaagataatgaaaattacccaaatgtgaaaaa




receptor 171
ggctctcatcaacatacttttagtgaccacgggctacatcatatgctttgttccttaccacat





tgtccgaatcccgtataccctcagccagacagaagtcataactgattgctcaaccaggatttc





actcttcaaagccaaagaggctacactgctcctggctgtgtcgaacctgtgctttgatcctat





cctgtactatcacctctcaaaagcattccgctcaaaggtcactgagacttttgcctcacctaa





agagaccaaggctcagaaagaaaaattaagatgtgaaaataatgcataaaagacaggattttt





tgtgctaccaattctggccttactgga





[Seq Id No 89]





210038_at
PRKCQ
protein kinase C,
Aatccattcatcctgattgggcatgaaatccatggtcaagaggacaagtggaaagtgagaggg




theta
aaggtttgctagacaccttcgcttgttatcttgtcaagatagaaaagatagtatcatttcacc





cttgccagtaaaaacctttccatccacccattctcagcagactccagtattggcacagtcact





cactgccattctcacactataacaagaaaagaaatgaagtgcataagtctcctgggaaaagaa





ccttaaccccttctcgtgccatgactggtgatttcatgactcataagcccctccgtaggcatc





attcaagatcaatggcccatgcatgctgtttgcagca





[Seq Id No 90]





210972_x_at
TRA@
T cell receptor
Ggaacaagacttcaggtcacgctcgatatccagaaccctgaccctgccgtgtaccagct



///
alpha locus /// T
gagagactctaaatccagtgacaagtctgtctgcctattcaccgattttgattctcaaa



TRDV2
cell receptor
caaatgtgtcacaaagtaaggattctgatgtgtatatcacagacaaaactgtgctagac



///
delta variable 2
atgaggtctatggacttcaagagcaacagtgctgtggcctggagcaacaaatctgactt



TRAV20
/// T cell
tgcatgtgcaaacgccttcaacaacagcattattccagaagacaccttcttccccagcc



///
receptor alpha
cagaaagttcctgtgatgtcaagctggtcgagaaaagctttgaaacagatacgaaccta



TRAC
variable 20 /// T
aactttcaaaacctgtcagtgattgggttccgaatcctcctcctgaaagtggccgggtt




cell receptor
taatctgctcatgacgctgcggctgtggtccagctgagatctgcaagattgtaagacag




alpha constant
cctgtgctccct





[Seq Id No 91]





211144_x_at
TRGC2
T cell receptor
Aaatgatacactactgctgcagctcacaaacacctctgcatattacatgtacctcctcct



///
gamma constant 2
gctcctcaagagtgtggtctattttgccatcatcacctgctgtctgcttggaagaacggc



TRGV2
/// T cell
tttctgctgcaatggagagaaatcataacagacggtggcacaaggaggccatcttttcct



///
receptor gamma
catcggttattgtccctagaagcgtcttctgaggatctagttgggctttctttctgggtt



TRGV9
variable 2 /// T
tgggccatttcagttctcatgtgtgtactattctatcattattgtataatggttttcaaa



///
cell receptor
ccagtgggcacacagagaacctcagtctgtaataacaatgaggaatagccatggcgatct



TARP
gamma variable 9
ccagcaccaatctctccatgttttccacagctcctccagccaacccaaatagcgcctgct



///
/// TCR gamma
atagtgtagacagcctgcggcttctagccttgtccctctcttagtgttctttaatcagat



LOC642
alternate reading
aactgcctggaagcctttcattttacacgccc



083
frame protein III
[Seq Id No 92]




hypothetical




protein L0C642083





211796_s_at
TRBV21-1
T cell receptor
gccatcagaagcagagatctcccacacccaaaaggccacactggtgtgcctggccacaggtt



///
beta variable 21-
tctaccccgaccacgtggagctgagctggtgggtgaatgggaaggaggtgcacagtggggtc



TRBV19
1 /// T cell
agcacagacccgcagcccctcaaggagcagcccgccctcaatgactccagatactgcctgag



///
receptor beta
cagccgcctgagggtctcggccaccttctggcagaacccccgcaaccacttccgctgtcaag



TRBV5-
variable 19 /// T
tccagttctacgggctctcggagaatgacgagtggacccaggatagggccaaacctgtcacc



4 ///
cell receptor
cagatcgtcagcgccgaggcctggggtagagcagactgtggcttcacctccgagtcttacca



TRBV3-
beta variable 5-4
gcaaggggtcctgtctgccaccatcctctatgagatcttgctagggaaggccaccttgtatg



1 ///
/// T cell
ctgtgctggtcagtgccctcgtgctgatggccatggtcaagagaaagga



TRBC1
receptor beta
[Seq Id No 93]




variable 3-1 ///




T cell receptor




beta constant 1




/// similar to T-




cell receptor




beta chain V




region CTL-L17




precursor





213193_x_at
TRBV19
T cell receptor
Tgactccagatactgcctgagcagccgcctgagggtctcggccaccttctggcagaaccg



///
beta variable 19
cccgcaaccacttccctgtcaagtccagttctacgggctctcggagaatgacgagtggac



TRBC1
/// T cell
ccaggatagggccaaacccgtcacccagatcgtcagcgccgaggcctggggtagagcaga




receptor beta
ctgtggctttacctcggtgtcctaccagcaaggggtcctgtctgccaccatcctctatga




variable 19 /// T
gatcctgctagggaaggccaccctgtatgctgtgctggtcagcncccttgtgttgatggc




cell receptor
catggtcaagagaaaggatttctgaaggcagccctggaagtggagttaggagcttctaac




beta constant 1
ccgtcatggtttcaatacacattcttcttttgccagcgcttctgaagagctgctctcacc




/// T cell
tctctgcatcccaatagatatccccctatgtgcatgcacacctgcacactcacggctgaa




receptor beta
atctccctaacccagggggaccttagcatgcctaagtga




constant 1
[Seq Id No 94]





213539_at
CD3D
CD3d molecule,
gggaacactgctctcagacattacaagactggacctgggaaaacgcatcctggacccacg




delta (CD3-TCR
aggaatatataggtgtaatgggacagatatatacaaggacaaagaatctaccgtgcaagt




complex)
tcattatcgaatgtgccagagctgtgtggagctggatccagccaccgtggctggcatcat





tgtcactgatgtcattgccactctgctccttgctttgggagtcttctgctttgctggaca





tgagactggaaggctgtctggggctgccgacacacaagctctgttgaggaatgaccaggt





ctatcagcccctccgagatcgagatgatgctcagtacagccaccttggaggaaactgggc





tcggaacaagtgaacctgagactggtggcttctagaagcagccattaccaactgtacct





[Seq Id No 95]





217147_s_at
TRAT1
T cell receptor
Tctcctttctcaccaatgggcaatagcccataattgaaataaatttctgattgaaaggt




associated
ataggaaacattaaaatgcattactaagagaagtaatataattttcttacaaagtattt




transmembrane
ttcccaaagatagctttactatttcaaaaattgtcaaattaatgcatgctccttacaac




adaptor 1
aaacaaatatcaaaaagagtttaggaattctactagccagagatagtcacttggagaaa





ctttctatatatccttctaaatatttttctgggcatgctcatgtatgtacatcagttgt





ttctttttattttgaaccaaaaatgtggtttcttttgtacacattacttaaactttctt





tccagtcaacaatatattgtggatttattttcactgttatatttaactatatataaata





cgcatatattgtaattttaatgtctgcttagcaccccactgataaccaaatcacag





[Seq Id No 96]





34210_at
CD52
CD52 molecule
Taatcggctcactataggaatttgcntcgaggccaagattcgnacgagnnngttcaaaa





gcagctaaaccaaaagaagcctccagacagccctgagatcacctaaaaagctgctacca





agacagccacgaagatcctaccaaaatgaagcgcttcctcttcctcctactcaccatca





gcctcctggttatggtacagatacaaactggactctcaggacaaaacgacaccagccaa





accagcagcccctcagcatccagcagcatgagcggaggcattttccttttcttcgtggc





caatgccataatccacctcttctgcttcagttgaggtgacacgtctcagccttagccct





gtgccccctgaaacannnnnnnnnnnnnnnnnnnagagaatcccctccatctttgggag





gggttgatgccagacatcaccaggttgtagaagttgacaggcagtgccatggggncaac





agccaaaataggggggtaatgatgtaggggccaagcagtgcccagctgggggtcaataa





agttacccttgtacttg





[Seq Id No 97]
















TABLE 4A







Table linking probe set id and the gene list of Table 4.









Probe Set ID
Gene Symbol
Gene Name





218802_at
FLJ20647
NA (not applicable)


224774_s_at
NAV1
neuron navigator 1


207651_at
GPR171
G protein-coupled receptor 171


205392_s_at
CCL14
chemokine (C-C motif) ligand 14


1555229_a_at
C1S
complement component 1, s subcomponent


209774_x_at
CXCL2
chemokine (C—X—C motif) ligand 2


211796_s_at
TRBV3-1
T cell receptor beta variable 3-1


210972_x_at
TRDV2
T cell receptor delta variable 2


210251_s_at
RUFY3
RUN and FYVE domain containing 3


225502_at
DOCK8
dedicator of cytokinesis 8


204224_s_at
GCH1
GTP cyclohydrolase 1 (dopa-responsive dystonia)


218950_at
CENTD3
centaurin, delta 3


218322_s_at
ACSL5
acyl-CoA synthetase long-chain family member 5


228094_at
AMICA1
adhesion molecule, interacts with CXADR antigen 1


204116_at
IL2RG
interleukin 2 receptor, gamma (severe combined




immunodeficiency)


202643_s_at
TNFAIP3
tumor necrosis factor, alpha-induced protein 3


209606_at
PSCDBP
pleckstrin homology, Sec7 and coiled-coil domains, binding




protein


205225_at
ESR1
estrogen receptor 1


213193_x_at
TRBC1
T cell receptor beta constant 1


204661_at
CD52
CD52 antigen (CAMPATH-1 antigen)


216920_s_at
LOC442535
NA


210915_x_at
TRBV19
T cell receptor beta variable 19


226218_at
IL7R
interleukin 7 receptor


209670_at
TRAC
T cell receptor alpha constant


209949_at
NCF2
neutrophil cytosolic factor 2 (65 kDa, chronic granulomatous




disease, autosomal 2)


226697_at
LOC92689
NA


206666_at
GZMK
c(“granzyme K (granzyme 3”, “tryptase II)”)


235831_at
NA
NA


1555630_a_at
RAB34
RAB34, member RAS oncogene family


207977_s_at
DPT
dermatopontin


1558290_a_at
PVT1
Pvt1 oncogene homolog, MYC activator (mouse)


215806_x_at
TRGC2
T cell receptor gamma constant 2


64064_at
GIMAP5
GTPase, IMAP family member 5


34210_at
CD52
CD52 antigen (CAMPATH-1 antigen)


213539_at
CD3D
CD3d antigen, delta polypeptide (TiT3 complex)


232313_at
TMEM132C
transmembrane protein 132C


201502_s_at
NFKBIA
nuclear factor of kappa light polypeptide gene enhancer in B-




cells inhibitor, alpha


211902_x_at
TRA@
T cell receptor alpha locus


217147_s_at
TRAT1
T cell receptor associated transmembrane adaptor 1


211144_x_at
LOC442535
NA


224710_at
RAB34
RAB34, member RAS oncogene family


209795_at
CD69
CD69 antigen (p60, early T-cell activation antigen)


232843_s_at
DOCK8
dedicator of cytokinesis 8


218805_at
GIMAP5
GTPase, IMAP family member 5


204057_at
IRF8
interferon regulatory factor 8


214470_at
KLRB1
killer cell lectin-like receptor subfamily B, member 1


236280_at
NA
NA


201474_s_at
ITGA3
integrin, alpha 3 (antigen CD49C, alpha 3 subunit of VLA-3




receptor)


235421_at
MAP3K8
mitogen-activated protein kinase kinase kinase 8


228532_at
C1orf162
chromosome 1 open reading frame 162


205890_s_at
UBD
ubiquitin D


209813_x_at
TRGV9
T cell receptor gamma variable 9


224772_at
NAV1
neuron navigator 1


224451_x_at
ARHGAP9
Rho GTPase activating protein 9


226117_at
TIFA
NA


213068_at
DPT
dermatopontin


1569942_at
NA
NA


219243_at
GIMAP4
GTPase, IMAP family member 4


202957_at
HCLS1
hematopoietic cell-specific Lyn substrate 1


218764_at
PRKCH
protein kinase C, eta


206118_at
STAT4
signal transducer and activator of transcription 4


236203_at
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 1


206170_at
ADRB2
adrenergic, beta-2-, receptor, surface


239237_at
NA
NA


214450_at
CTSW
cathepsin W (lymphopain)


201497_x_at
MYH11
myosin, heavy polypeptide 11, smooth muscle


219777_at
GIMAP6
GTPase, IMAP family member 6


211654_x_at
HLA-DQB1
major histocompatibility complex, class II, DQ beta 1


205758_at
CD8A
CD8 antigen, alpha polypeptide (p32)


202644_s_at
TNFAIP3
tumor necrosis factor, alpha-induced protein 3


1558034_s_at
CP
ceruloplasmin (ferroxidase)


223235_s_at
SMOC2
SPARC related modular calcium binding 2


232234_at
C20orf24
chromosome 20 open reading frame 24


1559584_a_at
C16orf54
chromosome 16 open reading frame 54


205831_at
CD2
CD2 antigen (p50), sheep red blood cell receptor


203812_at
SLIT3
slit homolog 3 (Drosophila)


222780_s_at
BAALC
brain and acute leukemia, cytoplasmic


218145_at
TRIB3
tribbles homolog 3 (Drosophila)


