OA20891A - Methods of diagnosing and treating cervical cancer. - Google Patents

Abstract

The present invention is related to diagnostic tests or rapid detections of different types of cancer, especially cancer and precancerous lesions. Especially, the invention relates to specific and useful protein biomarkers for the detection of said diseases, and to the methods for determination and detection of said biomarkers.

Description

METHODS OF DIAGNOSING AND TREATING CERVICAL CANCER

CROSS-REFERENCE TO RELATED APPLICATIONS

This application daims benefit of priority of MX/a/2019/005940 filed May 21, 2019, the entire contents of which is incorporated herein by reference in its entirety.

BACKGROUND OF THE INVENTION

FIELD OF THE INVENTION

The présent invention relates generally to methods of diagnosing and treating cervical cancer in a subject and more specifically to biomarkers used to diagnose cervical cancer.

BACKGROUND INFORMATION

Cervical cancer (CC) is one of the most common cancers among women worldwide. Among the risk factors related to this disease are infection with the human papilloma virus (HPV), the microbiome, risky sexual behavior, multiparity, smoking, prolonged use of honnonal contraceptives and environmental factors. Cervical cancer is a disease of slow and progressive évolution. It is preceded by cervical intraepithélial neoplasms, which are the lésions considered to be the préludé to this condition. These malignancîes or injuries can occur even 10 years before cervical cancer develops.

Human papillomavirus infection (HPV) causes more than 90% of cases. Other risk factors include smoking, a weak immune System, birth control pills, starting sex at a young âge, and having many sexual partners, but these are less important. Cervical cancer typically develops from precancerous changes over 10 to 20 years. About 90% of cervical cancer cases are squamous cell carcinomas, 10% are adenocarcinoma, and a small number are other types. Diagnosis is typically by cervical screening followed by a biopsy. Medical imaging is then done to détermine whether or not the cancer has spread.

Current methods of diagnosing cervical cancer are invasive. The most common method of diagnosing cervical cancer is by a smear screening with Papanicolaou staining, i.e. Pap smear. There is a need for non-invasive methods of detecting cervical cancer.

SUMMARY OF THE INVENTION

The présent invention is based on the séminal discovery that a collection of biomarkers can be used for the diagnosis of cervical cancer.

In one embodiment, the présent invention is directed to methods of detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from

Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type IH, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat Shock Protein Cognate 71 kDa, An.kyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof; and diagnosing cervical cancer based on the détection ofthe at least one polypeptide.

In one aspect, the sample is selected from the group consisting of blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospinal fluid (CSF), tear, vaginal fluid, feces, skin, and hair. In certain aspects the sample is a blood sample and the subject is human.

In another aspect, the at least one polypeptide is Famesyl pyrophosphate syndiase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, I-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, AIpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In an additional aspect, the at least one polypeptide is a polypeptide having at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 and a fragment thereof.

In a further aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow assay. In one aspect, the method also includes administerîng a treatment to the subject. In an additional aspect, the treatment is surgery, radiation, chemotherapy, targeted therapy and/or immunotherapy.

In another embodiment, the présent invention provides a method of diagnosing cervical cancer in a subject by detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofïbromin 1, Glyceraldehyde-3 phosphate dehydrogenase, Protein J containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-Iike protein 1 polycystic kidney disease, Heat shock protein cognate protein 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskelétal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subuniî of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof; and diagnosing cervical cancer based on the détection of at least one polypeptide.

In one aspect, the sample is blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospinal fluid (CSF), tear, vaginal fluid, feces, skin, and hair. In certain aspects, the sample is a blood sample and the subject is human.

In an additîonal aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofïbromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Cognate thermal shock protein 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In a further aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having an amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In another aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow assay. In one aspect, the method also includes administering a treatment to the subject. In certain aspects, the treatment is surgery, radiation, chemotherapy, targeted therapy and/or immunotherapy.

In an additional embodiment, the présent invention provides a method of treating cervical cancer in a subject in need thereof, the method is detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1 -20 or a fragment thereof; diagnosing cervical cancer based on the détection of the at least one polypeptide; and administering a treatment to the subject. In one aspect, the sample is a blood sample.

In an additional aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, I-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In a further embodiment, the at least one polypeptides is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide with an amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In another aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, micro fluidic device, latéral flow assay, vertical flow or immunoassay. In a spécifie aspect, the detectîng is by latéral flow assay. In an additional aspect, the treatment is selected from the group consisting of surgery, radiation, chemotherapy, targeted therapy and immunotherapy.

In a further aspect, the chemotherapy is Cisplatin, Carboplatin, Paclitaxel, Topotecan, docetaxel, ifosfamide, 5-fluorouracil, irinotecan, gemcitabine or mitomycin. In certain aspects, the targeted therapy is Bevacizumab and the immunotherapy is pembrolizumab.

In a further embodiment, the présent invention provides methods of predîcting a response to treatment for a subject having cervical cancer by detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Famésyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein I containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-lîke protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Giutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof; and predîcting a response to treatment based on the détection of the at least one polypeptide.

In one aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-Iactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In another aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO;1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In an addîtional aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, mîcrolluidic device, latéral flow assay, vertical flow or immunoassay. In a further aspect, the detecting is by latéral flow assay. In certain aspects, the treatment is surgery, radiation, chemotherapy, targeted therapy and immunotherapy.

In another embodiment, the présent invention provides methods for determining the stage of cervical cancer in a subject in need thereof by detecting at least one polypeptide in a sample from the subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 contaînîng fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuciear heterogeneous Ribonucleoprotein Al, 1-lîke protein 1 polycystic kidney disease, beat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuciear ribonucleopro teins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof; and determining the stage of cervical cancer in the subject based on the détection of the at least one polypeptide.

In one aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuciear heterogeneous Ribonucleoprotein Al, 1 -like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuciear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In another aspect, the at least one polypeptide îs a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ [DNO:1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In an addîtional aspect, the detecting is by protein microairay, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow assay. In a further aspect, the method also includes administering a treatment to the subject. In certain aspects, the treatment is surgery, radiation, chemotherapy, targeted therapy or immunotherapy. In one aspect, the cervical cancer is stage I, stage Π, stage III or stage IV.

In one embodiment, the présent invention provides a kit with a sample collection unit; a latéral flow device; and instructions for using the latéral flow device.

In one aspect, the latéral flow device detects at least one polypeptide selected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof.

In an additional aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-iactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPaseactivating protein, Cytoskeletal Keratin 78 type II, Alph-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione Stransferase Mu 3 or a fragment thereof. In a further aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In another aspect, the latéral flow device detects the at least one polypeptide by an immunoassay. In one aspect, the sample collection unit collects a blood sample.

In an additional aspect, the présent invention provides a use of the détection of at least one polypeptide for the diagnosis of cervical cancer în a subject in need thereof, wherein the at least one polypeptide is seiected from Famesyl pyrophosphate synthase, neurofibromin J, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, l-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type I-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence seiected from SEQ ID NOs: 1-20 or a fragment thereof.

In a further aspect, the at least one polypeptide is detected in a sample from the subject and the sample is a blood sample. In another aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide seiected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, I-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alph-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/BI, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence seiected from SEQ ID N Os :2-20 or a fragment thereof.

In another aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow or immunoassay. In certain aspects, the detecting is by latéral flow assay.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1 shows the workflows to obtain secreted proteins in vivo or ex vivo.

Figure 2 is a graph showing the growth kînetics of cell lines with and without fêtai bovine sérum (FBS).

Figure 3A show analysis of the cervical cancer line secretome and its négative control. Figure 3B illustrâtes the number of total protein in each cell line, the number of unique protein, and the protein shared between cell lines. Figure 3C is a graphical représentation of the data presented in Figure 3B.

Figure 4A shows a dotplot graph illustrating the label-free quantification (LFQ) of 200 CC cell line secretome proteins vs. their négative control. Figure 4B is a graph bar representing the expression profile of proteins of interest. Figure 4C is a beat map illustrating the label-free quantification (LFQ) of 200 CC cell line secretome proteins vs. their négative control.

Figure 5A illustrâtes the workilow to collect blood and sérum samples. Figure 5B illustrate the western blot analysis of FPS (famesyl pyrophosphatase) in mouse sera. Figure 5C illustrâtes the quantification of the data presented in Figure 5B.

Figure 6A illustrâtes the validation of the candidate protein Famesyl pyrophosphate synthase in the sera of patients with CC. Figure 6B illustrâtes the level of Famesyl pyrophosphate synthase protein detected in the sera of control patients. Figure 6C illustrâtes the quantification of the data presented in Figures 6A and 6B.

Figure 7A illustrâtes the validation of the candidate protein Famesyl pyrophosphate synthase in precancerous cervical lésions. Figure 7B illustrâtes the validation of the candidate protein Ankyrin-3 in precancerous cervical lésions. Figure 7C illustrâtes the quantification of the data presented in Figures 7A and 7B.

Figure 8A illustrâtes the détection of Famesyl pyrophosphate synthase by western blot in the sera of patients with pre-cancerous lésions Ll. Figure 8B illustrâtes the détection of Famesyl pyrophosphate synthase by western blot in the sera of patients with pre-cancerous lésions L2. Figure 8C illustrâtes the détection of Famesyl pyrophosphate synthase b y western blot in the sera of control patients. Figure 8D illustrâtes the quantification of the data provided in Figure 8A-8C.

Figure 9A illustrâtes the détection of Ankyrin-3 by western blot in the sera of patients with pre-cancerous lésions Ll. Figure 9B illustrâtes the détection of Ankyrin-3 by western blot in the sera of patients with pre-cancerous lésions L2. Figure 9C illustrâtes the détection of Ankyrin-3 by western blot in the sera of control patients. Figure 9D illustrâtes the quantification of the data provided in Figure 9A-9C.

DETAILED DESCRIPTION OF THE INVENTION

The présent invention is based on the séminal discovery that a collection of biomarkers can be used for the diagnosis of cervical cancer.

Before the présent compositions and methods are described, it is to be understood that this invention is not limited to particular compositions, methods, and experimental conditions described, as such compositions, methods, and conditions may vary. It is also to be understood that the terminology used herein is for puiposes of describing particular embodiments only, and is not intended to be limîting, since the scope of the présent invention will be limited only in the appended daims.

As used in this spécification and the appended daims, the singular forms “a”, “an”, and “the” include plural référencés unless the context clearly dictâtes otherwise. Thus, for example, references to “the method” includes one or more methods, and/or steps of the type described herein which will become apparent to those persons skilled in the art upon readîng this disclosure and so forth.

Ail publications, patents, and patent applications mentioned in this spécification are herein încorporated by reference to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incoiporated by reference.

Unless defined otherwise, ail technical and scientîfic ternis used herein hâve the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although any methods and materials similar or équivalent to those described herein can be used in the practice or testing of the invention, it will be understood that modifications and variations are encompassed within the spirit and scope of the instant disclosure. The preferred methods and materials are now described.

Cervical cancer (CC) is one of the most common cancers among women worldwide. Among the risk factors related to this disease are infection with the human papîlloma virus (HPV), the microbiome, risky sexual behavior, multiparity, smoking, prolonged use of hormonal contraceptives and enviromnental factors. Cervical cancer is a disease of slow and progressive évolution. It is preceded by cervical intraepithélial neoplasms, which are the lésions considered to be the préludé to this condition.

These lésions are generally asymptomatic, making it difficult to detect the disease in a timely manner, so if they are not detected by any of the conventional methods, there is a risk that they will develop to the State of CC. Due to this, the diagnosis of neoplastic lésions or cancer in early stages, from HPV infection, is extremely important to be able to channel and treat these cases in a timely and adéquate manner.

Currently the gold standard for the dîagnosis of CC is the Pap test, while for the détection of HPV the most widely used method is détection by PCR and sequencing of the viral genome. Although both methods are an international benchmark, these tests hâve technical limitations, since highly trained personnel, facilitîes and specialized equipment are required; Furthermore, it is not easily accessible to the entire female population and the existence of sociocultural beliefs prevent women from making diagnoses.

Molecular biomarkers would help in the détection of cervical cancer using noninvasive methods. These biomarkers will serve as détection, prognosis, or follow-up of treatment of preneoplastic lésions and cancers in early stages based on patient sérum samples. Thus being able to decrease the incidence of the disease that continues to be a public health problem in many low and high income countries.

Due to ali of the above, there is an urgent need to develop new and simpler disease détection methods that are applicable in early détection, spécifie, highly sensitive, inexpensive, and easily accessible to the population.

The methods, compositions, and kits disclosed herein may be used for the dîagnosis, prognosis, and/or monitoring the status or outcome of a cancer în a subject. In some embodiments, the dîagnosing, predîcting, and/or monitoring the status or outcome of a cancer comprises determining the malignancy or malignant potential of the cancer or tumor. Altematively, the dîagnosing, predîcting, and/or monitoring the status or outcome of a cancer comprises determining the stage of the cancer. The dîagnosing, predîcting, and/or monitoring the status or outcome of a cancer can comprise determining the tumor grade. Altematively, the dîagnosing, predîcting, and/or monitoring the status or outcome of a cancer comprises assessing the risk of developing a cancer. In some embodiments, the dîagnosing, predîcting, and/or monitoring the status or outcome of a cancer includes assessing the risk of cancer récurrence. In some embodiments, dîagnosing, predîcting, and/or monitoring the status or outcome of a cancer may comprise determining the efficacy of treatment.

In one embodiment, the présent invention is directed to methods of detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-Iactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, Idike protein 1 polycystic kidney disease. Beat Shock Protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type Π, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-147 or a fragment thereof; and diagnosing cervical cancer based on the détection of the at least one polypeptide. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof.

As used herein, the terms “detecf “detecting” or “détection” may describe either the general act of discovering or disceming or the spécifie observation of a polypeptide. Detecting may comprise determining the presence or absence of a polypeptide. Detecting may comprise quantifying a polypeptide. For example, detecting comprises determining the expression level of a polypeptide. For example, the polypeptide may comprise at least a portion of the polypeptides disclosed herein.

The polypeptides or biomarkers of the présent invention can be detected by any method that can be used for the spécifie détection and/or identification of a protein, peptide, fragment thereof, variant thereof, or mutant thereof. Examples of method of detecting protein include, but are not limited to: spectrometry methods, such as high-performance liquid chromatography (HPLC), partition chromatography, nomial-phase chromatography, displacement chromatography, reversedphase chromatography (RPC), size-exclusion chromatography, îon-exchange chromatography, bioaffinity chromatography, aqueous normal-phase chromatography, liquid chromatography-mass spectrometry (LC/MS); and antibody dépendent or immunoassay based methods, such as enzymelinked immunosorbent assay (ELISA), direct ELISA, sandwich ELISA, compétitive ELISA, reverse ELISA, protein immunoprécipitation (direct or indirect), individual protein immunoprécipitation (IP), protein complex immunoprécipitation (Co-IP), chromatin immunoprécipitation (ChIP), RNP Immunoprécipitation (R1P), immunoelectrophoresis, western blot, and protein immunostaîning. The polypeptides or biomarkers of the présent invention can also be detected using protein microarrays, latéral flow assays or vertical flow assays. In certain aspects, the polypeptides or biomarkers are detected using a latéral flow assay. A latéral flow assay is typically an immunoassay either a sandwich assay or compétitive assay. Typically these assays use a conjugated gold, carbon or colored latex nanoparticles. Multiplexed assays may also be performed using these methods.

As used herein, the term “subject” refers to any organisms that are screened using the diagnostic methods and treated using the treatment methods described herein. Such organisms preferably include, but are not limited to, mammals (e.g., murines, simians, equines, bovines, porcines, canines, felines, and the like), and most preferably includes humans.

The term “diagnosed,” as used herein, refers to the récognition of a disease by its signs and symptoms, or genetic analysis, pathological analysis, histological analysis, and the like. Specifically, the term refers to the diagnosis or détection of cervical cancer.

The biomarkers of the présent invention serve various fonctions within cells.

Famesylpyrophosphate synthase (FPPS), also known as Dîmethylallyltranstransferase (DMATT) or as famesyldiphosphate synthase (FDPS), is an enzyme that in humans is encoded by the FDPS gene and catalyzes the transformation of dimethylallylpyrophosphate (DMAPP) and isopentenyl pyrophosphate (IPP) into famesylpyrophosphate (FPP).

Neurofibromin 1 (NFÎ) is a gene in humans that is located on chromosome 17. NFI codes for neurofibromin, a GTPase-activating protein that negatively régulâtes RAS/MAPK pathway activity by acceleratîng the hydrolysis of Ras-bound GTP. NFI has a high mutation rate and mutations in NFI can alter cellular growth control, and neural development, resulting in neurofibromatosis type 1 (NFI, also known as von Recklinghausen syndrome).

Glyceraldehyde 3-phosphate dehydrogenase (abbreviated as GAP DH or less commonly as G3PDH) (EC 1.2.1.12) is an enzyme of ~37kDa that catalyzes the sixth step of glycolysis and thus serves to break down glucose for energy and carbon molécules. In addition to this long established metabolic fonction, GAPDH has recently been implicated in several non-metabolic processes, including transcription activation, initiation of apoptosis, ER to Golgi vesicle shuttling, and fast axonal, or axoplasmic transport.

Protein 1 containing fibronectin domain type III also known as Fibronectin type III domain containing protein-1 may be an activator of G protein signal ing. Protein 1 containing fibronectin domain type ΙΠ is encoded by the FNDC1 gene.

Eukaryotic initiation factor 4A-I is an ATP-dependent RNA helicase which is a subunit of the eIF4F complex invoived in cap récognition and is required for mRNA binding to ribosome. In the current model of translation initiation, eIF4A unwinds RNA secondary structures in the 5’-UTR of mRNAs which is necessary to allow efficient binding of the small ribosomal subunit, and subséquent scanning for the initiator codon. The protein îs encoded by the EIF4A1 gene.

L-lactate dehydrogenase chain B is involved in step 1 ofthe subpathway that synthesizes (S)-Iactate from pyruvate. The protein is encoded by the LDHB gene.

Nuclear heterogeneous Ribonucleoproteîn Al, also known as heterogeneous nuclear ribonucleoprteon Al, is involved in the packaging of pre-mRNA into hnRNP particles, transport of poiy(A) mRNA from the nucléus to the cytoplasm and may modulate splice site sélection. May bind to spécifie miRNA hairpins. Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1. Nuclear heterogeneous Rîbonucleoprotein Al is encoded by the HNRNPA1 gene.

1-like protein 1 polycystîc kidney disease, also known as polycystic kîdney disease protein 1-Iike 1, is a component of a ciliary calcium channel that Controls calcium concentration within primary ci lia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD2L1 in primary cilia and forms a calcium-permeant ciliary channel that régulâtes sonie hedgehog/SHH signaiing and GLI2 transcription. Does not constitute the pore-forming subunit. Also involved in left/right axis spécification downstream of nodal flow: forms a complex with PKD2 in cilia to facilitate flow détection in left/right patteming. Encoded by the PKDIL1 gene.

Heat Shock Protein Cognate 71 kDa is a molecular chaperone implicated in a wide variety of cellular processes, including protection of the proteome from stress, folding and transport of newly synthesized polypeptides, activation of proteolysis of misfolded proteins and the formation and dissociation of protein complexes. Plays a pivotai rôle in the protein qualîty control System, ensuring the correct folding of proteins, the re-folding of misfolded proteins and control 1 ing the targeting of proteins for subséquent dégradation. This is achieved through cycles of ATP binding, ATP hydrolysis and ADP release, inediated by co-chaperones. The co-chaperones hâve been shown to not only regulate different steps of the ATPase cycle of HSP70, but they also hâve an individual specificity such that one co-chaperone may promote folding of a substrate while another may promote dégradation. The affinity of HSP70 for polypeptides is regulated by its nucléotide bound State. In the ATP-bound form, it has a low affinity for substrate proteins. However, upon hydrolysis of the ATP to ADP, it undergoes a confonnational change that increases its affinity for substrate proteins. HSP70 goes through repeated cycles of ATP hydrolysis and nucléotide exchange, which permits cycles of substrate binding and release. The HSP70-associated co-chaperones are of three types: J-domain co-chaperones HSP40s (stimulate ATPase hydrolysis by HSP70), the nucléotide exchange factors (NEF) such as BAG 1/2/3 (facilitate conversion of HSP70 from the ADP-bound to the ATP-bound state thereby promoting substrate release), and the TPR domain chaperones such as

HOPX and STUB1. Acts as a repressor of transcriptional activation. Inhibits the transcriptional coactivator activity of C1TEDI on Smad-mediated transcription. Component of the PRPI9-CDC5L complex that forms an integra! part of the spliceosome and is required for activatîng pre-mRNA splicing. May hâve a scaffolding rôle in the spliceosome assembly as it contacts ail other components of the core complex. Binds bacterial lipopolysaccharide (LPS) and médiates LPSinduced inflammatory response, including TNF sécrétion by monocytes. Participâtes in the ERassociated dégradation (ERAD) quality control pathway in conjunction with J domain-containing co-chaperones and the E3 ligase STUBl. Interacts with VGF-derived peptide TLQP-21. This protein is encoded by the HSPA8 gene.

Ankyrîn 3 is found in skeleta! muscle and is required for costamere localization of DMD and betaDAGl (By similarity). Membrane-cytoskeleton linker. The protein may participate in the maintenance/targeting of ion channeis and cell adhesion molécules at the nodes of Ranvîer and axonal initial segments. Régulâtes KCNA1 channel activity in function of dietary Mg²⁺ levels, and thereby contributes to the régulation of rénal Mg²* reabsoiption. Ankyrin-3 is encoded by the ANK3 gene.

Rho 23 GTPase-actîvating protein, also known as Rho GTPase activatîng protein 23, is part of the RHO family of small GTPases which are învolved in signal transduction through transmembrane receptors, and they are inactive in the GDP-bound form and active in the GTPbound form. GTPase-actîvating proteins, such as ARHGAP23, inactivate RHO family proteins by stimulating their hydrolysis of GTP . Rho GTPase-actîvating protein 23 is encoded by the ARHGAP23 gene.

Keratins are the major structural proteins in épithélial cells, forming a cytoplasmic network of 10 to 12 nm wide intennedîate filaments and creating a scaffoîd that gives cells the ability to wîthstand mechanical and non-mechanical stresses. There are two types of cytoskeletal and microfibrillar keratin, I (acidic) and II (neutral to basic), i.e. Cytoskeletal Keratin 78 type II, also known as keratin, type II cytoskeletal 78. Cytoskeletal keratin 78 type II is encoded by the KRT78 gene.

Alpha 3 collagen chain (VI), also known as collagen alpha-3 (VI) chain, acts as a cellbînding protein. Collagen alpha-3(VI) chain is encoded by the COL6A3 gene.

Beta subunit of protéasome type-5, also known as Protéasome subunit beta type-5 and 20S protéasome subunit beta-5 is a protein that in humans is encoded by the PSMB5 gene. This protein is one of the 17 essentîal subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including betali, beta2i, beta5î) that contributes to the complété assembly of 20S protéasome complex. In partîcular, protéasome subunit beta type-5, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate dégradation. This protein contaîns chymotrypsin-like activity and is capable of cleaving after large hydrophobie residues of peptide. The eukaryotic protéasome recognîzed degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential fonction of a modified protéasome, the îmrnunoproteasonie, is the processing of class I MHC peptides. Beta subunit of protéasome type -5 is encoded by the PSMB5 gene.

Heterogeneous nuclear ribonucleoprotein (hnRNP) that associâtes with nascent premRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dépendent and serves to condense and stabilize the transcripts and minîmize tangling and knotting. Packaging plays a rôle in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs. Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucléus. Involved in transport of spécifie mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specificaliy recognizing and binding the A2RE (21 nucléotide hnRNP A2 response element) or the A2RE11 (dérivative 11 nucléotide oligonucleotide) sequence motifs présent on some mRNAs, and promûtes their transport to the cytoplasm. Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molécules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promûtes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts. Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs. Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs. Plays also a rôle in the activation ofthe innate immune response. Mechanistically, senses the presence of viral DNA in the nucléus, homodimerizes and is demethylated by JMJD6. In tum, translocates to the cytoplasm where it activâtes the TBK1IRF3 pathway, leading to interferon alpha/beta production. Heterogeneous nuclear ribonucleoproteins A2/B1 is a protein that in humans is encoded by the HNRNPA2B1 gene.

Histone H2B type 1-B is a core component of nucléosome. Nucléosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central rôle in transcription régulation, DNA repair, DNA réplication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucléosome remodeling. Histone H2B type 1-B is encoded by the H2BC3 gene.

Homolog of DnaJ subfamily C member 13, also known as DnaJ homolog subfamily C member 13, is învolved in membrane traffickîng through early endosomes, such as the early endosome to recycling endosome transport implicated in the recycling of transferrin and the early endosome to late endosome transport implicated in dégradation of EGF and EGFR. Involved in the régulation of endosomal membrane tubulation and régulâtes the dynamics of SNX1 on the endosomal membrane; via association with WASHC2 may link the WASH complex to the retromer SNX-BAR subcomplex. DnaJ homolog subfamily member 13 is encoded by the DNAJC13 gene.

Enolase 3 (ENO3), more commonly known as beta-enolase (ΕΝΟ-β), is an enzyme that in humans is encoded by the EN03 gene. This gene encodes one of the three enolase isoenzymes found in mammals. This isoenzyme is found in skeletal muscle cells in the adult where it may play a rôle in muscle development and régénération. A switch from alpha enolase to beta enolase occurs in muscle tissue during development in rodents. Mutations in this gene hâve been associated with glycogen storage disease. Altematively spliced transcript variants encoding different isoforms hâve been described.

Glutathione S-transferases (GSTs) are a family of enzymes that play an important rôle in détoxification b y catalyzing the conjugation of many hydrophobie and electrophiiic compounds with reduced glutathione. Based on their biochemical, immunologie, and structural properties, the soluble GSTs are categorized into four main classes: alpha, mu, pi, and thêta. The glutathione S-transferase pi gene (GSTP1) is a polymorphie gene encoding active, functionally different GSTP1 variant proteins that are thought to fonction in xenobiotic metabolism and play a rôle in susceptibility to cancer, and other diseases. Glutathione S-transferase P is an enzyme that in humans is encoded by the GSTP1 gene.

Glutathione S-transferase Mu 3 may govem uptake and détoxification of both endogenous compounds and xenobiotics at the testis and braîn blood barriers. Glutathione Stransferase Mu 3 is encoded by the GSTM3 gene.

The amino acid sequences for the biomarkers of the présent invention and variants thereof are shown in Table 1.

Table 1

Protein name /SEQ ID NO,	Amino acid sequence
Famesyl pyrophosphate synthase (FDPS) SEQ IDNO:1	MPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAW HSARCWCQAWTEEPRALCSSLRMNGDQNSDVYAQEKQDFVQHFS QIVRVLTEDEMGHPEIGDAIARLKEVLEYNAIGGKYNRGLTVWA FRELVEPRKQDADSLQRAWTVGWCVELLQAFFLVADDIMDSSLTR RGQICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQPYYLNLIE LFLQSSYQTEIGQTLDLLTAPQGNVDLVRFTEKRYKSIVKYKTAFY SFYLPIAAAMYMAGIDGEKEHANAKKILLEMGEFFQIQDDYLDLF GDPSVTGKIGTDIQDNKCSWLWQCLQRATPEQYQILKENYGQKE AEKVARVKALYEELDLPAVFLQYEEDSYSHIMALIEQYAAPLPPAV FLGLARKIYKRRK
Neurofibromin l (NF1) SEQ ID NO: 2	MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLIN ISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKC LAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELRNSA SGVLFSLSCNNFNAVFSRISTRLQELTVCSEDNVDVHD1ELLQYINV DCAKLKRLLKETAFKFKALKKVAQLAVINSLEKAFWNWVENYPD EFTKLYQIPQTDMAECAEKLFDLVDGFAESTKRKAAVWPLQIILLI LCPEIIQDISKDWDENNMNKKLFLDSLRKALAGHGGSRQLTESAA 1ACVKLCKASTYINWEDNSVIFLLVQSMVVDLKNLLFNPSKPFSRG SQPADVDLMIDCLVSCFRISPHNNQHFKICLAQNSPSTFHYVLVNS LHRIITNSALDWWPKIDAVYCHSVELRNMFGETLHKAVQGCGAHP AIRMAPSLTFKEKVTSLKFKEKPTDLETRSYKYLLLSMVKLIHADP KLLLCNPRKQGPETQGSTAELITGLVQLVPQSHMPEIAQEAMEALL VLHQLDSIDLWNPDAPVETFWEISSQMLFYICKKLTSHQMLSSTEIL KWLREILICRNKFLLKNKQADRSSCHFLLFYGVGCDIPSSGNTSQM SMDHEELLRTPGASLRKGKGNSSMDSAAGCSGTPPICRQAQTKLE VALYMFLWNPDTEAVLVAMSCFRHLCEEADIRCGVDEVSVHNLL PNYNTFMEFASVSNMMSTGRAALQKRVMALLRRIEHPTAGNTEA WEDTHAKWEQATKLILNYPKAKMEDGQAAESLHKTIVKRRMSHV SGGGS1DLSDTDSLQEWINMTGFLCALGGVCLQQRSNSGLATYSPP MGPVSERKGSMISVMSSEGNADTPVSKFMDRLLSLMVCNHEKVG LQ1RTNVKDLVGLELSPALYPMLFNKLKNTISKFFDSQGQVLLTDT NTQFVEQTIAIMKNLLDNHTEGSSEHLGQASIETMMLNLVRYVRV LGNMVHAIQIKTKLCQLVEVMMARRDDLSFCQEMKFRNKMVEYL TDWVMGTSNQAADDDVKCLTRDLDQASMEAVVSLLAGLPLQPEE GDGVELMEAKSQLFLKYFTLFMNLLNDCSEVEDESAQTGGRKRG MSRRLASLRHCTVLAMSNLLNANVDSGLMHS1GLGYHKDLQTRA TFMEVLTKILQQGTEFDTLAETVLADRFERLVELVTMMGDQGELPI AMALANVVPCSQWDELARVLVTLFDSRHLLYQLLWNMFSKEVEL ADSMQTLFRGNSLASKIMTFCFKVYGATYLQKLLDPLLRIVITSSD WQHVSFEVDPTRLEPSESLEENQRNLLQMTEKFFHAIISSSSEFPPQ LRSVCHCLYQATCHSLLNKATVKEKKENKKSVVSQRFPQNSIGAV GSAMFLRFINPAIVSPYEAGILDKKPPPRIERGLKLMSK1LQSIANHV LFTKEEHMRPFNDFVKSNFDAARRFFLDIASDCPTSDAVNHSLSFIS DGNVLALHRLLWNNQEKIGQYLSSNRDHKAVGRRPFDKMATLLA YLGPPEHKPVADTHWSSLNLTSSKFEEFMTRHQVHEKEEFKALKT LSIFYQAGTSKAGNPIFYYVARRFKTGQINGDLLIYHVLLTLKPYY AKPYEIWDLTHTGPSNRFKTDFLSKWFWFPGFAYDNVSAVYIY NCNSWVREYTKYHERLLTGLKGSKRLVFIDCPGKLAEHIEHEQQK LPAATLALEEDLKVFHNALKLAHKDTKVSIKVGSTAVQVTSAERT KVLGQSVFLNDIYYASEIEEICLVDENQFTLTIANQGTPLTFMHQEC

	EAIVQSIII-IIRTRWELSQPDSIPQHTKJRPKDVPGTLLNIALLNLGSSD PSLRSAAYNLLCALTCTFNLKIEGQLLETSGLCIPANNTLFIVS1SKT LAANEPHLTLEFLEECISGFSKSSIELKHLCLEYMTPWLSNLVRFCK HNDDAKRQRVTAILDKLITMTINEKQMYPSIQAKIWGSLGQITDLL DVVLDSFIKTSATGGLGSIKAEVMADTAVALASGNVKLVSSKVIG RMCKIIDKTCLSPTPTLEQHLMWDDIAILARYMLMLSFNNSLDVA AHLPYLFHVVTFLVATGPLSLRASTHGLVINIIHSLCTCSQLHFSEET KQVLRLSLTEFSLPKFYLLFGISKVKSAAVIAFRSSYRDRSFSPGSYE RETFALTSLETVTEALLEIMEACMRDIPTCKWLDQWTELAQRFAF QYNPSLQPRALVVFGCISKRVSHGQIKQIIRILSKALESCLKGPDTY NSQVLIEATVIALTKLQPLLNKDSPLHKALFWVAVAVLQLDEVNL YSAGTALLEQNLHTLDSLRIFNDKSPEEVFMAIRNPLEWHCKQMD HFVGLNFNSNFNFALVGHLLKGYRHPSPAIVARTVRILHFLLTLVN KHRNCDKFEVNTQSVAYLAALLTVSEEVRSRCSLKHRKSLLLTDIS MENVPMDTYPIHHGDPSYRTLKETQPWSSPKGSEGYLAATYPTVG QTSPRARKSMSLDMGQPSQANTKKLLGTRKSFDHLISDTKAPKRQ EMESGITTPPKMRRVAETDŸEMETQRISSSQQHPI-ILRKVSVSESNV LLDEEVLTDPKIQALLLTVLATLVKYTTDEFDQR1LYEYLAEASW FPKVFPVVHNLLDSKINTLLSLCQDPNLLNPIHGrVQSWYHEESPP QYQTSYLQSFGFNGLWRFAGPFSKQTQIPDYAELrVKFLDALIDTY LPGIDEETSEESLLTPTSPYPPALQSQLSITANLNLSNSMTSLATSQH SPGIDKENVELSPTTGHCNSGRTRHGSASQVQKQRSAGSFKRNSIK KIV
Glyceraldehyde-3 phosphate dehydrogenase (GAPDH)	MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVY MFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSKIKWGDA GAEYVVESTGVFTTMEKAGAHLQGGAKRVIISAPSADAPMFVMG VNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHA
SEQ ID NO:3	1TATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNG KLTGMAFRVPTANVSWDLTCRLEKPAKYDDIKKVVKQASEGPL KGILG YTEHQ VVS SDFNSDTHS STFDAGAGIALNDH FVKLIS WYDN EFGYSNRWDLMAHMASKE
Protein 1 containing fibronectin domain type III	MAPEAGATLRAPRRLSWAALLLLAALLPVASSAAASVDHPLKPRH VKLLSTKMGLKVTWDPPKDATSRPVEHYNIAYGKSLKSLKYIKVN AETYSFL1EDVEPGVVYFVLLTAENHSGVSRPVYRAESPPGGEWIEI
or Fibronectin Type III Domain Containing protein 1	DGFPIKGPGPFNETVTEKEVPNKTLRVRVRSSDDRLSVAWKAPRLS GAKSPRRSRGFLLGYGESGRKMNYVPLTRDERTHEIKKLASESVY VVSLQSMNSQGRSQPVYRAALTKRK1SEEDELDVPDDISVRVMSS
(FNDC1)	QSVLVSWVDPVLEKQKKVVASRQYTVRYREKGELARWDYKQIA NRRVLIENLIPDTVYEFAVRISQGERDGKWSTSVFQRTPESAPTTAP
SEQ ID NO:4	ENLNVWPVNGKPTVVAASWDALPETEGKVKEYILSYAPALKPFG AKSLTYPGDTTSALVDGLQPGERYLFKIRATNRRGLGPHSKAFIVA MPTTSKADVEQNTEDNGKPEKPEPSSPSPRAPASSQHPSVPASPQG RNAKDLLLDLKNKILANGGAPRKPQLRAKKAEELDLQSTEITGEEE LGSREDSPMSPSDTQDQKRTLRPPSRHGHSVVAPGRTAVRARMPA LPRREGVDKPGFSL ATQPRPGAPP S AS ASP AHHASTQGTSHRP SLP ASLNDNDLVDSDEDERAVGSLHPKGAFAQPRPALSPSRQSPSSVLR DRSSVHPGAKPASPARRTPHSGAAEEDSSASAPPSRLSPPHGGSSRL LPTQPHLSSPLSKGGKDGEDAPATNSNAPSRSTMSSSVSSHLSSRTQ VSEGAEASDGESHGDGDREDGGRQAEATAQTLRARPASGHFHLL RHKPFAANGRSPSRFSIGRGPRLQPSSSPQSTVPSRAHPRVPSHSDS HPKLSSGIHGDEEDEKPLPATWNDHVPSSSRQPISRGWEDLRRSP QRGASLHRKEPIPENPKSTGADTHPQGKYSSLASKAQDVQQSTDA DTEGHSPKAQPGSTDRHASPARPPAARSQQHPSVPRRMTPGRAPQ QQPPPPVATSQHHPGPQSRDAGRSPSQPRLSLTQAGRPRPTSQGRS HSSSDPYTASSRGMLPTALQNQDEDAQGSYDDDSTEVEAQDVRAP AHAARAKEAAASLPKHQQVESPTGAGAGGDHRSQRGHAASPARP

	SRPGGPQSRARVPSRAAPGKSEPPSKRPLSSKSQQSVSAEDDEEED AGFFKGGKEDLLSSSVPKWPSSSTPRGGKDADGSLAKEEREPA1AL APRGGSLAPVKRPLPPPPGSSPRASHVPSRLPPRSAATVSPVAGTHP WPQYTTRAPPGHFSTTPMLSLRQRMMHARFRNPLSRQPARPSYRQ GYNGRPNVEGKVLPGSNGKPNGQRIINGPQGTKWWDLDRGLVL NAEGRYLQDSHGNPLR1KLGGDGRTIVDLEGTPVVSPDGLPLFGQG RHGTPLANAQDKPILSLGGKPLVGLEVIKKTTHPPTTTMQPTTTTTP LPTTTTPRPTTATTRRTTTTRRTTTRRPTTTVRTl’TRTTTTTTPTPTT PIPTCPPGTLERHDDDGNLIMSSNGIPECYAEEDEFSGLETDTAVPT EEAYVIYDEDYEFETSRPPTTTEPSTTATTPRV1PEEGAISSFPEEEFD LAGRKRFVAPYVTYLNKDPSAPCSLTDALDHFQVDSLDEIIPNDLK KSDLPPQHAPRNITWAVEGCHSFVIVDWDKATPGDWTGYLVYS ASYEDFIRNKWSTQASSVTHLPIENLKPNTRYYFKVQAQNPHGYG PISPSVSFVTESDNPLLVVRPPGGEPIWIPFAFKHDPSYTDCHGRQY VKRTWYRKFVGVVLCNSLRYKIYLSDNLKDTFYSIGDSWGRGED HCQFVDSHLDGRTGPQSYVEALPTIQGYYRQYRQEPVRFGNIGFGT PYYYVGWYECGVSIPGKW
Eukaryotic initiation factor 4ΑΊ	MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLR
(EIF4A1)	GIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFA1S1LQQ IELDLKATQALVLAPTRELAQQIQKWMALGDYMGASCHACIGGT
SEQ ID NO:5	NVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDE ADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFM RDPIRILVKKEELTLEG1RQFYINVEREEWKLDTLCDLYETLTITQA VIFINTRRKVDWLTEKMHARDFTVSAMHGDMDQKERDVIMREFR SGSSRVLITTDLLARG1DVQQVSLVINYDLPTNRENY1HRIGRGGRF GRKGVAINMVTEEDKRTLRDIETFYNTSIEEMPLNVADLI
L-lactate dehydrogenase chain B	MATLKEKLIAPVAEEEATVPNNKITVVGVGQVGMACAISILGKSLA
(LDHB)	DELALVDVLEDKLKGEMMDLQHGSLFLQTPKIVADKDYSVTANS K.IVWTAGVRQQEGESRLNLVQRNVNVFKFIIPQ1VKYSPDCIIIVVS
SEQ ID NO:6	NPVDILTYVTWKLSGLPKHRVIGSGCNLDSARFRYLMAEKLGÏHPS SCHGWILGEHGDSSVAVWSGVNVAGVSLQELNPEMGTDNDSEN WKEVHKMVVESAYEVIKLKGYTNWAIGLSVADLIESMLKNLSRIH PVSTMVKGMYGŒNEVFLSLPCILNARGLTSVINQKLKDDEVAQLK KS ADTLWDIQKDLKDL
Nuclear heterogeneous Ribonucleoprotein Al	MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCWM RDPNTKRSRGFGFVTYATVEEVDAAMNARPF1KVDGRVVEPKRAV
(HNRNPA1)	SREDSQRPGAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVIEIM TDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKALS
SEQIDNO:7	KQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRG GFGGSRGGGGYGGSGDGYNGFGNDGGYGGGGPGYSGGSRGYGS GGQGYGNQGSGYGGSGSYDSYNNGGGGGFGGGSGSNFGGGGSY NDFGNYNNQSSNFGPMKGGNFGGRSSGPYGGGGQYFAKPRNQGG YGGSSSSSSYGSGRRF
Polycystic kidney disease protein 1like 1	MAEEAAQNISDDQERCLQAACCLSFGGELSVSTDKSWGLHLCSCS PPGGGLWVEVYANHVLLMSDGKCGCPWCALNGKAEDRESQSPSS
(PKD1L1)	SASRQKNIWKTTSEAALSVVNEKTQAVVNEKTQAPLDCDNSADRI PIIKPFIIIARAWSSGGPRFHHRRLCATGTADSTFSALLQLQGTTSAA
SEQ ID NO: 8	APCSLKMEASCCVLRLLCCAEDVATGLLPGTVTMETPTKVARPTQ TSSQRVPLWPISHFPTSPRSSHGLPPGIPRTPSFTASQSGSEILYPPTQ HPPVAILARNSDNFMNPVLNCSLEVEARAPPNLGFRVHMASGEAL CLMMDFGDSSGVEMRLHNMSEAMAVTAYHQYSKGIFFHLLHFQL DMSTYKEAETQNTTLNVYLCQSENSCLEDSDPSNLGYELISAFVTK GVYMLKAVIYNEFHGTEVELGPYYVEIGHEAVSAFMNSSSVHEDE VLVFADSQVNQKSTVVIHHFPSIPSYNVSFISOTOVGDSOAWHSMT

	VWYKMQSVSVYTNGTVFATDTDITFTAVTKETIPLEFEWYFGEDP PVRTTSRSIKKRLSIPQWYRVMVKASNRMSSVVSEPHVIRVQKKIV ANRLTSPSSALVNASVAFECWINFGTDVAYLWDFGDGTVSLGSSS SSHVYSREGEFTVEVLAFNNVSASTLRQQLFIVCEPCQPPLVKNMG PGKVQIWRSQPVRLGVTFEAAVFCDISQGLSYTWNLMDSEGLPVS LPAAVDTHRQTLILPSHTLEYGNYTALAKVQIEGSVVYSNYCVGLE VRAQAPVSVISEGTHLFFSRTTSSPIVLRGTQSFDPDDPGATLRYHW ECATAGSPAHPCFDSSTAHQLDAAAPTVSFEAQWLSDSYDQFLVM LRVSSGGRNSSETRVFLSPYPDSAFRFVfflSWVSFKDTFVNWNDEL SLQAMCEDCSEIPNLSYSWDLFLVNATEKNRIEVPFCRVVGLLGSL GLGAISESSQLNLLPTEPGTADPDATTTPFSREPSPVTLGQPATSAPR GTPTEPMTGVYWIPPAGDSAVLGEAPEEGSLDLEPGPQSKGSLMT GRSERSQPTHSPDPHLSDFEAYYSDIQEA1PSGGRQPAKDTSFPGSG PSLSAEESPGDGDNLVDPSLSAGRAEPVLMIDWPKALLGRAVFQG YSSSGITEQTVTIKPYSLSSGETYVLQVSVASKHGLLGKAQLYLTV NPAPRDMACQVQPHHGLEAHTVFSVFCMSGKPDFHYEFSYQIGNT SKHTLYHGRDTQYYFVLPAGEHLDNYKVMVSTEITDGKGSKVQP CTWVTVLPRYHGNDCLGEDLYNSSLKNLSTLQLMGSYTEIRNYIT VITRILSRLSKEDKTASCNQWSRIQDALISSVCRLAFVDQEEMIGSV LMLRDLVSF SNKLGFMS AVLILKYTRALLAQGQFS GPFVTDKGVRL ELIGLISRVWEVSEQENSKEEVYRHEEGITVISDLLLGCLSLNHVST GQMEFRTLLHYNLQSSVQSLGSVQVHLPGDLAGHSPAGAETQSPC YISQLILFKKNPYPGSQAPGQIGGVVGLNLYTCSSRRPINRQWLRKP VMVEFGEEDGLDNRRNKTTFVLLRDKVNLHQFTELSENPQESLQ1E IEFSKP VTRAFPVMLLVRF SEKPTP SDFLVKQIYF WDE SIVQIYIPAA SQKDASVGYLSLLDADYDRKPPNRYLAKAVNYTVHFQWIRCLFW DKREWKSERFSPQPGTSPEKVNCSYHRLAAFALLRRKLKASFEVS DISKLQSHPENLLPSIFIMGSVILYGFLVAKSRQVDHHEKKKAGYIF LQEASLPGHQLYAVVIDTGFRAPARLTSKVYIVLCGDNGLSETKEL SCPEKPLFERNSRHTFILSAPAQLGLLRKIRLWHDSRGPSPGWFISH VMVKELHTGQGWFFPAQCWLSAGRHDGRVERELTCLQGGLGFR KLFYCKFTEYLEDFHVWLSVYSRPSSSRYLHTPRLTVSFSLLCVYA CLTALVAAGGQEQPHLDVSPTLGSFRVGLLCTLLASPGAQLLSLLF RLSKEAPGSARVEPHSPLRGGAQTEAPHGPNSWGRIPDAQEPRKQP ASAILSGSGRAQRKAASDNGTACPAPKLQVHGADHSRTSLMGKSH CCPPHTQAPSSGLEGLMPQWSRALQPWWSSAVWAICGTASLACSL GTGFLAYRFGQEQCVQWLHLLSLSWCCIFITQPLMVCLMALGFA WKRRADNHFFTESLCEATRDLDSELAERSWTRLPFSSSCSIPDCAG EVEKVLAARQQARHLRWAHPPSKAQLRGTRQRMRRESRTRAALR DISMDILMLLLLLCVIYGRFSQDEYSLNQAIRKEFTRNARNCLGGL RNIADWWDWSLTTLLDGLYPGGTPSARVPGAQPGALGGKCYLIGS SVIRQLKVFPRHLCKPPRPFSALIEDSIPTCSPEVGGPENPYLIDPEN QNVTLNGPGGCGTREDCVLSLGRTRTEAHTALSRLRASMWIDRST RAVSVHFTLYNPPTQLFTSVSLRVEILPTGSLVPSSLVESFSIFRSDS ALQYHLMLPQLVFLALSLIHLCVQLYRMMDKGVLSYWRKPRNWL ELSVVGVSLTYYAVSGHLVTLAGDVTNQFHRGLCRAFMDLTLMA SWNQRARWLRGILLFLFTLKCVYLPGIQNTMASCSSMMRHSLPSIF VAGLVGALMLAALSHLHRFLLSMWVLPPGTFTDAFPGLLFHFPRR SQWCLLGLSKSDQRAMACYFGILLIVSATLCFGMLRGFLMTLPQ KRKSFQSKSFVRLKDVTAYMWEKVLTFLRLETPKLEEAEMVENH NYYLDEFANLLDELLMKINGLSDSLQLPLLEKTSNNTGEARTEESP LVDISSYQAAEPADIKDF
Cognate thermal shock protein 71 kDa	MSKGPAVGIDLGTTYSCVGVFQHGKVEnANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH
or heat shock protein cognate 71 kDa	WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTA
(HSPA8)	AAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGD

SEQ ID NO:9

THLGGEDFDNRMVNHFIAEFKRKHKKDISENKRAVRRLRTACERA KRTLS S STQASIETOSLYEGIDF YTSITRARFEELNADLFRGTLDPVE KALRDAKLDKSQIHDIVLVGGSTRIPK1QKLLQDFFNGKELNKSINP DEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVM TVLIKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLL GKFELTGIPPAPRG VPQIEVTFD1DANGILNVS AVDKSTGKENKITIT NDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFN MKATVEDEKLQGKINDEDKQKILDKCNE1INWLDKNQTAEKEEFE HQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASS GPTIEEVD

Anikirina-3 or Ankyrin-3 (ANK3) SEQ ID NO: 10

MAIIAASQLKKNRDLEINAEEEPEKK.RKHRKRSRDRK.KKSDANAS YLRAARAGHLEKALDYIKNGVDIN1CNQNGLNALHLASKEGHVEV VSELLQREANVDAATKKGNTALHIASLAGQAEVVKVLVTNGANV NAQSQNGFTPLYMAAQENHLEVVKFLLDNGASQSLATEDGFTPLA VALQQGHDQWSLLLENDTKGKVRLPALHIAARKDDTKAAALLL QNDNNADVESKSGFTPLHIAAHYGNINVATLLLNRAAAVDFTARN DITPLHVASKRGNANMVKLLLDRGAKIDAKTRDGLTPLHCGARSG HEQWEMLLDRAAPILSKTKNGLSPLHMATQGDHLNCVQLLLQH NVPVDDVTNDYLTALHVAAHCGHYKVAKVLLDKKANPNAKALN GFTPLHIACKKNRIKVMELLLKFIGASIQAVTESGLTPIHVAAFMGH VNIVSQLMHHGASPNTTNVRGETALHMAARSGQAEVVRYLVQDG AQVEAKAKDDQTPLHISARLGKADIVQQLLQQGASPNAATTSGYT PLHLSAREGHEDVAAFLLDHGASLSITTKKGFTPLHVAAKYGKLE VANLLLQKSASPDAAGKSGLTPLHVAAHYDNQKVALLLLDQGAS PHAAAKNGYTPLHIAAKKNQMDIATTLLEYGADANAVTRQGÎASV HLAAQEGHVDMVSLLLGRNANVNLSNKSGLTPLHLAAQEDRVNV AEVLVNQGAHVDAQTKMGYTPLHVGCHYGNIKIVNFLLQHSAKV NAKTKNGYTPLHQAAQQGHTHIINVLLQNNASPNELTVNGNTALG 1ARRLGYISVVDTLKIVTEETMTTTTVTEKHKMNVPETMNEVLDM SDDEVRKANAPEMLSDGEYISDVEEGEDAMTGDTDKYLGPQDLK ELGDDSLPAEGYMGFSLGARSASLRSFSSDRSYTLNRSSYARDSM MIEELLVPSKEQHLTFTREFDSDSLRHYSWAADTLDNVNLVSSPIH SGFLVSFMVDARGGSMRGSRHHGMRJIIPPRK.CTAPTRITCRLVKR HKLANPPPMVEGEGLASRLVEMGPAGAQFLGPVIVEIPHFGSMRG KERELIVLRSENGETWKEHQFDSKNEDLTELLNGMDEELDSPEELG KKRICRIITKDFPQYFAVVSRÏKQESNQIGPEGGILSSTTVPLVQASFP EGALTKRIRVGLQAQPVPDEÏVKKILGNKATFSPIVTVEPRRRKFHK PITMTIPVPPPSGEGVSNGYKGDTTPNLRLLCSITGGTSPAQWEDIT GTTPLTFIKDCVSFTTNVSARFWLADCHQVLETVGLATQLYRELIC VPYMAKFWFAKMNDPVESSLRCFCMTDDKVDKTLEQQENFEEV ARSKD1EVLEGKPIYVDCYGNLAPLTKGGQQLVFNFYSFKENRLPF SIKIRDTSQEPCGRLSFLKEPKTTKGLPQTAVCNLNITLPAHKKETE SDQDDEIEKTDRRQSFASLALRKRYSYLTEPGMIERSTGATRSLPTT YSYKPFFSTRPYQSWTTAPITVPGPAKSGFTSLSSSSSNTPSASPLKS IWSVSTPSPIKSTLGASTTSSVKSISDVASPIRSFRTMSSPIKTVVSQS PYNIQVSSGTLARAPAVTEATPLKGLASNSTFSSRTSPVTTAGSLLE RSSITMTPPASPKSNINM YS S SLPFKSIIT S AAPLIS SPLKS VVSPVKS AVDVIS S AKITMAS SLS SP VKQMPGHAE VALVNGSISPLKYPS S STL INGCKATATLQEKISSATNSVSSVVSAATDTVEKVFSTTTAMPFSPL RSYVSAAPSAFQSLRTPSASALYTSLGSSISATTSSVTSSIITVPVYSV VNVLPEPALKKLPDSNSFTKSAAALLSPIKTLTTETHPQPHFSRTSSP VKS SLFLAPS ALKLSTPSSLS SSQEILKD V AEMKEDLMRMT AILQTD VPEEKPFQPELPKEGRIDDEEPFKIVEKVKEDLVKVSEILKKDVCVD NKGSPKSPKSDKGHSPEDDWIEFSSEEIREARQQAAASQSPSLPERV QVKAKAASEKDYNLTKVIDYLTNDIGSS SLTNLKYKFEDAKKDGE ERQKRVLKPAIALQEHKLKMPPASMRTSTSEKELCKMADSFFGTD TILESPDDrSQHDQDKSPLSDSGFETRSEKTPSAPOSAESTGPKPLFH

	EVPIPPVITETRTEWHVIRSYDPSAGDVPQTQPEEPVSPKPSPTFME LEPKPTTSS1KEKVKAFQMKASSEEDDHNRVLSKGMRVKEETHITT TTRMVYHSPPGGEGASERIEETMSVHDIMKAFQSGRDPSKELAGLF EHKSAVSPDVHKSAAETSAQHAEKDNQMKPKLERIIEVHIEKGNQ AEPTEVIIRETKKHPEKEMYVYQKDLSRGDINLKDFLPEKHDAFPC SEEQGQQEEEELTAEESLPSYLESSRVNTPVSQEEDSRPSSAQLISD DSYKTLKLLSQHSIEYHDDELSELRGESYRFAEKMLLSEKLDVSHS DTEESVTDHAGPPSSELQGSDKRSREKIATAPKKEILSKIYKDVSEN GVGKVSKDEHFDKVTVLHYSGNVSSPKHAMWMRFTEDRLDRGR EKLIYEDRVDRTVKEAEEKLTEVSQFFRDKTEKLNDELQSPEKKAR PKNGKEYSSQSPTSSSPEKVLLTELLASNDEWVKARQHGPDGQGF PKAEEKAPSLPSSPEKMVLSQQTEDSKSTVEAKGSISQSKAPDGPQ SGFQLKQSKLSSIRLKFEQGTHAKSKDMSQEDRKSDGQSRIPVKKI QESKLPVYQVFAREKQQKAIDLPDESVSVQKDFMVLKTKDEHAQS NEFVVNDSGSDNVKKQRTEMSSKAMPDSFSEQQAKDLACHITSDL ATRGPWDKKVFRTWESSGATNNKSQKEKLSHVLVHDVRENHIGH PESKSVDQKNEFMSVTERERKLLTNGSLSEIKEMTVKSPSKKVLYR EYVVKEGDHPGGLLDQPSRRSESSAVSHIPVRVADERRMLSSNIPD GFCEQSAFPKHELSQKLSQSSMSKETVETQHFNSIEDEKVTYSEISK VSKF1QSYVGLCPPLEETETSPTKSPDSLEFSPGKESPSSDVFDHSPID GLEKLAPLAQTEGGKEIKTLPVYVSFVQVGKQYEKEIQQGGVKKII SQECKTVQETRGTFYTTRQQKQPPSPQGSPEDDTLEQVSFLDSSGK SPLTPETPSSEEVSYEFTSKTPDSLIAYIPGKPSPIPEVSEESEEEEQA KSTSLKQTTVEETAVEREMPNDVSKDSNQRPKNNRVAYIEFPPPPP LDADQIESDKKHHYLPEKEVDMIEVNLQDEHDKYQLAEPVIRVQP PSPVPPGADVSDSSDDESIYQPVPVKKYTFKLKEVDDEQKEKPKAS AEKASNQKELESNGSGKDNEFGLGLDS PQNEIAQNG NNDQSITECS IATTAEFSHDTDATE1DSLDGYDLQDEDDGLTESDSKLPIQAMEIKK D1WNTEGILKPADRSFSQSKLEVIEEEGKVGPDEDKPPSKSSSSEKT PDKTDQKSGAQFFTLEGRHPDRSVFPDTYFSYKVDEEFATPFKTVA TKGLDFDPWSNNRGDDEVFDSKSREDETKPFGLAVEDRSPATTPD TTPARTPTDESTPTSEPNPFPFHEGKMFEMTRSGAIDMSKRDFVEE RLQFFQIGEHTSEGKSGDQGEGDKSMVTATPQPQSGDTTVETNLE RNVETPTVEPNPSIPTSGECQEGTSSSGSLEKSAAATNTSKVDPKLR TPIKMGISASTMTMKKEGPGEITDKJEAVMTSCQGLENETITMISNT ANSQMGVRPHEKHDFQKDNFNNNNNLDS STIQTDNIMSNIVLTEH S APTCTTEKDNP VKVS S GKKTGVLQGHCVRDKQKVLGEQQKTKE LIGIRQKSKLPIKATSPKDTFPPNHMSNTKASKMKQVSQSEKTKAL ITS SC VDVKS RIPVKNTHRDNIIAVRKACATQKQGQPEKGKAKQL PSKLPVKVRSTCVTTTTTTATTTTTTTTTTTTSCTVKVRKSQLKEV CKHSIEYFKGISGETLKLVDRLSEEEKKMQSELSDEEESTSRNTSLS ETSRGGQPSVTTKSARDKKTEAAPLKSKSEKAGSEKRSSRRTGPQS PCERTDIRMAIVADHLGLSWTELARELNFSVDEINQIRVENPNSLIS QSFMLLKKWVTRDGKNATTDALTSVLTKINRIDIVTLLEGPIFDYG NISGTRSFADENNVFFLDPVDGWQNETSSGNLESCAQARRVTGGLL DRLDDSPDQCRDSITSYLKGEAGKFEANGSHTEITPEAKTKSYFPES QNDVGKQSTKETLKPKIHGSGHVEEPASPLAAYQKSLEETSKLIIEE TKPCVPVSMKKMSRTSPADGKPRLSLHEEEGSSGSEQKQGEGFKV KTKKEIRHVEKKSHS
Rho 23	MNGVAFCLVGIPPRPEPRPPQLPLGPRDGCSPRRPFPWQGPRTLLL
or Rho GTPase-activating protein 23	YKSPQDGFGFTLRHF1VYPPESAVHCSLKEEENGGRGGGPSPRYRL EPMDTIFVKNVKEDGPAHRAGLRTGDRLVKVNGESVIGKTYSQVI
(ARHGAP23)	ALIQNSDDTLELS1MPKDEDILQLAYSQDAYLKGNEPYSGEARSIPE PPPICYPRKTYAPPARASTRATMVPEPTSALPSDPRSPAAWSDPGLR
SEQ ID NO; 11	VPPAARAHLDNSSLGMSQPRPSPGAFPHLSSEPRTPRAFPEPGSRVP PSRLECQQALSHWLSNQVPRRAGERRCPAMAPRARSASQDRLEEV AAPRPWPCSTSQDALSQLGOEGWHRARSDDYt.SRATRSAFAi.GPG