242881_x_at
LOC440160
NA


1558972_s_at
C6orf190
chromosome 6 open reading frame 190


229723_at
TAGAP
T-cell activation GTPase activating protein


235391_at
FAM92A1
family with sequence similarity 92, member A1


219938_s_at
PSTPIP2
proline-serine-threonine phosphatase interacting protein 2


212587_s_at
PTPRC
protein tyrosine phosphatase, receptor type, C


210982_s_at
HLA-DRA
major histocompatibility complex, class II, DR alpha


211200_s_at
EFCAB2
EF-hand calcium binding domain 2


210260_s_at
TNFAIP8
tumor necrosis factor, alpha-induced protein 8


228869_at
SLIC1
NA


205987_at
CD1C
CD1c antigen


213888_s_at
TRAF3IP3
TRAF3 interacting protein 3


212671_s_at
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 1


242986_at
NAV1
neuron navigator 1


212999_x_at
HLA-DQB1
major histocompatibility complex, class II, DQ beta 1


212588_at
PTPRC
protein tyrosine phosphatase, receptor type, C


212592_at
IGJ
immunoglobulin J polypeptide, linker protein for




immunoglobulin alpha and mu polypeptides


203471_s_at
PLEK
pleckstrin


209671_x_at
TRA@
T cell receptor alpha locus


228054_at
TMEM44
transmembrane protein 44


216191_s_at
TRA@
T cell receptor alpha locus


205419_at
EBI2
Epstein-Barr virus induced gene 2 (lymphocyte-specific G




protein-coupled receptor)


220330_s_at
SAMSN1
SAM domain, SH3 domain and nuclear localisation signals, 1


213008_at
KIAA1794
KIAA1794


201425_at
ALDH2
aldehyde dehydrogenase 2 family (mitochondrial)


1552613_s_at
CDC42SE2
CDC42 small effector 2


205696_s_at
GFRA1
GDNF family receptor alpha 1


211339_s_at
ITK
IL2-inducible T-cell kinase


208894_at
HLA-DRA
major histocompatibility complex, class II, DR alpha


228071_at
GIMAP7
GTPase, IMAP family member 7


222496_s_at
FLJ20273
NA


206687_s_at
PTPN6
protein tyrosine phosphatase, non-receptor type 6


210375_at
PTGER3
prostaglandin E receptor 3 (subtype EP3)


219440_at
RAI2
retinoic acid induced 2


208450_at
LGALS2
lectin, galactoside-binding, soluble, 2 (galectin 2)


203665_at
HMOX1
heme oxygenase (decycling) 1


227995_at
NA
NA


227346_at
ZNFN1A1
zinc finger protein, subfamily 1A, 1 (Ikaros)


205159_at
CSF2RB
colony stimulating factor 2 receptor, beta, low-affinity




(granulocyte-macrophage)


205559_s_at
PCSK5
proprotein convertase subtilisin/kexin type 5


212886_at
CCDC69
coiled-coil domain containing 69


1552612_at
CDC42SE2
CDC42 small effector 2


205488_at
GZMA
granzyme A (granzyme 1, cytotoxic T-lymphocyte-associated




serine esterase 3)


217767_at
C3
complement component 3


208296_x_at
TNFAIP8
tumor necrosis factor, alpha-induced protein 8


223484_at
C15orf48
chromosome 15 open reading frame 48


204070_at
RARRES3
retinoic acid receptor responder (tazarotene induced) 3


214719_at
LOC283537
NA


209687_at
CXCL12
chemokine (C—X—C motif) ligand 12 (stromal cell-derived




factor 1)


224773_at
NAV1
neuron navigator 1


231882_at
NA
NA


215223_s_at
SOD2
superoxide dismutase 2, mitochondrial


232617_at
CTSS
cathepsin S


210554_s_at
CTBP2
C-terminal binding protein 2


219528_s_at
BCL11B
B-cell CLL/lymphoma 11B (zinc finger protein)


207861_at
CCL22
chemokine (C-C motif) ligand 22


222592_s_at
ACSL5
acyl-CoA synthetase long-chain family member 5


1554966_a_at
DOC1
NA


204204_at
SLC31A2
solute carrier family 31 (copper transporters), member 2


219926_at
POPDC3
popeye domain containing 3


204135_at
DOC1
NA


217995_at
SQRDL
sulfide quinone reductase-like (yeast)


230233_at
RASGEF1B
RasGEF domain family, member 1B


227265_at
FGL2
fibrinogen-like 2


228372_at
C10orf128
chromosome 10 open reading frame 128


204912_at
IL10RA
interleukin 10 receptor, alpha


219454_at
EGFL6
EGF-like-domain, multiple 6


206295_at
IL18
interleukin 18 (interferon-gamma-inducing factor)


226219_at
ARHGAP30
Rho GTPase activating protein 30


218736_s_at
PALMD
palmdelphin


223322_at
RASSF5
Ras association (RalGDS/AF-6) domain family 5


209603_at
GATA3
GATA binding protein 3


204687_at
DKFZP564O0823
NA


222895_s_at
BCL11B
B-cell CLL/lymphoma 11B (zinc finger protein)


201010_s_at
TXNIP
thioredoxin interacting protein


226818_at
DTX4
deltex 4 homolog (Drosophila)


208335_s_at
DARC
Duffy blood group, chemokine receptor


213566_at
RNASE6
ribonuclease, RNase A family, k6


205685_at
CD86
CD86 antigen (CD28 antigen ligand 2, B7-2 antigen)


201531_at
ZFP36
zinc finger protein 36, C3H type, homolog (mouse)


202391_at
BASP1
brain abundant, membrane attached signal protein 1


201804_x_at
CKAP1
cytoskeleton associated protein 1


206082_at
HCP5
HLA complex P5


206204_at
GRB14
growth factor receptor-bound protein 14


228563_at
GJA7
gap junction protein, alpha 7, 45 kDa (connexin 45)


219054_at
FLJ14054
NA


205844_at
VNN1
vanin 1


203741_s_at
ADCY7
adenylate cyclase 7


223280_x_at
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


205624_at
CPA3
carboxypeptidase A3 (mast cell)


209193_at
PIM1
pim-1 oncogene


210072_at
CCL19
chemokine (C-C motif) ligand 19


226068_at
SYK
spleen tyrosine kinase


216155_at
NAV1
neuron navigator 1


205484_at
SIT1
signaling threshold regulating transmembrane adaptor 1


228812_at
NA
NA


219368_at
NAP1L2
nucleosome assembly protein 1-like 2


206407_s_at
CCL13
chemokine (C-C motif) ligand 13


203761_at
SLA
Src-like-adaptor


236295_s_at
NOD3
NA


206099_at
PRKCH
protein kinase C, eta


217143_s_at
TRD@
T cell receptor delta locus


218899_s_at
BAALC
brain and acute leukemia, cytoplasmic


229391_s_at
RP1-93H18.5
NA


219093_at
FLJ20701
NA


219710_at
SH3TC2
SH3 domain and tetratricopeptide repeats 2


206978_at
CCR2
chemokine (C-C motif) receptor 2


204655_at
CCL5
chemokine (C-C motif) ligand 5


211991_s_at
HLA-DPA1
major histocompatibility complex, class II, DP alpha 1


223922_x_at
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


208983_s_at
PECAM1
platelet/endothelial cell adhesion molecule (CD31 antigen)


222108_at
AMIGO2
adhesion molecule with Ig-like domain 2


1553102_a_at
CCDC69
coiled-coil domain containing 69


221698_s_at
CLEC7A
C-type lectin domain family 7, member A


206637_at
P2RY14
purinergic receptor P2Y, G-protein coupled, 14


226459_at
PIK3AP1
phosphoinositide-3-kinase adaptor protein 1


209613_s_at
ADH1B
alcohol dehydrogenase IB (class I), beta polypeptide


225802_at
TOP1MT
topoisomerase (DNA) I, mitochondrial


224859_at
CD276
CD276 antigen


209480_at
HLA-DQB1
major histocompatibility complex, class II, DQ beta 1


219213_at
JAM2
junctional adhesion molecule 2


208747_s_at
C1S
complement component 1, s subcomponent


224356_x_at
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


226625_at
TGFBR3
transforming growth factor, beta receptor III (betaglycan,




300 kDa)


1554240_a_at
ITGAL
c(“integrin, alpha L (antigen CD11A (p180), lymphocyte




function-associated antigen 1”, “alpha polypeptide)”)


202948_at
IL1R1
interleukin 1 receptor, type I


219666_at
MS4A6A
membrane-spanning 4-domains, subfamily A, member 6A


215193_x_at
HLA-DRB1
major histocompatibility complex, class II, DR beta 1


232024_at
GIMAP2
GTPase, IMAP family member 2


1559263_s_at
ZC3H12D
zinc finger CCCH-type containing 12D


219737_s_at
PCDH9
protocadherin 9


222838_at
SLAMF7
SLAM family member 7


227983_at
MGC7036
NA


223809_at
RGS18
regulator of G-protein signalling 18


213831_at
HLA-DQA1
major histocompatibility complex, class II, DQ alpha 1


203416_at
CD53
CD53 antigen


226841_at
MPEG1
NA


228552_s_at
SSBP4
single stranded DNA binding protein 4


231262_at
NA
NA


206898_at
CDH19
cadherin 19, type 2


210835_s_at
CTBP2
C-terminal binding protein 2


227584_at
NAV1
neuron navigator 1


223059_s_at
FAM107B
family with sequence similarity 107, member B


221671_x_at
IGKC
immunoglobulin kappa constant


205786_s_at
ITGAM
integrin, alpha M (complement component 3 receptor 3




subunit)


216194_s_at
CKAP1
cytoskeleton associated protein 1


209312_x_at
HLA-DRB1
major histocompatibility complex, class II, DR beta 1


235639_at
CDH19
cadherin 19, type 2


233562_at
MGC16291
NA


232476_at
DDEF2
development and differentiation enhancing factor 2


202510_s_at
TNFAIP2
tumor necrosis factor, alpha-induced protein 2


222484_s_at
CXCL14
chemokine (C—X—C motif) ligand 14


207277_at
CD209
CD209 antigen


204724_s_at
COL9A3
collagen, type IX, alpha 3


239196_at
ANKRD22
ankyrin repeat domain 22


209734_at
NCKAP1L
NCK-associated protein 1-like


212977_at
CMKOR1
chemokine orphan receptor 1


204670_x_at
HLA-DRB5
major histocompatibility complex, class II, DR beta 5


208885_at
LCP1
lymphocyte cytosolic protein 1 (L-plastin)


209612_s_at
ADH1B
alcohol dehydrogenase IB (class I), beta polypeptide


233955_x_at
CXXC5
CXXC finger 5


228776_at
GJA7
gap junction protein, alpha 7, 45 kDa (connexin 45)


1553906_s_at
FGD2
FYVE, RhoGEF and PH domain containing 2


221760_at
MAN1A1
mannosidase, alpha, class 1A, member 1


223361_at
C6orf115
chromosome 6 open reading frame 115


229390_at
RP1-93H18.5
NA


203915_at
CXCL9
chemokine (C—X—C motif) ligand 9


223058_at
FAM107B
family with sequence similarity 107, member B


219789_at
NPR3
natriuretic peptide receptor C/guanylate cyclase C




(atrionatriuretic peptide receptor C)


205285_s_at
FYB
FYN binding protein (FYB-120/130)


203868_s_at
VCAM1
vascular cell adhesion molecule 1


204236_at
FLI1
Friend leukemia virus integration 1


224516_s_at
CXXC5
CXXC finger 5


202368_s_at
TRAM2
translocation associated membrane protein 2


224795_x_at
IGKC
immunoglobulin kappa constant


235238_at
SHC4
SHC (Src homology 2 domain containing) family, member 4


227791_at
SLC9A9
solute carrier family 9 (sodium/hydrogen exchanger), member 9


207238_s_at
PTPRC
protein tyrosine phosphatase, receptor type, C


204897_at
PTGER4
prostaglandin E receptor 4 (subtype EP4)


213975_s_at
LILRB1
leukocyte immunoglobulin-like receptor, subfamily B (with




TM and ITIM domains), member 1


228964_at
PRDM1
PR domain containing 1, with ZNF domain


228362_s_at
RP1-93H18.5
NA


244061_at
ARHGAP15
Rho GTPase activating protein 15


1553313_s_at
SLC5A3
solute carrier family 5 (inositol transporters), member 3


212538_at
DOCK9
dedicator of cytokinesis 9


226043_at
GPSM1
G-protein signalling modulator 1 (AGS3-like, C. elegans)


1405_i_at
CCL5
chemokine (C-C motif) ligand 5


204222_s_at
GLIPR1
GLI pathogenesis-related 1 (glioma)


221087_s_at
APOL3
apolipoprotein L, 3


203932_at
HLA-DMB
major histocompatibility complex, class II, DM beta


225895_at
SYNPO2
synaptopodin 2


221651_x_at
NA
NA


231929_at
NA
NA


229543_at
RP1-93H18.5
NA


211367_s_at
CASP1
caspase 1, apoptosis-related cysteine peptidase (interleukin 1,




beta, convertase)


210038_at
PRKCQ
protein kinase C, theta


205403_at
IL1R2
interleukin 1 receptor, type II


220066_at
CARD15
caspase recruitment domain family, member 15


1555812_a_at
ARHGDIB
Rho GDP dissociation inhibitor (GDI) beta


208306_x_at
HLA-DRB4
major histocompatibility complex, class II, DR beta 4


218854_at
SART2
squamous cell carcinoma antigen recognized by T cells 2


203523_at
LSP1
lymphocyte-specific protein 1


207992_s_at
AMPD3
adenosine monophosphate deaminase (isoform E)


228660_x_at
SEMA4F
sema domain, immunoglobulin domain (Ig), transmembrane




domain (TM) and short cytoplasmic domain, (semaphorin) 4F


218170_at
ISOC1
isochorismatase domain containing 1


1555759_a_at
CCL5
chemokine (C-C motif) ligand 5


227253_at
HPS3
Hermansky-Pudlak syndrome 3


211990_at
HLA-DPA1
major histocompatibility complex, class II, DP alpha 1


212998_x_at
HLA-DQB1
major histocompatibility complex, class II, DQ beta 1


204778_x_at
HOXB7
homeobox B7


204834_at
FGL2
fibrinogen-like 2


205039_s_at
ZNFN1A1
zinc finger protein, subfamily 1A, 1 (Ikaros)


232543_x_at
ARHGAP9
Rho GTPase activating protein 9


209710_at
GATA2
GATA binding protein 2


200612_s_at
AP2B1
adaptor-related protein complex 2, beta 1 subunit


201487_at
CTSC
cathepsin C


201939_at
PLK2
polo-like kinase 2 (Drosophila)