	ALVSPRFERCGWASQRSSARTPACPTRDLPGPQAPPPSGLQGLDDL GYIGYRSYSPSFQRRTGLLHALSFRDSPFGGLPTFNLAQSPASFPPE ASEPPRVVRPEPSTRALEPPAEDRGDEVVLRQKPPTGRKVQLTPAR QMNLGFGDESPEPEASGRGERLGRKVAPLATTEDSLASIPF1DEPTS PSIDLQAKHVPASAVVSSAMNSAPVLGTSPSSPTFTFTLGRHYSQD CS SIK AGRRSS YLLAITTERSKSCDDGLNTFRDEGRVLRRLPNRIP S LRMLRSFFTDGSLDSWGTSEDADAPSKRHSTSDESDATFSDIRREG WLYYKQILTKKGKKAGSGLRQWKRVYAALRARSLSLSKERREPG PAAAGAAAAGAGEDEAAPVCIGSCLVDISYSETKRRHVFRLTTAD FCEYLFQAEDRDDMLGWIRAIRENSRAEGEDPGCANQALISKKLN DYRKVSHSSGPKADSSPKGSRGLGGLKSEFLKQSAARGLRTQDLP AGSKDDSAAAPKTPWGINIIKKNKKAAPRAFGVRLEECQPATENQ RVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPGD INLQDERWQDLNVISSLLKSFFRKLPEPLFTDDKYNDFIEANRIEDA RERMRTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRN LALVFGPTLVRTSEDNMTDMVTHMPDRYKIVETLIQHSDWFFSDE EDKGERTPVGDKEPQAVPN1EYLLPNIGRTVPPGDPGSDSTTCSSAK SKGSWAPKKEPYAREMLAISFISAVNRKRKKRREARGLGSSTDDD SEQEAHKPGAGATAPGTQERPQGPLPGAVAPEAPGRLSPPAAPEER PAADTRSIVSGYSTLSTMDRSVCSGASGRRAGAGDEADDERSELS HVETDTEGAAGAGPGGRLTRRPSFSSHHLMPCDTLARRRLARGRP DGEGAGRGGPRAPEPPGSASSSSQESLRPPAAALASRPSRMEALRL RLRGTADDMLAVRLRRPLSPETRRRRSSWRRHTVVVQSPLTDLNF NEWKELGGGGPPEPAGARAHSDNKDSGLSSLESTKARAPSSAASQ PPAPGDTGSLQSQPPRRSAASRLHQCL
Cytoskeletal Keratin 78 type Π	MSLSPCRAQRGFSARSACSARSRGRSRGGFSSRGGFSSRSLNSFGG
or Keratin, type II cytoskeletal 78	CLEGSRGSTWGSGGREGVRFGEWSGGPGLSLCPPGGIQEVTINQNL LTPLKIEIDPQFQWRTQETQEIRTLNNQFASFIDKVRFLEQQNKVL
(KRT78)	ETKWHLLQQQGLSGSQQGLEPVFEACLDQLRKQLEQLQGERGAL DAELKACRDQEEEYKSKYEEEAHRRATLENDFVVLKKDVDGVFL
SEQ ID NO: 12	SKMELEGKLEALREYLYFLKHLNEEELGQLQTQASDTSWLSMDN NRYLDFSSÏITEVRARYEEIARSSKAEAEALYQTKYQELQVSAQLH GDRMQETKVQISQLHQEIQRLQSQTENLKKQNASLQAAITDAEQR GELALKDAQAKVDELEAALRMAKQNLARLLCEYQELTSTKLSLD VEIATYRRLLEGEECRMSGECTSQVTISSVGGSAVMSGGVGGGLG STCGLGSGKGSPGSCCTSIVTGGSNIILGSGKDPVLDSCSVSGSSAG S SCHTILKKTVESSLKTSITY
Alpha-3 collagen chain (VI)	MRKHRHLPLVAVFCLFLSGFPTTHAQQQQADVKNGAAADIIFLVD
or Collagen type VI, alpha 3	SSWTIGEEHFQLVREFLYDVVKSLAVGENDFHFALVQFNGNPHTE FLLNTYRTKQEVLSHISNMSYIGGTNQTGKGLEYIMQSHLTKAAGS RAGDGVPQVIVVLTDGHSKDGLALPSAELKSADVNVFAIGVEDAD
(COL6A3)	EGALKEIASEPLNMHMFNLENFTSLHDIVGNLVSCVHSSVSPERAG DTETLKDITAQDSADIIFLIDGSNNTGSVNFAVILDFLVNLLEKLPIG
SEQ IDNO:13	TQQIRVGWQFSDEPRTMFSLDTYSTKAQVLGAVKALGFAGGELA NIGLALDFWENHFTRAGGSRVEEGVPQVLVLISAGPSSDEIRYGV VALKQASVFSFGLGAQAASRAELQHIATDDNLVFTVPEFRSFGDLQ EKLLPYIVGVAQRHIVLKPPTIVTQVIEVNKRDIVFLVDGSSALGLA NFNAIRDFIAKVIQRLEIGQDLIQVAVAQYADTVRPEFYFNTHPTKR evitavrkmkpldgsalytgsaldfvrnnlftssagyraaegipkl LVLITGGKSLDEISQPAQELKRSS1MAFAIGNKGADQAELEEIAFDS SLVFIPAEFRAAPLQGMLPGLLAPLRTLSGTPEVHSNKRDIIFLLDGS ANVGKTNFPYVRDFVMNLVNSLDIGNDNIRVGLVQFSDTPVTEFS LNTYQTKSD1LGHLRQLQLQGGSGLNTGSALSYVYANHFTEAGGS RIREHVPQLLLLLTAGQSEDSYLQAANALTRAGILTFCVGASQANK AELEQIAFNPSLVYLMDDFSSLPALPQOLIOPLTTYVSGGVEEVPLA

	QPESKRDILFLFDGSANLVGQFPVVRDFLYKIIDELNVKPEGTRIAV AQYSDDVKWSRFDEHQSKPEILNLVKRMKIKTGKALNLGYALDY AQRYIFVKSAGSR1EDGVLQFLVLLVAGRSSDRVDGPASNLKQSGV VPFIFQAKNADPAELEQIVLSPAFILAAESLPKIGDLHPQIVNLLK.SV HNGAPAPVSGEKDWFLLDGSEGVRSGFPLLKEFVQRWESLDVG QDRVRVAWQYSDRTRPEFYLNSYMNKQDVVNAVRQLTLLGGPT PNTGAALEFVLRNILVSSAGSRITEGVPQLLIVLTADRSGDDVRNPS WVKRGGAVPIGIGIGNADITEMQTISFIPDFAVAIPTFRQLGTVQQ VISERVTQLTREELSRLQPVLQPLPSPGVGGKRDVVFLIDGSQSAGP EFQYVRTLIERLVDYLDVGFDTTRVAVÏQFSDDPKVEFLLNAHSSK DEVQNAVQRLRPKGGRQINVGNALEYVSRNÏFKRPLGSRIEEGVPQ FLVLIS SGKSDDEVDDPAVELKQFGV APFTIARNADQEELVKJ SLSP EYVFSVSTFRELPSLEQKLLTPITTLTSEQIQKLLASTRYPPPAVESD AADIVFLIDSSEGVRPDGFAHIRDFVSRJVRRLNIGPSKVRVGVVQF SNDVFPEFYLKTYRSQAPVLDAIRRLRLRGGSPLNTGKALEFVARN LFVKSAGSRIEDGVPQHLVLVLGGKSQDDVSRFAQVIRSSGIVSLG VGDRNIDRTELQTITNDPRLVFTVREFRELPN1EERIMNSFGPSAATP APPGVDTPPPSRPEKKKADrVFLLDGSINFRRDSFQEVLRFVSEIVD TVYEDGDSIQVGLVQYNSDPTDEFFLKDFSTKRQIIDAINKVVYKG GRHANTKVGLEHLRVNHFVPEAGSRLDQRVPQIAFVITGGKSVED AQDVSLALTQRGVKVFAVGVRN1DSEEVGKIASNSATAFRVGNVQ ELSELSEQVLETLHDAMHETLCPGVTDAAKACNLDVILGFDGSRD QNVFVAQKGFESKVDAILNRISQMHRVSCSGGRSPTVRVSVVANT PSGPVEAFDFDEYQPEMLEKFRNMRSQFIPYVLTEDTLKVYLNKFR QSSPDSVKVVIHFTDGADGDLADLHRASENLRQEGVRALILVGLE RVVNLERLMHLEFGRGFMYDRPLRLNLLDLDYELAEQLDNIAEKA CCGVPCKCSGQRGDRGPIGSIGPKGIPGEDGYRGYPGDEGGPGERG PPGVNGTQGFQGCPGQRGVKGSRGFPGEKGEVGEIGLDGLDGEDG DKGLPGSSGEKGNPGRRGDKGPRGEKGERGDVGIRGDPGNPGQDS QERGPKGETGDLGPMGVPGRDGVPGGPGETGKNGGFGRRGPPGA KGNKGGPGQPGFEGEQGTRGAQGPAGPAGPPGLIGEQGISGPRGS GGAAGAPGERGRTGPLGRKGEPGEPGPKGGIGNRGPRGETGDDGR DGVGSEGRRGKKGERGFPGYPGPKGNPGEPGLNGTTGPKGIRGRR GNSGPPGIVGQKGDPGYPGPAGPKGNRGDSIDQCALIQS1KDKCPC CYGPLECPVFPTELAFALDTSEGVNQDTFGRMRDWLSIVNDLTIA ESNCPRGARVAVVTYNNEVTTEIRFADSKRKSVLLDKIKNLOAL TSKQQSLETAMSFVARNTFKRVRNGFLMRKVAVFFSNTPTRASPQ LREAVLKLSDAGITPLFLTRQEDRQUNALQINNTAVGHALVLPAG RDLTDFLENVLTCHVCLDICNIDPSCGFGSWRPSFRDRRAAGSDVD IDMAFILDSAETTTLFQFNEMKKYIAYLVRQLDMSPDPKASQHFAR VAWQHAPSESVDNASMPPVKVEFSLTDYGSKEKLVDFLSRGMTQ LQGTRALGSAIEYT1ENVFESAPNPRDLKIVVLMLTGEVPEQQLEEA QRVILQAKCKGYFFWLGIGRKVNIKEVYTFASEPNDVFFKLVDKS TELNEEPLMRFGRLLPSFVSSENAFYLSPDIRKQCDWFQGDQPTKN LVKFGFIKQVNVPNNVTSSPTSNPVTTTKPVTTTKPVTTTTKPVTTT TKPVTIINQPSVKPAAAKPAPAKPVAAKPVATKMATVRPPVAVKP ATAAKPVAAKPAAVRPPAAAAAKPVATKPEVPRPQAAKPAATKP ATTKPMVKMSREVQVFEITENSAKLHWERAEPPGPYFYDLTVTSA HDQSLVLKQNLTVTDRVIGGLLAGQTYHVAVVCYLRSQVRATYH GSFSTKK.SQPPPPQPARSASSSTINLMVSTEPLALTETDICKLPKDEG TCRDFILKWYYDPNTKSCARFWYGGCGGNENKFGSQKECEKVCA PVLAKPGVISVMGT
Beta subunit of protéasome type-5	MALASVLERPLPVNQRGFFGLGGRADLLDLGPGSLSDGLSLAAPG
or Protéasome subunit beta type-5	WGVPEEPGIEMLHGTTTLAFKFRHGVIVAADSRATAGAYIASQTV KKVIEINPYLLGTMAGGAADCSFWERLLARQCRIYELRNKERISVA
(PSMB5)	AASKLLANMVYQYKGMGLSMGTMICGWDKRGPGLYYVDSEGNR ISGATFS VGSGS VYAYG VMDRGYS YDLEVEO ΑΥΠΤ. A R R A ΓΥΟ A TY

SEQIDNO:14	RDAYSGGAVNLYHVREDGWIRVSSDNVADLHEKYSGSTP
Heterogeneous nuclear ribonucleoproteins A2/B1 (IINRNPA2B1) SEQ ID NO: 15	MEKTLETVPLERKKREKEQFRKEFIGGLSFETTEESLRNYYEQWGK LTDCVVMRDPASKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRV VEPKRAVAREESGKPGAHVTVKKLFVGGIKEDTEEHHLRDYFEEY GKIDTIEIITDRQSGKKRGFGFVTFDDHDPVDK1VLQKYHTINGHNA EVRKALSRQEMQEVQSSRSGRGGNFGFGDSRGGGGNFGPGPGSNF RGGSDGYGSGRGFGDGYNGYGGGPGGGNFGGSPGYGGGRGGYG GGGPGYGNQGGGYGGGYDNYGGGNYGSGNYNDFGNYNQQPSN YGPMKSGNFGGSRNMGGPYGGGNYGPGGSGGSGGYGGRSRY
Histone H2B type 1 -B (HIST1H2BB) SEQ IDNO: 16	MPEPSKSAPAPKKGSKKAITKAQKKDGKKRKRSRKESYSIYVYKV LKQVHPDTGISSKAMGIMNSFVNDIFERIAGEASRLAHYNKRSTITS REIQTAVRLLLPGELAKHAVSEGTKAVTKYTSSK
homolog ofDnal subfamîly C member 13 or DnaJ homolog subfamîly C member 13 (DNAJC13) SEQ ID NO: 17	MNIIRENKDLACFYTTKHSWRGKYKRVFSVGTHAITTYNPNTLEV TNQWPYGDICSISPVGKGQGTEFNLTFRKGSGKKSETLKFSTEHRT ELLTEALRFRTDFSEGKITGRRYNCYKHHWSDSRKPVILEVTPGGF DQINPATNRVLCSYDYRNIEGFVDLSDYQGGFCILYGGFSRLHLFA SEQREEIIKSAIDHAGNY1GISLRJRK.EPLEFEQYLNLRFGKYSTDESI TSLAEFWQKISPRHSEPVKRVLALTETCLVERDPATYNIATLKPLG EVFALVCDSENPQLFTIEFIKGQVRKYSSTERDSLLASLLDGVRASG NRDVCVKMTPTHKGQRWGLLSMPVDEEVESLHLRFLATPPNGNF ADAVFRFNANISYSGVLHAVTQDGLFSENKEKLINNAITALLSQEG DVVASNAELESQFQAVRRLVASKAGFLAFTQLPKFRERLGVKVVK ALKRSNNGIIHAAVDMLCALMCPMHDDYDLRQEQLNKASLLSSK KFLENLLEKFNSH VDHGTGALVIS S LLDFLTFALC AP YSETTEGQQF DMLLEMVASNGRTLFKLFQHPSMAIIKGAGLVMKAIIEEGDKEIAT KMQELALSEGALPRHLHTAMFTISSDQRMLTNRQLSRI-ILVGLWTA DNATATNLLKRILPPGLLAYLESSDLVPEKDADRMHVRDNVKIAM DQYGKFNKVPEWQRLAGKAAKEVEKFAKEKVDLVLMHWRDRM GIAQKENINQKPVVLRKRRQRIKIEANWDLFYYRFGQDHARSNLI WNFKTREELKDTLESEMRAFNIDRELGSANVISWNHHEFEVKYEC LAEEIKIGDYYLRLLLEEDENEESGSIKRSYEFFNELYHRFLLTPKV NMKCLCLQALAIVYGRCHEEIGPFTDTRYIIGMLERCTDKLERDRLI LFLNKLILNKKNVKDLMDSNGIRILVDLLTLAHLHVSRATVPLQSN VIEAAPDMKRESEKEWYFGNADKERSGPYGFHEMQELWTKGML NAKTRCWAQGMDGWRPLQSIPQLKWCLLASGQAVLNETDL·ATLI LNMLITMCGYFPSRDQDNAIIRPLPKVKRLLSDSTCLPHIIQLLLTFD PILVEKVAILLYHIMQDNPQLPRLYLSGVFFF1MMYTGSNVLPVAR FLKYTHTKQAFKSEETKGQDIFQRSILGHILPEAMVCYLENYEPEKF SEIFLGEFDTPEAIWSSEMRRLMIEKIAAHLADFTPRLQSNTRALYQ YCPIP1INYPQLENELFCNIYYLKQLCDTLRFPDWPIKDPVKLLKDTL DAWKKEVEKKPPMMSIDDAYEVLNLPQGQGPHDESKIRKAYFRL AQKYHPDKNPEGRDMFEKVNKAYEFLCTKSAKIVDGPDPENIILIL KTQSILFNRHKEDLQPYKYAGYPMLIRTITMETSDDLLFSKESPLLP AATELAFHTVNCSALNAEEERRENGLEVLQEAFSRCVAVLTRASK PSDMSVQVCGYISKCYSVAAQFEECREKITEMPSIIKDLCRVLYFG KS1PRVAALGVECVSSFAVDFWLQTHLFQAGILWYLLGFLFNYDY TLEESGIQKSEETNQQEVANSLAKLSVHALSRLGGYLAEEQATPEN PTIRKSLAGMLTPYVARKLAVASVTEILKMLNSNTESPYLIWNNST RAELLEFLESQQENMIKKGDCDKTYGSEFVYSDHAKELIVGEIFVR VYNEVPTFQLEVPKAF'AASLLDYIGSQAQYLHTFMAITHAAKVESE QHGDRLPRVEMALEALRNVIKYNPGSESECIGHFKLIFSLLRVE1GA GQ VQQL ALEVVN1VTSNQDC VNNIAE S M VLS SLLALLHSLPSSRQI.

	VLETLYALTSSTKIIKEAMAKGALIYLLDMFCNSTHPQVRAQTAEL FAKMTADKLIGPKVRITLMKFLPSVFMDAMRDNPEAAVHIFEGTH ENPELIWNDNSRDKVSTTVREMMLEHFKNQQDNPEANWKLPEDF AVVFGEAEGELAVGGVFLRIFIAQPAWVLRKPREFL1ALLEKLTELL EKNNPHGETLETLTMATVCLFSAQPQLADQVPPLGHLPKVIQAMN HRNNAIPKSAIRVIHALSENELCVRAMASLETIGPLMNGMKKRADT VGLACEAINRMFQKEQSELVAQALKADLVPYLLKLLEGIGLENLD SPAATKAQIVKALKAMTRSLQYGEQVNEILCRSSVWSAFKDQKHD LF1SESQTAGYLTGPGVAGYLTAGTSTSVMSNLPPPVDHEAGDLGY QT
Beta enolase (ENO3) SEQ ID NO: 18	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTGIYE ALELRDGDKGRYLGKGVLKAVENINNTLGPALLQKKLSVVDQEK VDKFMIELDGTENKSKFGANAJLGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDL1LPVPAFNVINGGSHAGNKLAMQEFMILPVGASSFKE AMRIGAEVYHHLKGVIKAKYGKDATNVGDEGGFAPNILENNEAL ELLKTAIQAAGYPDKVVIGMDVAASEFYRNGKYDLDFKSPDDPAR HITGEKLGELYKSFIKNYPWSIEDPFDQDDWATWTSFLSGVNIQIV GDDLTVTNPKR1AQAVEKKACNCLLLKVNQIGSVTESIQACKLAQS NGWGVMVSHRSGETEDTFIADLVVGLCTGQIKTGAPCRSERLAKY NQLMRIEEALGDKAIFAGRKFRNPKAK
Glutathione S-transferase P (GSTPI) SEQ ID NO: 19	MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEVVTVETWQEGS LKASCLYGQLPKFQDGDLTLYQSNTILRHLGRTLGLYGKDQQEAA LVDMVNDGVEDLRCKY1SLIYTNYEAGKDDYVKALPGQLKPFETL LSQNQGGKTFIVGDQISFADYNLLDLLL1HEVLAPGCLDAFPLLSAY VGRLSARPKLKAFLASPEYVNLPINGNGKQ
Glutathione S-transferase Mu 3 (GSTM3) SEQ ID NO: 20	MSCESSMVLGYWD1RGLAHAIRLLLEFTDTSYEEKRYTCGEAPDY DRSQWLDVKFKLDLDFPNITYLLDGKNKITQSNAILRYIARKHNM CGETEEEKIRVD1IENQVMDFRTQLIRLCYSSDHEKLKPQYLEELPG QLKQFSMFLGKFSWFAGEKLTFVDFLTYDILDQNR1FDPKCLDEFP NLKAFMCRFEALEKIAAYLQSDQFCKMPINNKMAQWGNKPVC
Famesyl pyrophosphate synthase Variant 2 SEQ ID NO:21	MPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAW HSARCWCQAWTEEPRALCSSLRMNGDQNSDVYAQEKQDFVQHFS QIVRVLTEDEMGHPEIGDA1ARLKEVLEYNAIGGKYNRGLTVWA FREL VEPRKQD ADSLQRA WT VGWC VELLQAFFLVADD1MD S S LTR RGQICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQPYYLNLIE LFLQSSYQTEIGQTLDLLTAPQGNVDLVRFTEKRYKSIVKYKTAFY SFYLPIAAAMYMAGIDGEKEHANAKK.ILLEMGEFFQIQDDYLDLF GDPSVTGKIGTDIQDNKCSWLWQCLQRATPEQYQILKENYGQKE AEKVARVK.ALYEELDLPAVFLQYEEDSYSHIMALIEQYAAPLPPAV FLGLARKIYKRRK
Famesyl pyro phosphate synthase Variant 3 SEQ ID NO:22	MNGDQNSDVYAQEKQDFVQHFSQ1VRVLTEDEMGHPEIGDAIARL KEVLEYNAIGGKYNRGLTVVVAFRELVEPRKQDADSLQRAWTVG WCVELLQAFFLVADD1MDSSLTRRGQICWYQKPGVGLDAINDANL LEACIYRLLKLYCREQPYYLNLIELFLQSSYQTEIGQTLDLLTAPQG NVDLVRFTEKRYKSIVKYKTAFYSFYLPIAAAMYMAGIDGEKEHA NAKKILLEMGEFFQIQDDYLDLFGDPSVTGKIGTDIQDNKCSWLVV QCLQRATPEQYQILKENYGQKEAEKVARVKALYEELDLPAVFLQY EEDSYSHIMALIEQYAAPLPPAVFLGLARKIYKRRK
Famesyl pyrophosphate synthase Variant 4 SEQ ID NO:23	MNGDQNSDVYAQEKQDFVQHFSQIVRVLTEDEMGHPEIGDAIARL KEVLEYNAIGGKYNRGLTVWAFRELVEPRKQDADSLQRAWTVG WCVELLQAFFLVADDIMDSSLTRRGQICWYQKPGVGLDAINDANL LEACIYRLLKLYCREOPYYLNLIELFLOSSYOTEIGOTLDT.I.TAPQG

	NVDLVRFTEKRYKSIVKYKTAFYSFYLPIAAAMYMAGIDGEKEHA NAKKILLEMGEFFQIQDDYLDLFGDPSVTGKIGTDIQDNKCSWLVV QCLQRATPEQYQILKENYGQKEAEKVARVKALYEELDLPAVFLQY EEDSYSHIMALIEQY AAPLPPAVFLGLARKIYKRRK
Famesy] pyrophosphate synthase Variant 5 SEQ ID NO:24	MDSSLTRRGQICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQ PYYLNLIELFLQSSYQTEIGQTLDLLTAPQGNVDLVRFTEKRYKSIV KYKTAFYSFYLP1AAAMYMAGIDGEKEHANAKKILLEMGEFFQIQ DDYLDLFGDPSVTGKIGTDIQDNKCSWLVVQCLQRATPEQYQILK ENYGQKEAEKVARVKALYEELDLPAVFLQYEEDSYSH1MALIEQY AAPLPPAVFLGLARKIYKRRK
Famesyl pyro phosphate synthase Variant 6 SEQ ID NO:25	MNGDQNSDVYAQEKQDF VQH FSQIVRVLTEDEMGHPEIGD AI ARL KEVLEYNAIGGKYNRGLTVVVAFRELVEPRKQDADSLQRAWTVG WCVELLQAFFLVADDIMDSSLTRRGQICWYQKPGVGLDAINDANL LEACIYRLLKLYCREQPYYLNLIELFLQSSYQTEIGQTLDLLTAPQG NVDLVRFTEKRYKSIVKYKTAFYSFYLPIAAAMYMAGIDGEKEHA NAKKILLEMGEFFQIQDDYLDLFGDPSVTGKIGTDIQDNKCSWLVV QCLQRATPEQYQILKENYGQKEAEKVARVKALYEELDLPAVFLQY EEDSYSHIMALIEQY AAPLPPAVFLGLARKIYKRRK
Famesy] pyrophosphate synthase Variant 7 SEQ ID NO: 26	MPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAW HSARCWCQAWTEEPRALCSSLRMNGDQNSDVYAQEKQDFVQHFS QIVRVLTEDEMGHPEIGDAIARI.KEVLEYNAIGGKYNRGLTVVVA FRELVEPRKQDADSLQRAWTVGWCVELLQAFFLVADDIMDSSLTR RGQICWYQKPGVGLDAINDANLLEACIYRLLKLYCREQPYYLNLIE LFLQSSYQTEIGQTLDLLTAPQGNVDLVRFTEKRYKSIVKYKTAFY SFYL
Famesyl pyrophosphate synthase Variant 8 SEQ ID NO:27	MPLSRWLRSVGVFLLPAPYWAPRERWLGSLRRPSLVHGYPVLAW HSARCWCQAWTEEPRALCSSLRMNGDQNSDVYAQEKQDFVQHFS QIVRVLTEDEMGHPEIGDAIARLKEVLEYNAIGGKYNRGLTVVVA FRELVEPRKQDADSLQRAWTVGWCVELLQAFFLVADDIMDS
Neurofibromin 1 Variant 2 SEQ ID NO:28	MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLIN ISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKC LAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELRNSA SGVLFSLSCNNFNAVFSRISTRLQELTVCSEDNVDVHDIELLQYINV DCAKLKRLLKETAFKFKALKKVAQLAVINSLEKAFWNWVENYPD EFTKLYQIPQTDMAECAEKLFDLVDGFAESTKRKAAVWPLQIILLI LCPEIIQDISKDWDENNMNKKLFLDSLRKALAGHGGSRQLTESAA IACVKLCKASTYINWEDNSVIFLLVQSMVVDLKNLLFNPSKPFSRG SQPADVDLMIDCLVSCFR1SPHNNQHFKICLAQNSPSTFHYVLVNS LHRUTNSALDWWPKIDAVYCHSVELRNMFGETLHKAVQGCGAHP AIRMAPSLTFKEKVTSLKFKEKPTDLETRSYKYLLLSMVKLIHADP KLLLCNPRKQGPETQGSTAELITGLVQLVPQSHMPEIAQEAMEALL VLHQLDSIDLWNPDAPVETFWEISSQMLFYICKKLTSHQMLSSTEIL KWLREIL1C RNKFLLKNKQ ADRS SCHFLLF YG VGCDIP S SGNTSQM SMDHEELLRTPGASLRKGKGNSSMDSAAGCSGTPPICRQAQTKLE VALYMFLWNPDTEAVLVAMSCFRHLCEEAD1RCGVDEVSVHNLL PNYNTFMEFASVSNMMSTGRAALQKRVMALLRRIEHPTAGNTEA WEDTHAKWEQATKLILNYPKAKMEDGQAAESLHKTIVKRRMSHV SGGGSIDLSDTDSLQEWINMTGFLCALGGVCLQQRSNSGLATYSPP MGPVSERKGSMISVMSSEGNADTPVSKFMDRLLSLMVCNHEKVG LQIRTNVKDLVGLELSPALYPMLFNKLKNTISKFFDSQGQVLLTDT NTQFVEQTIAIMKNLLDNHTEGSSEHLGQASIETMMLNLVRYVRV LGNMVHAIQIKTKLCQLVEVMMARRDDLSFCQEMKFRNKMVEYL TDWVMGTSNQAADDDVKCLTRDLDQASMEAVVSLLAGLPLQPEE

	GDGVELMEAKSQLFLKYFTLFMNLLNDCSEVEDESAQTGGRKRG MSRRLASLRHCTVLAMSNLLNANVDSGLMHSIGLGYHKDLQTRA TFMEVLTKILQQGTEFDTLAETVLADRFERLVELVTMMGDQGELPI AMALANVVPCSQWDELARVLVTLFDSRHLLYQLLWNMFSKEVEL ADSMQTLFRGNSLASKIMTFCFKVYGATYLQKLL.DPLLRIVITSSD WQHVSFEVDPTRLEPSESLEENQRNLLQMTEKFFHAIISSSSEFPPQ LRSVCHCLYQVVSQRFPQNSIGAVGSAMFLRFINPAIVSPYEAGILD KKPPPRIERGLKLMSKILQSIANHVLFTKEEHMRPFNDFVKSNFDA ARRFFLD1ASDCPTSDAVNHSLSFISDGNVLALHRLLWNNQEKIGQ YLSSNRDHKAVGRRPFDKMATLLAYLGPPEHKPVADTHWSSLNL TSSKFEEFMTRHQVHEKEEFKALKTLSIFYQAGTSKAGNPIFYYVA RRFKTGQINGDLLIYHVLLTLKPYYAKPYEIWDLTHTGPSNRFKT DFLSKWFVVFPGFAYDNVSAVYIYNCNSWVREYTKYHERLLTGL KGSKRLVFIDCPGKLAEHIEHEQQKLPAATLALEEDLKVFHNALKL AHKDTKVSIKVGSTAVQVTSAERTKVLGQSVFLNDIYYASEIEEICL VDENQFTLTIANQGTPLTFMHQECEAIVQSIIHIRTRWELSQPDSIPQ HTKIRPKDVPGTLLNIALLNLGSSDPSLRSAAYNLLCALTCTFNLKI EGQLLETSGLCIPANNTLFIVSISKTLAANEPHLTLEFLEECISGFSKS SIELKHLCLEYMTPWLSNLVRFCKHNDDAKRQRVTAILDKL1TMTI NEKQMYPSIQAKIWGSLGQITDLLDVVLDSFIKTSATGGLGSIKAE VMADTAVALASGNVKLVSSKVIGRMCKIIDKTCLSPTPTLEQHLM WDDIAILARYMLMLSFNNSLDVAAHLPYLFHWTFLVATGPLSLR ASTHGLVINIIHSLCTCSQLHFSEETK.QVLRLSLTEFSLPKFYLLFGIS KVKSAAVIAFRSSYRDRSFSPGSYERETFALTSLETVTEALLEIMEA CMRDIPTCKWLDQWTEL AQRFAFQYNPSLQPRAL VVFGCIS KRVS HGQIKQIIRILSKALESCLKGPDTYNSQVLIEATVIALTKLQPLLNKD SPLHKALFWVAVAVLQLDEVNLYSAGTALLEQNLHTLDSLRIFND KSPEEVFMAIRNPLEWHCKQMDHFVGLNFNSNFNFALVGHLLKG YRHPSPAIVARTVRILHTLLTLVNKFIRNCDKFEVNTQSVAYLAALL TVSEEVRSRCSLKHRKSLLLTDISMENVPMDTYPIHHGDPSYRTLK ETQPWSSPK.GSEGYLAATYPTVGQTSPRARKSMSLDMGQPSQANT KKLLGTRKSFDHLISDTKAPKRQEMESGITTPPKMRRVAETDYEM ETQR1SSSQQHPHLRKVSVSESNVLLDEEVLTDPKIQALLLTVLATL VKYTTDEFDQRILYEYLAEASWFPKVFPWHNLLDSKINTLLSLC QDPNLLNPIHGIVQSVVYHEESPPQYQTSYLQSFGFNGLWRFAGPF SKQTQIPDYAELIVKFLDALIDTYLPGIDEETSEESLLTPTSPYPPAL QSQLSITANLNLSNSMTSLATSQHSPGIDKENVELSPTTGHCNSGRT RHGSASQVQKQRSAGSFKRNSIKK1V
Neurofibromin 1 Variant 3 SEQ ID NO:29	MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLIN ISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKC LAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQFIAAELRNSA SGVLFSLSCNNFNAVFSRISTRLQELTVCSEDNVDVHDIELLQYINV DCAKLKRLLKETAFKFKALKKVAQLAVINSLEKAFWNWVENYPD EFTK.LYQIPQTDMAECAEKLFDLVDGFAESTKRKAAVWPLQIILLI LCPEIIQDISKDVVDENNMNKKLFLDSLRKALAGHGGSRQLTESAA IACVKLCKASTYINWEDNSVIFLLVQSMVVDLKNLLFNPSKPFSRG SQPADVDLMIDCLVSCFRISPHNNQHFKICLAQNSPSTFHYVLVNS LHRIITNSALDWWPKIDAVYCHSVELRNMFGETLHKAVQGCGAHP AIRMAPSLTFKEKVTSLKFKEKPTDLETRSYKYLLLSMVKLIHADP KLLLCM’RKQGPETQGSTAELITGLVQLVPQSHMPEIAQEAMEALL VLHQLDSIDLWNPDAPVETFWEIRYMYFYFLNSTFKFYFVFLS
Neurofîbromin 1 Variant 4 SEQ ID NO:30	NWEDNSVIFLLVQSMWDLKNLLFNPSKPFSRGSQPADVDLMIDC LVSCFRJSPHNNQHFKICLAQNSPSTFHYVLVNSLHRIITNSALDWW PKIDAVYCHSVELRNMFGETLHKAVQGCGAHPAIRMAPSLTFKEK VTSLKFKEKPTDLETRSYKYLELSMVKLIHADPKLLLCNPRKQGPE TQGSTAELITGLVQLVPQSHMPEIAQEAMEALLVLHOLDSIDLWNP

	DAPVETFWEISSQMLFYICKKLTSHQMLSSTEILKWLREIL1CRNKF LLKNKQADRSSCHFLLFYGVGCDIPSSGNTSQMSMDHEELLRTPG ASLRKGKGNSSMDSAAGCSGTPPICRQAQTKLEVALYMFLWNPDT EAVLVAMSCFREILCEEADIRCGVDEVSVHNLLPNYNTFMEFASVS NMMSTGRAALQKRVMALLRRJEHPTAGNTEAWEDTHAKWEQAT KLILNYPKAKMEDGQAAESLHKTIVKRRMSHVSGGGSIDLSDTDS LQEWINMTGFLCALGGVCLQQRSNSGLATYSPPMGPVSERKGSMI SVMSSEGNADTPVSKFMDRLLSLMVCNHEKVGLQIRTNVKDLVG LELSPALYPMLFNKLKNTISKFFDSQGQVLLTDTNTQFVEQTIAIMK NLLDNHTEGSSEHLGQASIETMMLNLVRYVRVLGNMVHAIQIKTK LCQLVEVMMARRDDLSFCQEMKFRNKMVEYLTDWVMGTSNQA ADDDVKCLTRDLDQASMEAWSLLAGLPLQPEEGDGVELMEAKS QLFLKYFTLFMNLLNDCSEVEDESAQTGGRKRGMSRRLASLRHCT VLAMSNLLNANVDSGLMHSIGLGYHKDLQTRATFMEVLTKILQQ GTEFDTLAETVLADRFERLVELVTMMGDQGELPIAMALANVVPCS QWDELARVLVTLFDSRHLLYQLLWNMFSKEVELADSMQTLFRGN SLASKIMTFCFKVYGATYLQKLLDPLLRIV1TSSDWQHVSFEVDPT RLEPSESLEENQRNLLQMTEKFFH AIIS S S SEFPPQLRS VCHCLYQ V VSQRFPQNSIGAVGSAMFLRFINPAIVSPYEAGILDKKPPPRIERGLK LMSKILQSIANHVLFTKEEHMRPFNDFVKSNFDAARRFFLDIASDC PTSDAVNHSLSFISDGNVLALHRLLWNNQEKIGQYLSSNRDHKAV GRRPFDKMATLLAYLGPPEHKPVADTI-IWSSLNLTSSKFEEFMTRH QVHEKEEFKALKTLSIFYQAGTSKAGNPIFYYVARRFKTGQINGDL LIYHVLLTLKPYYAKPYEIVVDLTHTGPSNRFKTDFLSKWFWFPG FAYDNVSAVYIYNCNSWVREYTKYHERLLTGLKGSKRLVF1DCPG KLAEHIEHEQQKLPAATLALEEDLKVFHNALKLAHKDTKVSIKVG STAVQVTSAERTKVLGQSVFLNDIYYASEIEEICLVDENQFTLTIAN QGTPLTFMHQECEAIVQSIIHIRTRWELSQPDSIPQHTKIRPKDVPGT LLNIALLNLGSSDPSLRSAAYNLLCALTCTFNLKIEGQLLETSGLCIP ANNTLFIVSISKTLAANEPHLTLEFLEECISGFSKSSIELKHLCLEYM TPWLSNLVRFCKHNDDAKRQRVTAILDKLITMTINEKQMYPSIQA K1WGSLGQITDLLDVVLDSFIKTSATGGLGSIKAEVMADTAVALAS GNVKLVSSKVIGRMCKIIDKTCLSPTPTLEQHLMWDDIAILARYML MLSFNNSLDVAAHLPYLFHWTFLVATGPLSLRASTHGLVINIIHSL CTCSQLHFSEETKQVLRLSLTEFSLPKFYLLFGISKVKSAAVIAFRSS YRDRSFSPGSYERETFALTSLETVTEALLEIMEACMRDIPTCKWLD QWTELAQRFAFQYNPSLQPRALWFGCISKRVSHGQ1KQIIRJLSKA LESCLKGPDTYNSQVLIEATVIALTKLQPLLNKDSPLHKALFWVAV AVLQLDEVNLYSAGTALLEQNLirrLDSLRIFNDKSPEEVFMAIRNP LEWHCKQMDHFVGLNFNSNFNFALVGHLLKGYRHPSPA1VARTV RILHTLLTLVNKHRNCDKFEVNTQSVAYLAALLTVSEEVRSRCSLK HRKSLLLTDISMENVPMDTYPIHHGDPSYRTLKETQPWSSPKGSEG YLAATYPTVGQTSPRARKSMSLDMGQPSQANTKKLLGTRKSFDHL ISDTKAPKRQEMESGITTPPKMRRVAETDYEMETQRISSSQQHPHL RKVSVSESNVLLDEEVLTDPKIQALLLTVLATLVKYTTDEFDQR1L YEYLAEASVVFPKVFPWHNLLDSKINTLLSLCQDPNLL-NPIHGIVQ SWYHEESPPQYQTSYLQSFGFNGLWRFAGPFSKQTQIPDYAELIV KFLDALIDTYLPGIDEETSEESLLTPTSPYPPALQSQLS1TANLNLSNS MTSLATSQHSPASLPCSKSAVFMQLFPHQGIDKENVELSPTTGHCN SGRTRHGSASQVQKQRSAGSFKRNSIKKIV
Neurofibromin 1 Variant 5	MAAHRPVEWVQAVVSRFDEQLPIKTGQQNTHTKVSTEHNKECLIN ISKYKFSLVISGLTTILKNVNNMRIFGEAAEKNLYLSQLIILDTLEKC
SEQ ID NO:31	LAGQPKDTMRLDETMLVKQLLPEICHFLHTCREGNQHAAELRNSA SGVLFSLSCNNFNAVFSRISTRLQELTVCSEDNVDVHDIELLQYINV DCAKLKRLLKETAFKFKALKKVAQLAVINSLEKAFWNWVENYPD EFTKLYQIPQTDMAECAEKLFDLVDGFAESTKRKAAVWPLQIILLI LCPEÏIQDISKDWDENNMNKKLFLDSLRKALAGHGG SRQLTESAA

	IACVKLCKASTYINWEDNSVIFLLVQSMVVDLKNLLFNPSKPFSRG SQPADVDLMIDCLVSCFRISPHNNQHFKICLAQNSPSTFHYVLVNS LHRIITNSALDWWPKIDAVYCHSVELRNMFGETLHKAVQGCGAHP AIRMAPSLTFKEKVTSLKFKEKPTDLETRSYKYLLLSMVKLIHADP KLLLCNPRKQGPETQGSTAELITGLVQLVPQSHMPEIAQEAMEVRG K
Neurofibromin 1 Variant 6 SEQ ID NO:32	MHQECEATVQSIIHIRTRWELSQPDSIPQHIKIRPKDVPGTLLNIALL NLGSSDPSLRSAAYNLLCALTCTFNLK1EGQLLETSGLCIPANNTLFI VSISKTLAANEPHLTLEFLEECISGFSKSSIELKHLCLEYMTPWLSNL VRFCKHNDDAKRQRVTAILDKLITMTINEKQMYPSIQAKIWGSLG QITDLLDVVLDSFIKTSATGGLGS1KAEVMADTAVALASGNVKLVS SK
Neurofibromin 1 Variant 7 SEQ ID NO:33	MKRCWSNSCCQKSAIFFTPVVKETSMQLNFGILPLGFYFLSAATTS MQSLVAFLPETAFKFKALKKVAQLAVINSLEKAFWNWVENYPDE FTKLYQIPQTDMAECAEKLFDLVDGFAESTKRKAAVWPLQIILLIL CPEIIQDISKDWDENNMNKVRRAKLFPLYLDVKQFILLKVCITLGL LFKQSISGNHLNDHFRFLCLMDLEETYSYIILFGRGKIIPGNEQRFKII P
Neurofïbromin 1 Variant 8 SEQ ID NO:34	XIHGIVQSVVYHEESPPQYQTSYLQSFGFNGLWRFAGPFSKQTQIP DYAELIVKFLDALIDTYLPGIDEETSEESLLTPTSPYPPALQSQLSITA NLNLSNSMTSLATSQHSPGQ
Glyceraldehyde-3 phosphate dehydrogenase Variant 2 SEQ ID NO: 3 5	MVYMFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSKIKW GDAGAEYWESTGVFTTMEKAGAHLQGGAKRVIISAPSADAPMFV MGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTV HAITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPEL NGKLTGMAFRVPTANVSVVDLTCRLEKPAKYDD1KKWKQASEG PLKGILGYTEHQVVSSDFNSDTHSSTFDAGAGIALNDHFVKLISWY DNEFGYSNRVVDLMAHMASKE
Glyceraldehyde-3 phosphate dehydrogenase Variant 3 SEQ ID NO: 3 6	MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVY MFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSK1KWGDA GAEYWESTGVFTTMEKAGAHLQGGAKRV1ISAPSADAPMFVMG VNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHA ITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNG KLTGMAFRVPTANVSWDLTCRLEKPAKYDDIKKWKQASEGPL KGILGYTEHQWSSDFNSDTHSSTFDAGAGIALNDHFVKLISWYDN EFGYSNRWDLMAHMASKE
Glyceraldehyde-3 phosphate dehydrogenase Variant 4 SEQ ID NO:37	MGKVKVGVNGFGRIGRLVTRAAFNSGKVDIVAINDPFIDLNYMVY MFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSKIKWGDA GAEYVVESTGVFTTMEKAGAHLQGGAKRVIISAPSADAPMFVMG VNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTVHA ITATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPELNG KLTGMAFRVPTANVSWDLTCRLEKPAKYDDIKKVVKQASEGPL KGILGYTEHQ V VS SDFNSDTHS STFDAGAG1ALNDHFVKLIS WYDN EFGYSNRWDLMAHMASKE
Glyceraldehyde-3 phosphate dehydrogenase Variant 5 SEQ ID NO:38	MEEMRDPSKIKWGDAGAEYWESTGVFTTMEKAGAHLQGGAKR VIISAPSADAPMFVMGVNHEKYDNSLKIISNASCTTNCLAPLAKVIH DNFGIVEGLMTTVHAITATQKTVDGPSGKLWRDGRGALQNIIPAST GAAKAVGKVIPELNGKLTGMAFRVPTANVSVVDLTCRLEKPAKY DDIKKVVKQASEGPLKGILGYTEHQWSSDFNSDTHSSTFDAGAGI ALNDHFVKLISWYDNEFGYSNRWDLMAHMASKE__________

Glyceraldehyde-3 phosphate dehydrogenase Variant 6	MVYMFQYDSTHGKFHGTVKAENGKLVINGNPITIFQERDPSKIKW GDAGAEYWESTGVFTTMEKAGAHLQGGAKRVIISAPSADAPMFV MGVNHEKYDNSLKIISNASCTTNCLAPLAKVIHDNFGIVEGLMTTV FIA1TATQKTVDGPSGKLWRDGRGALQNIIPASTGAAKAVGKVIPEL
SEQ ID NO:39	NGKLTGMAFRVPTANVSVVDLTCRLEKPAKYDDIKKVVKQASEG PLKGILGYTEHQWSSDFNSDTHSSTFDAGAGIALNDHFVKLISWY DNEFGYSNRWDLMAHMASKE
Fibronectîn Type III Domain Containing protein 1 Variant 2	XPRHVKLLSTKMGLKVTWDPPKDATSRPVEHYNIAYGKSLKSLKY IKVNAETYSFLIEDVEPGVVYFVLLTAENHSGVSRPVYRAESPPGG EW1EIDGFPIKGPGPFNETVTEKEVPNKPLRVRVRSSDDRLSVAWK APRLSGAKSPRRSRGFLLGYGESGRKMNYVPLTRDERTHEIKKLAS
SEQ ID NO.40	ESVYVVSLQSMNSQGRSQPVYRAALTKRKISEEDELDVPDDISVRV MSSQSVLVSWVDPVLEKQKKWASRQYTVRYREKGELARWDYK QIANRRVLIENLIPDTVYEFAVRISQGERDGKWSTSVFQRTPESAPT TAPENLNVWPVNGKPTWAASWDALPETEGKVKASKADVEQNTE DNGKPEKPEPSSPSPRAPASSQHPSVPASPQGRNAKDLLLDLKNKIL ANGGAPRKPQLRAKKAEELDLQSTEITGEEELGSREDSPMSPSDTQ DQKRTLRPPSRHGHSVVAPGRTAVRARMPALPRREGVDKPGFSLA TQPRPGAPPSASASPAHHASTQGTSHRPSLPASLNDNDLVDSDEDE RAVGSLHPKGAFAQPRPALSPSRQSPSSVLRDRSSVHPGAKPASPA RRTPHSG AAEEDSS ASAPPS RLSPPHGGS SRLLPTQPHLS SPLSKGG KDGEDAPATNSNAPSRSTMSSSVSSHLSSRTQVSEGAEASDGESHG DGDREDGGRQAEATAQTLRARPASGHFHLLRHKPFAANGRSPSRF SIGRGPRLQPSSSPQSTVPSRAHPRVPSHSDSHPKLSSGIHGDEEDEK PLPATVVNDHVPSSSRQP1SRGWEDLRRSPQRGASLHRKEP1PENPK STGADTHPQGKYSSLASKAQDVQQSTDADTEGHSPKAQPGSTDRJH ASPARPPAARSQQHPSVPRRMTPGRAPQQQPPPPVATSQHHPGPQS RDAGRSPSQPRLSLTQAGRPRPTSQGRSHSSSDPYTASSRGMLPTA LQNQDEDAQGSYDDDSTEVEAQDVRAPAHAARAKEAAASLPKHQ QVESPTGAG AGGDHRSQRGHAASPARP SRPGGPQS RARVPSRAAP GKSEPPSKRPLS SKSQQS VS AEDDEEEDAGFFKGGKEDLLSS S VPK WPSSSTPRGGKDADGSLAKEEREPA1ALAPRGGSLAPVKRPLPPPP GSSPRASHVPSRLPPRSAATVSPVAGTHPWPQYTTRAPPGHFSTTP MLSLRQRMMHARFRNPLSRQPARPSYRQGYNGRPNVEGKVLPGS NGKPNGORIINGPQGTKWWDLDRGLVLNAEGRYLQDSHGNPLRI KLGGDGRTIVDLEGTPVVSPDGLPLFGQGRHGTPLANAQDKPILSL GGKPLVGLEVIKK.TTHPPTTTMQPTTTTTPLPTTTTPRPTTATTRRT TTTRRT'TrRRPTTTVRTTTRTTTTTTPTPTTPIPTCPPGTLERHDDDG NLIMSSNGIPECYAEEDEFSGLETDTAVPTEEAYVIYDEDYEFETSR PPTTTEPSTTATTPRVIPEEGAISSFPEEEFDLAGRKRFVAPYVTYLN KDPSAPCSLTDALDHFQVDSLDETIPNDLKKSDLPPQHAPRNITWA VEGCHSFV1VDWDKATPGDVVTGYLVYSASYEDFIRNKWSTQASS vthlpienlkpntryyfkvqaqnpi-igygpispsvsfvtesdnpi.lv VRPPGGEPIWIPFAFKHDPSYTDCHGRQYVKRTWYRKFVGVVLCN SLRYKIYLSDNLKDTFYSIGDSWGRGEDHCQFVDSHLDGRTGPQS YVEALPTIQGYYRQYRQEPVRFGNIGFGTPYYYVGWYECGVSIPG KW
Eukaryotic initiation factor 4A-I Variant 2	MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLR G1YAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQ
SEQ ID NO:41	IELDLKATQALVLAPTRELAQQIQKWMALGDYMGASCHACIGGT NVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDE ADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFM RDPIRILVKKEELTLEGIRQFYINVEREEWKLDTLCDLYETLTITQA VIFINTRRKVDWLTEKMHARDFTVSAMHGDMDQKERDVIMREFR SGSSRVLÏTTDLLGKLYPQNRSRWTVWP

Eukaryotic initiation factor 4A-I Variant 3 SEQ ID NO:42	MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLR GIYAYGFEKPSA1QQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQ IELDLKATQALVLAPTRELAQQIQKVVMALGDYMGASCHACIGGT NVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDE ADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFM RDPIRILVKKEELTLEGIRQFYINVEREEWKLDTLCDLYETLTITQA VIFINTRRKVDWLTEKMHARDFTVSAMHGDMDQKERDVIMREFR SGSSRVLITTDLLNRSRWTVWP
Eukaryotic initiation factor 4A-I Variant 4 SEQ ID NO:43	MEPEGVIESNWNEIVDSFDDMNLSESLLRGIYAYGFEKPSAIQQRAI LPC1KGYDVIAQAQSGTGKTATFAISILQQIELDLKATQALVLAPTR ELAQQIQKVVMALGDYMGASCHACIGGTNVRAEVQKLQMEAPHI IVGTPGRVFDMLNRRYLSPKYIKMFVLDEADEMLSRGFKDQIYDIF QKLNSNTQWLLSATMPSDVLEVTKKFMRDPIRILVKKEELTLEG1 RQFYINVEREEWKLDTLCDLYETLTIT
Eukaryotic initiation factor 4A-1 Variant 5 SEQ ID NO:44	XVVMALGDYMGASCHACIGGTNVRAEVQKLQMEAPHIIVGTPGR VFDMLNRRYLSPKYIKMFVLDEADEMLSRGFKDQIYDIFQKLNSN TQWLLSATMPSDVLEVTKKFMRDP1RILVKKEELTLEGIRQFYINV EREEWKLDTLCDLYETLTITQAVIF1NTRRKVDWLTEKMHARDFT VSAMHGDMDQKERDVIMREFRSGSSRVLITTDLLGKLYPQNRSRW TVWP
Eukaryotic initiation factor 4A-I Variant 6 SEQ ID NO:45	MSASQDSRSRDNGPDGMEPEGVTESNWNEIVDSFDDMNLSESLLR GIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQ IELDLKATQALVLAPTRELAQQKVVMALGDYMGASCHACIGGTN VRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDEA DEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLEVTKKFMR DP1R1LVKKEELTLEGIRQFYINVEREEWKLDTLCDLYETLTITQAVI FINTRRKVDWLTEKMHARDFTVSAM
Eukaryotic initiation factor 4A-I Variant 7 SEQ ID NO:46	MSASQDSRSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLR GIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQ IELDLKATQALVLAPTRELAQQIQKWMALGDYMGASCHACIGGT NVRAEVQKLQMEAPH1IVGTPGRVFDMLNRRYLSPKYIKMFVLDE ADEMLSRGFKDQIYDIFQKLNSNTQEELTLEGIRQFYINVEREEWK LDTLCDLYETLTITQAVIFINTRRKVDWLTEKMHARDFTVSA
Eukaryotic initiation factor 4A-1 Variant 8 SEQ ID NO:47	MEPEGVIESNWNEIVDSFDDMNLSESLLRGIYAYGFEKPSAIQQRA1 LPCIKGYDVIAQAQSGTGKTATFAISILQQIELDLKAT
Eukaryotic initiation factor 4 A4 Variant 9 SEQ ID NO:48	XAWAHCARGRHRPRPPTSGSRDNGPDGMEPEGVIESNWNEIVDSF DDMNLSESLLRGIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTG KTATFAISILQQIELDLKATQALVLAPTRELAQQIQKVVMALGDYM GASCHACIGGTNVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLS PKYIKMFVLDEADEMLSRGFKDQIYDIFQKL
Eukaryotic initiation factor 4A-I Variant 10 SEQ ID NO:49	MSASQDSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLLRGI YAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTATFAISILQQIE LDLKATQALVLAPTRELAQQIQKVVMALGDYMGASCHACIGGTN VRAEVQKLQMEAPHIIVGTPGRVFDMLNRRYLSPKYIKMFVLDEA DEMLS
Eukaryotic initiation factor 4A-1 Variant 11	MNLSESLLRGIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKT ATFATSILQQIELDLKATQALVLAPTRELAQQIQKVVMALGDYMG

SEQ ID NO:50	ASCHACIGGTNVRAEVQKJ.QMEAPH1IVGTPGRVFDMLNRRYLSP KYIKMFVLDEADEMLSRGFKDQIYDI
Eukaryotic initiation factor 4A-I Variant 12 SEQ IDNO;51	MNLSESLLRGIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKT ATFAISILQQIELDLKATQALVLAPTRELAQQIQKVVMALGDYMG ASCFIACIGGTNVRAEVQKLQMEAPHIIVGTPGRVFDMLNRRY
Eukaryotic initiation factor 4A-I Variant 13 SEQ ID NO:52	MFVLDEADEMLSRGFKDQIYDIFQKLNSNTQVVLLSATMPSDVLE VTKKFMRDPIRILVKKEELTLEGIRQFYINVEREEWKLDTLCDLYE TLTITQAVIFINTRRKVDWLTEKMHA
Eukaryotic initiation factor 4A-I Variant 14 SEQ ID NO:53	MGRSTFLRGSRDNGPDGMEPEGVIESNWNEIVDSFDDMNLSESLL RGIYAYGFEKPSAIQQRAILPCIKGYDVIAQAQSGTGKTA
L-lactate dehydrogenase chain B Variant 2 SEQ ID NO:54	MATLKEKLIAPVAEEEATVPNNKITVVGVGQVGMACAISILGK.SLA DELALVDVLEDKLKGEMMDLQHGSLFLQTPKIVADKDYSVTANS KIVWTAGVRQQEGESRLNLVQRNVNVFKFIIPQIVKYSPDCIIIVVS NPVDILTYVTWKLSGLPKHRVIGSGCNLDSARFRYLMAEKLGIHPS SCHGWILGEHGDSSVAVWSGVNVAGVSLQELNPEMGTDNDSEN WKEVHKMWESAYEVIKLKGYTNWA1GLSVADLIESMLKNLSRIH PVSTMVKGMYGIENEVFLSLPCILNARGLTSVINQKLKDDEVAQLK KSADTLWDIQKDLKDL
L-lactate dehydrogenase chain B Variant 3 SEQ ID NO:55	MATLKEKLIAPVAEEEATVPNNK1TVVGVGQVGMACA1SILGKSLA DELALVDVLEDKLKGEMMDLQHGSLFLQTPKIVADKDYSVTANS KIVWTAGVRQQEGESRLNLVQRNVNVFKF1IPQIVKYSPDCIIIVVS NPVDILTYVTWKLSGLPKHRVIGSGCNLDSARFRYLMAEKLGIHPS SCHGWILGEHGDSSVAVWSGVNVAGVSLQELNPEMGTDNDSEN WKEVHKMVVESAYEVIKLKGYTNWAIGLSVADLIESMLKNLSRIH PVSTMVKGMYGFENEVFLSLPCILNARGLTSVINQKLKDDEVAQLK KS ADTLWDIQKDLKDLXLVS SRL
L-lactate dehydrogenase chain B Variant 4 SEQ ID NO:56	MATLKEKLIAPVAEEEATVPNNKITVVGVGQVGMACAISILGKSLA DELALVDVLEDKLKGEMMDLQHGSLFLQTPKIVADKDYSVTANS K1VVVTAGVRQQEGESRLNLVQRNVNVFKF1IPQIVKYSPDCI1IVVS NPVDILTY VT WKLSGLPKHRVIG SGCNLDS ARFRYLM AEKLGIHPS SCHGWILGEHGDSSVAVWSGVNVAGVSLQELNPEMGTDNDSEN WKEVH
L-lactate dehydrogenase chain B Variant 5 SEQ ID NO:57	MATLKEKLIAPVAEEEATVPNNKJTVVGVGQVGMACAISILGKSLA DELALVDVLEDKLKGEMMDLQHGSLFLQTPKIVADKDYSVTANS KIVWTAGVRQQEGESRLNLVQRNVNVFKFIIPQIVKYSPDCIIIV
L-lactate dehydrogenase chain B Variant 6 SEQ ID NO:58	MATLKEKL1APVAEEEATVPNNKITVVGVGQVGMACA1SILGKSLA DELALVDVLEDKLKGEMMDLQHGSLFLQTPKIVADKDYSVTANS KIWVTAGVRQQ
Nuclear heterogeneous Ribonucleoprotein Al Variant 2 SEQ ID NO:59	MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCVVM RDPNTKRSRGFGFVTYATVEEVDAAMNARPHKVDGRVVEPKRAV SREDSQRPGAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVIEIM TDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKALS KQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRG

	GFGGSRGGGGYGGSGDGYNGFGNDGSNFGGGGSYNDFGNYNNQ S SNFGPMKGGNFGGRS SGPYGGGGQYFAKPRNQGGYGGS S SS S S Y GSGRRF
Nuciear heterogeneous Ribonucleoprotein Al Variant 3 SEQ ID NO:60	MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCWM RDPNTKRSRGFGFVTYAEVEEVDAAMNARPHKVDGRVVEPKRAV SREDSQRPGAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVIE1M TDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKALS KQEMASASSSQRGRSGSGNFGGGSYNDFGNYNNQSSNFGPMKGG NFGGRSSGPYGGGGQYFAKPRNQGGYGGSSSSSSYGSGRRF
Nuciear heterogeneous Ribonucleoprotein Al Variant 4 SEQIDNO:61	MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCWM RDPNTKRSRGFGFVTYATVEEVDAAMNARPHKVDGRVVEPKRAV SREDSQRPGAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVIEIM TDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKALS KQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRGGNFSGRG IGDGYNGFGNDGSNFGGGGSYNDFGNYNNQSSNFGPMKGGNFGG RSSGPYGGGGQYF AKPRNQGGYGGS S S SS SYGSGRRF
Nuciear heterogeneous Ribonucleoprotein Al Variant 5 SEQ ID NO:62	K.IEVIEIMTDRGSGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNC EVRKALSKQEMASASSSQRGRSGSGNFGGGRGGGFGGNDNFGRG GNFSGRGGFGGSRGGGGYGGSGDGYNGFGNDGSNFGGGGSYNDF GNYNNQSSNFGPMKGGNFGGRSSGPYGGGGQYEAKPRNQGGYG GSSSSSSYGSGRRF
Nuciear heterogeneous Ribonucleoprotein Al Variant 6 SEQ ID NO:63	MRDSLLVAKFLGTQDLCLFLNLALSPKEPEQLRKLFIGGLSFETTDE SLRSHFEQWGTLTDCVVMRDPNTKRSRGFGFVTYATVEEVDAAM NARPHKVDGRVVEPKRAVSREDSQRPGAHLTVKKIFVGGIKEDTE EHHLRDYFEQYGKIEVIEIMTDRGSGKKRGFAFVTFDDHDSVDKIV IQK.YHTVNGHNCEVRKALSKQEMASASSSQRGRSGSGNFGGGRG GGFGG
Nuciear heterogeneous Ribonucleoprotein Al Variant 7 SEQ ID NO:64	MRDPNTKRSRGFGFVTYATVEEVDAAMNARPHKVDGRVVEPKR AVSREDSQRPGAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEVI EIMTDRGSGKKRGFAFVTFDDHDS
Nuciear heterogeneous Ribonucleoprotein Al Variant 8 SEQ ID NO:65	MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCVVM RDPNTKRSRGFGFVTYATVEEVDAAMNARPHKVDGRVVEPKRAV SREDSQRPGAHLTVKKIFVGGFGGSRGGGGYGGSGDGYNGFGND GSNFGGGGSYNDFGNYNNQSSN
Nuciear heterogeneous Ribonucleoprotein Al Variant 9 SEQ ID NO:66	MSKSESPKEPEQLRKLFIGGLSFETTDESLRSHFEQWGTLTDCVDS QRPGAHLTVKKIFVGGIKEDTEEHHLRDYFEQYGKIEV1EIMTDRG SGKKRGFAFVTFDDHDSVDKIVIQKYHTVNGHNCEVRKALSKQE MASASSSQR
Polycystic kidney disease protein 1like 1 Variant 2 SEQ ID NO:67	XSRLRASMWIDRSTRAVSVHFTLYNPPTQLFTSVSLRVEILPTGSLV PSSLVESFSIFRSDSALQYHLMLPQLVFLALSLIHLCVQLYRMMDK GVLSYWRKPRNWLELSVVGVSLTYYAVSGHLVTLAGDVTNQFHR GLCRAFMDLTLMASWNQRARWLRGILLFLFTLKCVYLPGIQNTM ASCSSMMRHSLPSIFVAGLVGALMLAALSHLHRFLLSMWVLPPGT FTDAFPGLLFHFPRRSQKDCLLGLSKSDQRAMACYFGILLIVSATL CFGMLRGFLMTLPQKRKSFQSKSFVRLKDVTAYMWEKVLTFLRL ETPKLEEAEMVENHNYYLDEFANLLDELLMKINGLSDSLQLPT.LF-

	KTSNNTGEARTEESPLVDISSYQAAESLTLVTQTEVQWHDLGSLQP PHPRFKQFSCLSLPSSWDYRRVPLCLANF
Polycystic kidney disease protein 1like 1 Variant 3 SEQ ID NO:6S	XVGGPENPYLiDPENQNVTLNGPGGCGTREDCVLSLGRTRTEAHT ALSRLRASMWIDRSTRAVSVHFTLYNPPTQLFTSVSLRVEILPTGSL VPSSLVESFSIFRSDSALQYHLMLPQLVFLALSLIHLCVQLYRMMD KGVLSYWRKPRNWLEVASLVSFSFEK
Heat shock protein cognate 71 kDa Variant 2 SEQ ID NO:69	MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAWQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAWTVPAYFNDSQRQATKDAGT1AGLNVLRIINEPTA AAIAYGLDKKVGAERNVLIFDLGGGTFDVS1LT1EDGIFEVKSTAGD THLGGEDFDNRMVNHFIAEFKRKHKKDISENKRAVRRLRTACERA KRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVE KALRDAKLDKSQIHDIVLVGGSTRIPK1QKLLQDFFNGKELNKSINP DEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLG1ETAGGVM TVLKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLL GKFELTGIPPAPRGVPQIEVTFD1DANG1LNVSAVDKSTGKENKITIT NDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFN MKATVEDEKLQGKINDEDKQKÎLDKCNEIINWLDKNQTAEKEEFE HQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASS GPTIEEVD
Heat shock protein cognate 71 kDa Variant 3 SEQ ID NO: 70	MSKGPAVG1DLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRJFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAVVTVPAYFNDSQRQATKJDAGTIAGLNVLRHNEPTA AAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGD THLGGEDFDNRMVNHFIAEFKRKHKJGDISENKRAVRRLRTACERA KRTLSSSTQAS1EIDSLYEGIDFYTSITRARJFEELNADLFRGTLDPVE KALRDAKLDKSQIHDIVLVGGSTRJPKIQKLLQDFFNGKELNKSINP DEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVM TVLIKRNTTIPTKQTQTFTTYSDNQPGVL1QVYEGERAMTKDNNLL GKFELTGIPPAPRGVPQIEVTFDIDANG1LNVSAVDKSTGKENKITIT NDKGRJLSKED1ERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFN MKATVEDEKLQGK.1NDEDKQKILDKCNEIINWLDKNQTAEKEEFE HQQKELEKVCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASS GPTIEEVD
Heat shock protein cognate 71 kDa Variant 4 SEQ ID NO:71	MSKGPAVGÏDLGTTYSCVGVFQHGKVEIÏANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMWNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRUNEPl A AAIAYGLDKKVGAERNVLIFDLGGGTFDVSILTIEDGIFEVKSTAGD THLGGEDFDNRMVNl·IFIAEFKRKHKKDISENKRAVRRLRTACERA KRTLSSSTQASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVE KALRDAKLDKSQ1HD1VLVGGSTRIPKIQKLLQDFFNGKELNKSINP DEAVAYGAAVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVM TVLIKRNTT1PTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLL GKFELTGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
Heat shock protein cognate 71 kDa Variant 5 SEQ ID NO:72	MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKATKDAGTIAGLNVLRIINEPTAAAIAYGLDKKVGAERNVLIF DLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVNHFIAE

	FKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIE1DSLYEGI DFYTSITRARFEELNADLFRGTLDPVEKALRDAKLDKSQIHDIVLV GGSTRIPKIQKLLQDFFNGKELNK.SINPDEAVAYGAAVQAAILSGD KSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTIPTKQTQTFTT YSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAPRGVPQIEV TFDIDANGILNVSAVDKSTGKENKITITNDKGRLSKEDEERMVQEA EKYKAEDEKQRDKVSSKNSLESYAFNMKATVEDEKLQGKINDED KQKILDKCNEIINWLDKNQTAEKEEFEHQQKELEKVCNPIITKLYQ SAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
Heat shock protein cognate 71 kDa Variant 6 SEQ ID NO: 73	MVNHFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASI EIDSLYEGIDFYTS1TRARFEELNADLFRGTLDPVEKALRDAKLDKS QIHDIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYGAAV QAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTTÏPT KQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNLLGKFELTGIPPAP RGVPQIEVTFDIDANGILNVSAVDKSTGKENKITITNDKGRLSKEDI ERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFNMKATVEDEKLQ GKINDEDKQKILDKCNEIINWLDKNQTAEKEEFEHQQKELEKVCN PIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
Heat shock protein cognate 71 kDa Variant 7 SEQ ID NO: 74	MSKGPAVGIDLGTTYSCVGVFQHGKVEI1ANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKHKKJDISENKRAVRRLRTACERAKRTLSSSTQ ASIEIDSLYEGIDFYTSITRARFEELNADLFRGTLDPVEKALRDAKL DKSQIHDIVLVGGSTR1PKIQKLLQDFFNGKELNKSINPDEAVAYGA AVQAAILSGDKSENVQDLLLLDVTPLSLGIETAGGVMTVLIKRNTT IPTKQTQTFTTYSDNQPGVL1QVYEGERAMTKDNNLLGKFELTGIP PAPRGVPQIEVTFDIDANGILNVSAVDKSTGKENKITITNDKGRLSK EDIERMVQEAEK.YKAEDEKQRDKVS S KNSLESYAFNMKATVEDE KLQGKINDEDKQKILDKCNEIINWLDKNQTAEKEEFEHQQKELEK VCNPIITKLYQSAGGMPGGMPGGFPGGGAPPSGGASSGPTIEEVD
Heat shock protein cognate 71 kDa Variant S SEQ ID NO:75	MNPTNTVFDAKRLIGRRFDDAVVQSDMKHWPFMVVNDAGRPKV QVEYKGETKSFYPEEVSSMVLTKMKEIAEAYLGKTVTNAVVTVPA YFNDSQRQATKDAGTJAGLNVLRIINEPTAAAIAYGLDKKVGAER NVLIFDLGGGTFDVSILTIEDGIFEVKSTAGDTHLGGEDFDNRMVN HFIAEFKRKHKKDISENKRAVRRLRTACERAKRTLSSSTQASIEIDS LYEGIDFYTSITRARFEELNADLFRGTLDPVEKALRDAKLDKSQIH DIVLVGGSTRIPKIQKLLQDFFNGKELNKSINPDEAVAYG
Heat shock protein cognate 71 kDa Variant 9 SEQ ID NO:76	MSKGPAVG1DLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERL1GDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTA AAIAYGLDK
Heat shock protein cognate 71 kDa Variant 10 SEQ ID NO:77	MTVLIKRNTTIPTKQTQTFTTYSDNQPGVLIQVYEGERAMTKDNNL LGKFELTGIPPAPRGVPQIEVTFDIDANGILNVSAVDKSTGKENKITI TNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVSSKNSLESYAFN MKATVEDEKLQGKINDEDKQKILDKCNEIINWLDKNQTAEKEEFE HQQKELEKVCNP1ITKLYQSAGGMPGGMPGGFPGGGAPP
Heat shock protein cognate 71 kDa Variant 11 SEQ ID NO:78	MTKDNNLLGKFELTGIPPAPRGVPQIEVTFDIDANGILNVSAVDKST GKENKITITNDKGRLSKEDIERMVQEAEKYKAEDEKQRDKVS S KN SLESYAFNMKATVEDEKLQGKINDEDKQKILDKCNEHNWLDKNQ TAEKEEFEHQQKE
Heat shock protein cognate 71 kDa	M SKGP AVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTP S YVAFT

Variant 12 SEQ ID NO:79	DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAWTVPAYFNDSQRQATKDAGTIAGLNVLR
Fleat shock protein cognate 71 kDa Variant 13 SEQ ID NO:80	MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAK.RLIGRRFDDAWQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAE
Heat shock protein cognate 71 kDa Variant 14 SEQ ID NO:81	MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTP S YVAFT DTERLIGDAAKNQVAMNPTNTVEDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAWTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTA AAIAY
Heat shock protein cognate 71 kDa Variant 15 SEQ ID NO:82	MSKGPAVG1DLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFETKSFYPEEVSSMVLTKMKEIA EAYLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPT AAAIAYGLDKKVGAERNVLIFDLGGGTFDVSI
Heat shock protein cognate 71 kDa Variant 16 SEQ ID NO:83	MSKGPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAFT DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGKTVTNAVVTVPAYFNDSQRQATKDAGTIAGLNVLRIINEPTA
Heat shock protein cognate 71 kDa Variant 17 SEQ ID NO:84	MSK.GPAVGIDLGTTYSCVGVFQHGKVEIIANDQGNRTTPSYVAF'f DTERLIGDAAKNQVAMNPTNTVFDAKRLIGRRFDDAVVQSDMKH WPFMVVNDAGRPKVQVEYKGETKSFYPEEVSSMVLTKMKEIAEA YLGK
Ankyrin-3 Variant 2 SEQ ID NO:85	MASSASSSPAGTEDSAPAQGGFGSDYSRSSRKSDANASYLRAARA GHLEKALDYIKNGVDINICNQNGLNALHLASKEGHVEVVSELLQR EANVDAATKKGNTALHIASLAGQAEVVKVLVTNGANVNAQSQN GFTPLYMAAQENHLEWKFLLDNGASQSLATEDGFTPLAVALQQG HDQVVSLLLENDTKGKVRLPALHIAARKDDTKAAALLLQNDNNA DVESKSGFTPLHIAAHYGNINVATLLLNRAAAVDFTARNDITPLHV ASKRGNANMVKLLLDRGAKIDAKTRDGLTPLHCGARSGHEQVVE MLLDRAAPILSKTKNGLSPLHMATQGDHLNCVQLLLQHNVPVDD VTNDYLTALHVAAHCGHYKVAKVLLDKKANPNAK.ALNGFTPLHI ACKKNRIKVMELLLKHGASIQAVTESGLTPIHVAAFMGHVNIVSQL MHHGASPNTTNVRGETALHMAARSGQAEVVRYLVQDGAQVEAK AKDDQTPLHISARLGKADIVQQLLQQGASPNAATTSGYTPLHLSAR EGHEDVAAFLLDHGASLSITTKKGFTPLHVAAKYGKLEVANLLLQ KSASPDAAGKSGLTPLHVAAHYDNQKVALLLLDQGASPHAAAKN GYTPLHIAAKKNQMDIATTLLEYGADANAVTRQGIASVHLAAQEG HVDMVSLLLGRNANVNLSNKSGLTPLHLAAQEDRVNVAEVLVNQ GAHVDAQTKMGYTPLHVGCHYGNIKIVNFLLQHSAKVNAKTKNG YTPLHQAAQQGHTHIINVLLQNNASPNELTVNGNTALGIARRLGYI SWDTLKIVTEETMTTTTVTEKHKMNVPETMNEVLDMSDDEVRK ANAPEMLSDGEYISDVEEGEDAMTGDTDKYLGPQDLKELGDDSLP AEGYMGFSLGARSASLRSFSSDRSYTLNRSSYARDSMM1EELLVPS KEQHLTFTREFDSDSLRHYSWAADTLDNVNLVSSPIHSGFLVSFMV DARGGSMRGSRHHGMRIIIPPRKCTAPTRITCRLVKRHKLANPPPM VEGEGLASRLVEMGPAGAQFLGPV1VEIPHFGSMRGKERELIVLRS ENGETWKEHQFDSKNEDLTELLNGMDEELDSPEELGKKRICR1ITK DFPQYFAVVSRIKQESNQIGPEGGILSSTTVPLVQASFPEGALTKRIR VGLQAQPVPDEIVKKILGNKATFSPIVTVEPRRRKFHKPITMTIPVPP PSGEGVSNGYKGDTTPNLRLLCSITGGTSPAQWEDITGTTPLTF1KD

	CVSFTTNVSARFWLADCHQVLETVGLATQLYRELICVPYMAKFVV FAKMNDPVESSLRCFCMTDDKVDKTLEQQENFEEVARSKDIEVLE GKPIYVDCYGNLAPLTKGGQQLVFNFYSFKENRLPFSIKIRDTSQEP CGRLSFLKEPKTTKGLPQTAVCNLNITLPAHKKIEKTDRRQSFASL ALRKRYSYLTEPGMSPQSPCERTDIRMA1VADHLGLSWTELARELN FSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNATTDALTSVLT KINRIDIVTLLEGPIFDYGNISGTRSFADENNVFHDPVDGYPSLQVE LETPTGLHYTPPTPFQQDDYFSDISSIESPLRTPSRLSDGLVPSQGNIE HSADGPPVVTAEDASLEDSKLEDSVPLTEMPEAVDVDESQLENVC LSWQNETSSGNLESCAQARRVTGGLLDRLDDSPDQCRDSITSYLK GEAGKFEANGSHTEITPEAKTKSYFPESQNDVGKQSTKETLKPKIH GSGHVEEPASPLAAYQKSLEETSKLIIEETKPCVPVSMKKMSRTSPA DGKPRLSLHEEEGSSGSEQKQGEGFKVKTKKEIRI-IVEKKSHS
Ankyrin-3 Variant 3 SEQ ID NO:S6	MSEEPKEKNAKPAHRKRKGKKSDANASYLRAARAGHLEKALDYI KNGVDIN1CNQNGLNALHLASKEGHVEWSELLQREANVDAATK KGNTALHIASLAGQAEWKVLVTNGANVNAQSQNGFTPLYMAAQ ENHLEWKFLLDNGASQSLATEDGFTPLAVALQQGHDQVVSLLLE NDTKGKVRLPALHIAARKDDTKAAALLLQNDNNADVESKSGFTPL HIAAHYGNINVATLLLNRAAAVDFTARNDITPLHVASKRGNANMV KLLLDRGAKIDAKTRDGLTPLHCGARSGHEQVVEMLLDRAAPILS KTKNGLSPLHMATQGDHLNCVQLLLQHNVPVDDVTNDYLTALHV AAHCGHYKVAK.VLLDKKANPNAKALNGFTPLHIACKKNRIKVME LLLKHGASIQAVTESGLTPIHVAAFMGHVNIVSQLMHHGASPNTT NVRGETALHMAARSGQAEVVRYLVQDGAQVEAKAKDDQTPLHIS ARLGKADIVQQLLQQGASPNAATTSGYTPLHLSAREGHEDVAAFL LDHGASLSITTKKGFTPLEIVAAKYGKLEVANLLLQKSASPDAAGK SGLTPLHVAAHYDNQKVALLLLDQGASPHAAAKNGYTPLHIAAK KNQMDIATTLLEYGADANAVTRQGIASVHLAAQEGHVDMVSLLL GRNANVNLSNKSGLTPLHLAAQEDRVNVAEVLVNQGAHVDAQT KMGYTPLHVGCHYGN1KIVNFLLQHSAKVNAKTKNGYTPLHQAA QQGHTHIINVLLQNNASPNELTVNGNTALGIARRLGYISWDTLKl VTEETMTTTTVTEKHKMNVPETMNEVLDMSDDEVRKANAPEMLS DGEYISDVEEGNRCTWYKIPKVQEFTVKSEDAMTGDTDKYLGPQD LKELGDDSLPAEGYMGFSLGARSASLRSFSSDRSYTLNRSSYARDS MMIEELLVPSKEQHLTFTREFDSDSLRHYSWAADTLDNVNLVSSPI HSGFLVSFMVDARGGSMRGSRFIHGMRIIIPPRKCTAPTRITCRLVK RHKLANPPPMVEGEGLASRLVEMGPAGAQFLGPVIVEIPHFGSMR GKEREL1VLRSENGETWKEHQFDSKNEDLTELLNGMDEELDSPEEL GKKRICRIITKDFPQYFAVVSRIKQESNQIGPEGGILSSTTVPLVQAS FPEGALTKRIRVGLQAQPVPDEIVKKILGNKATFSPIVTVEPRRRKF FIKPITMTIPVPPPSGEGVSNGYKGDTTPNLRLLCS1TGGTSPAQWED ITGTTPLTFIKDCVSFTTNVSARFWLADCHQVLETVGLATQLYRELI CVPYMAKFVVFAKMNDPVESSLRCFCMTDDKVDKTLEQQENFEE VARSKDIEVLEGKPIYVDCYGNLAPLTKGGQQLVFNFYSFKENRLP FSIKIRDTSQEPCGRLSFLKEPKTTKGLPQTAVCNLNITLPAHKK.IEK TDRRQSFASLALRKRYSYLTEPGMSPQSPCERTDIRMAIVADHLGL SWTELARELNFSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNA TTDALTSVLTKINRIDIVTLLEGP1FDYGNTSGTRSFADENNVFHDPV DGYPSLQVELETPTGLHYTPPTPFQQDDYFSDISSIESPLRTPSRLSD GLVPSQGNIEHSADGPPVVTAEDASLEDSKLEDSVPLTEMPEAVDV DESQLENVCLSWQNETSSGNLESCAQARRVTGGLLDRLDDSPDQC RDSITSYLKGEAGKFEANGSHTEITPEAKTKSYFPESQNDVGKQST KETLKPKIHGSGHVEEPASPLAAYQKSLEETSKLIIEETKPCVPVSM KKMSRTSPADGKPRLSLHEEEGSSGSEQKQGEGFKVKTKKEIRHV EKKSHS
Ankyrin-3	MALPQSEDAMTGDTDKYLGPQDLKELGDDSLPAEGYMGFST.GAR |

Variant 4	SASLRSFSSDRSYTLNRSSYARDSMMIEELLVPSKEQHLTFTREFDS DSLRHYSWAADTLDNVNLVSSPIHSGFLVSFMVDARGGSMRGSR
SEQ ID NO:S7	HHGMRIIIPPRKCTAPTRITCRLVKRHKLANPPPMVEGEGLASRLVE MGPAGAQFLGPVIVEIPHFGSMRGKERELIVLRSENGETWKEHQFD SKNEDLTELLNGMDEELDSPEELGKKRICRI1TKDFPQYFAVVSRIK QESNQ1GPEGGILSSTTVPLVQASFPEGALTKRIRVGLQAQPVPDEI VKK1LGNKATFSPIVTVEPRRRKFFIKPITMTIPVPPPSGEGVSNGYK GDTTPNLRLLCSITGGTSPAQWEDITGTTPLTFIKDCVSFTTNVSAR FWLADCHQVLETVGLATQLYRELICVPYMAKFVVFAKMNDPVES SLRCFCMTDDKVDKTLEQQENFEEVARSKDIEVLEGKPIYVDCYG NLAPLTKGGQQLVFNFYSFKENRLPFSIKIRDTSQEPCGRLSFLKEP KTTKGLPQTAVCNLN1TLPAHKKIEKTDRRQSFASLALRKRYSYLT EPGMSPQSPCERTDIRMAIVADHLGLSWTELARELNFSVDEINQIR VENPNSLISQSFMLLKKWVTRDGKNATTDALTSVLTKJNRIDIVTL LEGPIFDYGNISGTRSFADENNVFHDPVDGYPSLQVELETPTGLHY TPPTPFQQDDYFSDISSIESPLRTPSRLSDGLVPSQGNIEHSADGPPV VTAEDASLEDSKLEDSVPLTEMPEAVDVDESQLENVCLSWQNETS SGNLESCAQARRVTGGLLDRLDDSPDQCRDSITSYLKGEAGKFEA NGSHTEFrPEAKTKSYFPESQNDVGKQSTKETLKPKIHGSGHVEEP ASPLAAYQKSLEETSKLIIEETKPCVPVSMKKMSRTSPADGKPRLSL HEEEGSSGSEQKQGEGFKVKTKKEIRHVEKKSHS
Ankyrin-3 Variant 5	XFLVSFMVDARGGSMRGSRHHGMRIIIPPRKCTAPTRITCRLVKRH KLANPPPMVEGEGLASRLVEMGPAGAQFLGPVIVEIPHFGSMRGK EREL1VLRSENGETWKEHQFDSKNEDLTELLNGMDEELDSPEELGK
SEQ1DNO:88	KRICR1ITKDFPQYFAWSRIKQESNQIGPEGGILSSTTVPLVQASFPE GALTKRIRVGLQAQPVPDEIVKKILGNKATFSPIVTVEPRRRKFHKP ITMTIPVPPPSGEGVSNGYKGDTTPNLRLLCSITGGTSPAQWEDITG TTPLTFIKDCVSFTTNVSARFWLADCHQVLETVGLATQLYRELICV PYMAKFWFAKMNDPVESSLRCFCMTDDKVDKTLEQQENFEEVA RSKDIEVLEGKPIYVDCYGNLAPLTKGGQQLVFNFYSFKENRLPFSI KIRDTSQEPCGRLSFLKEPKTTKGLPQTAVCNLNITLPAHKKIEKTD RRQSFASLALRKRYSYLTEPGMKTVERSTGATRSLPTTYSYKPFFS TRPYQSWTTAPITVPGPAKSGFTSLSSSSSNTPSASPLKSIWSVSTPS PIK.STLGASTTSSVKSISDVASPIRSFRTMSSPIKTWSQSPYNIQVSS GTLARAPAVTEATPLKGLASNSTFSSRTSPVTTAGSLLERSSITMTP PASPKSNTNMYSSSLPFKSIITSAAPLISSPLKSWSPVKSAVDVISSA KITMASSLSSPVKQMPGHAEVALVNGSISPLKYPSSSTLINGCKATA TLQEKISSATNSVSSVVSAATDTVEKVFSTTTAMPFSPLRSYVSAAP SAFQSLRTPSASALYTSLGSSISATTSSVTSSIITVPVYSVVNVLPEPA LKKLPDSNSFTKSAAALLSPIKTLTTETHPQPHFSRTSSPVKSSLFLA PSALKLSTPSSLSSSQEILKDVAEMKEDLMRMTAILQTDVPEEKPFQ PELPKEGR1DDEEPFKIVEKVKEDLVKVSEILKKDVCVDNKGSPKSP KSDKGHSPEDDWIEFSSEEIREARQQAAASQSPSLPERVQVKAKAA SEKDYNLTKVIDYLTNDIGSSSLTNLKYKFEDAKKDGEERQKRVL KPAIALQEHKLKMPPASMRTSTSEKELCKMADSFFGTDTILESPDD FSQHDQDKSPLSDSGFETRSEKTPSAPQSAESTGPKPLFHEVPTPPVI TETRTEWHVIRSYDPSAGDVPQTQPEEPVSPKPSPTFMELEPKPTT SSIKEKYKAFQMKASSEEDDHNRVLSKGMRVKEETHITTTTRMVY HSPPGGEGASERIEETMSVHDIMKAFQSGRDPSKELAGLFEHKSAV SPDVHKSAAETSAQHAEKDNQMKPKLERIIEVHIEKGPQSPCERTDI RMAIVADFILGLSWTELARELNFSVDEINQIRVENPNSLISQSFMLL KKWVTRDGKNATTDALTSVLTKINRIDIVTLLEGPIFDYGNISGTRS FADENNVFHDPVDGWQNETSSGNLESCAQARRVTGGLLDRLDDS PDQCRDSITSYLKGEAGKFEANGSHTEITPEAKTKSYFPESQNDVG KQSTKETLKPKIHGSGHVEEPASPLAAYQKSLEETSKLIIEETKPCV PVSMKKMSRTSPADGKPRLSLHEEEGSSGSEQKQGEGFKVKTKKE IRHVEKKSHS