203547_at
CD4
CD4 antigen (p55)


228376_at
GGTA1
glycoprotein, alpha-galactosyltransferase 1


207574_s_at
GADD45B
growth arrest and DNA-damage-inducible, beta


213560_at
GADD45B
growth arrest and DNA-damage-inducible, beta


219525_at
FLJ10847
NA


204411_at
KIF21B
kinesin family member 21B


200953_s_at
CCND2
cyclin D2


201859_at
PRG1
proteoglycan 1, secretory granule


223044_at
SLC40A1
solute carrier family 40 (iron-regulated transporter), member 1


213537_at
HLA-DPA1
major histocompatibility complex, class II, DP alpha 1


216841_s_at
SOD2
superoxide dismutase 2, mitochondrial


205081_at
CRIP1
cysteine-rich protein 1 (intestinal)


226382_at
LOC283070
NA


219519_s_at
SIGLEC1
sialic acid binding Ig-like lectin 1, sialoadhesin


1558586_at
ZNF11B
zinc finger protein 11B


217028_at
CXCR4
chemokine (C—X—C motif) receptor 4


217478_s_at
HLA-DMA
major histocompatibility complex, class II, DM alpha


204438_at
MRC1
mannose receptor, C type 1


211366_x_at
CASP1
caspase 1, apoptosis-related cysteine peptidase (interleukin 1,




beta, convertase)


204249_s_at
LMO2
LIM domain only 2 (rhombotin-like 1)


221081_s_at
DENND2D
DENN/MADD domain containing 2D


32128_at
CCL18
chemokine (C-C motif) ligand 18 (pulmonary and activation-




regulated)


220005_at
P2RY13
purinergic receptor P2Y, G-protein coupled, 13


209924_at
CCL18
chemokine (C-C motif) ligand 18 (pulmonary and activation-




regulated)


242458_at
ANGPTL1
angiopoietin-like 1


230391_at
NA
NA


213475_s_at
ITGAL
c(“integrin, alpha L (antigen CD11A (p180), lymphocyte




function-associated antigen 1”, “alpha polypeptide)”)


207458_at
C8orf51
chromosome 8 open reading frame 51


235306_at
GIMAP8
GTPase, IMAP family member 8


227780_s_at
NA
NA


205841_at
JAK2
Janus kinase 2 (a protein tyrosine kinase)


202687_s_at
TNFSF10
tumor necrosis factor (ligand) superfamily, member 10


212067_s_at
C1R
complement component 1, r subcomponent


236908_at
ACPL2
acid phosphatase-like 2


223827_at
TNFRSF19
tumor necrosis factor receptor superfamily, member 19


213652_at
PCSK5
proprotein convertase subtilisin/kexin type 5


219631_at
LRP12
low density lipoprotein-related protein 12


1557116_at
NA
NA


208981_at
PECAM1
platelet/endothelial cell adhesion molecule (CD31 antigen)


209685_s_at
PRKCB1
protein kinase C, beta 1


238488_at
IPO11
importin 11


1568736_s_at
DLGAP1
discs, large (Drosophila) homolog-associated protein 1


238439_at
PRKAR2B
protein kinase, cAMP-dependent, regulatory, type II, beta


205027_s_at
MAP3K8
mitogen-activated protein kinase kinase kinase 8


211742_s_at
EVI2B
ecotropic viral integration site 2B


202269_x_at
GBP1
guanylate binding protein 1, interferon-inducible, 67 kDa


204533_at
CXCL10
chemokine (C—X—C motif) ligand 10


229163_at
CAMK2N1
calcium/calmodulin-dependent protein kinase II inhibitor 1


1556579_s_at
MED12L
mediator of RNA polymerase II transcription, subunit 12




homolog (yeast)-like


201566_x_at
ID2
inhibitor of DNA binding 2, dominant negative helix-loop-helix




protein


201220_x_at
CTBP2
C-terminal binding protein 2


214677_x_at
IGLJ3
immunoglobulin lambda joining 3


235175_at
GBP4
guanylate binding protein 4


232001_at
LOC439949
NA


228427_at
FBXO16
F-box protein 16


214617_at
PRF1
perforin 1 (pore forming protein)


202369_s_at
TRAM2
translocation associated membrane protein 2


202625_at
LYN
v-yes-1 Yamaguchi sarcoma viral related oncogene homolog


213618_at
CENTD1
centaurin, delta 1


209970_x_at
CASP1
caspase 1, apoptosis-related cysteine peptidase (interleukin 1,




beta, convertase)


218035_s_at
FLJ20273
NA


206715_at
TFEC
transcription factor EC


1563473_at
PPP1R16B
protein phosphatase 1, regulatory (inhibitor) subunit 16B


204118_at
CD48
CD48 antigen (B-cell membrane protein)


201137_s_at
HLA-DPB1
major histocompatibility complex, class II, DP beta 1


230538_at
SHC4
SHC (Src homology 2 domain containing) family, member 4


1568822_at
GTPBP5
GTP binding protein 5 (putative)


229625_at
GBP5
guanylate binding protein 5


212233_at
MAP1B
microtubule-associated protein 1B


209202_s_at
EXTL3
exostoses (multiple)-like 3


209083_at
CORO1A
coronin, actin binding protein, 1A


205226_at
PDGFRL
platelet-derived growth factor receptor-like


227640_s_at
RP9
retinitis pigmentosa 9 (autosomal dominant)


223168_at
RHOU
ras homolog gene family, member U


1553132_a_at
MTAC2D1
membrane targeting (tandem) C2 domain containing 1


214038_at
CCL8
chemokine (C-C motif) ligand 8


219505_at
CECR1
cat eye syndrome chromosome region, candidate 1


214669_x_at
IGKC
immunoglobulin kappa constant


233123_at
SLC40A1
solute carrier family 40 (iron-regulated transporter), member 1


209195_s_at
ADCY6
adenylate cyclase 6


204846_at
CP
ceruloplasmin (ferroxidase)


204642_at
EDG1
endothelial differentiation, sphingolipid G-protein-coupled




receptor, 1


239744_at
RGS3
regulator of G-protein signalling 3


206545_at
CD28
CD28 antigen (Tp44)


228339_at
NA
NA


218739_at
ABHD5
abhydrolase domain containing 5


224358_s_at
MS4A7
membrane-spanning 4-domains, subfamily A, member 7


1559425_at
PRKCH
protein kinase C, eta


231577_s_at
GBP1
guanylate binding protein 1, interferon-inducible, 67 kDa


231032_at
LOC286071
NA


207655_s_at
BLNK
B-cell linker


242546_at
NA
NA


211066_x_at
PCDHGC3
protocadherin gamma subfamily C, 3


216714_at
CCL13
chemokine (C-C motif) ligand 13


1562031_at
JAK2
Janus kinase 2 (a protein tyrosine kinase)


212763_at
CAMSAP1L1
calmodulin regulated spectrin-associated protein 1-like 1


205440_s_at
NPY1R
neuropeptide Y receptor Y1


227458_at
CD274
CD274 antigen


226303_at
PGM5
phosphoglucomutase 5


204613_at
PLCG2
phospholipase C, gamma 2 (phosphatidylinositol-specific)


202688_at
TNFSF10
tumor necrosis factor (ligand) superfamily, member 10


221477_s_at
SOD2
superoxide dismutase 2, mitochondrial


201236_s_at
BTG2
BTG family, member 2


205569_at
LAMP3
lysosomal-associated membrane protein 3


215121_x_at
IGLC1
immunoglobulin lambda constant 1 (Mcg marker)


202255_s_at
SIPA1L1
signal-induced proliferation-associated 1 like 1


215051_x_at
AIF1
allograft inflammatory factor 1


209138_x_at
IGLC2
immunoglobulin lambda constant 2 (Kern-Oz-marker)


232311_at
B2M
beta-2-microglobulin


1555756_a_at
CLEC7A
C-type lectin domain family 7, member A


221756_at
MGC17330
NA


238544_at
IGF1R
insulin-like growth factor 1 receptor


204512_at
HIVEP1
human immunodeficiency virus type I enhancer binding protein 1


230728_at
FKBP14
FK506 binding protein 14, 22 kDa


201720_s_at
LAPTM5
lysosomal associated multispanning membrane protein 5


223395_at
ABI3BP
ABI gene family, member 3 (NESH) binding protein


200905_x_at
HLA-E
major histocompatibility complex, class I, E


202207_at
ARL4C
ADP-ribosylation factor-like 4C


207076_s_at
ASS
argininosuccinate synthetase


211368_s_at
CASP1
caspase 1, apoptosis-related cysteine peptidase (interleukin 1,




beta, convertase)


204628_s_at
ITGB3
integrin, beta 3 (platelet glycoprotein IIIa, antigen CD61)


207540_s_at
SYK
spleen tyrosine kinase


213603_s_at
RAC2
ras-related C3 botulinum toxin substrate 2 (rho family, small




GTP binding protein Rac2)


1557222_at
NA
NA


206804_at
CD3G
CD3g antigen, gamma polypeptide (TiT3 complex)


209542_x_at
IGF1
insulin-like growth factor 1 (somatomedin C)


228858_at
NA
NA


207843_x_at
CYB5A
cytochrome b5 type A (microsomal)


223924_at
TTC25
tetratricopeptide repeat domain 25


1552497_a_at
SLAMF6
SLAM family member 6


241701_at
ARHGAP21
Rho GTPase activating protein 21


213819_s_at
FLOT1
flotillin 1


213095_x_at
AIF1
allograft inflammatory factor 1


228153_at
IBRDC2
IBR domain containing 2


213007_at
KIAA1794
KIAA1794


217525_at
OLFML1
olfactomedin-like 1


204220_at
GMFG
glia maturation factor, gamma


203508_at
TNFRSF1B
tumor necrosis factor receptor superfamily, member 1B


217629_at
NA
NA


226659_at
DEF6
differentially expressed in FDCP 6 homolog (mouse)


200904_at
HLA-E
major histocompatibility complex, class I, E


206571_s_at
MAP4K4
mitogen-activated protein kinase kinase kinase kinase 4


232746_at
CMKOR1
chemokine orphan receptor 1


1563461_at
NA
NA


204233_s_at
CHKA
choline kinase alpha


226865_at
NA
NA


227361_at
HS3ST3B1
heparan sulfate (glucosamine) 3-O-sulfotransferase 3B1


204923_at
CXorf9
chromosome X open reading frame 9


204774_at
EVI2A
ecotropic viral integration site 2A


202270_at
GBP1
guanylate binding protein 1, interferon-inducible, 67 kDa


243099_at
NFAM1
NFAT activating protein with ITAM motif 1


242874_at
NA
NA


229127_at
ATP5J
ATP synthase, H+ transporting, mitochondrial F0 complex,




subunit F6


224771_at
NAV1
neuron navigator 1


215379_x_at
IGLC2
immunoglobulin lambda constant 2 (Kern-Oz-marker)


222142_at
CYLD
cylindromatosis (turban tumor syndrome)


229367_s_at
GIMAP6
GTPase, IMAP family member 6


212713_at
MFAP4
microfibrillar-associated protein 4


214023_x_at
TUBB2B
tubulin, beta 2B


203413_at
NELL2
NEL-like 2 (chicken)


236583_at
NA
NA


212657_s_at
IL1RN
interleukin 1 receptor antagonist


227231_at
KIAA1211
NA


244023_at
SYK
spleen tyrosine kinase


206134_at
ADAMDEC1
ADAM-like, decysin 1


204894_s_at
AOC3
amine oxidase, copper containing 3 (vascular adhesion protein




1)


204502_at
SAMHD1
SAM domain and HD domain 1


218002_s_at
CXCL14
chemokine (C—X—C motif) ligand 14


205421_at
SLC22A3
solute carrier family 22 (extraneuronal monoamine transporter),




member 3


215561_s_at
IL1R1
interleukin 1 receptor, type I


217138_x_at
IGLV3-25
immunoglobulin lambda variable 3-25


1556185_a_at
NA
NA


219681_s_at
RAB11FIP1
RAB11 family interacting protein 1 (class I)


205251_at
PER2
period homolog 2 (Drosophila)


224896_s_at
TTL
tubulin tyrosine ligase


209899_s_at
SIAHBP1
NA


201721_s_at
LAPTM5
lysosomal associated multispanning membrane protein 5


241671_x_at
FLJ22536
NA


218499_at
RP6-
NA



213H19.1


235804_at
NA
NA


207677_s_at
NCF4
neutrophil cytosolic factor 4, 40 kDa


227609_at
EPSTI1
epithelial stromal interaction 1 (breast)


227035_x_at
LOC441212
NA


206385_s_at
ANK3
ankyrin 3, node of Ranvier (ankyrin G)


1565602_at
PCDH9
protocadherin 9


228908_s_at
C21orf86
chromosome 21 open reading frame 86


223952_x_at
DHRS9
dehydrogenase/reductase (SDR family) member 9


38149_at
ARHGAP25
Rho GTPase activating protein 25


235688_s_at
TRAF4
TNF receptor-associated factor 4


214181_x_at
LST1
leukocyte specific transcript 1


222725_s_at
PALMD
palmdelphin


1555852_at
TAP1
transporter 1, ATP-binding cassette, sub-family B (MDR/TAP)


210319_x_at
MSX2
msh homeobox homolog 2 (Drosophila)


220485_s_at
SIRPG
signal-regulatory protein gamma
















TABLE 5







Primers and probes used for Q-PCR in standard 96 well plates











Gene






name
Forward primers
Reverse primers
TaqMan Probes





IL7R
TCC-TAC-CAG-CCT-TTG-CCT-CTT
CCA-TAC-TTG-GCT-TTT-CTG-AAG-CA
FAM-CTT-CAA-TGT-GGT-TTC-






CAT-GGG-MGB





CD3D
GTT-GAG-GAA-TGA-CCA-GGT-CTA-
AAG-GTG-GCT-GTA-CTG-AGC-ATC-A
FAM-CCT-CCG-AGA-TCG-AG-



TCA-G

MGB





CD52
TCA-GCC-TCC-TGG-TTA-TGG-TAC-
TGG-TTT-GGC-TGG-TGT-CGT-T
FAM-CAA-ACT-GGA-CTC-TCA-



AG

GGA-C-MGB





UBD
TGA-GGA-GCT-GCC-CTT-GTT-TC
CTG-GAG-GAG-GTG-CCT-CTT-TG
FAM-CAT-CAC-CTG-ACT-CCA-





CA-MGB





GPR171
GAA-GTC-ATA-ACT-GAT-TGC-TCA-
GAC-ACA-GCC-AGG-AGC-AGT-GTA-G
FAM-TCA-CTC-TTC-AAA-GCC-



ACC-A

AAA-GA-MGB





GMZK
GTC-TGT-GCA-GGA-GAT-GGC-AA
GGG-CCC-CCT-GAG-TCA-CC
FAM_TTA-CAG-GAA-TCC-TGG-





C_MGB





PRKCQ
ATC-CAT-GGT-CAA-GAG-GAC-AAG-
GAC-AAG-ATA-ACA-AGC-GAA-GGT-GTC
FAM_CAA-ACC-TTC-CCT-CTC-



TGG-A

ACT_MGB





STAT4
GTC-CCA-CAA-CAA-TTG-AAA-CTG-
GTG-CGT-CAG-AGT-TTA-TCC-TGT-CAT
FAM_TGA-AGT-CTC-CTT-ATT-



C

CTG-CT_MGB





TRDV2
GGT-CGA-GAA-AAG-CTT-TGA-AAC-
GGA-ACC-CAA-TCA-CTG-ACA-GGT-T
FAM_ACG-AAC-CTA-AAC-TTT-



AG

C_MGB





TRAT1
AAG-CCA-CCC-CAT-CTG-CAC
CTG-TGA-TCA-AGT-GAG-GCG-TAG
FAM_CAA-CCA-ATG-AAA-CAC-





AGA-TG_MGB





TRBV19
GAG-GCC-TGG-GGT-AGA-GCA-G
AGA-GGA-TGG-TGG-CAG-ACA-GG
FAM_TGT-CCT-ACC-AGC-AAG-





GG_MGB





CD69
AAT-CAT-AGC-TCT-CAT-TGC-CTT-
TGT-CTG-ATG-GCA-TTG-AGA-ATG-TG
FAM_CCA-ATA-CAA-TTG-TCC-



ATC-AG

AGG-CC_MGB





INDO1
CCA-GCA-GAC-TGC-TGG-TGG-A
GGC-ATA-TAT-CTT-CTC-ATG-TCC-TGG-A
FAM_ACA-TGC-TGC-TCA-GTT-





C_MGB





H3F3A
CAG-CTA-TCG-GTG-CTT-TGC-AG
GAT-AGC-ACA-CAG-GTT-GGT-GTC-TTC
FAM_CAA-GTG-AGG-CCT-ATC-





T_MGB





CD45R
GAG-ATG-CCT-GAT-GGT-TCA-AGT-
TTC-TTC-AAA-CTG-ATT-GTA-TTC-CAC-C
FAM_CAG-TAC-ATC-TTG-ATC-



AGA-G

CAT-C_MGB





CD45RO
GGC-AAA-GCC-CAA-CAC-CTT-C
CAG-AAG-GGC-TCA-GAG-TGG-TTG-T
FAM_TGC-CTA-CCT-TAA-TGC-





C_MGB





FoxP3
CAC CTG GCT GGG AAA ATG G
GGAGCC CTT GTC GGA TGA T
FAM_CAA GGC TTC ATC TGT





G_MGB





CD20
CAT-ACA-ATC-TCT-GTT-CTT-GGG-
TCA-TTC-TCA-ACG-ATG-CCA-GCT-A
FAM_TCA-GTG-ATG-CTG-ATC-



CAT-T

TT_MGB





TLR9
CGC-CAG-ACC-CTC-TGG-AGA-A
GCC-TGC-ACC-AGG-AGA-GAC-A
FAM_TTC-TGC-CGC-AGC-G_MGB





ITGB3
AAG-TCC-ATC-CTG-TATG-TGG-
GAG-CAG-GAC-CAC-CAG-GAT-GT
FAM_AGT-GTC-CCA-AGG-GC_MGB



TAG-AAG-AG





TLR3
GGA-AAG-GCT-AGC-AGT-CAT-CCA
GTG-GAG-GAT-GCA-CAC-AGC-AT
FAM_ATG-AGA-CAG-ACT-TTG-





CC_MGB





ThR4
CCA-GAA-CTG-CAG-GTG-CTG-G
GGT-GGC-TTA-GGC-TCT-GAT-ATG-C
FAM_CCA-GGT-GTG-AAA-TCC-





AGA-CA_MGB











TLR7
Assay-on-demand Hs00152971_m1 (Applied Biosystens)





TLR10
Assay-on-demand Hs01675179_m1 (Applied Biosystems)


variant 1





IRF1
Assay-on-demand Hs00971965_m1 (Applied Biosystems)
















TABLE 6







Gene included into the TaqMan ® Immune Profiling Array












Gene
Target




Assay ID
Symbol
Exons
NCBI Gene Reference














Hs00174092_m1
IL1A
6
NM_000575, M15329, X02531, X02851, X56086, CR457414, BC035169, BC013142,






BT007014





Hs00174097_m1
IL1B
5
NM_000576, K02770, M15330, M54933, X02532, X56087, AF043335, BC008678,





CR407679, BT007213





Hs00174114_m1
1L2
2
NM_000586, U25676,,V00564,,X01586,,S82692, S77835, S77834, AF228636,





BC066255, BC066256, BC06





C066254, AY523040, BC070338 A14844





Hs00174117_m1
1L3
2
NM_000588, M17115, M14743, M20137, BC066274, BC066276, BC066272, BC066273,





BC069472





Hs00174122_m1
1L4
3
NM_172348, NM_000589, M13982, X81851, AF043336, BC066277, BC067514, BC067515,





BC070123, AB1





Hs00174200_m1
ILS
2
NM_000879, X12705, X04688, BC066282





Hs00174131_m1
1L6
3
NM_000600, X04403, M14584, M18403, M29150, X04430, X04602, M54894, S56892,





CR450296, BT019748





9749, A09363, BC015511





Hs00174202_m1
1L7
2
NM_000880, J04156, BC047698





Hs00174103_m1
1L8
1
NM_000584, M17017, M26383, Z11686, Y00787, CR542151, AK131067, BC013615,





BT007067





Hs00174125_m1
1L9
3
NM_000590, M30134, X17543, S63356, BC066284, BC066283, BC066285, BC066286





Hs99999901_s1
18S
1
X03205





Hs00174086_m1
IL10
3
NM_000572, M57627, AF043333, AY029171, CR541993





Hs00168405_m1
IL12A
2
NM_000882, M65271, M65291, AF101062, AF180562, BG702253





Hs00233688_m1
IL12B
3
NM_002187, M65272, M65290, AF180563, BC067501, BC067498, BC067499, BC067500,





BC067502, BC07





Hs00174379_m1
IL13
1
NM_002188, L06801, X69079, BC096141, BC096139





Hs00174106_m1
1L15
1
NM_000585, U14407





Hs00174383_m1
IL17
2
NM_002190, Z58820, U32659, BC066251 ,BC066252, BC066253, BC067504, BC067503,





BC067505





Hs00155517_m1
IL18
4
NM_001562, D49950, U90434, AF077611, AY266351, CR541973, CR542001, AY044641,





BCO15863, BC00





Hs00234142_m1
CCL3
1
NM_002983, M25315, D63785, M23452, D00044, X03754, BC071834





Hs00171149_m1
CCL19
1
NM_006274, AB000887, U77180, U88321, CR456868, BC027968





Hs00234140_m1
CCL2
1
NM_002982, M24545, M28226, X14768, S69738, S71513, AV733621, BC009716,





BT007329





Hs00174575_m1
CCL5
2
NM_002985, M21121, AF043341, BC008600, AF266753





Hs00174150_m1
CCR2
1
NM_000647, U03882, BC074751





Hs99999919_m1
CCR4
N/A
NM_005508, BC069139, BC071751, BC074935





Hs00152917_m1
CCR5
2
NM_000579, U54994, BC038398





Hs00171054_m1
CCR7
1
NM_001838, L31581, L08176, BC035343, AK127810





Hs00171041_m1
CXCR3
1
NM_001504, X95876





Hs00171042_m1
CXCLI0
1
NM_001565, X02530, BC010954





Hs00171138_m1
CXCL11
1
NM_005409, Y15220, U59286, AF030514, AF002985, U66096, BC005292, AF352781,





BC012532, BT00678





Hs00174164_m1
CSF1
4
NM_172210, NM_172211, NM_172212, NM_000757, U22386, M37435, M76453, M64592,





M27087, X05825,





Hs00171266_m1
CSF2
3
NM_000758, M10663, M11220, AY720441, AF510855





Hs00357085_g1
CSF3
1
NM_172219, NM_000759, M17706, X03438, X03655, CR541891





Hs00234174_m1
STAT3
N/A
NM_139276, AJ012463, L29277, BC014482





Hs00174517_m1
NFKB2
6
NM_002502, U09609, X61498, X61499, S76638, BC002844, BT009769





Hs00395088_m1
IKBKB
8
NM_001556, AF029684, AF031416, AF080158, AB209090, BX648165





Hs00167894_m1
CD3E
1
NM_000733, X03884, B1910359





Hs00181217_m1
CD4
2
NM_000616, M12807, BT019791, BT019811, BC025782





Hs00233520_m1
CD8A
5
NM_171827, NM_001768, M12824, M12628, AY039664, AK124156, BC025715, AK097942





Hs00174333_m1
CD19
4
NM_001770, M21097, XI3312, BC006338, AK130657, BC052294





Hs00166229_m1
IL2RA
1
NM_000417, X01057, K03122, AK223313





Hs00174796_m1
CD28
2
NM_006139, J02988, BC093698





Hs00233552_m1
CD38
1
NM_001775, D84276, M34461, BC007964, CD688069





Hs00374176_m1
CD40
1
NM_152854, NM_001250, AJ300189, BC064518, BC012419, BM761221, AK222896





Hs00365634_g1
PTPRC
1
NM_080921, NM_080922, NM_080923, NM_002838, Y00062, BC017863, BC014239





Hs00154355_m1
CD68
6
NM_001251, S57235, BC015557, BT009923, AK222492, AK222514





Hs00175478_m1
CD80
2
NM_005191, M27533, AY197777, AY197778, AY081815, BC042665





Hs00199349_m1
CD86
2
NM_175862, NM_006889, L25259, U04343, CR541844, BC040261





Hs00175480_m1
CTLA4
1
NM_005214, L15006, BC069566, BC070162, BC074842, BC074893, AY209009,





AF414120, AF486806





Hs00163934_m1
CD40LG
4
NM_000074, L07414, X67878, Z15017, X68550, BC071754, BC074950





Hs00219575_m1
HLA-DRA
1
NM_019111, J00194, M60334, M35979, K01171, M60333, CR457013, BC071659,





BC032350





Hs99999917_m1
HLA-DRB1
N/A
NM_002124,M11161, M33600, X03069, DQ002917





Hs00203436_m1
TBX21
1
NM_013351, AF093098, AF241243, BC039739, AK223634





Hs00188346_m1
TNFRSF18
2
NM_148901, NM_148902, NM_004195, AF117297, AF125304, AF241229, BT019531,





BT019532, AY358877





Hs00359999_m1
ICOS
1
NM_012092, AB023135, AJ277832, BC028006, BC028210





Hs00167248_m1
NOS2A
11
NM_153292, NM_000625, AB022318, U05810, D26525, L24553, X73029, U20141,





U31511, S75615





Hs00153350_m1
BCL2
1
NM_000633, M13994, M14745, X06487, BC027258





Hs00169141_m1
BCL2L1
1
NM 001191, Z23116





Hs00180269_m1
BAX
3
NM_138761, NM_138763, NM_138765, NM_004324, L22473, L22474, U19599, AF247393,





AF250190, AJ586909, AJ586910, BM706954, BC014175, AJ417988





Hs00164932_m1
ICAM1
2
NM_000201, M24283, J03132, X06990, AF340038, AF340039, BC015969, AK130659, BT006854





Hs00174583_m1
SELP
1
NM_003005, M25322, BC068533





Hs00174057_m1
SELE
4
NM_000450, M24736, M30640





Hs00157965_m1
HM0X1
2
NM_002133, M23041, X06985, CR456505, CR541945, CR541968, BT019785, BC001491





Hs00153133_m1
PTGS2
5
NM_000963, M90100, L15326, AJ634912, AY462100, BC013734, AY151286





Hs00166915_m1
REN
1
NM_000537, CR536498, BC047752, BC033474





Hs00189742_m1
LRP2
17
NM_004525, U33837, AY265357, AY265358





Hs00411908_m1
MYH6
23
NM_002471, D00943





Hs00192564_m1
RPL3L
3
NM_005061, U65581, BC050413





Hs00167927_m1
CYP1A2
2
NM_000761, M55053, Z00036, AF182274, BC067425, BC067427, BC067424, BC067429,





BC067426, BC067428





Hs00167982_m1
CYP7A1
3
NM_000780, X56088, M93133





Hs00174143_m1
IFNG
1
NM_000619, X13274, V00543, X87308, BC070256, AY255837, AY255839, AY044154,





AF506749





Hs00169473_m1
PRF1
1
NM_005041, M28393, X13224, BC063043, BC047695






indicates data missing or illegible when filed














TABLE 7A







Geomean ratio between responder and non-responder groups












Gene
Ratio
LL
UL
















CCL5
7.83
3.09
19.84



FASLG
7.57
2.77
20.70



GNLY
8.82
3.61
21.56



GZMB
12.15
4.38
33.71



PRF1
11.07
4.85
25.28



IFNG
21.19
5.36
83.86



ICOS
13.44
3.44
52.51



TBX21
13.93
3.63
53.41



CD8A
11.60
4.22
31.90



CD3E
12.78
3.55
46.04



CXCL11
4.71
1.44
15.35



CXCL10
7.39
2.56
21.39



CXCR3
16.96
3.10
92.90



CD20
9.46
1.35
66.42



FOXP3
5.57
2.58
12.04



INDO
13.62
2.89
64.20



CD45Ro
4.02
1.84
8.79



CD45R
4.92
1.90
12.77



CD69
5.84
2.00
17.06



TRBV19
11.15
3.56
34.94



TRAT1
9.67
2.77
33.80



TRDV2
7.05
2.79
17.82



STAT4
3.41
1.75
6.65



PRKCQ
7.41
3.24
16.94



GMZK
9.20
2.60
32.49



GPR171
5.25
2.47
11.17



UBD
14.68
3.95
54.65



CD52
6.17
1.96
19.41



CD3D
10.03
3.07
32.77



IL7R
6.49
2.08
20.26



IRF1
5.54
2.83
10.83



TLR7
3.44
1.50
7.89

















TABLE 8 (BELOW)