Ankyrin-3 Variant 6	XPVIVEIPHFGSMRGKERELIVLRSENGETWKEHQFDSKNEDLTEL LNGMDEELDSPEELGKKRICRIITKDFPQYFAWSRIKQESNQIGPE GGILSSTTVPLVQASFPEGALTKRIRVGLQAQPVPDEIVKKILGNKA
SEQ ID NO:89	TFSPIVTVEPRRRKFHKPITMTIPVPPPSGEGVSNGYKGDTTPNLRL LCSITGGTSPAQWEDITGTTPLTFIKDCVSFTTNVSARFWLADCHQ VLETVGLATQLYRELICVPYMAKFVVFAKMNDPVESSLRCFCMTD DKVDKTLEQQENFEEVARSKDIEVLEGKPIYVDCYGNLAPLTKGG QQLVFNFYSFKENRLPFSIKIRDTSQEPCGRLSFLKEPKTTKGLPQT AVCNLNITLPAHKKETESDQDDEIEKTDRRQSFASLALRPQSPCERT DIRMAIVADHLGLSWTELARELNFSVDEINQIRVENPNSLISQSFML LKKWVTRDGKNATTDALTSVLTKINRIDIVTLLEGPIFDYGNISGTR SFADENNVFHDPVDGYPSLQVELETPTGLHYTPPTPFQQDDYFSDI SSIESPLRTPSRLSDGLVPSQGNIEHSADGPPWTAEDASLEDSKLE DSVPLTEMPEAVDVDESQLENVCLSEYPQYLGNLAGSPKDVKPAE PRKLGVSSEQQEKGKSGPDEEMMEEKLKSLFEDIQLEEGVESEEMT EEKVQAILKRVQQAELEMSSITGWQNETSSGNLESCAQARRVTGG LLDRLDDSPDQCRDSITSYLKGEAGKFEANGSHTEITPEAKTKSYFP ESQNDVGKQSTKETLKPKniGSGHVEEPASPLAAYQKSLEETSKLII EETKPCVPVSMKKMSRTSPADGKPRLSLHEEEGSSGSEQKDLKDS ESDSSSEEERRVTTRVIRRRLIIKGEEAKNIPGESVTEEQFTDEEGNLI TRKITRKVLRRIVIPQERKRDDVQGEGFKVKTKKEIRI-IVEKKSHS
Ankyrin-3 Variant 7	PKTTKGLPQTAVCNLNITLPAHKKETESDQDDEIEKTDRRQSFASL ALRKRYSYLTEPGMSPQSPCERTDIRMAIVADHLGLSWTELARELN FSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNATTDALTSVLT
SEQ ID NO:90	KINRIDIVTLLEGPIFDYGNÏSGTRSFADENNVFHDPVDGYPSLQVE LETPTGLITYTPPTPFQQDDYFSDISSIESPLRTPSRLSDGLVPSQGN1E HSADGPPWTAEDASLEDSKLEDSVPLTEMPEAVDVDESQLENVC LSWQNETSSGNLESCAQARRVTGGLLDRLDDSPDQCRDSITSYLK. GEAGKFEANGSHTEITPEAKTKSYFPESQNDVGKQSTKETLKPKIH GSGHVEEPASPLAAYQKSLEETSKLIIEETKPCVPVSMKKMSRTSPA DGKPRLSLHEEEGSSGSEQKQGEGFKVKTKKEIRHVEKKSHS
Ankyrin-3 Variant 8	XLARELNFSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNATTD ALTSVLTKINRIDIVTLLEGPIFDYGNISGTRSFADENNVFHDPVDG MP ï
SEQ ID N0:91
Ankyrin-3 Variant 9	XGPDEDKPPSKSSSSEKTPDKTDQKSGAQFFTLEGRHPDRSVFPDT YFSYKVDEEFATPFKTVATKGLDFDPWSNNRGDDEVFDSKSREDE TKPFGLAVEDRSPATTPDTTPARTPTDESTPTSEPNPFPFHEGKMFE
SEQ ID NO:92	MTRSGAIDMSKRDFVEERLQFFQIGPQSPCERTDIRMAIVADHLGL SWTELARELNFSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNA TIDALTSVLTKINRIDIVTLLEGPIFDYGNISGTRSFADENNVFHDPV DGWQNETSSGNLESCAQARRVTGGLLDRLDDSPDQCRDSITSYL
Ankyrin-3 Variant 10	MAVEEGESFPEQSDANASYLRAARAGHLEKALDYIKNGVDIN1CN QNGLNALHLASKEGHVEWSELLQREANVDAATKKGNTALHIAS
SEQ ID NO:93	LAGQAEWKVLVTNGANVNAQSQNGFTPLYMAAQENHLEWKF LLDNGASQSLATEDGFTPLAVALQQGHDQVVSLLLENDTKGKVRL PALHIAARKDDTKAAALLLQNDNNADVESKSGFTPLHIAAHYGNI NVATLLLNRAAAVDFTARNDITPLHVASKRGNANMVKLLLDRGA KIDAKTR
Ankyrin-3 Variant 11	MAVEEGESFPEQSDANASYLRAARAGHLEKALDYIKNGVDINICN QNGLNALHLASKEGHVEVVSELLQREANVDAATKKGNTALHIAS LAGQAEVVKVLVTNGANVNAQSQNGFTPLYMAAQENHLEWKF

SEQ ID NO:94	LLDNGASQSLATEDGFTPLAVALQQGHDQVVSLLLENDTKGKVRL PALHIAARKDDTKAAALLLQNDNNADVESKSGFTPLHIAAHYGN1 NVATLLLNRAAAVDFTARNDITPLHVASKRGNANMVKLLLDRGA KIDAKTR
Ankyrin-3 Variant 12 SEQ ID NO:95	XTVATKGLDFDPWSNNRGDDEVFDSKSREDETKPFGLAVEDRSPA TTPDTTPARTPTDESTPTSEPNPFPFHEGKMFEMTRSGAIDMSKRDF VEERLQFFQIGPQSPCERTDIRMAIVADHLGLSWTELARELNFSVD EINQIRVENPNSLISQSFMLLKKWVTRDGKNATTDALTSVLTKINRI DIVTLLEGPIFDYGNISGTRSFADENNVFHDPVDGYPSLQVELETPT GLHYTPPTP
Ankyrin-3 Variant 13 SEQ ID NO:96	XWQNETSSGNLESCAQARRVTGGLLDRLDDSPDQCRDSITSYLKG EAGKFEANGSHTE1TPEAKTKSYFPESQNDVGKQSTKETLKPK.IHG SGHVEEPASPLAAYQKSLEETSKLIIEETKPCVPVSMKKMSRTSPAD GKPRLSLHEEEGSSGSEQKGEGFKVKTKKEIRHVEKKSHS
Ankyrin-3 Variant 14 SEQ ID NO:97	MNVPETMNEVLDMSDDEGNRCTWYK1PKVQEFTVKSEDAMTGD TDKYLGPQDLKELGDDSLPAEGYMGFSLGARSARYFVVAVFHS
Ankyrin-3 Variant 15 SEQ ID NO;98	MTGDTDKYLGPQDLKELGDDSLPAEGYMGFSLGARSASLRSFSSD RSYTLNRSSYARDSMMIEELLVPSKEQHLTFTREFDSDSLRHYSWA ADTLDNVNLVSSPIHSGFLVSFMVDARGGSMRGSRHHGMRIIIPPR KCTAPTRITCRLVKRHKLANPPPMVEGEGLASRLVEMGPAGAQFL GPVIVEIPHFGSM
Ankyrin-3 Variant 16 SEQ ID NO:99	SPDQCRDSITSYLKGEAGKFEANGSHTEITPEAKTKSYFPESQNDV GKQSTKETLKPK1HGSGHVEEPASPLAAYQKSLEETSKLIIEETKPC VPVSMKKMSRTSPADGKPRLSLHEEEGSSGSEQKVKSPGAAPTRM TACCYKQGEGFKVKTKKEIRHVEKKSHS
Ankyrin-3 Variant 17 SEQ ID N0:100	XLARELNFSVDEINQIRVENPNSLISQSFMLLKKWVTRDGKNATTD ALTSVLTKINRIDIVTLLEGPIFDYGNISGTRSFADENNVFHDPVDVS PNVLSSIGYPSLQVELETPTGLHYTPPTPFQQDDYFSDISSIESPLRTP SRLSDGLVPSQGNIEHSADGPPVVTAEDASLEDSKLEDSVPLTEMP EAVDVDESQLENVCLSWQNETSSGNLES
Ankyrin-3 Variant 18 SEQ IDNO:101	XEDAMTGDTDKYLGPQDLKELGDDSLPAEGYMGFSLGARSASPK1 SLRSFSSDRSYTLNRSSYARDSMMIEELLVPSKEQHLTFTREFDSDS LRHYSWAADTLDNVNLVSSPIHSGYSSPLPQYDSRFLVSFMVDAR GGSMRGSRHHGMRIIIPPRKCTAPTRITCRLVKRHKLANPPPMVEG EGLASRLVEMGPAGAQFL
Ankyrin-3 Variant 19 SEQ ID NO:102	XSSPIHSGFLVSFMVDARGGSMRGSRHHGMRIIIPPRKCTAPTRITC RLVKRHKLANPPPMVEGEGLASRLVEMGPAGAQFLGKLHLPTNPP PVNEGESLVSRILQLGPQGTKFIGPVIVEIPHFGSMRGKERELIVLRS ENGETWKEHQFDSKNEDLTELLNGMDEELDSPEELGKKRICRIITK DFPQYFAWS
Ankyrin-3 Variant 20 SEQ ID NO:103	MTGDTDKYLGPQDLKELGDDSLPAEGYMGFSLGARSASLRSFSSD RSYTLNRSSYARDSMMIEELLVPSKEQ
Ankyrin-3 Variant 21	XIEKTDRRQSFASLALRKRYSYLTEPGMSPQSPCERTDIRMAIVAD HLGLSWTELARELNFSVDEINQ1RVENPNSLISQSFMLLKKWVTRD

Ankyrin-3 Variant 22 SEQ ID NO:IÛ5	XSPLAAYQKSLEETSKLIIEETKPCVPVSMKKMSRTSPADGKPRLSL HEEEGSSGSEQKVKSPGAAPTRMTACCYKDLKDSESDSSSEEERR VTTRVIRRRLIIKGEEAKNIPGESVTEEQFTDEEGNLITRKITRKVLR R1VIPQERKRDDVQGEGFKVKTKKEIRFIVEKKSHS
Ankyrin-3 Variant 23 SEQ ID NO:1Q6	MTGDTDKYLGPQDLKELGDDSLPAEGYMGFSLGARSASLRSFSSD RSYTLNRSSYARDSMMIEELLVPSKEQHLTFTREFDSDSLRHYSWA ADTLDNVNLVSSPIHSGFLVSFMVDARGGSMRGSRHHGMRIIIPPR KCTAPTRITCRLVKRHKLANPP
Ankyrin-3 Variant 24 SEQ ID NO:107	MTGDTDKYLGPQDLKELGDDSLPAEGYMGFSLGARSASHAASTV AKELTDKTGRTNLSHIFQN
Rho GTPase-activating protein 23 Variant 2 SEQ ID NO: 108	MKSRPTKQKLKQRGILKERVFGCDLGEHLLNSGFEVPQVLQSCTA FIERYGIVDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYVQDIHS VGSLCKLYFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDVIQQ LPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPNLLRSK QIESACFSGTAAFMEVR1QSWVEFILNHVDVLFSGRISMAMQEGA ASLSRPKSLLVSSPSTKLLTLEEAQARTQAQVNSPIVTENKYIEVGE GPAALQGKFHTIIEFPLERKRPQNKMKKSPVGSWRSFFNLGKSSSV SKRKLQRNESEPSEMKAMALKGGRAEGTLRSAKSEESLTSLHAVD GDSKLFRPRRPRSSSDALSASFNGEMLGNRCNSYDNLPHDNESEEE GGLLH1PALMSPHSAEDVDLSPPDIGVASLDFDPMSFQCSPPKAESE CLESGASFLDSPGYSKDKPSANKKDAETGSSQCQTPGSTASSEPVS PLQEKLSPFFTLDLSPTEDKSSKPSSFTEKWYAFSPKIGRKLSKSPS MSISEPISVTLPPRVSEVIGTVSNTTAQNASSSTWDKCVEERDATNR SPTQIVKMKTNETVAQEAYESEVQPLDQVAAEEVELPGKEDQSVS S SQSKAVASGQTQTGA VTHDPPQD S VP VS S VS UPPPPPPKNVARM LALALAESAQQASTQSLK.RPGTSQAGYTNYGDIAVATTEDNLSSS YSAVALDKAYFQTDRPAEQFHLQNNAPGNCDHPLPETTATGDPTH SNTTESGEQHHQVDLTGNQPHQAYLSGDPEKARITSVPLDSEKSDD HVSFPEDQSGKNSMPTVSFLDQDQSPPRFYSGDQPPSYLGASVDKL HHPLEFADKSPTPPNLPSDKIYPPSGSPEENTSTATMTYMTTTPATA QMSTKEASWDVAEQPTTADFAAATLQRTHRTNRPLPPPPSQRSAE QPPVVGQVQAATNIGLNNSHKVQGVVPVPERPPEPRAMDDPASAF ISDSGAAAAQCPMATAVQPGLPEKVRDGARVPLLHLRAESVPAHP CGFPAPLPPTRMMESKM1AAIHSSSADATSSSNYHSFVTASSTSVD DALPLPLPVPQPKHASQKTVYSSFARPDVTTEPFGPDNCLHFNMTP NCQYRPQSVPPHHNKLEQHQVYGARSEPPASMGLRYNTYVAPGR NASGHHSKPCSRVEYVSSLSSSVRNTCYPEDIPPYPTIRRVQSLHAP PSSMIRSVPISRTEVPPDDEPAYCPRPLYQYKPYQSSQARSDYHVTQ LQPYFENGRVHYRYSPYSSSSSSYYSPDGALCDVDAYGTVQLRPL HRLPNRDFAFYNPRLQGKSLYSYAGLAPRPRANVTGYFSPNDHNV VSMPPAADVKE1TYTSWDLEDMEKYRMQSIRRESRARQKVKGPV MSQYDNMTPAVQDDLGGIYVIHLRSKSDPGKTGLLSVAEGKESRH AAKAISPEGEDRFYRRHPEAEMDRAHHHGGHGSTQPEKPSLPQKQ SSLRSRKLPDMGCSLPEHRAHQEASHRQFCESKNGPPYPQGAGQL DYGSKGIPDTSEPVSYHNSGVKYAASGQESLRLN'HKEVRLSKEME RPWVRQPSAPEKHSRDCYKEEEHLTQSIVPPPKPERSHSLKLHHTQ NVERDPSVLYQYQPHGKRQSSVTVVSQYDNLEDYHSLPQHQRGV FGGGGMGTYVPPGFPHPQSRTYATALGQGAFLPAELSLQHPETQIH AE
Rho GTPase-activating protein 23 Variant 3	MKSRPTKQKLKQRGILKERVFGCDLGEHLLNSGFEVPQVLQSCTA FIERYGIVDGIYRLSGVASNIQRLRHEFDSEHVPDLTKEPYVQDIHS VGSLCKLYFRELPNPLLTYQLYEKFS D AVS A ATDEERLIK1HD VIQQ

SEQ ID NO:109	LPPPHYRTLEFLMRHLSLLADYCSITNMI1AKNLAIVWAPNLLRSK QIESACFSGTAAFMEVRIQSXAA'EFILNHVDVLFSGRISMAMQEGA ASLSRPKSLLVSSPSTKLLTLEEAQARTQAQVNSPIVTENKYIEVGE GPAALQGKFHTIIEFPLERKRPQNKMKKSPVGSWRSFFNLGKSSSV SKRKLQRNESEPSEMKAMALKGGRAEGTLRSAKSEESLTSLHAVD GDSKLFRPRRPRSSSDALSASFNGEMLGNRCNSYDNLPHDNESEEE GGLLHIPALMSPHSAEDVDLSPPDIGVASLDFDPMSFQCSPPKAESE CLESGASELDSPGYSKDKPSANKKDAETGSSQCQTPGSTASSEPVS PLQEKLSPFFTLDLSPTEDKSSKPSSFTEKWYAFSPKIGRKLSKSPS MSISEPISVTLPPRVSEVIGTVSNTTAQNASSSTWDKCVEERDATNR SPTQIVKMKTNETVAQEAYESEVQPLDQVAAEEVELPGKEDQSVS SSQSKAVASGQTQTGAVTHDPPQDSVPVSSVSLIPPPPPPKNVARM LALALAESAQQASTQSLKRPGTSQAGYTNYGDIAVATTEDNLSSS YSAVALDKAYFQTDRPAEQFHLQNNAPGNCDHPLPETTATGDPTH SNTTESGEQHHQVDLTGNQPHQAYLSGDPEKARITSVPLDSEKSDD HVSFPEDQSGKNSMPTVSFLDQDQSPPRFYSGDQPPSYLGASVDKL HHPLEFADKSPTPPNLPSDKIYPPSGSPEENTSTATMTYMTTTPATAJ QMSTKEASWDVAEQPTTADFAAATLQRTHRTNRPLPPPPSQRSAE QPPVVGQVQAATNIGLNNSHKVQGVVPVPERPPEPRAMDDPASAF ISDSGAAAAQCPMATAVQPGLPEKVRDGARVPLLHLRAESVPAIIP CGFPAPLPPTRMMESKMIAAJHSSSADATSSSNYHSFVTASSTSVD DALPLPLPVPQPKHASQKTVYSSFARPDVTTEPFGPDNCLHFNMTP NCQYRPQSVPPHHNKLEQHQVYGARSEPPASMGLRYNTYVAPGR NASGHHSKPCSRVEYVSSLSSSVRNTCYPED1PPYPT1RRVQSLHAP PSSMIRSVPISRTEVPPDDEPAYCPRPLYQYKPYQSSQARSDYHVTQ LQPYFENGRVHYRYSPYSSSSSSYYSPDGALCDVDAYGTVQLRPL HRLPNRDFAFYNPRLQGKSLYSYAGLAPRPRANVTGYFSPNDHNV VSMPPAADVKHTYTSWDLEDMEKYRMQSIRRESRARQKVKGPV MSQYDNMTPAVQDDLGGIYVIHLRSKSDPGKTGLLSVAEGKESRH AAKAISPEGEDRFYRKHPEAEMDRAHHHGGHGSTQPEKPSLPQKQ SSLRSRKLPDMGCSLPEHRAHQEASHRQFCESKNGPPYPQGAGQL DYGSKGIPDTSEPVSYHNSGVKYAASGQESLRLNHKEVRLSKEME RPWVRQPSAPEKHSRDCYKEEEHLTQSIVPPPKPERSHSLKLHHTQ NVERDPSVLYQYQPHGKRQSSVTVVSQYDNLEDYHSLPQHQRGV FGGGGMGTYVPPGFPHPQSRTYATALGQGAFLPAELSLQHPETQIH AE
Rho GTPase-actîvating protein 23 Vari ant 4	MARGADVPEIPGDLTLKTCGSTASMKVKHVKKLPFTKGHFPKMA ECAHFHYENVEFGS1QLSLSEEQNEVMKNGCESKELVYLVQIACQ GKSWIVKRSYEDFRVLDKHLHLCIYDRRFSQLSELPRSDTLKDSPE
SEQ IDNOillO	SVTQMLMAYLSRLSAIAGNKINCGPALTWMEIDNKGNHLLVHEES SINTPAVGAAHVIKRYTARAPDELTLEVGDIVSVIDMPPKVLSTWW RGKHGFQVGLFPGHCVELINQKVFQSVTNSVPKPVSKKHGKLITFL RTFMKSRP1XQKLKQRGILKERVFGCDLGEHLLNSGFEVPQVLQS CTAFIERYGIVDGIYRLSGVASNÎQRJLRHEFDSEHVPDLTKEPYVQD IHSVGSLCKI.YFRELPNPLLTYQLYEKFSDAVSAATDEERLIKIHDV IQQLPPPHYRTLEFLMRHLSLLADYCSITNMHAKNLAIVWAPNLLR SKQIESACFSGTAAFMEVR1QSVVVEFILNHVDVLFSGRISMAMQE GAASLSRPKSLLVSSPSTKLLTLEEAQARTQAQVNSPIVTENKYIEV GEGPAALQGKFHTIIEFPLERKRPQNKMKKSPVGSWRSFFNLGKSS SVSKRKLQRNESEPSEMKAMALKGGRAEGTLRSAKSEESLTSLHA VDGDSKLFRPRRPRSSSDALSASFNGEMLGNRCNSYDNLPHDNES EEEGGLLHIPALMSPHSAEDVDLSPPDIGVASLDFDPMSFQCSPPKA ESECLESGASFLDSPGYSKDKPSANKKDAETGSSQCQTPGSTASSE PVSPLQEKLSPFFTLDLSPTEDKSSKPSSFTEKVVYÀFSPKIGRKLSK SPSMSISEPISVTLPPRVSEVIGTVSNTTAQNASSSTWDKCVEERDA TNRSPTQIVKMKTNETVAQEAYESEVQPLDQVAAEEVELPGKEDQ S VSSSQSKAVASGQTQTGTVCFPPFFL

Rho GTPase-activating protein 23 Variant 5	MKSSVHSEEDDFVPELHRNVHPRERPDWEETLSAMARGADVPEIP GDLTLKTCGSTASMKVKHVKKSTTPGLMGCDNIHRLPFTKGHFPK MAECAHFHYENVEFGSIQLSLSEEQNEVMKNGCESKELVYLVQIA
SEQ ID NO: 111	CQGKSWIVKRSYEDFRVLDKHLHLC1YDRRFSQLSELPRSDTL
Cytoskeletal Keratin 78 type II Variant 2	MEGHEASPAQVGQGDRGKVRFLEQQNKVLETKWHLLQQQGLSG SQQGLEPVFEACLDQLRKQLEQLQGERGALDAELKACRDQEEEYK SKYEEEAHRRATLENDFVVLKKDVDGVFLSKMELEGKLEALREYL
SEQ ID N0:112	YFLKHLNEEELGQLQTQASDTSVVLSMDNNRYLDFSSIITEVRARY EEIARSSKAEAEALYQTKYQELQVSAQLHGDRMQETKVQISQLHQ EIQRLQSQTENLKKQNASLQAAITDAEQRGELALKDAQAKVDELE AALRMAKQNLARLLCEYQELTSTKLSLDVEIATYRRLLEGEECRM SGECTSQVTISSVGGSAVMSGGVGGGLGSTCGLGSGKGSPGSCCTS 1VTGGSNI1LGS GKDPVLDSCSVSGS S AGS S CHTILKKTVES S LKTSIT Y $
Cytoskeletal Keratin 78 type II Variant 3	XDVEIATYRRLLEGEECSLGGRQRCHVWRSWWRLGEHLWTR

SFQ IDNO:113

Collagen type VI, alpha 3 Variant 2

MRKHRHLPLVAVFCLFLSGFPTTHAQQQQAAQDSADIIFLIDGSNN TGS VNFAVILDFLVNLLEKLPIGTQQIRVGVVQFS DEPRTMFS LDTY STKAQVLGAVKALGFAGGELANIGLALDFVVENHFTRAGGSRVEE

SEQ ID NO:114

GVPQVLVLISAGPSSDEIRYGVVALKQASVFSFGLGAQAASRAELQ HIATDDNLVFTVPEFRSFGDLQEKLLPY1VGVAQRHIVLKPPTIVTQ VIEVNKRDIVFLVDGSSALGLANFNAIRDFIAKVIQRLEIGQDLIQV AVAQYADTVRPEFYFNTFIPTKREVITAVRKMKPLDGSALYTGSAL DFVRNNLFTSSAGYRAAEGIPKLLVLITGGKSLDEISQPAQELKRSSI MAFAÏGNKGADQAELEEIAFDSSLVFIPAEFRAAPLQGMLPGLLAP LRTLSGTPEVHSNKRDIIFLLDGSANVGKTNFPYVRDFVMNLVNSL DIGNDNIRVGLVQFSDTPVTEFSLNTYQTKSDILGHLRQLQLQGGS GLNTGSALSYVYANHFTEAGGSRIREHVPQLLLLLTAGQSEDSYLQ AANALTRAGILTFCVGASQ ANKAELEQIAFNPSLVYLMDDFS SLPA LPQQLIQPLTTYVSGGVEEVPLAQPESKRJDILFLFDGSANLVGQFPV VRDFLYKIIDELNVKPEGTRIAVAQYSDDVKVESRFDEHQSKPEILN LVKRMKIKTGKALNLGYALDYAQRYIFVKSAGSRIEDGVLQFLVL LVAGRSSDRVDGPASNLKQSGVVPFIFQAKNADPAELEQIVLSPAFI LAAESLPKIGDLHPQIVNLLKSVHNGAPAPVSGEKDVVFLLDGSEG VRSGFPLLKEFVQRVVESLDVGQDRVRVAVVQYSDRTRPEFYLNS YMNKQDVVNAVRQLTLLGGPTPNTGAALEFVLRNILVSSAGSRIT EGVPQLLIVLTADRSGDDVRNPSVWKRGGAVPIGIGIGNADITEM QTISFIPDFAVAIPTFRQLGTVQQVISERVTQLTREELSRLQPVLQPL PSPGVGGKRDVVFLIDGSQSAGPEFQYVRTLIERLVDYLDVGFDTT RVAVIQFSDDPKXŒFLLNAHSSKDEVQNAVQRLRPKGGRQINVGN ALEYVSRNIFKRPLGSRIEEGVPQFLVLISSGKSDDEVDDPAVELKQ FGVAPFTIARNADQEELVKISLSPEYVFSVSTFRELPSLEQKLLTPrr TLTSEQIQKLLASTRYPPPAVESDAADIVFLIDSSEGVRPDGFAHIRD FVSRIVRRLNIGPSKVRVGWQFSFTOVFPEFYLKTYRSQAPVLDAI RRLRLRGGSPLNTGKALEFVARNLFVKSAGSRIEDGVPQHLVLVL G GKSQDDVSRFAQVI RS SGIVSLGVGDRNIDRTELQTITNDPRLVFT VREFRELPNIEERJMNSFGPSAATPAPPGVDTPPPSRPEKKKADIVFL LDGSINFRRDSFQEVLRFVSEIVDTVYEDGDSIQVGLVQYNSDPTD EFFLKDFSTKRQIIDAINKWYKGGRHANTKVGLEHLRVNHFVPEA GSRLDQRVPQIAFVITGGKSVEDAQDVSLALTQRGVKVFAVGVRN IDSEEVGKIASNSATAFRVGNVQELSELSEQVLETLHDAMHETLCP