Correlation matrix between 30 genes























Variable
Ig_IL7R
Ig_CD3D
Ig_CD52
Ig_UBD
Ig_GPR171
Ig_GMZK
Ig_PRKCQ
Ig_STAT4





Ig_IL7R
1.00
0.90
0.91
0.79
0.80
0.80
0.83
0.84


Ig_CD3D
0.90
1.00
0.94
0.93
0.89
0.93
0.88
0.88


Ig_CD52
0.91
0.94
1.00
0.80
0.83
0.82
0.84
0.83


Ig_UBD
0.79
0.93
0.80
1.00
0.82
0.91
0.80
0.82


Ig_GPR17
0.80
0.89
0.83
0.82
1.00
0.81
0.94
0.92


Ig_GMZK
0.80
0.93
0.82
0.91
0.81
1.00
0.83
0.85


Ig_PRKC
0.83
0.88
0.84
0.80
0.94
0.83
1.00
0.93


Ig_STAT4
0.84
0.88
0.83
0.82
0.92
0.85
0.93
1.00


Ig_TRDV2
0.88
0.96
0.91
0.86
0.94
0.87
0.93
0.89


Ig_TRAT1
0.92
0.96
0.89
0.89
0.85
0.95
0.89
0.91


Ig_TRBV1
0.92
0.99
0.95
0.91
0.90
0.92
0.91
0.89


Ig_CD69
0.85
0.92
0.92
0.80
0.80
0.88
0.87
0.87


Ig_CD45R
0.90
0.91
0.88
0.80
0.83
0.88
0.89
0.90


Ig_CD45R
0.84
0.91
0.83
0.83
0.86
0.90
0.89
0.88


Ig_INDO
0.76
0.89
0.79
0.91
0.81
0.87
0.83
0.83


Ig_FOXP3
0.78
0.80
0.75
0.74
0.83
0.78
0.91
0.84


Ig_CD20
0.87
0.82
0.88
0.69
0.67
0.74
0.74
0.74


Ig_CXCR3
0.84
0.89
0.82
0.85
0.74
0.86
0.79
0.78


Ig_CXCL1
0.65
0.84
0.68
0.92
0.76
0.83
0.72
0.73


Ig_CXCL1
0.54
0.74
0.60
0.81
0.75
0.74
0.71
0.77


Ig_CD3E
0.86
0.94
0.92
0.81
0.85
0.87
0.88
0.83


Ig_CD8A
0.77
0.93
0.82
0.89
0.88
0.91
0.91
0.87


Ig_TBX21
0.91
0.97
0.93
0.90
0.83
0.87
0.81
0.81


Ig_ICOS
0.85
0.94
0.87
0.89
0.78
0.87
0.78
0.79


Ig_IFNG
0.75
0.91
0.78
0.92
0.74
0.92
0.75
0.78


Ig_PRF1
0.76
0.92
0.82
0.89
0.88
0.91
0.91
0.87


Ig_GZMB
0.80
0.92
0.89
0.86
0.90
0.84
0.88
0.87


Ig_GNLY
0.74
0.87
0.84
0.77
0.85
0.83
0.88
0.82


Ig_FASLG
0.68
0.87
0.78
0.85
0.82
0.85
0.81
0.81


Ig_CCL5
0.77
0.93
0.83
0.91
0.83
0.92
0.81
0.82


















Variable
Ig_TRDV2
Ig_TRAT1
Ig_TRBV19
Ig_CD69
Ig_CD45R
Ig_CD45RO
Ig_INDO
Ig_FOXP3





Ig_IL7R
0.88
0.92
0.92
0.85
0.90
0.84
0.76
0.78


Ig_CD3D
0.96
0.96
0.99
0.92
0.91
0.91
0.89
0.80


Ig_CD52
0.91
0.89
0.95
0.92
0.88
0.83
0.79
0.75


Ig_UBD
0.86
0.89
0.91
0.80
0.80
0.83
0.91
0.74


Ig_GPR17
0.94
0.85
0.90
0.80
0.83
0.86
0.81
0.83


Ig_GMZK
0.87
0.95
0.92
0.88
0.88
0.90
0.87
0.78


Ig_PRKC
0.93
0.89
0.91
0.87
0.89
0.89
0.83
0.91


Ig_STAT4
0.89
0.91
0.89
0.87
0.90
0.88
0.83
0.84


Ig_TRDV2
1.00
0.92
0.97
0.88
0.91
0.91
0.83
0.85


Ig_TRAT1
0.92
1.00
0.96
0.92
0.95
0.93
0.87
0.82


Ig_TRBV1
0.97
0.96
1.00
0.93
0.92
0.91
0.87
0.83


Ig_CD69
0.88
0.92
0.93
1.00
0.92
0.90
0.80
0.79


Ig_CD45R
0.91
0.95
0.92
0.92
1.00
0.97
0.83
0.86


Ig_CD45R
0.91
0.93
0.91
0.90
0.97
1.00
0.86
0.83


Ig_INDO
0.83
0.87
0.87
0.80
0.83
0.86
1.00
0.80


Ig_FOXP3
0.85
0.82
0.83
0.79
0.86
0.83
0.80
1.00


Ig_CD20
0.76
0.83
0.83
0.86
0.78
0.69
0.66
0.65


Ig_CXCR3
0.84
0.88
0.89
0.83
0.82
0.82
0.78
0.73


Ig_CXCL1
0.79
0.77
0.81
0.69
0.68
0.75
0.82
0.64


Ig_CXCL1
0.72
0.68
0.70
0.67
0.64
0.70
0.74
0.59


Ig_CD3E
0.94
0.91
0.95
0.93
0.87
0.86
0.76
0.75


Ig_CD8A
0.92
0.89
0.93
0.88
0.85
0.87
0.82
0.81


Ig_TBX21
0.92
0.92
0.97
0.87
0.86
0.87
0.82
0.72


Ig_ICOS
0.89
0.90
0.93
0.87
0.83
0.84
0.78
0.68


Ig_IFNG
0.82
0.88
0.89
0.83
0.78
0.82
0.87
0.71


Ig_PRF1
0.91
0.89
0.92
0.88
0.84
0.88
0.83
0.81


Ig_GZMB
0.91
0.87
0.93
0.87
0.83
0.85
0.80
0.77


Ig_GNLY
0.86
0.83
0.87
0.87
0.80
0.82
0.78
0.78


Ig_FASLG
0.86
0.83
0.87
0.86
0.79
0.85
0.75
0.68


Ig_CCL5
0.88
0.88
0.92
0.87
0.80
0.84
0.81
0.68


















Variable
Ig_CD20
Ig_CXCR3
Ig_CXCL10
Ig_CXCL11
Ig_CD3E
Ig_CD8A
Ig_TBX21
Ig_ICOS





Ig_IL7R
0.87
0.84
0.65
0.54
0.86
0.77
0.91
0.85


Ig_CD3D
0.82
0.89
0.84
0.74
0.94
0.93
0.97
0.94


Ig_CD52
0.88
0.82
0.68
0.60
0.92
0.82
0.93
0.87


Ig_UBD
0.69
0.85
0.92
0.81
0.81
0.89
0.90
0.89


Ig_GPR17
0.67
0.74
0.76
0.75
0.85
0.88
0.83
0.78


Ig_GMZK
0.74
0.86
0.83
0.74
0.87
0.91
0.87
0.87


Ig_PRKC
0.74
0.79
0.72
0.71
0.88
0.91
0.81
0.78


Ig_STAT4
0.74
0.78
0.73
0.77
0.83
0.87
0.81
0.79


Ig_TRDV2
0.76
0.84
0.79
0.72
0.94
0.92
0.92
0.89


Ig_TRAT1
0.83
0.88
0.77
0.68
0.91
0.89
0.92
0.90


Ig_TRBV1
0.83
0.89
0.81
0.70
0.95
0.93
0.97
0.93


Ig_CD69
0.86
0.83
0.69
0.67
0.93
0.88
0.87
0.87


Ig_CD45R
0.78
0.82
0.68
0.64
0.87
0.85
0.86
0.83


Ig_CD45R
0.69
0.82
0.75
0.70
0.86
0.87
0.87
0.84


Ig_INDO
0.66
0.78
0.82
0.74
0.76
0.82
0.82
0.78


Ig_FOXP3
0.65
0.73
0.64
0.59
0.75
0.81
0.72
0.68


Ig_CD20
1.00
0.73
0.51
0.47
0.82
0.68
0.79
0.74


Ig_CXCR3
0.73
1.00
0.81
0.73
0.87
0.89
0.89
0.90


Ig_CXCL1
0.51
0.81
1.00
0.90
0.73
0.87
0.81
0.84


Ig_CXCL1
0.47
0.73
0.90
1.00
0.65
0.81
0.67
0.72


Ig_CD3E
0.82
0.87
0.73
0.65
1.00
0.91
0.92
0.91


Ig_CD8A
0.68
0.89
0.87
0.81
0.91
1.00
0.88
0.90


Ig_TBX21
0.79
0.89
0.81
0.67
0.92
0.88
1.00
0.95


Ig_ICOS
0.74
0.90
0.84
0.72
0.91
0.90
0.95
1.00


Ig_IFNG
0.67
0.82
0.89
0.73
0.83
0.89
0.87
0.90


Ig_PRF1
0.68
0.85
0.86
0.79
0.91
0.98
0.87
0.88


Ig_GZMB
0.71
0.85
0.80
0.75
0.90
0.92
0.89
0.90


Ig_GNLY
0.68
0.77
0.74
0.69
0.89
0.89
0.80
0.83


Ig_FASLG
0.63
0.78
0.83
0.81
0.87
0.93
0.85
0.88


Ig_CCL5
0.68
0.89
0.91
0.81
0.91
0.96
0.91
0.94


















Variable
Ig_IFNG
Ig_PRF1
Ig_GZMB
Ig_GNLY
Ig_FASLG
Ig_CCL5







Ig_IL7R
0.75
0.76
0.80
0.74
0.68
0.77



Ig_CD3D
0.91
0.92
0.92
0.87
0.87
0.93



Ig_CD52
0.78
0.82
0.89
0.84
0.78
0.83



Ig_UBD
0.92
0.89
0.86
0.77
0.85
0.91



Ig_GPR17
0.74
0.88
0.90
0.85
0.82
0.83



Ig_GMZK
0.92
0.91
0.84
0.83
0.85
0.92



Ig_PRKC
0.75
0.91
0.88
0.88
0.81
0.81



Ig_STAT4
0.78
0.87
0.87
0.82
0.81
0.82



Ig_TRDV2
0.82
0.91
0.91
0.86
0.86
0.88



Ig_TRAT1
0.88
0.89
0.87
0.83
0.83
0.88



Ig_TRBV1
0.89
0.92
0.93
0.87
0.87
0.92



Ig_CD69
0.83
0.88
0.87
0.87
0.86
0.87



Ig_CD45R
0.78
0.84
0.83
0.80
0.79
0.80



Ig_CD45R
0.82
0.88
0.85
0.82
0.85
0.84



Ig_INDO
0.87
0.83
0.80
0.78
0.75
0.81



Ig_FOXP3
0.71
0.81
0.77
0.78
0.68
0.68



Ig_CD20
0.67
0.68
0.71
0.68
0.63
0.68



Ig_CXCR3
0.82
0.85
0.82
0.77
0.78
0.89



Ig_CXCL1
0.89
0.86
0.80
0.74
0.83
0.91



Ig_CXCL1
0.73
0.79
0.75
0.69
0.81
0.81



Ig_CD3E
0.83
0.91
0.90
0.89
0.87
0.91



Ig_CD8A
0.89
0.98
0.92
0.89
0.93
0.96



Ig_TBX21
0.87
0.87
0.89
0.80
0.85
0.91



Ig_ICOS
0.90
0.88
0.90
0.83
0.88
0.94



Ig_IFNG
1.00
0.90
0.85
0.82
0.84
0.93



Ig_PRF1
0.90
1.00
0.94
0.92
0.93
0.95



Ig_GZMB
0.85
0.94
1.00
0.92
0.91
0.92



Ig_GNLY
0.82
0.92
0.92
1.00
0.86
0.88



Ig_FASLG
0.84
0.93
0.91
0.86
1.00
0.93



Ig_CCL5
0.93
0.95
0.92
0.88
0.93
1.00








indicates data missing or illegible when filed














TABLE 9A







18 best models obtained by logistic regression.











Predictor
R2 (%)
Chi-square Score















PRF1
55
16



IRF1
50
14



GZMB
46
14



GNLY
45
14



CD8A
46
14



PRKCQ
45
14



FOXP3
42
13



IFNG
52
13



CCL5
45
13



GPR171
41
12



TRBV19
44
11



CD3E
39
11



TBX21
44
11



FASLG
39
11



CXCL10
35
10



ICOS
39
10



CXCR3
35
9



CXCL11
22
6

















TABLE 10







Percentage of correct classification calculated using the


logistic regression model for some genes.