	LDGSINFRRDSFQEVLRFVSEIVDTVYEDGDSIQVGLVQYNSDPTD EFFLKDFSTKRQ1IDAINKVVYKGGRHANTKVGLEHLRVNHFVPEA GSRLDQRVPQIAFVITGGKSVEDAQDVSLALTQRGVKVFAVGVRN IDSEEVGKIASNSATAFRVGNVQELSELSEQVLETLHDAMHETLCP GVTDAAKACNLDVILGFDGSRDQNVFVAQKGFESKVDAILNRISQ MHRVSCSGGRSPTVRVSVVANTPSGPVEAFDFDEYQPEMLEKFRN MRSQHPYVLTEDTLKVYLNKFRQSSPDSVKVVII-IFTDGADGDLAD LHRASENLRQEGVRALILVGLERVVNLERLMHLEFGRGFMYDRPL RLNLLDLDYELAEQLDNIAEKACCGVPCKCSGQRGDRGPIGSIGPK GIPGEDGYRGYPGDEGGPGERGPPGVNGTQGFQGCPGQRGVKGSR GFPGEKGEVGEIGLDGLDGEDGDKGLPGSSGEKGNPGRRGDKGPR GEKGERGDVGIRGDPGNPGQDSQERGPKGETGDLGPMGVPGRDG VPGGPGETGKNGGFGRRGPPGAKGNKGGPGQPGFEGEQGTRGAQ GPAGPAGPPGLIGEQGISGPRGSGGAAGAPGERGRTGPLGRKGEPG EPGPKGGIGNRGPRGETGDDGRDGVGSEGRRGKKGERGFPGYPGP KGNPGEPGLNGTTGPKGIRGRRGNSGPPGÏVGQKGDPGYPGPAGP KGNRGDSIDQCAL1QS1KDKCPCCYGPLECPVFPTELAFALDTSEGV NQDTFGRMRDVVLS1VNDLTIAESNCPRGARVAVVTYNNEVTTEI RFADSKRKSVLLDKIKNLQVALTSKQQSLETAMSFVARNTFKRVR NGFLMRKVAVFFSNTPTRASPQLREAVLKLSDAGITPLFLTRQEDR QL1NALQINNTAVGHALVLPAGRDLTDFLENVLTCHVCLDICNIDP SCGFGSWRPSFRDRRAAGSDVDIDMAFILDSAETTTLFQFNEMKK YIAYLVRQLDMSPDPKASQHFARVAVVQHAPSESVDNASMPPVK VEFSLTDYGSKEKLVDFLSRGMTQLQGTRALGSAIEYTIENVFESA PNPRDLKIVVLMLTGEVPEQQLEEAQRVILQAKCKGYFFVVLGIGR ΚνΝΙΚΕνΥΤΡΑ5ΕΡΝθνΕΕΚΕνϋΚ5ΤΕΕΝΕΕΡΕΜΡΕΟΕΕΕΡ5Εν55Ε NAFYLSPDIRKQCDWFQGDQPTKNLVKFGHKQVNVPNNVTSSPTS NPVTTTKPVTTTKPVTI'TTKPVTTTTKPVriINQPSVKPAAAKPAPA KPVAAKPVATKMATVRPPVAVKPATAAKPVAAKPAAVRPPAAAA AKPVATKPEVPRPQAAKPAATKPATTKPMVKMSREVQVFEITENS AKLHWERAEPPGPYFYDLTVTSAHDQSLVLKQNLTVTDRVIGGLL AGQTYHVAVVCYLRSQVRATYHGSFSTKKSQPPPPQPARSASSSTI NLMVSTEPLALTETDICKLPKDEGTCRDFILKWYYDPNTKSCARF WYGGCGGNENKFGSQKECEKVCAPVLAKPGVISVMGT
Collagen type VI. alpha 3 Variant 3	MRKFIRHLPLVAVFCLFLSGFPTTHAQQQQAAQDSADIIFLIDGSNN TGSVNFAVILDFLVNLLEKLPIGTQQIRVGWQFSDEPRTMFSLDTY STKAQVLGAVKALGFAGGELANÏGLALDFVVENHFTRAGGSRVEE
SEQ ID N0:115	OVPQVLVLISAGPSSDEIRYGWALKQASVFSFGLGAQAASRAELQ HIATDDNLVFTVPEFRSFGDLQEKLLPYIVGVAQRHIVLKPPTIVTQ VIEVNKRDIVFLVDGSSALGLANFNA1RDFIAKVIQRLEIGQDLIQV AVAQYADTVRPEFYFNTHPTKREVITAVRKMKPLDGSALYTGSAL DFVRNNLFTS SAGYRAAEGIPKLLVLITGGKSLDEISQPAQELKRS SI MAF AIGNKG ADQ AELEEIAFDS S LVFIP AEFRAAPLQGMLPGLLAP LRTLSGTPEVHSNKRD11FLLDGSANVGKTNFPYVRDFVMNLVNSL DIGNDNIRVGLVQFSDTPVTEFSLNTYQTKSDILGHLRQLQLQGGS GLNTGSALSYVYANHFTEAGGSRIREHVPQLLLLLTAGQSEDSYLQ AANALTRAGILTFCVGASQANKAELEQIAFNPSLVYLMDDFSSLPA LPQQLIQPLTTYVSGGVEEVPLAQPESKRDILFLFDGSANLVGQFPV VRDFLYKIIDELNVKPEGTRIAVAQYSDDVKVESRFDEHQSKPEILN LVKRMKIKTGKALNLGYALDYAQRYIFVKSAGSRIEDGVLQFLVL LVAGRSSDRVDGPASNLKQSGWPF1FQAKNADPAELEQIVLSPAFI LAAESLPKIGDLHPQIVNLLKSVHNGAPAPVSGEKDVVFLLDGSEG VRSGFPLLKEFVQRVVESLDVGQDRVRVAVVQYSDRTRPEFYLNS YMNKQDWNAVRQLTLLGGPTPNTGAALEFVLRNILVSSAGSRIT EGVPQLLIVLTADRSGDDVRNPSVVVKRGGAVPIGIGIGNADITEM QTISFÎPDFAVAIPTFRQLGTVQQVISERVTQLTREELSRLQPVLQPL PSPGVGGKRDVVFLIDGSQSAGPEFQYVRTLIERLVDYLDVGFDTT

	RVAVIQFSDDPKVEFLLNAHSSKDEVQNAVQRLRPKGGRQINVGN ALEYVSRNIFKRPLGSRIEEGVPQFLVLISSGKSDDEVDDPAVELKQ FGVAPFTIARNADQEELVKISLSPEYVFSVSTFRELPSLEQKLLTPIT TLTSEQIQKLLASTRYPPPAVESDAADIVFLIDSSEGVRPDGFAHIRD FVSRIVRRLNIGPSKVRVGWQFSNDVFPEFYLKTYRSQAPVLDA1 RRLRLRGGSPLNTGKALEFVARNLFVKSAGSRIEDGVPQHLVLVL GGKSQDDVSRFAQVIRSSGIVSLGVGDRNIDRTELQTITNDPRLVFT VREFRELPNIEERIMNSFGPSAATPAPPGVDTPPPSRPEKKKADÏVFL LDGSINFRRDSFQEVLRFVSEIVDTVYEDGDSIQVGLVQYNSDPTD EFFLKDFSTKRQIIDAINKVVYKGGRHANTKVGLEHLRVNHFVPEA GSRLDQRVPQIAFVITGGKSVEDAQDVSLALTQRGVKVFAVGVRN IDSEEVGKIASNSATAFRVGNVQELSELSEQVLETLHDAMHETLCP GVTDAAKACNLDVILGFDGSRDQNVFVAQKGFESK.VDAILNRISQ MHRVSCSGGRSPTVRVSVVANTPSGPVEAFDFDEYQPEMLEKFRN MRSQHPYVLTEDTLKVYLNKFRQSSPDSVKVVIHFTDGADGDLAD LHRASENLRQEGVRALILVGLERVVNLERLMHLEFGRGFMYDRPL RLNLLDLDYELAEQLDNIAEKACCGVPCKCSGQRGDRGPIGSIGPK. GIPGEDGYRGYPGDEGGPGERGPPGVNGTQGFQGCPGQRGVKGSR GFPGEKGEVGEIGLDGLDGEDGDKGLPGSSGEKGNPGRRGDKGPR GEKGERGDVGIRGDPGNPGQDSQERGPKGETGDLGPMGVPGRDG VPGGPGETGKNGGFGRRGPPGAKGNKGGPGQPGFEGEQGTRGAQ GPAGPAGPPGLIGEQGISGPRGSGGAAGAPGERGRTGPLGRKGEPG EPGPKGGIGNRGPRGETGDDGRDGVGSEGRRGKKGERGFPGYPGP KGNPGEPGLNGTTGPKGIRGRRGNSGPPGIVGQKGDPGYPGPAGP KGNRGDSIDQCALIQSIKDKCPCCYGPLECPVFPTELAFALDTSEGV NQDTFGRMRDVVLSIVNDLTIAESNCPRGARVAVVTYNNEVTTEI RF ADSKRKS VLLDKIKNLQVALTSKQQ SLETAMSFVARNTFKRVR NGFLMRKVAVFFSNTPTRASPQLREAVLKLSDAGITPLFLTRQEDR QLINALQINNTAVGHALVLPAGRDLTDFLENVLTCHVCLDICNIDP SCGFGSWRPSFRDRRAAGSDVDIDMAFILDSAETTTLFQFNEMKK YIAYLVRQLDMSPDPKASQHFARVAV VQHAP SE S VDNASMPPVK VEFSLTDYGSKEKLVDFLSRGMTQLQGTRALGSAIEYTIENVFESA PNPRDLKIVVLMLTGEVPEQQLEEAQRVILQAKCKGYFFVVLGIGR KVNIKEVYTFASEPNDVFFKLVDKSTELNEEPLMRFGRLLPSFVSSE NAFYLSPDIRKQCDWFQGDQPTKNLVKFGFIKQVNVPNNVTSSPTS NPVTTTKPVTTTKPVTTTTKPVTTTTKPVTIINQPSVKPAAAKPAPA KPVAAKPVATKMATVRPPVAVKPATAAKPVAAKPAAVRPPAAAA AKPVATKPEWRPQAAKPAATKPATTKPMVKMSREVQVFEITENS AKLHWERAEPPGPYFYDLTVTSAHDQSLVLKQNLTVTDRVIGGLL AGQTYHVAVVCYLRSQVRATYHGSFSTKKSQPPPPQPARSASSSTI NLMVSTEPLALTETD1CKLPKDEGTCRDFILKWYYDPNTKSCARF WYGGCGGNENKFGSQKECEKVCAPVLAKPGVISVMGT
Collagen type VI, alpha 3 Variant 4	MRKFIRHLPLVAVFCLFLSGFPTTI-IAQQQQAVIEVNKRDIVFLVDG SSALGLANFNAIRDFIAKV1QRLEIGQDLIQVAVAQYADTVRPEFYF NTHPTKREVITAVRKMKPLDGSALYTGSALDFVRNNLFTSSAGYR
SEQ ID N0:116	AAEGIPKLLVLITGGKSLDEISQPAQELKRSSIMAFAIGNKGADQAE LEEIAFDSSLVFIPAEFRAAPLQGMLPGLLAPLRTLSGTPEESKRDIL FLFDGSANLVGQFPVVRDFLYKIIDELNVKPEGTRIAVAQYSDDVK VESRFDEHQSKPEILNLVKRMKIKTGKALNLGYALDYAQRYIFVKS AGSRIEDGVLQFLVLLVAGRSSDRVDGPASNLKQSGWPFIFQAKN ADPAELEQIVLSPAFILAAESLPKIGDLHPQIVNLLKSVHNGAPAPV SGEKDWFLLDGSEGVRSGFPLLKEFVQRWESLDVGQDRVRVAV VQYSDRTRPEFYLNSYMNKQDWNAVRQLTLLGGPTPNTGAALE FVLRNILVSSAGSRITEGVPQLLIVLTADRSGDDVRNPSVVVKRGG AVPIGIGIGNADITEMQT1SFIPDFAVAIPTFRQLGTVQQVISERVTQL TREELSRLQPVLQPLPSPGVGGKRDVVFLIDGSQSAGPEFQYVRTLI ERLVDYLDVGFDTTRVAVIQFSDDPKVEFLLNAHSSKDEVQNAVQ

	RERPKGGRQINVGNALEYVSRNIFKRPLGSRIEEGXTQFLVLISSGK SDDEVDDPAVELKQFGVAPFTIARNADQEELVKISLSPEYVFSVSTF RELPSLEQKLLTPITTLTSEQIQKLLASTRYPPPAVESDAADIVFLIDS SEGVRPDGFAHIRDFVSRIVRRLNIGPSKVRVGWQFSNDVFPEFYL KTYRSQAPVLDAIRRLRLRGGSPLNTGKALEFVARNLFVKSAGSRI EDGVPQHLVLVLGGKSQDDVSRFAQVIRSSGIVSLGVGDRNIDRTE LQTITNDPRLVFTVREFRELPNIEERIMNSFGPSAATPAPPGVDTPPP SRPEKKKADIVFLLDGSINFRRDSFQEVLRFVSEIVDTVYEDGDSIQ VGLVQYNSDPTDEFFLKDFSTKRQIIDAINKWYKGGRHANTKVG LEHLRVNHFVPEAGSRLDQRVPQIAFVITGGKSVEDAQDVSLALTQ RGVKVFAVGVRNIDSEEVGKIASNSATAFRVGNVQELSELSEQVLE TLHDAMHETLCPGVTDAAKACNLDVILGFDGSRDQNVFVAQKGF ESKVDAILNRISQMHRVSCSGGRSPTVRVSWANTPSGPVEAFDFD EYQPEMLEKFRNMRSQHPYVLTEDTLKVYLNKFRQSSPDSVKWI HFTDGADGDLADLHRASENLRQEGVRALILVGLERVVNLERLMH LEFGRGFMYDRPLRLNLLDLDYELAEQLDNIAEKACCGVPCKCSG QRGDRGPIGS1GPKGIPGEDGYRGYPGDEGGPGERGPPGVNGTQGF QGCPGQRGVKGSRGFPGEKGEVGEIGLDGLDGEDGDKGLPGSSGE KGNPGRRGDKGPRGEKGERGDVGIRGDPGNPGQDSQERGPKGET GDLGPMGVPGRDGVPGGPGETGKNGGFGRRGPPGAKGNKGGPG QPGFEGEQGTRGAQGPAGPAGPPGLIGEQGISGPRGSGGAAGAPGE RGRTGPLGRKGEPGEPGPKGGIGNRGPRGETGDDGRDGVGSEGRR GKKGERGFPGYPGPKGNPGEPGLNGTTGPKGIRGRRGNSGPPGIVG QKGDPGYPGPAGPKGNRGDSIDQCALIQSIKDKCPCCYGPLECPVF PTELAFALDTSEGVNQDTFGRMRDVVLSIVNDLTIAESNCPRGARV AVVTYNNEVTTEIRFADSKRKSVLLDKÏKNI.QVALTSKQQSLETA MSFVARNTFKRVRNGFLMRKVAVFFSNTPTRASPQLREAVLKLSD AGITPLFLTRQEDRQLINALQINNTAVGHALVLPAGRDLTDFLENV LTCHVCLDICNIDPSCGFGSWRPSFRDRRAAGSDVDIDMAF1LDSA ETTTLFQFNEMKKYIAYLVRQLDMSPDPKASQHFARVAWQHAPS ESVDNASMPPVKVEFSLTDYGSKEKLVDFLSRGMTQLQGTRALGS AIEYTIENVFESAPNPRDLKIWLMLTGEVPEQQLEEAQRVILQAKC KGYFFVVLGIGRKVNIKEVYTFASEPNDVFFKLVDKSTELNEEPLM RFGRLLPSFVSSENAFYLSPDIRKQCDWFQGDQPTKNLVKFGHKQ VNVPNNVTSSPTSNPVTTTKPVTTTKPVTTTTKPVTTTTKPVTIINQ PSVKPAAAKPAPAKPVAAKPVATKMATVRPPVAVKPATAAKPVA AKPAAVRPPAAAAAKPVATKPEVPRPQAAKPAATKPATTKPMVK MSREVQVFEITENSAKLHWERAEPPGPYFYDLTVTSAHDQSLVLK QNLTVTDRVIGGLLAGQTYHVAVVCYLRSQVRATYHGSFSTKKSQ PPPPQPARSASSSTINLMVSTEPLALTETDICKLPKDEGTCRDFILKW YYDPNTKSCARFWYGGCGGNENKFGSQKECEKVCAPVLAKPGVI SVMGT
Collagen type VI, alpha 3 Variant 5	MRKHRHLPLVAVFCLFLSGFPTTHAQQQQAAQDSADIIFLIDGSNN TGSVNFAVILDFLVNLLEKLPIGTQQIRVGVVQFSDEPRTMFSLDTY
SEQ ID N0:117	STKAQVLGAVKALGFAGGELANIGLALDFVVENHFTRAGGSRVEE GVPQVLVLISAGPSSDEIRYGWALKQASVFSFGLGAQAASRAELQ HIATDDNLVFTVPEFRSFGDLQEKLLPYIVGVAQRHIVLKPPTIVTQ VIEVNKRDIVFLVDGSSALGLANFNAIRDFIAKVIQRLEIGQDLIQV AVAQYADTVRPEFYFNTHPTKREVITAVRKMKPLDGSALYTGSAL DFVRNNLFTSSAGYRAAEGIPKLLVLITGGKSLDEISQPAQELKRSSI MAFAIGNKGADQAELEEIAFDSSLVFIPAEFRAAPLQGMLPGLLAP lrtlsgtpevhsnkrdiiflldgsanvgktnfpyvrdfvmnlvnsl DIGNDNIRVGLVQFSDTPVTEFSLNTYQTKSDILGHLRQLQLQGGS GLNTGSALSYVYANHFTEAGGSRIREHVPQLLLLLTAGQSEDSYLQ aanaltragiltfcvgasqankaeleqiafnpslvylmddfsslpa lpqqliqplttyvsggveevplaqpeskrdilflfdgsanlvgqfpv vrdflykiidelnvkpegtriavaoysddvkvesrfdehqskpf.tt.n

	LVKRMK1KTGKALNLGYALDYAQRYIFVKSAGSRIEDGVLQFLVL LVAGRSSDRVDGPASNLKQSGVVPFIFQAK.NADPAELEQIVLSPAFI LAAESLPKIGDLHPQIVNLLKSVHNGAPAPVSGEKDVVFLLDGSEG VRSGFPLLKEFVQRVVESLDVGQDRVRVAVVQYSDRTRPEFYLNS YMNKQDWNAVRQLTLLGGPTPNTGAALEFVLRNILVSSAGSRIT EGVPQLLIVLTADRSGDDVRNPSWVKRGGAVPIGIGIGNADITEM QTISFIPDFAVAIPTFRQLGTVQQVISERVTQLTREELSRLQPVEQPL PSPGVGGKRDVVFLIDGSQSAGPEFQYVRTLIERLVDYLDVGFDET RVAVIQFSDDPKVEFLLNAHSSKDEVQNAVQRLRPKGGRQINVGN ALEYVSRNIFKRPLGSRIEEGVPQFLVLISSGKSDDEVDDPAVELKQ FGVAPFTIARNADQEELVKISLSPEYVFSVSTFRELPSLEQKLLTPIT TLTSEQIQKLLASTRYPPPGEMGASEVLLGAFSI
Collagen type VI, alpha 3 Variant 6	MRKHRHLPLVAVFCLFLSGFPTTHAQQQQAVIEVNKRDIVFLVDG SSALGLANFNAIRDFIAKVIQRLEIGQDLIQVAVAQYADTVRPEFYF NTHPTKREVITAVRKMKPLDGSALYTGSALDFVRNNLFTSSAGYR
SEQ ID N0:118	AAEGIPKLLVLITGGKSLDEISQPAQELKRSSIMAFAIGNKGADQAE LEEIAFDSSLVFIPAEFRAAPLQGMLPGLLAPLRTLSGTPEVHSNKR DIIFLLDGSANVGKTNFPYVRDFVMNLVNSLDIGNDNIRVGLVQFS DTPVTEFSLNTYQTKSDILGHLRQLQLQGGSGLNTGSALSYVYAN HFTEAGGSRIREHVPQLLLLLTAGQSEDSYLQAANALTRAGILTFC VGASQANKAELEQ1AFNPSLVYLMDDFSSLPALPQQLIQPLTTYVS GGVEEVPLAQPESKRDILFLFDGSANLVGQFPVVRDFLYKIIDELNV KPEGTRIAVAQYSDDVKVESRFDEHQSKPEILNLVKRMKIKTGKAL NLGYALDYAQRYIFVKSAGSRIEDGVLQFLVLLVAGRSSDRVDGP ASNLKQSGVVPFIFQAKNADPAELEQIVLSPAFILAAESLPK.IGDLH PQIVNLLKSVHNGAPAPVSGEKDWFLLDGSEGVRSGFPLLKEFVQ RVVESLDVGQDRVRVAVVQYSDRTRPEFYLNSYMNKQDWNAV RQLTLLGGPIPNTGAALEFVLRNILVSSAGSRITEGVPQLLIVLTAD RSGDDVRNPSVWKRGGAVPIGIGIGNADITEMQTISFIPDFAVAIPT FRQLGTVQQ VISER VTQLTREELSRLQPVLQPLPSPGVGGKRD WF LIDGSQSAGPEFQYVRTLIERLVDYLDVGFDTTRVAVIQFSDDPKV EFLLNAHSSKDEVQNAVQRLRPKGGRQINVGNALEYVSRNIFKRP LGSR1EEGVPQFLVLISSGKSDDEVDDPAVELKQFGVAPFTIARNAD QEELVKISLSPEYVFSVSEFRELPSLEQKLLTPITTLTSEQIQKLLAST RYPPPGEMGASEVLLGAFSI
Collagen type VI, alpha 3 Variant 7	MRKHRHLPLVAVFCLFLSGFPTTHAQQQQAVIEVNKRDIVFLVDG SSALGLANFNAIRDFIAKVIQRLEIGQDLIQVAVAQYADTVRPEFYF NTHPTKREVITAVRKMKPLDGSALYTGSALDFVRNNLFTSSAGYR
SEQ ID N0:119	AAEGIPKLLVLITGGKSLDEISQPAQELKRSSIMAFAIGNKGADQAE LEEIAFDSSLVFIPAEFRAAPLQGMLPGLLAPLRTLSGTPEESKRDIL FLFDGSANLVGQFPVVRDFLYKI1DELNVKPEGTRIAVAQYSDDVK VESRFDEHQSKPEILNLVKRMKIKTGKALNLGYALDYAQRYTFVKS AGSRIEDGVLQFLVLLVAGRSSDRVDGPASNLKQSGVVPFIFQAKN ADPAELEQIVLSPAFILAAESLPKIGDLHPQIVNLLKSVHNGAPAPV SGEKDWFLLDGSEGVRSGFPLLKEFVQRWESLDVGQDRVRVAV VQYSDRTRPEFYLNSYMNKQDVVNAVRQLTLLGGPTPNTGAALE FVLRNILVS S AGSRITEG VPQLLIVLTADRSGDD VRNP S WVKRGG AVPIGIGIGNADITEMQTISFIPDFAVAIPTFRQLGTVQQVISERVTQL TREELSRLQPVLQPLPSPGVGGKRDWFLIDGSQSAGPEFQYVRTLI ERLVDYLDVGFDTTRVAVIQFSDDPKVEFLLNAHSSKDEVQNAVQ RLRPKGGRQÏNVGNALEYVSRNIFKRPLGSRIEEGVPQFLVLISSGK SDDEVDDPAVELKQFGVAPFTIARNADQEELVKJSLSPEYVFSVSTF RELPSLEQKLLTPITTLTSEQIQKLLASTRYPPPAVESDAAD1VFLIDS SEGVRPDGFAHIRDFVSRIVRRLNIGPSKVRVGWQFSNDVFPEFYL KTYRSQAPVLDAIRRLRLRGGSPLNTGKALEFVARNLFVKSAGSRI EDGVPQHLVLVLGGKSQDDVSRFAQVIRSSGIVSLGVGDRNIDRTE

	LQTITNDPRLVFTVREFRELPNIEERIMNSFGPSAATPAPPGVDTPPP SRPEKKKAD1VFLLDGSINFRRDSFQEVLRFVSEIVDTVYEDGDSIQ VGLVQYNSDPTDEFFLKDFSTKRQ1IDAINKVVYKGGRHANTKVG LEHLRVNHFVPEAGSRLDQRVPQIAFVITGGKSVEDAQDVSLALTQ RGVKVFAVGVRNIDSEEVGKIASNSATAFRVGNVQELSELSEQVLE TLHDAMHETLCPGVTDAAKACNLDVILGFDGSRDQNVFVAQKGF ESKVDA1LNRISQMHRVSCSGGRSPTVRVSWANTPSGPVEAFDFD EYQPEMLEKFRNMRSQHPYVLTEDTLKVYLNKFRQSSPDSVKWI HFTDGADGDLADLHRASENLRQEGVRALILVGLERVVNLERLMH LEFGRGFMYDRPLRLNLLDLDYELAEQLDN1AEKACCGVPCKCSG QRGDRGPIGSIGPKGIPGEDGYRGYPGDEGGPGERGPPGVNGTQGF QGCPGQRGVKGSRGFPGEKGEVGEIGLDGLDGEDGDKGLPGSSGE KGNPGRRGDKGPRGEKGERGDVGIRGDPGNPGQDSQERGPKGET GDLGPMGVPGRDGVPGGPGETGKNGGFGRRGPPGAKGNKGGPG QPGFEGEQGTRGAQGPAGPAGPPGLIGEQGISGPRGSGGAAGAPGE RGRTGPLGRKGEPGEPGPKGGIGNRGPRGETGDDGRDGVGSEGRR GKKGERGFPGYPGPKGNPGEPGLNGTTGPKGIRGRRGNSGPPGIVG QKGDPGYPGPAGPKGNRGDSIDQCALIQSIKDKCPFHGPLECPVFP TELAFALDTSEGVNQDTFGRMRDWLSIVNDLTIAESNCPRGARV AVVTYNNEVTTEIRFADSKRKSVLLDKIKNLQVALTSKQQSLETA MSFVARNTFKRVRNGFLMRKVAVFFSNTPTRASPQLREAVLKLSD AGITPLFLTRQEDRQLINALQINNTAVGHALVLPAGRDLTDFLENV LTCHVCLDICNIDPSCGFGSWRPSFRDRRAAGSDVDIDMAFILDSA ETTTLFQFNEMKKYIAYLVRQLDMSPDPKASQHFARVAWQHAPS ESVDNASMPPVKVEFSLTDYGSK.EKLVDFLSRGMTQLQGTRALGS AIEYTIENVFESAPNPRDLKIVVLMLTGEVPEQQLEEAQRVILQAKC KGYFFVVLGIGRKVNIKEVYTFASEPNDVFFKLVDKSTELNEEPLM RFGRLLPSFVSSENAFYLSPD1RKQCDWFQGDQPTKNLVKFGHKQ VNVPNNVTSSPTSNPVTTTKPVTTTKPVTTTTKPVTTTTKPVTI1NQ PSVKPAAAKPAPAKPVAAKPVATKMATVRPPVAVKPATAAKPVA AKPAAVRPPAAAAAKPVATKPEVPRPQAAKPAATKPATTKPMVK MSREVQVFEITENSAKLHWERAEPPGPYFYDLTVTSAHDQSLVLK QNLTVTDRVIGGLLAGQTYHVAVVCYLRSQVRATYHGSFSTKKSQ PPPPQPARSASSSTINLMVSTEPLALTETDICKLPKDEGTCRDFILKW YYDPNTKSCARFWYGGCGGNENKFGSQKECEKVCAPVLAKPGVI SVMGT
Collagen type VI, alpha 3 Variant 8 SEQ ID NO:120	MRKHRHLPLVAVFCLFLSGFPTTHAQQQQADVKNGAAADIIFLVD SSWTIGEEHFQLVREFLYDVVKSLAVGENDFHFALVQFNGNPHTE FLLNTYRTKQEVLSHISNMSYIGGTNQTGKGLEYIMQSHLTKAAGS RAGDGVPQVIVVLTDGHSKDGLALPSAELKSADVNVFAIGVEDAD EGALKEIASEPLNMHMFNLENFTSLHDIVGNLVSCVHSSVSPERAG DTETLKDITAQDSADIIFLIDGSNNTGSVNFAVILDFLVNLLEKLPIG TQQIRVGVVQFSDEPRTMFSLDTYSTKAQVLGAVKALGFAGGELA NIGLALDFWENHFTRAGGSRVEEGVPQVLVLISAGPSSDEIRYGV VALKQASVFSFGLGAQAASRAELQHIATDDNLVFTVPEFRSFGDLQ EKLLPYIVGVAQRHIVLKPPTIVTQVIEVNKRDIVFLVDGSSALGLA NFNAIRDFIAKVIQRLEIGQDLIQVAVAQYADTVRPEFYFNTHPTKR EVITAVRKMKPLDGSALYTGSALDFVRNNLFTSSAGYRAAEGIPKL LVLITGGKSLDEISQPAQELKRSSIMAFAIGNKGADQAELEEIAFDS SLVFIPAEFRAAPLQGMLPGLLAPLRTLSGTPEESKRDILFLFDGSA NLVGQFPVVRDFLYKIIDELNVKPEGTRIAVAQYSDDVKVESRFDE HQSKPE1LNLVKRMKI
Collagen type VI, alpha 3 Variant 9 SEQ IDNO:121	PIGTQQIRVGVVQFSDEPRTMFSLDTYSTKAQVLGAVKALGFAGG ELANIGLALDFVVENHFTRAGGSRVEEGVPQVLVLISAGPSSDEIRY GVVALKQASVFSFGLGAQAASRAELQHIATDDNLVFTVPEFRSFG DLQEKLLPYIVGVAQRHIVLKPPTIVTQEYGLNENW