Model
Percentage of patients correctly classified







PRF1
86.6%



IRF1
89.7%



GZMB
82.8%



GNLY
82.8%



CD8A
82.8%



PRKCQ
89.7%



FOXP3
86.2%



IFNG
89.7%



CCL5
79.3%



GPR171
82.8%



TRBV19
86.2%



CDE3
75.9%



TBX21
82.8%



FASLG
75.9%



CXCL10
75.9%



ICOS
75.9%



CXR3
75.9%



CXCL11
72.4%




















TABLE 11A







Probe

Gene
Patient Identity Number



















Set
Gene Title
Symbol
14
52
66
37
16
13
55
56
5
60






















1555759_a_at
chemokine (C-C
CCL5
3.148
3.204
3.208
3.096
3.055
3.049
3.096
3.208
2.664
2.835



motif) ligand 5


1555834_at
Ubiquitin
UCHL1
7.911
2.4
2.324
5.169
5.06
2.401
3.561
2.627
4.868
2.401



carboxyl-



terminal esterase



L1 (ubiquitin



thiolesterase)


1558290_a_at
Pvt1 oncogene
PVT1
10.849
10.579
11.312
10.154
9.815
10.752
11.192
9.514
10.132
8.752



homolog, MYC
///



activator
LOC441378



(mouse) ///



LOC441378


1569942_at
CDNA clone

5.295
3.843
4.837
5.187
3.748
5.656
3.518
6.042
6.463
4.378



IMAGE: 4796388


204661_at
CD52 antigen
CD52
5.673
5.506
8.56
5.104
5.814
5.755
4.087
4.785
3.839
4.29



(CAMPATH-1



antigen) ///



CD52 antigen



(CAMPATH-1



antigen)


205890_s_at
ubiquitin D
UBD
4.731
7.003
9.226
4.138
3.687
8.103
3.242
6.126
3.231
7.706


206118_at
signal
STAT4
4.336
3.291
4.142
2.396
3.235
3.291
2.382
2.439
2.663
2.948



transducer and



activator of



transcription 4


206666_at
granzyme K
GZMK
6.187
5.357
7.079
2.659
2.571
5.033
2.225
3.383
2.567
3.104



(granzyme 3;



tryptase II) ///



granzyme K



(granzyme 3;



tryptase II)


207072_at
interleukin 18
IL18RAP
2.225
2.237
2.232
2.232
2.231
2.232
2.227
2.237
2.227
2.237



receptor



accessory



protein


207651_at
G protein-
GPR171
3.961
7.086
4.363
4.635
3.271
5.499
3.426
4.679
3.42
4.672



coupled receptor



171


209606_at
pleckstrin
PSCDBP
4.553
5.031
5.888
4.679
3.194
3.996
3.036
3.285
3.692
3.473



homology, Sec7



and coiled-coil



domains,



binding protein



/// pleckstrin



homology, Sec7



and coiled-coil



domains,



binding protein


209949_at
neutrophil
NCF2
6.058
6.184
3.286
6.305
4.585
3.866
4.672
3.294
4.457
3.802



cytosolic factor



2 (65 kDa,



chronic



granulomatous



disease,



autosomal 2)


210038_at
protein kinase
PRKCQ
2.362
2.18
2.415
2.178
2.364
2.358
2.577
2.181
2.179
2.191



C, theta


210629_x_at
leukocyte
LST1
5.649
6.559
6.72
5.368
5.367
3.893
3.484
6.134
4.775
5.283



specific



transcript 1


210972_x_at
T cell receptor
TRA@
4.292
6.159
7.116
3.791
4.059
6.091
5.234
5.057
4.291
4.842



alpha locus /// T
///



cell receptor
TRDV2



delta variable 2
///



/// T cell
TRAV20



receptor alpha
///



variable 20 /// T
TRAJ17



cell receptor
///



alpha joining 17
TRAC



/// T cell



receptor alpha



constant


211144_x_at
T cell receptor
TRGC2
2.887
2.261
4.452
2.257
2.193
3.203
2.347
2.453
2.332
2.196



gamma constant 2


211796_s_at
T cell receptor
TRBV21-
3.275
3.556
7.359
2.877
2.424
5.177
2.521
2.728
2.297
2.909



beta variable 21-
1 ///



1 /// T cell
TRBV19



receptor beta
///



variable 19 /// T
TRBV5-



cell receptor
4 ///



beta variable 5-4
TRBV3-



/// T cell
1 ///



receptor beta
TRBC1



variable 3-1 /// T



cell receptor



beta constant 1


212671_s_at
major
HLA-
8.1
7.479
6.553
8.223
6.574
7.356
7.347
5.884
6.068
5.558



histocompatibility
DQA1



complex, class
///



II, DQ alpha 1
HLA-



/// major
DQA2



histocompatibility



complex, class



II, DQ alpha 2


213193_x_at
T cell receptor
TRBV19
4.185
3.787
7.027
3.011
2.962
4.53
3.096
3.192
2.829
3.058



beta variable 19
///



/// T cell
TRBC1



receptor beta



variable 19 /// T



cell receptor



beta constant 1



/// T cell



receptor beta



constant 1


213539_at
CD3D antigen,
CD3D
3.179
4.399
7.52
3.352
3.182
5.87
2.8
3.183
3.178
3.626



delta



polypeptide



(TiT3 complex)


213560_at
Growth arrest
GADD45B
4.967
5.948
6.218
5.528
4.673
5.367
5.49
3.67
5.735
5.048



and DNA-



damage-



inducible, beta


216261_at
integrin, beta 3
ITGB3
8.21
2.588
4.394
3.536
6.237
4.486
3.088
6.729
6.77
2.606



(platelet



glycoprotein



IIIa, antigen



CD61)


217147_s_at
T cell receptor
TRAT1
3.914
4.251
5.453
2.871
2.292
4.283
2.327
2.887
2.277
2.308



associated



transmembrane



adaptor 1


217478_s_at
major
HLA-
8.989
8.655
8.599
9.516
8.621
7.051
8.181
8.129
7.41
8.04



histocompatibility
DMA



complex, class



II, DM alpha


218950_at
centaurin, delta 3
CENTD3
9.212
7.139
8.794
8.51
8.32
7.438
9.077
8.075
9.012
7.142


220330_s_at
SAM domain,
SAMSN1
4.712
4.228
5.117
4.641
4.804
3.557
2.702
4.246
3.492
3.828



SH3 domain and



nuclear



localisation



signals, 1


222934_s_at
C-type lectin
CLEC4E
5.382
4.219
2.931
2.753
2.511
3.812
4.494
2.512
3.917
3.417



domain family



4, member E


223827_at
tumor necrosis
TNFRSF19
4.16
3.985
5.98
2.86
5.91
3.239
4.301
6.268
5.029
4.931



factor receptor



superfamily,



member 19


224771_at
neuron
NAV1
7.893
6.773
7.352
7.998
8.385
7.571
7.077
7.277
6.956
7.304



navigator 1


224772_at
neuron
NAV1
10.827
9.319
9.458
9.799
10.771
10.304
9.47
9.943
9.752
9.998



navigator 1


224773_at
neuron
NAV1
8.959
7.241
7.742
9.332
9.582
8.051
8.427
8.479
7.795
7.564



navigator 1


224774_s_at
neuron
NAV1
7.288
6.204
7.292
8.109
7.683
6.486
7.056
5.947
6.406
6.181



navigator 1


227145_at
lysyl oxidase-
LOXL4
11.368
8.235
10.93
12.565
12.636
12.563
7.768
11.858
12.092
11.62



like 4


227584_at
Neuron
NAV1
11.735
10.222
10.601
10.533
11.778
11.041
10.121
11.247
10.732
11.00



navigator 1


227812_at
tumor necrosis
TNFRSF19
11.9
11.787
12.618
10.566
12.747
11.729
11.115
12.911
12.125
11.83



factor receptor



superfamily,



member 19


229723_at
T-cell activation
TAGAP
5.224
4.874
5.527
5.091
2.501
3.01
4.398
2.891
3.472
3.425



GTPase



activating



protein


232024_at
GTPase, IMAP
GIMAP2
8.489
7.321
7.275
6.411
7.83
6.861
6.317
8.172
7.42
7.119



family member 2


238544_at
Insulin-like
IGF1R
6.79
8.031
9.43
5.969
7.331
7.827
8.887
6.322
9.011
7.444



growth factor 1



receptor


242886_at
Chromosome 17
C17orf63
10.066
10.766
9.654
8.976
9.813
9.864
10.039
9.839
8.819
9.808



open reading



frame 63


242986_at
Neuron
NAV1
9.936
9.155
9.341
10.292
10.071
9.41
9.098
9.552
8.465
8.663



navigator 1


34210_at
CD52 antigen
CD52
6.58
6.581
9.446
5.799
6.518
6.798
4.246
6.008
3.469
5.289



(CAMPATH-1



antigen)






indicates data missing or illegible when filed

















TABLE 11B







Probe

Gene
Patient Identity Number














Set
Gene Title
Symbol
75
2
65
20
10





1555759_a_at
chemokine
CCL5
4.665
5.498
7.109
3.207
5.121



(C-C motif)



ligand 5


1555834_at
Ubiquitin
UCHL1
2.329
2.36
2.4
2.399
2.358



carboxyl-



terminal



esterase L1



(ubiquitin



thiolesterase)


1558290_a_at
Pvt1
PVT1
8.59
7.403
8.63
8.588
9.536



oncogene
///



homolog,
LOC441378



MYC



activator



(mouse) ///



LOC441378


1569942_at
CDNA clone

3.605
3.324
4.066
2.849
4.189



IMAGE: 4796388


204661_at
CD52 antigen
CD52
8.008
8.301
9.702
8.979
9.415



(CAMPATH-



1 antigen) ///



CD52 antigen



(CAMPATH-



1 antigen)


205890_s_at
ubiquitin D
UBD
11.687
10.159
11.582
7.52
9.692


206118_at
signal
STAT4
5.794
5.481
4.044
5.157
6.026



transducer



and activator



of



transcription 4


206666_at
granzyme K
GZMK
7.615
9.057
9.338
6.513
8.013



(granzyme 3;



tryptase II) ///



granzyme K



(granzyme 3;



tryptase II)


207072_at
interleukin 18
IL18RAP
4.76
2.358
2.233
3.154
2.235



receptor



accessory



protein


207651_at
G protein-
GPR171
8.491
8.969
8.37
6.884
8.501



coupled



receptor 171


209606_at
pleckstrin
PSCDBP
6.808
6.788
8.373
6.524
7.997



homology,



Sec7 and



coiled-coil



domains,



binding



protein ///



pleckstrin



homology,



Sec7 and



coiled-coil



domains,



binding



protein


209949_at
neutrophil
NCF2
6.928
6.845
7.973
5.572
5.428



cytosolic



factor 2



(65 kDa,



chronic



granulomatous



disease,



autosomal 2)


210038_at
protein
PRKCQ
4.981
4.768
2.406
2.836
6.907



kinase C,



theta


210629_x_at
leukocyte
LST1
7.078
6.711
6.926
5.831
6.424



specific



transcript 1


210972_x_at
T cell
TRA@
7.913
8.072
11.25
6.451
10.646



receptor
///



alpha locus
TRDV2



/// T cell
///



receptor delta
TRAV20



variable 2 ///
///



T cell
TRAJ17



receptor
///



alpha
TRAC



variable 20 ///



T cell



receptor



alpha joining



17 /// T cell



receptor



alpha



constant


211144_x_at
T cell
TRGC2
6.096
4.892
6.456
2.624
6.163



receptor



gamma



constant 2


211796_s_at
T cell
TRBV21-
7.924
8.11
10.708
6.84
9.737



receptor beta
1 ///



variable 21-1
TRBV19



/// T cell
///



receptor beta
TRBV5-



variable 19 ///
4 ///



T cell
TRBV3-



receptor beta
1 ///



variable 5-4
TRBC1



/// T cell



receptor beta



variable 3-1



/// T cell



receptor beta



constant 1


212671_s_at
major
HLA-
10.798
9.601
11.257
9.336
8.87



histocompatibility
DQA1



complex,
///



class II, DQ
HLA-



alpha 1 ///
DQA2



major



histocompatibility



complex,



class II, DQ



alpha 2


213193_x_at
T cell
TRBV19
7.553
7.871
10.191
6.704
9.248



receptor beta
///



variable 19 ///
TRBC1



T cell



receptor beta



variable 19 ///



T cell



receptor beta



constant 1 ///



T cell



receptor beta



constant 1


213539_at
CD3D
CD3D
8.208
8.038
9.64
7.257
8.387



antigen, delta



polypeptide



(TiT3



complex)


213560_at
Growth arrest
GADD45B
7.243
5.936
6.794
7.57
6.389



and DNA-



damage-



inducible,



beta


216261_at
integrin, beta
ITGB3
2.545
2.691
2.651
2.592
2.59



3 (platelet



glycoprotein



IIIa, antigen



CD61)


217147_s_at
T cell
TRAT1
6.748
6.139
8.028
5.044
7.377



receptor



associated



transmembrane



adaptor 1


217478_s_at
major
HLA-
10.873
10.838
11.541
9.389
10.193



histocompatibility
DMA



complex,



class II, DM



alpha


218950_at
centaurin,
CENTD3
7.911
7.983
5.552
6.866
7.456



delta 3


220330_s_at
SAM
SAMSN1
7.494
6.244
4.271
5.243
7.151



domain, SH3



domain and



nuclear



localisation



signals, 1


222934_s_at
C-type lectin
CLEC4E
6.912
6.523
6.984
5.384
4.588



domain



family 4,



member E


223827_at
tumor
TNFRSF19
3.043
3.308
2.721
2.855
3.48



necrosis



factor



receptor



superfamily,



member 19


224771_at
neuron
NAV1
6.378
7.607
6.624
6.24
6.483



navigator 1


224772_at
neuron
NAV1
9.184
10.073
8.059
7.897
8.937



navigator 1


224773_at
neuron
NAV1
7.427
7.781
5.878
5.855
6.881



navigator 1


224774_s_at
neuron
NAV1
5.706
7.087
5.432
5.724
5.939



navigator 1


227145_at
lysyl oxidase-
LOXL4
3.699
7.798
3.703
4.953
8.792



like 4


227584_at
Neuron
NAV1
10.236
10.828
8.45
9.758
9.512



navigator 1


227812_at
tumor
TNFRSF19
9.962
9.478
9.706
8.939
11.568



necrosis



factor



receptor



superfamily,



member 19


229723_at
T-cell
TAGAP
6.398
6.009
9.043
7.032
8.532



activation



GTPase



activating



protein


232024_at
GTPasc,
GIMAP2
9.137
9.127
8.794
7.948
9.093



IMAP family



member 2


238544_at
Insulin-like
IGF1R
7.023
6.644
6.255
4.359
6.899



growth factor



1 receptor


242886_at
Chromosome
C17orf63
9.338
10.004
7.65
7.978
8.744



17 open



reading frame



63


242986_at
Neuron
NAV1
8.777
8.689
8.154
6.863
8.461



navigator 1


34210_at
CD52 antigen
CD52
9.102
9.324
10.652
10.24
10.103



(CAMPATH-



1 antigen)













Probe
Patient Identity Number
















Set
19
23
26
27
38
8
67







1555759_a_at
3.656
4.159
4.664
5.256
5.411
3.034
3.11



1555834_at
2.398
2.463
2.401
2.4
2.4
5.041
2.40



1558290_a_at
8.46
9.384
9.409
8.504
8.57
10.616
9.90



1569942_at
2.198
3.972
3.61
3.392
2.944
5.832
4.38



204661_at
6.144
8.556
8.487
11.34
10.289
4.082
8.69



205890_s_at
8.088
9.801
12.384
10.657
10.131
3.178
9.54



206118_at
5.775
6.731
5.845
8.349
6.709
2.383
3.09



206666_at
7.564
8.532
8.921
8.337
9.328
2.305
6.371



207072_at
2.264
2.512
2.239
3.2
4.126
2.222
2.23



207651_at
8.037
8.578
10.668
10.834
9.404
3.046
6.32



209606_at
7.366
7.301
7.101
10.455
7.959
2.232
7.231



209949_at
6.643
7.499
6.281
6.48
7.213
3.405
7.449



210038_at
4.108
5.51
5.272
8.218
4.73
2.179
2.301



210629_x_at
6.69
7.323
6.834
7.058
8.828
3.779
7.287



210972_x_at
7.331
8.326
9.727
11.544
8.3
4.292
6.411



211144_x_at
2.689
6.279
7.941
7.365
6.31
2.189
2.64



211796_s_at
6.456
8.211
9.022
11.111
8.316
2.293
5.74



212671_s_at
9.39
9.435
10.008
10.974
10.757
2.679
7.61



213193_x_at
5.828
7.936
8.266
11.152
7.722
2.83
5.47



213539_at
6.635
8.381
9.075
10.519
8.841
2.311
6.07



213560_at
7.236
7.105
6.776
7.114
6.774
3.402
7.12



216261_at
2.553
2.609
4.561
2.622
2.557
6.05
2.60



217147_s_at
7.56
6.512
7.612
9.246
8.077
2.281
3.00



217478_s_at
9.475
10.475
9.998
11.266
10.161
7.109
9.33



218950_at
5.891
7.35
5.522
5.804
6.245
8.04
8.20



220330_s_at
6.458
7.429
8.583
8.421
7.405
2.325
6.71



222934_s_at
6.678
6.941
4.589
4.731
5.877
3.019
7.66



223827_at
2.8
2.854
2.977
2.796
3.43
4.669
2.99



224771_at
4.678
6.467
6.537
3.882
5.375
6.798
5.73



224772_at
8.214
8.963
9.472
7.529
7.742
9.418
8.41



224773_at
5.668
6.94
7.344
4.953
7.035
7.352
6.47



224774_s_at
3.907
6.432
6.166
5.262
5.989
6.48
5.91



227145_at
7.205
9.531
9.214
9.691
3.702
11.838
8.60



227584_at
8.8
10.254
10.798
8.769
9.367
10.568
9.56



227812_at
11.39
9.998
10.948
9.083
10.541
12.176
10.5



229723_at
5.424
7.084
6.786
10.798
7.081
3.21
5.29



232024_at
9.673
10.09
9.763
10.696
9.891
6.523
8.29



238544_at
5.442
6.574
4.359
5.264
3.677
9.187
5.44



242886_at
5.974
8.959
9.284
6.208
7.589
9.344
7.33



242986_at
5.136
8.727
8.749
4.83
5.92
8.296
6.75



34210_at
7.423
9.382
9.344
11.944
10.812
2.854
9.44








indicates data missing or illegible when filed














TABLE 14







Correlation of Patient Identity Numbers and Clinical Outcome


after MAGE Immunotherapy













Progressive
Stable
Mixed

Too



Disease
Disease
Responders
Responders
Early
















Patient
160
19
20
38
138


ID
30
77
67
136
91


No.
8
127
2
75
124



109
65
11
120
150



60
119
53
27
163



55
23
59
118
122



100
145
96



37

10



52

26/1



81



14



66



106



133



129



74



113



36



9



155



15



5



56



16



13



98



28



108



71



145



121



80



132



3



85



135



134



82



154



39
















APPENDIX A





R object of class nnet for neural network clinical outcome prediction of patients.







$n












[1]
489
2
1







$nunits











[1]
493











$nconn

























[1]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[19]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[37]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[55]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[73]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[91]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[109]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[127]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[145]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[163]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[181]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[199]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[217]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[235]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[253]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[271]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[289]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[307]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[325]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[343]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[361]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[379]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[397]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[415]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[433]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[451]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[469]
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0


[487]
0
0
0
0
0
490
980
983







$conn

























[1]
0
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17


[19]
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35


[37]
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53


[55]
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71


[73]
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89


[91]
90
91
92
93
94
95
96
97
98
99
100
101
102
103
104
105
106
107


[109]
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125


[127]
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143


[145]
144
145
146
147
148
149
150
151
152
153
154
155
156
157
158
159
160
161


[163]
162
163
164
165
166
167
168
169
170
171
172
173
174
175
176
177
178
179


[181]
180
181
182
183
184
185
186
187
188
189
190
191
192
193
194
195
196
197


[199]
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215


[217]
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
232
233


[235]
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251


[253]
252
253
254
255
256
257
258
259
260
261
262
263
264
265
266
267
268
269


[271]
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287


[289]
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305


[307]
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323


[325]
324
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341


[343]
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359


[361]
360
361
362
363
364
365
366
367
368
369
370
371
372
373
374
375
376
377


[379]
378
379
380
381
382
383
384
385
386
387
388
389
390
391
392
393
394
395


[397]
396
397
398
399
400
401
402
403
404
405
406
407
408
409
410
411
412
413


[415]
414
415
416
417
418
419
420
421
422
423
424
425
426
427
428
429
430
431


[433]
432
433
434
435
436
437
438
439
440
441
442
443
444
445
446
447
448
449


[451]
450
451
452
453
454
455
456
457
458
459
460
461
462
463
464
465
466
467


[469]
468
469
470
471
472
473
474
475
476
477
478
479
480
481
482
483
484
485


[487]
486
487
488
489
0
1
2
3
4
5
6
7
8
9
10
11
12
13


[505]
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31


[523]
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49


[541]
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67


[559]
68
69
70
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85


[577]
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103


[595]
104
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121


[613]
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139


[631]
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
156
157


[649]
158
159
160
161
162
163
164
165
166
167
168
169
170
171
172
173
174
175


[667]
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193


[685]
194
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211


[703]
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229


[721]
230
231
232
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247


[739]
248
249
250
251
252
253
254
255
256
257
258
259
260
261
262
263
264
265


[757]
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283


[775]
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301


[793]
302
303
304
305
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[676]
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[681]
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[686]
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[691]
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[696]
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[701]
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[706]
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[711]
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[716]
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[721]
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[726]
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[731]
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[736]
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[741]
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[746]
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[751]
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[756]
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[761]
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[766]
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[771]
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[776]
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[781]
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[786]
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[791]
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[796]
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[801]
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[806]
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[811]
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[816]
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[821]
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[826]
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[831]
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[836]
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[841]
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[846]
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[851]
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[856]
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[861]
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[866]
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[871]
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[876]
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[881]
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[886]
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[891]
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[896]
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[901]
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[906]
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[911]
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[916]
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[921]
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[926]
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[931]
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[936]
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[941]
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[946]
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[951]
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[956]
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[961]
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[966]
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[971]
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[976]
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[981]
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[,1]











$fitted.values










1
9.999958e−01



2
0.000000e+00



3
0.000000e+00



4
0.000000e+00



5
0.000000e+00



6
9.999958e−01



7
9.999958e−01



8
9.999958e−01



9
9.999958e−01



10
9.999958e−01



11
9.999958e−01



12
0.000000e+00



13
9.999958e−01



14
0.000000e+00



15
0.000000e+00



16
0.000000e+00



17
9.999958e−01



18
6.820198e−06



19
6.825022e−06



20
3.118923e−05



21
0.000000e+00



22
0.000000e+00



23
9.999958e−01



24
0.000000e+00



25
0.000000e+00



26
9.999958e−01



27
0.000000e+00



28
9.999958e−01



29
9.999958e−01



30
0.000000e+00



31
0.000000e+00







$residuals










1
4.189989e−06



2
0.000000e+00



3
0.000000e+00



4
0.000000e+00



5
0.000000e+00



6
4.189989e−06



7
4.189989e−06



8
4.189989e−06



9
4.189989e−06



10
4.189989e−06



11
4.189989e−06



12
0.000000e+00



13
4.189989e−06



14
0.000000e+00



15
0.000000e+00



16
0.000000e+00



17
4.189989e−06



18
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19
−6.825022e−06



20
−3.118923e−05



21
0.000000e+00



22
0.000000e+00



23
4.189989e−06



24
0.000000e+00



25
0.000000e+00



26
4.189989e−06



27
0.000000e+00



28
4.189989e−06



29
4.189989e−06



30
0.000000e+00



31
0.000000e+00











$lev








[1]
“NR” “R”












$call



nnet.formula(formula = f ~ .,



data = data, MaxNWts = 10000,



maxit = 250, size = 2, skip = FALSE,



rang = 0.7, decay = 0, Hess = FALSE,



trace = TRUE, abstol = 1e−04,



reltol = 1e−08, metric =



“euclidean”, subset = training)

















APPENDIX B





R object of class Ida for linear discriminant analysis clinical outcome


prediction of patients.


















NR
R











$prior










0.5862069
0.4137931







$counts










17
12











$scaling











LD1







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5.230642e−03



X209734_at
−5.196811e−03



X209774_x_at
2.951233e−02



X209795_at
−6.624457e−03



X209813_x_at
2.371992e−02



X209899_s_at
7.998200e−04



X209924_at
3.375216e−02



X209949_at
3.781916e−02



X209970_x_at
2.564418e−02



X210038_at
6.929319e−03



X210072_at
1.293525e−02



X210251_s_at
1.756383e−02



X210260_s_at
−1.082042e−03



X210319_x_at
−1.726655e−02



X210375_at
2.483769e−03



X210554_s_at
−2.077789e−02



X210835_s_at
−7.455480e−03



X210915_x_at
3.172003e−03



X210972_x_at
6.080266e−03



X210982_s_at
9.635875e−03



X211066_x_at
−1.164103e−02



X211144_x_at
4.992137e−02



X211200_s_at
−4.031722e−02



X211339_s_at
−8.002311e−03



X211366_x_at
3.593000e−02



X211367_s_at
6.231728e−02



X211368_s_at
2.045696e−02



X211654_x_at
2.874123e−02



X211742_s_at
−1.282275e−02



X211796_s_at
6.744624e−03



X211902_x_at
1.350420e−03



X211990_at
−1.552756e−02



X211991_s_at
−2.759634e−03



X212067_s_at
−9.461685e−03



X212233_at
8.400376e−03



X212538_at
7.226797e−03



X212587_s_at
−5.979921e−03



X212588_at
−7.824565e−04



X212592_at
3.516261e−03



X212657_s_at
2.978857e−02



X212671_s_at
−2.602076e−02



X212713_at
3.233683e−02



X212763_at
−3.275778e−03



X212886_at
3.683799e−03



X212977_at
9.877644e−03



X212998_x_at
5.090511e−03



X212999_x_at
3.695828e−02



X213007_at
−3.352605e−02



X213008_at
−4.189798e−03



X213068_at
2.658290e−02



X213095_x_at
1.421934e−02



X213193_x_at
2.914348e−03



X213475_s_at
−4.914118e−04



X213537_at
−8.357035e−03



X213539_at
7.487953e−03



X213560_at
−4.020759e−03



X213566_at
5.845149e−03



X213603_s_at
−5.088264e−03



X213618_at
1.305106e−02



X213652_at
8.548287e−03



X213819_s_at
8.196495e−03



X213831_at
1.631173e−02



X213888_s_at
8.134177e−05



X213975_s_at
−2.095655e−02



X214023_x_at
−2.237865e−02



X214038_at
2.389479e−02



X214181_x_at
−8.976012e−03



X214450_at
1.788553e−02



X214470_at
2.213217e−02



X214617_at
1.563590e−02



X214669_x_at
1.972879e−03



X214677_x_at
3.809399e−03



X224719_at
1.439531e−03



X215051_x_at
1.072135e−02



X215121_x_at
4.118073e−03



X215193_x_at
2.105556e−04



X215223_s_at
1.530709e−02



X215379_x_at
7.064224e−03



X215561_s_at
−2.385977e−02



X215806_x_at
1.767858e−02



X216155_at
−3.705145e−02



X216191_s_at
4.747897e−02



X216194_s_at
−4.006836e−02



X216714_at
2.405266e−02



X216841_s_at
8.716417e−03



X216920_s_at
3.911396e−03



X217028_at
5.128469e−03



X217138_x_at
9.357220e−03



X217143_s_at
7.546655e−03



X217147_s_at
−1.958024e−02



X217478_s_at
−1.327997e−02



X217525_at
−1.717356e−02



X217629_at
7.854937e−03



X217767_at
−5.238491e−03



X217995_at
−6.809023e−03



X218002_s_at
9.869321e−03



X218035_s_at
1.245016e−03



X218145_at
−3.291834e−02



X218170_at
−7.323517e−03



X218322_s_at
−8.250237e−03



X218499_at
5.140903e−04



X218736_s_at
2.138520e−02



X218739_at
2.714745e−03



X218764_at
−9.158772e−03



X218802_at
5.152377e−02



X218805_at
−2.574003e−03



X218854_at
3.989147e−03



X218899_s_at
−3.411423e−02



X218950_at
−4.336176e−02



X219054_at
4.975575e−03



X219093_at
2.082412e−02



X219213_at
−4.341432e−03



X219243_at
2.233332e−03



X219368_at
−1.134073e−03



X219440_at
2.580567e−02



X219454_at
3.065280e−02



X219505_at
5.933108e−03



X219519_s_at
2.660637e−02



X219525_at
4.320312e−03



X219528_s_at
1.066797e−02



X219631_at
−2.616546e−02



X219666_at
1.182519e−02



X219681_s_at
8.705075e−03



X219710_at
−1.046131e−02



X219737_s_at
−6.473357e−02



X219777_at
−6.023843e−03



X219789_at
8.550214e−03



X219926_at
−8.456673e−03



X219938_s_at
1.596546e−02



X220005_at
6.859902e−03



X220066_at
7.525339e−03



X220330_s_at
3.751801e−03



X220485_s_at
2.962480e−03



X221081_s_at
−4.394394e−03



X221087_s_at
8.161216e−03



X221477_s_at
1.240372e−02



X221651_x_at
1.118009e−02



X221671_x_at
5.247343e−03



X221698_s_at
−1.058842e−02



X221756_at
−1.209965e−02



X221760_at
−1.764419e−02



X222108_at
4.026916e−02



X222142_at
−3.508958e−02



X222484_s_at
−8.096999e−03



X222496_s_at
−4.133924e−03



X222592_s_at
1.511240e−02



X222725_s_at
2.808005e−02



X222780_s_at
−2.679162e−02



X222838_at
4.550716e−03



X222895_s_at
−2.841100e−02



X223044_at
5.255602e−02



X223058_at
9.381819e−03



X223059_s_at
8.539393e−03



X223168_at
−4.973917e−03



X223235_s_at
4.953002e−04



X223280_x_at
6.016285e−03



X223322_at
−1.188607e−02



X223361_at
−5.418802e−03



X223395_at
1.411881e−02



X223484_at
1.743558e−02



X223809_at
2.119400e−02



X223827_at
−1.852331e−02



X223922_x_at
8.293530e−03



X223924_at
−2.212120e−02



X223952_x_at
3.606709e−02



X224356_x_at
4.977366e−03



X224358_s_at
−9.225797e−04



X224451_x_at
−4.781080e−03



X224516_s_at
−1.494258e−02



X224710_at
−2.279989e−02



X224771_at
−1.243246e−02



X224772_at
−4.059490e−02



X224773_at
−7.626004e−03



X224774_s_at
−1.743111e−02



X224795_x_at
5.385788e−03



X224859_at
−1.540871e−02



X224896_s_at
−4.228341e−03



X225502_at
3.460051e−03



X225802_at
−2.887415e−02



X225895_at
4.741893e−03



X226043_at
1.277772e−02



X226068_at
5.224876e−03



X226117_at
2.490399e−02



X226218_at
−1.341873e−02



X226219_at
4.175131e−03



X226303_at
4.358878e−02



X226382_at
6.264514e−04



X226459_at
4.497883e−03



X226625_at
4.213244e−02



X226659_at
−4.064464e−03



X226697_at
−5.986636e−02



X226818_at
2.581249e−02



X226841_at
1.092228e−02



X226865_at
−2.335927e−02



X227035_x_at
8.655280e−03



X227231_at
−1.692593e−02



X227253_at
1.018350e−02



X227265_at
1.360205e−02



X227346_at
−1.295157e−02



X227361_at
−5.811243e−03



X227458_at
1.893847e−02



X227584_at
−2.425646e−02



X227609_at
3.029790e−02



X227640_s_at
−5.262288e−03



X227780_s_at
1.333635e−02



X227791_at
1.583168e−02



X227983_at
−1.027572e−02



X227995_at
−1.414606e−02



X228054_at
−1.428632e−03



X228071_at
−8.103128e−03



X228094_at
9.305227e−03



X228153_at
1.840560e−02



X228339_at
1.115556e−02



X228362_s_at
1.505306e−02



X228372_at
−1.233323e−02



X228376_at
3.005129e−03



X228427_at
1.441232e−02



X228532_at
−1.984789e−02



X228552_s_at
1.488213e−02



X228563_at
5.478160e−03



X228660_x_at
−3.321971e−03



X228776_at
1.735059e−02



X228812_at
2.966052e−02



X228858_at
8.798795e−03



X228869_at
1.576960e−02



X228908_s_at
1.715903e−02



X228964_at
1.578864e−02



X229127_at
2.437139e−02



X229163_at
−1.306446e−03



X229367_s_at
8.285081e−03



X229390_at
9.455414e−03



X229391_s_at
2.152998e−02



X229543_at
1.337527e−02



X229625_at
1.390034e−02



X229723_at
1.284379e−02



X230233_at
6.517225e−03



X230391_at
−1.165179e−02



X230538_at
−4.922326e−02



X230728_at
−3.921071e−02



X231032_at
1.220460e−02



X231262_at
8.401904e−03



X231577_s_at
−4.352510e−03



X231882_at
−1.597680e−02



X231929_at
−7.190517e−03



X232001_at
−2.527809e−02



X232024_at
1.562502e−02



X232234_at
1.979601e−02



X232311_at
−5.811767e−04



X232313_at
3.438576e−02



X232476_at
−1.156007e−02



X232543_x_at
−6.890048e−03



X232617_at
2.120826e−03



X232746_at
−1.032038e−02



X232843_s_at
−1.582714e−03



X233123_at
3.841746e−02



X233562_at
−6.149035e−02



X233955_x_at
−2.411061e−02



X235175_at
−8.822903e−03



X235238_at
−4.455537e−02



X235306_at
−1.163963e−02



X235391_at
9.692727e−03



X235421_at
−7.303012e−04



X235639_at
−3.367098e−02



X235688_s_at
−1.717805e−03



X235804_at
−1.564079e−03



X235831_at
2.675921e−03



X236203_at
−8.187551e−03



X236280_at
6.197497e−03



X236295_s_at
4.606321e−03



X236583_at
2.311931e−03



X236908_at
−2.109408e−02



X238439_at
3.286334e−02



X238488_at
2.932061e−02



X238544_at
1.183049e−03



X239196_at
4.987304e−02



X239237_at
3.319884e−02



X239744_at
−1.276710e−02



X241671_x_at
−6.586756e−03



X241701_at
−8.761918e−03



X242458_at
−1.194306e−02



X242546_at
4.355118e−03



X242874_at
5.607680e−03



X242881_x_at
−6.062508e−03



X242986_at
2.749620e−03



X243099_at
1.186699e−02



X244023_at
−1.018460e−02



X244061_at
1.229564e−03



X32128_at
2.935196e−02



X34210_at
3.776762e−03



X38149_at
4.937711e−04



X64064_at
−3.336735e−03













$lev



[1] “NR” “R”



$svd



[1] 7.995862



$N



[1] 29



$call



lda(formula = f ~ ., data = datatr)

















APPENDIX C





R object of class naiveBayes for naïve Bayes clinical outcome


prediction of patients.







$apriori


Y










NR
R







17
12















Y
[,1]
[,2]











tablestables$X1405_i_at


X1405_i_at











NR
−0.1639258
0.5851902



R
0.6748740
0.6631486







tables$X1552497_a_at


X1552497_a_at











NR
−0.3029996
0.6800071



R
0.6607734
0.8223674







tables$X1552612_at


X1552612_at











NR
−0.2523340
0.5485271



R
0.4450904
0.5434438







tables$X1552613_s_at


X1552613_s_at











NR
−0.2165343
0.5894093



R
0.4800677
0.4432806







tables$X1553102_a_at


X1553102_a_at











NR
−0.2474064
0.5834113



R
0.7071397
0.7121750







tables$X1553132_a_at


X1553132_a_at











NR
−0.1377405
0.3946696



R
0.4961300
0.4509575







tables$X1553313_s_at


X1553313_s_at











NR
0.2393526
0.6100254



R
−0.3838373
0.3940848







tables$X1553906_s_at


X1553906_s_at











NR
−0.3915645
0.6474232



R
0.2882052
0.3076821







tables$X1554240_a_at


X1554240_a_at











NR
0.01780307
0.4865912



R
0.88377535
0.8029798







tables$X1554966_a_at


X1554966_a_at











NR
−0.1357018
0.3678133



R
0.6662706
0.6833596







tables$X1555229_a_at


X1555229_a_at











NR
−0.2263265
0.3882668



R
0.5467680
0.4361597







tables$X1555630_a_at


X1555630_a_at











NR
0.2005512
0.3578418



R
−0.6088957
0.7683101







tables$X1555756_a_at


X1555756_a_at











NR
−0.2186897
0.5247142



R
0.4061700
0.5187056







tables$X1555759_a_at


X1555759_a_at











NR
0.08037061
0.5249017



R
0.85078348
0.7360755







tables$X1555812_a_at


X1555812_a_at











NR
−0.4493812
0.8437685



R
0.4087372
0.6145611







tables$X1555852_at


X1555852_at











NR
−0.3431720
0.6409197



R
0.3060830
0.4160286







tables$X1556185_a_at


X1556185_a_at











NR
−0.3542416
0.4573215



R
0.3876607
0.8113095







tables$X1556579_s_at


X1556579_s_at











NR
−0.08046679
0.2880584



R
0.58371780
0.7445854







tables$X1557116_at


X1557116_at











NR
−0.4470538
0.6892889



R
0.3267151
0.4124078







tables$X1557222_at


X1557222_at











NR
−0.04818824
0.402835



R
0.74360000
0.863980







tables$X1558034_s_at


X1558034_s_at











NR
−0.2487822
0.4220782



R
0.4252406
0.4675114







tables$X1558290_a_at


X1558290_a_at











NR
0.3179399
0.5555339



R
−0.4890204
0.4786095







tables$X1558586_at


X1558586_at











NR
−0.2298781
0.4177707



R
0.3950435
0.5416909







tables$X1558972_s_at


X1558972_s_at











NR
−0.2797971
0.5418070



R
0.4745703
0.5335784







tables$X1559263_s_at


X1559263_s_at











NR
−0.3833393
0.5703645



R
0.3494365
0.4676936







tables$X1559425_at


X1559425_at











NR
−0.2287316
0.5560199



R
0.4282525
0.4558128







tables$X1559584_a_at


X1559584_a_at











NR
−0.4622881
0.5846900



R
0.3021721
0.4028788







tables$X1562031_at


X1562031_at











NR
−0.3551523
0.4862453



R
0.1736934
0.4872335







tables$X1563461_at


X1563461_at











NR
0.3566529
0.5512415



R
−0.2706966
0.6822506







tables$X1563473_at


X1563473_at











NR
−0.4074615
0.5896901



R
0.2254661
0.4096997







tables$X1565602_at


X1565602_at











NR
0.4490349
0.6371381



R
−0.1986003
0.5670284







tables$X1568736_s_at


X1568736_s_at











NR
0.6111740
0.9655418



R
−0.1669456
0.3464934







tables$X1568822_at


X1568822_at











NR
0.4611639
0.6061123



R
−0.1089934
0.3960131







tables$X1569942_at


X1569942_at











NR
0.4441859
0.7007245



R
−0.2886340
0.3295043







tables$X200612_s_at


X200612_s_at











NR
0.2054340
0.4467337



R
−0.4553481
0.5048914







tables$X200904_at


X200904_at











NR
−0.2660950
0.4738856



R
0.3014091
0.4032104







tables$X200905_x_at


X200905_x_at











NR
−0.1327891
0.5236164



R
0.4735567
0.3948498







tables$X200953_s_at


X200953_s_at











NR
−0.2814847
0.8261769



R
0.5757425
0.6362976







tables$X201010_s_at


X201010_s_at











NR
−0.3613038
0.7929993



R
0.4944130
0.2677128







tables$X201137_s_at


X201137_s_at











NR
−0.3646008
0.7012958



R
0.3957589
0.4949475







tables$X201220_x_at


X201220_x_at











NR
0.08672472
0.5177988



R
−0.48143253
0.5513205







tables$X201236_s_at


X201236_s_at











NR
−0.1198028
0.5613972



R
0.5331348
0.5322952







tables$X201425_at


X201425_at











NR
−0.5116596
0.7193710



R
0.4964073
0.5304284







tables$X201474_s_at


X201474_s_at











NR
0.6028068
0.6299064



R
−0.2457276
0.3007111







tables$X201487_at


X201487_at











NR
−0.4225210
0.8252371



R
0.3171429
0.4591150







tables$X201497_x_at


X201497_x_at











NR
−0.3200855
0.4908815



R
2.5010094
2.6712499







tables$X201502_s_at


X201502_s_at











NR
−0.3308824
0.4722939



R
0.5454167
0.3159327







tables$X201531_at


X201531_at











NR
−0.1938551
0.3744374



R
0.5269050
0.5074891







tables$X201566_x_at


X201566_x_at











NR
−0.2981010
0.6780610



R
0.3509438
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levels



[1] “NR” “R”



call



naiveBayes.default(x = X, y = Y,



laplace = laplace)









Claims
  • 1-31. (canceled)
  • 31. A method of designating a patient as having a responder or a non-responder gene profile to Mage cancer immunotherapy comprising the steps of: a) analyzing a patient derived tumor sample for upregulation of one or more of the following genes: CCL5, TRAT1, STAT4, PRKCQ, GPR171, UBD, CD52, CD3D, PRF1, CD8A, CXCL10, CD69, TRBV19, TRDV2, IL7R, GZMK, and CD45R; andb) characterizing the patient from which the sample was derived as a having a responder or a non-responder gene profile based on the results of step (a), wherein upregulation of at least one of said genes indicates the patient has a responder gene profile.
  • 32. A kit comprising at least one component for performing an analysis on a patient derived sample to identify a responder according to the method of claim 31.
  • 33. A method of inducing a responder gene profile in a patient characterised as a non-responder comprising the step of stimulating a systemic immune or inflammatory response in the patient by radiotherapy or administering effective amount of interferon.
Priority Claims (2)
Number Date Country Kind
0610949.0 Jun 2006 GB national
0700761.0 Jan 2007 GB national
PCT Information
Filing Document Filing Date Country Kind 371c Date
PCT/EP2007/004915 5/31/2007 WO 00 12/2/2008