Protéasome subunit beta type-5 Variant 2 SEQ ID NO: 122	MALASVLERPLPVNQRGFFGLGGRADLLDLGPGSLSDGLSLAAPG WGVPEEPGIEMLHGTTTLAFKFRHGVIVAADSRATAGAYIASQTV KKVÏEINPYLLGTMAGGAADCSFWERLLARQCRIYELRNKERISVA AASKLLANMVYQYKGMGLSMGTMICGWDKRGPVSEVLCLKPKS FGMYLFCGCAERIGNMARPLLRGQ
Protéasome subunit beta type-5 Variant 3 SEQ ID NO1123	MAGGAADCSFWERLLARQCRIYELRNKERISVAAASKLLANMVY QYKGMGLSMGTMICGWDKRGPGLYYVDSEGNRISGATFSVGSGS VYAYGVMDRGYSYDLEVEQAYDLARRAIYQATYRDAYSGGAVN LYHVREDGWIRVS SDNVADLHEKYSGSTP
Protéasome subunit beta type-5 Variant 4 SEQ ID NO: 124	MALAS VLERPLPVNQRGFFGLGGRADLLDLGPGSLSDGLSLAAPG WGVPEEPGIEMLHGTTTLAFKASTTWTVKGTGFQGPPSL
Protéasome subunit beta type-5 Variant 5 SEQ ID NO:125	XGIEMLHGTTTLAFKFRHGVIVAADSRATAGAYIASQTVKKVIEIN PYLLGTMAGGAADCSFWERLLARQCRIYELRNKERISVAAASKLL ANMVYQYKGMGLSMGTMICGWDKRGPG
Heterogeneous nuclear ribonucleoproteins A2/B1 Variant 2 SEQ ID NO:126	MEREKEQFRKLFIGGLSFETTEESLRNYYEQWGKLTDCVVMRDPA SKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRVVEPKRAVAREES GKPGAHVTVKKLFVGGIKEDTEEHHLRDYFEEYGKIDTIEIITDRQS GKKRGFGFVTFDDHDPVDKIVLQKYHTINGHNAEVRKALSRQEM QEVQSSRSGRGGNFGFGDSRGGGGNFGPGPGSNFRGGSDGYGSGR GFGDGYNGYGGGPGGGNFGGSPGYGGGRGGYGGGGPGYGNQGG GYGGGYDNYGGGNYGSGNYNDFGNYNQQPSNYGPMKSGNFGGS RNMGGPYGGGNYGPGGSGGSGGYGGRSRY
Heterogeneous nuclear ribonucleoproteins A2/B1 Variant 3 SEQ ID NO: 127	MEREKEQFRKLFIGGLSFETTEESLRNYYEQWGKLTDCVVMRDPA SKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRVVEPKRAVAREES GKPGAHVTVKKLFVGGIKEDTEEHHLRDYFEEYGKIDTIEIITDRQS GKKRGFGFVTFDDHDPVDKIVLQKYHTINGHNAEVRKALSRQEM QEVQSSRSGRGGNFGFGDSRGGGGNFGPGPGSNFRGGSDGYGSGR GFGDGYNGYGGGPGGGNFGGSPGYGGGRGGYGGGGPGYGNQGG GYGGGYDNYGGGNYGSGNYNDFGNYNQQPSNYGPMKSGNFGGS RNMGGPYGGGNYGPGGSGGSGGYGGRSRY
Heterogeneous nuclear ribonucleoproteins A2/B1 Variant 4 SEQ ID NO:128	MEKTLETVPLERKKREKEQFRKLFIGGLSFETTEESLRNYYEQWGK LTDCVVMRDPASKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRV VEPKRAVAREESGKPGAHVTVKKLFVGGIKEDTEEHHLRDYFEEY GKIDTIEIITDRQSGKK.RGFGFVTFDDHDPVDKIVLQKYHTINGHNA EVRKALSRQEMQEDLEVAILEVAPVMEEEEEDMVVEDLDMATRV GATEWMTTMEEEIMEVEITMILEIITSNLLTTVQ
Beta enolase Variant 2 SEQ ID NO:129	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTGIYE ALELRDGDKGRYLGKGVLKAVENTNNTLGPALLQKKLSVVDQEK VDKFMŒLDGTENKSKFGANAILGVSLAVCKAGAAEKGWLYRHI ADLAGNPDLILPVPAFNVINGGSHAGNKLAMQEFMILPVGASSFKE AMRIGAEVYI-IHLKGVIKAKYGKDATNVGDEGGFAPNILENNEAL ELLKTAIQAAGYPDK.VVIGMDVAASEFYRNGKYDLDFKSPDDPAR HITGEKLGELYKSFIKNYPWSIEDPFDQDDWATWTSFLSGVNIQIV GDDLTVTNPKRIAQAVEKKACNCLLLKVNQIGSVTESIQACKLAQS NGWGVMVSHRSGETEDTFIADLVVGLCTGQIKTGAPCRSERLAKY NQLMRJEEALGDKAIFAGRKFRNPKAK

Beta enolase Variant 3 SEQ IDNO:130	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTGIYE ALELRDGDKGRYLGKGVLKAVENINNTLGPALLQKKLSVVDQEK VDKFMIELDGTENKSKFGANAILGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDLILPVPAFNVINGGSHAGNKLAMQEFMILPVGASSFKE AMRIGAEVYHHLKGVIKAKYGKDATNVGDEGGFAPNILENNEAL ELLKTAIQAAGYPDKVVIGMDVAASEFYRNGKYDLDFKSPDDPAR HITGEKLGELYKSFIKNYPWSIEDPFDQDDWATWTSFLSGVNIQIV GDDLTVTNPKRIAQAVEKKACNCLLLKVNQIGSVTESIQACKLAQS NGWGVMVSHRSGETEDTFIADLVVGLCTGQIKTGAPCRSERLAKY NQLMRIEEALGDKAIFAGRKFRNPKAK
Beta enolase Variant 4 SEQ ID N0:131	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTGIYE ALELRDGDKGRYLGKAKFGANAILGVSLAVCKAGAAEKGVPLYR HIADLAGNPDLILPVPAFNVINGGSHAGNKLAMQEFMILPVGASSF KEAMRIGAEVYHHLKGVIKAKYGKDATNVGDEGGFAPNILENNE ALELLKTAIQAAGYPDKVVIGMDVAASEFYRNGKYDLDFKSPDDP ARHITGEKLGELYKSFIKNYPWSIEDPFDQDDWATWTSFLSGVNI QIVGDDLTVTNPKRIAQAVEKKACNCLLLKVNQIGSVTESIQACKL AQSNGWGVMVSHRSGETEDTFIADLWGLCTGQ1KTGAPCRSERL AKYNQLMRIEEALGDKAÏFAGRKFRNPKAK
Beta enolase Variant 5 SEQ IDNO:132	MAMQKIFARE1LDSRGNPTVEVDLFITAKGRFRAAVPSGASTGIYE ALELRDG DKG RYLGKGVLKAVENINNTLGPALLQKKLS VVDQEK VDKFMIELDGTENKSKFGANAILGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDLILPVP AFNVINGGSHAGNKLAMQEFMILPVGASSFKE AMRIGAEVYHFILKGVIKAKYGKDATNVGDEGG
Beta enolase Variant 6 SEQ ID NO:133	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTG1YE ALELRDGDKGRYLGKGVLKAVENINNTLGPALLQKKLS VVDQEK VDKFMIELDGTENKSKFGANAILGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDLILPVP AFNVINGGSHAGNKLAMQEFMILPVGASSFKE AMRIGAEVYHHLKGVI
Beta enolase Variant 7 SEQ ID NO: 134	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTGIYE ALELRDGDKGRYLGKGVLKAVENINNTLGPALLQKKLS VVDQEK VDKFMIELDGTENKSKFGANAILGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDLILPVP
Beta enolase Variant 8 SEQ ID NO:135	MAMQKIFARE1LDSRGNPTVEVDLHTAKGRFRAAVPSGASTGJYE ALELRDGDKGRYLGKGVLKAVENINNTLGPALLQKKLSVVDQEK VDKFMIELDGTENKSKFGANAILGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDLILPVP
Beta enolase Variant 9 SEQ ID NO:136	MAMQKIFAREILDSRGNPTVEVDLHTAKGRFRAAVPSGASTGIYE ALELRDGDKGRYLGKGVLKAVENINNTLGPALLQKKLSVVDQEK VDKFMIELDGTENKSKFGANAILGVSLAVCKAGAAEKGVPLYRHI ADLAGNPDLILPVP AFNVIN
Beta enolase Variant 10 SEQ ID NO:137	MAMQKIFAREILDSRGNPTVEVDLHTAK
Glutathione S-transferase P Variant 2 SEQ ID NO:138	MPPYTVVYFPVRGRCAALRMLLADQGQSWKEEWTVETWQEGS LKASCLYGQLPKFQDGDLTLYQSNTILRHLGRTLGLYGKDQQEAA LVDMVNDGVEDLRCKYISLIYTNYISFADYNLLDLLLIHEVLAPGC LDAFPLLSAYVGRLSARPKLKAFLASPEYVNLPINGNGKQ

Glutathione S-transferase P Variant 3 SEQ IDNO:139	EAGKDDYVKALPGQLKPFETLLSQNQGGKTFIVGDQVSIWPHAVP SSPPSASRWTQVSPSLTTTCWTCC
Glutathione S-transferase Mu 3 Variant 2 SEQ ID NO:140	MSCE S SMVLGYWDIRGLAHAIRLLLEFTDTSYEEKRYTCGEAPDY DRSQWLDVKFKLDLDFPNLPYLLDGKNKITQSNAILRYIARKHNM CGETEEEKIRVDIIENQVMDFRTQLIRLCYSSDHEKLKPQYLEELPG QLKQFSMFLGKFSWFAGEKLTFVDFLTYD
Glutathione S-transferase Mu 3 Variant 3 SEQ ID NO:141	MSCESSMVLGYWDIRGLAHAIRLLLEFTDTSYEEKRYTCGEAPDY DRSQWLDVKFKLDLDFPNLPYLLDGKNKITQSNAILRYIARKHNM CGETEEEKIRVDIIENQVMDFRTQLIRLCYSSDHEKLKPQYLEELPG QLKQFSMFLGKFSWFAGEKLTFVDFLTYDILDQNRIFDPKCLDEFP NLKAFMCRFGDVLHFLYKTLTAPLGPADP
Rho 23 GTPase-activating protein Variant 2 SEQ ID NO: 142	MNGVAFCLVGIPPRPEPRPPQLPLGPRDGCSPRRPFPWQGPRTLLL YKSPQDGFGFTLRHFIVYPPESAVHCSLKEEENGGRGGGPSPRYRL EPMDTIFVKNVKEDGPAHRAGLRTGDRLVKVNGESVIGKTYSQVI ALIQNSDDTLELSIMPKDEDILQLAYSQDAYLKGNEPYSGEARSIPE PPPICYPRKTYAPPARASTRATMVPEPTSALPSDPRSPAAWSDPGLR VPPAARAHLDNSSLGMSQPRPSPGAFPHLSSEPRTPRAFPEPGSRVP PSRJLECQQALSHWLSNQVPRRAGERRCPAMAPRARSASQDRLEEV AAPRPWPCSTSQDALSQLGQEGWHRARSDDYLSRATRSAEALGPG ALVSPRFERCGWASQRS S ARTPACPTRDLPGPQ APPPSGLQGLDDL GYIGYRSYSPSFQRRTGLLHALSFRDSPFGGLPTFNLAQSPASFPPE ASEPPRVVRPEPSTRALEPPAEDRGDEVVLRQKPPTGRKVQLTPAR QMNLGFGDESPEPEASGRGERLGRKVAPLATTEDSLASIPFIDEPTS PSIDLQAKHVP AS AVVS S AMNS AP VLGTSPS SPTFTFTLGRHYSQD CSSIKAGRRSSYLLA1TTERSKSCDDGLNTFRDEGRVLRRLPNRIPS LRMLRSFFTDGSLDSWGTSEDADAPSKRHSTSDLSDATFSDIRREG WLYYKQ1LTKKGKKAGSGLRQWKRVYAALRARSLSLSKERREPG PAAAGAAAAGAGEDEAAPVCIGSCLVD1SYSETKRRHVFRLTTAD FCEYLFQAEDRDDMLGWIRAIRENSRAEGEDPGCANQALISKKLN DYRKVSHSSGPKADSSPKGSRGLGGLKSEFLKQSAARGLRTQDLP AGSKDDSAAAPK.TPWGINIIKKNKKAAPRAFGVRLEECQPATENQ RVPLIVAACCRIVEARGLESTGIYRVPGNNAVVSSLQEQLNRGPGD INLQDERWQDLNV1SSLLKSFFRKLPEPLFTDDKYNDFIEANRIEDA RERMRTLRKLIRDLPGHYYETLKFLVGHLKTIADHSEKNKMEPRN LALVFGPTLVRTSEDNMTDMVTHMPDRYKIVETLIQHSDWFFSDE EDKGERTPVGDKEPQAVPNIEYLLPNIGRTVPPGDPGSADLLEI
ARHGAP23 Variant 3 SEQ ID NO:143	MDTIFVKNVKEDGPAHRAGLRTGDRLVKVNGESVIGKTYSQVIAL IQNSDDTLELSIMPKDEDILQLAYSQDAYLKGNEPYSGEARSIPEPP PICYPRKTYA
ARHGAP23 Variant 4 SEQ IDNO:144	XFFSDEEDKGERTPVGDKEPQAVPNIEYLLPNIGRTVPPGDPGSDST TCS SAKSKVRMKAILK A
ARHGAP23 Variant 5 SEQ ID NO:145	XTFSDIRREG W LYYKQILTKKGKAEDRDDMLGWIRAIRENS RAEG EDPGCANQALISKK.LNDYRKVSI-ISSGPKADSSPKGSRGLGGLKSEF LKQSAARGLRTQDLPAGSKDDSAAAPKTPWGINIIKKNKKAAPRA FGVRLEECQPATENQRVPLIVAACCRI
ARHGAP23	IRDLPGEIYYETLKFLVGHLKTIADHSEKNKMEPRNLALVFGPTLVR

Rho 23	METESESSTLGDDSVFWLESEVIIQVTDCEEEEREEKFRKMKSSVH SEEDDFVPELHRNVHPRERPDWEETLSAMARGADVPEIPGDLTLK
or Rho GTPase-activating protein 23	TCGSTASMKVKHVKKLPFTKGHFPKMAECAHFHYENVEFGSIQLS LSEEQNEVMKNGCESKELVYLVQIACQGKSWIVKRSYEDFRVLDK
(ARHGAP23)	HLHLCIYDRRFSQLSELPRSDTLKDSPESVTQMLMAYLSRLSAIAG NKINCGPALTWMEIDNKGNHLLVHEESSINTPAVGAAHVIKRYTA
SEQ ID NO:147	RAPDELTLEVGDIVSVIDMPPKVLSTWWRGKHGFQVGLFPGHCVE LINQKVPQSVTNSVPKPVSKKHGKLITFLRTFMKSRPTKQKLKQRG ILKERVFGCDLGEHLLNSGFEVPQVLQSCTAFIERYGIVDGIYRLSG VASNIQRLRHEFDSEHVPDLTKEPYVQDIHSVGSLCKLYFRELPNPL LTYQLYEKFSDAVSAATDEERLIKIHDVIQQLPPPHYRTLEFLMRHL SLLADYCSITNMHAKNLAIVWAPNLLRSKQIESACFSGTAAFMEVR IQSVVVEFILNHVDVLFSGRISMAMQEGAASLSRPKSLLVSSPSTKL LTLEEAQARTQAQVNSPIVTENKYIEVGEGPAALQGKFHTIIEFPLE RKRPQNKMKKSPVGSWRSFFNLGKSSSVSKRKLQRNESEPSEMKA MALKGGRAEGTLRS AKSEESLTS LH AVDGD S KLFRPRRPRS S SD AL SASFNGEMLGNRCNSYDNLPHDNESEEEGGLLHIPALMSPHSAED $ VDLSPPDIGVASLDFDPMSFQCSPPKAESECLESGASFLDSPGYSKD KPSANKKDAETGSSQCQTPGSTASSEPVSPLQEKLSPFFTLDLSPTE DKSSKPSSFTEKVVYAFSPKIGRKLSKSPSMSISEPISVTLPPRVSEVI GTVSNTTAQNASSSTWDKCVEERDATNRSPTQIVKMKTNETVAQE AYESEVQPLDQVAAEEVELPGKEDQSVSSSQSKAVASGQTQTGAV THDPPQDSVPVSSVSLIPPPPPPKNVARMLALALAESAQQASTQSL KRPGTSQ AGYTNYGDIAV ATTEDNLS SS YS AVALDKAYFQTDRPA EQFHLQNNAPGNCDHPLPETTATGDPTHSNTTESGEQI-IHQVDLTG NQPHQ AYLSGDPEKARITS VPLDSEKSDDHVS FPEDQSGKNSMPTV SFLDQDQSPPRFYSGDQPPSYLGASVDKLHHPLEFADKSPTPPNLPS DKIYPPSGSPEENTSTATMTYMTTTPATAQMSTKEASWDVAEQPT TADFAAATLQRTHRTNRPLPPPPSQRSAEQPPVVGQVQAATNIGLN NSHKVQGVVPVPERPPEPRAMDDPASAFISDSGAAAAQCPMATAV QPGLPEKVRDGARVPLLHLRAESVPAHPCGFPAPLPPTRMMESKM IAA1HSSSADATSSSNYHSFVTASSTSVDDALPLPLPVPQPKHASQK TVYSSFARPDVTTEPFGPDNCLHFNMTPNCQYRPQSVPPHHNKLE QHQVYGARSEPPASMGLRYNTYVAPGRNASGHHSKPCSRVEYVS SLSSSVRNTCYPEDIPPYPTIRRVQSLHAPPSSM1RSVPISRTEVPPDD EP AYCPRPLYQYKP YQS S QARSDYHVTQLQPYFENGRVHYRYSP Y S SSS SS YYSPDGALCDVD AYGTVQLRPLHRLPNRDFAFYNPRLQG KSLYSYAGLAPRPRANVTGYFSPNDHNVVSMPPAADVKHTYTSW DLEDMEKYRMQSIRRESRARQKVKGPVMSQYDNMTPAVQDDLG GIYVIHLRSKSDPGKTGLLSVAEGKESRHAAKAISPEGEDRFYRRH PEAEMDRAHHHGGHGSTQPEKPSLPQKQSSLRSRKLPDMGCSLPE HRAHQEASHRQFCESKNGPPYPQGAGQLDYGSKGIPDTSEPVSYH NSGVKYAASGQESLRLNHKEVRLSKEMERPWVRQPSAPEKHSRD CYKEEEHLTQSIVPPPKPERSHSLKLHHTQNVERDPSVLYQYQPHG KRQSSVTVVSQYDNLEDYHSLPQHQRGVFGGGGMGTYVPPGFPH PQSRTYATALGQGAFLPAELSLQHPETQIHAE

As used herein the ternis “sequence identity” or “sequence homology,” which can be used interchangeably, refer to an exact amino acid-to-amino acid correspondence of two polypeptide sequences. Typically, techniques for determining sequence identity include determining the amino 5 acid sequence of a polypeptide, and comparing these sequences to a second amino acid sequence. Two or more sequences can be compared by determining their “percent identity,” also referred to as “percent homology.” The percent identity to a référencé sequence, which may be a sequence within a longer molécule, may be calculated as the number of exact matches between two optimally aligned sequences divided by the length ofthe reference sequence and rnuliiplied by 100. Percent identity may also be determined, for example, by comparing sequence information using the advanced BLAST computer program, including version 2.2.9, available from the National Instilutes of Health. The BLAST program is based on the alignment method of Karlin and Altschul, Proc. Natl. Acad, Sci. USA 87:2264-2268 (1990) and as discussed in .Altschul. et al., J. Mol. Biol. 215:403-410 (1990): Karlin and Altschul, Proc. NalL Acad. Sci. USA 90:5873-5877 (1993); and Altschul et al., Nucleic Acids Res. 25:3389-3402 (1997). Brie fl y, the BLAST program de fines identity as the number of identical aligned symbols (i.e., nucléotides or amino acids), divided by the total number of symbols in the shorter of the two sequences. The program may be used to déterminé percent identity over the entire length of the sequences being compared. Default parameters are provided to optimize searches with short query sequences, for example, with the blastp program. The program also aîlows use of an SEG flher to mask-off segments of the query sequences as determined by the SEG program of Wootton and Pederhen, Computers and Chemistry 17: 149-163 (1993). Ranges of desired degrees of sequence identity are approximately 80% to 100% and integer values in between. Percent identities between a disciosed sequence and a elaimed sequence can be at least about 70%, 71%, 72%, 73%, 74%. 75%. 76%, 77%. 78%, 79%, 80%, 81%. 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%. 91%, 92%. 93%, 94%, 95%, 96%, 97%, 98%, 99%, or more, or complété (100%) sequence identity. In general, an exact match indicates 100% identity over the length of the reference sequence. In some cases, reference to percent sequence identity refers to sequence identity as measured using BLAST (Basic Local Alignment Search Tool). In other cases, ClustalW can be used for multiple sequence alignment. StÎU other programs for comparing sequences and/or assessing sequence identhy include the Nccdleman-Wunsch algorithm and the Smith-Walennan algorithm (see, e.g., the EMBOSS Water aligner. Optimal alignment may be assessed using any suitable parameters of a chose» algorithm, including default parameters.

In one aspect, the sequence identity is at least about 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%. 79%. 8Ü%, 81%, 82%, 83%, 84%, 85%, 86%. 87%, 88%, 89%, 90%, 91%. 92%, 93%. 94%. 95%. 96%. 97%, 98%. 99%, or 100% (complété) sequence identity (homology). In one aspect, the sequence identity is over a région of at least about 10, 50, 100, 150, 200, 250, 300, 350,

400, 450, 500, 550, 600, 650, 700, 750, 800, 850, 900, 950, 1000, 1100. 1200, 1300, 1400, 1500, 1600, 1700, 1800, 1900, 2000, 2100, 2200, 2300, 2400, 2500, 2600, 2700, 2800, 2900, 3000 or more amino acids, or the full length of a polypeptide.

As used herein, the term “fragment” refers at least 10 consecutive amino acids of a polypeptide that can be detected using methods known in the art. Fragment may refer to an “active” fragment which is a portion of the polypeptide required for polypeptide fonction. The fragment can be an “immunogenic” fragment which is a portion of the polypeptide which binds an antibody.

As used herein, a “sample” or “biologîcal sample” is meant to refer to any “biological specimen” collected from a subject, and that is représentative of the content or composition of the source of the sample, considered in its entirety. A sample can be collected and processed directly for analysis, or be stored under proper storage conditions to maintain sample quality until analyses are completed. Ideally, a stored sample remains équivalent to a freshly-collected specimen. The source of the sample can be an internai organ, vein, artery, or even a fluid. Non-limiting examples of sample include blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospinal fluid (CSF), tear, vaginal fluid, feces, skin, and hair. In one aspect, the sample is selected from the group consisting of blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospinal fluid (CSF), tear, vaginal fluid, feces, skin, and hair. In certain aspects the sample is a blood sample and the subject is human. Blood samples include whole blood, plasma and sérum.

The at least one protein refers to one or more proteins. In an aspect, the at least one polypeptide comprises 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20 or more proteins. In one aspect the at least one protein is selected from the group consisting of Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat Shock Protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In another aspect, the at least one protein is selected from the group consisting of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:10, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID

NO;20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25, SEQ ID NO;26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO;29, SEQ ID NO:30, SEQ ID NO:31, SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37, SEQ ID NO:38, SEQ ID NO:39, SEQ ID NÛ:40, SEQ ID NO:4I, SEQ ID NO:42, SEQ ID NO:43, SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49, SEQ ID NO:50, SEQ ID NO;51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55, SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:60, SEQ ID NO:61, SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67, SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO:70, SEQ ID NO:7I, SEQ ID NO:72, SEQ ID NO:73, SEQ ID NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79, SEQ ID NO:80, SEQ ID NO:81, SEQ ID NO;82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID NO:91, SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID NO:96, SEQ ID NO:97, SEQ ID NO;98, SEQ ID NO;99, SEQ ID NQ:100, SEQ ID NO:101, SEQ ID NO:102, SEQ ID NO:103, SEQ ID NOJ04, SEQ ID NO:(05, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO: 111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO:115, SEQ ID NO:116, SEQ ID NO:117, SEQ ID NO:118, SEQ ID NO:119, SEQ ID NO:120, SEQ ID NO:121, SEQ ID NO:122, SEQ ID NO: 123, SEQ ID NO:124, SEQ ID NO:I25, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO: 131, SEQ ID NO: 132, SEQ ID NO: 133, SEQ ID NO: 134, SEQ ID NO: 135, SEQ ID NO: 136, SEQ ID NO: 137, SEQ ID NO: 138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO; 145, SEQ ID NO: 146, SEQ ID NO: 147 or a fragment thereof.

In one aspect the at least one protein is selected from the group consisting of Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat Shock Protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteîns A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamîly C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a combination thereof. In another aspect, the at least one protein is selected from the group consisting of SEQ ID

NO:1, SEQ ID NO:2, SEQ ID NO:3, SEQ ID NO:4, SEQ ID NO:5, SEQ ID NO:6, SEQ ID NO:7, SEQ ID NO:8, SEQ ID NO:9, SEQ ID NO:IO, SEQ ID NO:11, SEQ ID NO:12, SEQ ID NO:13, SEQ ID NO: 14, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19,

SEQ ID NO:20, SEQ ID NO:21, SEQ ID NO:22, SEQ ID NO:23, SEQ ID NO:24, SEQ ID NO:25,

SEQ ID NO:26, SEQ ID NO:27, SEQ ID NO:28, SEQ ID NO:29, SEQ ID NO:30, SEQ ID NO:31,

SEQ ID NO:32, SEQ ID NO:33, SEQ ID NO:34, SEQ ID NO:35, SEQ ID NO:36, SEQ ID NO:37,

SEQ ID NO:38, SEQ ID NO:39, SEQ ID NO:40, SEQ ID NO:41, SEQ ID NO:42, SEQ ID NO:43,

SEQ ID NO:44, SEQ ID NO:45, SEQ ID NO:46, SEQ ID NO:47, SEQ ID NO:48, SEQ ID NO:49,

SEQ ID NO:50, SEQ ID NO:51, SEQ ID NO:52, SEQ ID NO:53, SEQ ID NO:54, SEQ ID NO:55,

SEQ ID NO:56, SEQ ID NO:57, SEQ ID NO:58, SEQ ID NO:59, SEQ ID NO:6Û, SEQ ID NO:61,

SEQ ID NO:62, SEQ ID NO:63, SEQ ID NO:64, SEQ ID NO:65, SEQ ID NO:66, SEQ ID NO:67,

SEQ ID NO:68, SEQ ID NO:69, SEQ ID NO;70, SEQ ID NO:71, SEQ ID NO:72, SEQ ID NO:73,

SEQ ÏD NO:74, SEQ ID NO:75, SEQ ID NO:76, SEQ ID NO:77, SEQ ID NO:78, SEQ ID NO:79,

SEQ IDNO:80, SEQ ID N0:81, SEQ ID NO:82, SEQ ID NO:83, SEQ ID NO:84, SEQ ID NO:85, SEQ ID NO:86, SEQ ID NO:87, SEQ ID NO:88, SEQ ID NO:89, SEQ ID NO:90, SEQ ID N0:91,

SEQ ID NO:92, SEQ ID NO:93, SEQ ID NO:94, SEQ ID NO:95, SEQ ID N0:96, SEQ ID NO:97,

SEQ ID NO:98, SEQ ID NO:99, SEQ ID NO: 100, SEQ ID NO: 101, SEQ ID NO: 102, SEQ ID NO:103, SEQ ID NO:104, SEQ ID NO:105, SEQ ID NO:106, SEQ ID NO:107, SEQ ID NO:108, SEQ ID NO: 109, SEQ ID NO: 110, SEQ ID NO:111, SEQ ID NO: 112, SEQ ID NO: 113, SEQ ID NO: 114, SEQ ID NO: 115, SEQ ID NO: 116, SEQ ID NO: 117, SEQ ID NO: 118, SEQ ID NO: 119, SEQ ID NO:120, SEQ ID NO:12I, SEQ ID NO:122, SEQ ID NO:123, SEQ ID NO:124, SEQ ID NO: 125, SEQ ID NO: 126, SEQ ID NO: 127, SEQ ID NO: 128, SEQ ID NO: 129, SEQ ID NO: 130, SEQ ID NO:I31, SEQ ID NO:132, SEQ ID NO:133, SEQ ID NO:134, SEQ ID NO:135, SEQ ID NO:136, SEQ ID NO: 137, SEQ ID NO:138, SEQ ID NO: 139, SEQ ID NO: 140, SEQ ID NO: 141, SEQ ID NO: 142, SEQ ID NO: 143, SEQ ID NO: 144, SEQ ID NO: 145, SEQ ID NO: 146, SEQ ID NO: 147 or a combination thereof.

The biomark ers of the présent invention may be used individually or in combinations for the diagnosis of cervical cancer. Any combination of the biomarkers listed above and in Table 1 can be used for the diagnosis of cervical cancers.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III,

Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1 -like protein 1 polycystic kidney disease, Beat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamîly C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In an additional aspect, the at least one polypeptide comprises a polypeptide having at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 and at least one polypeptide selected from a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase and neurofibromin I; Famesyl pyrophosphate synthase and Glyceraldehyde-3 phosphate dehydrogenase; Famesyl pyrophosphate synthase and Protein 1 containing fibronectin domain type ΓΙΙ; Famesyl pyrophosphate synthase and Eukaryotic initiation factor 4A-I; Famesyl pyrophosphate synthase and L-lactate dehydrogenase chain B; Famesyl pyrophosphate synthase and Nuclear heterogeneous Ribonucleoprotein Al; Famesyl pyrophosphate synthase and polycystic kidney disease protein 1-hke 1; Famesyl pyrophosphate synthase and heat shock protein Cognate 71 kDa; Famesyl pyrophosphate syndiase and Ankyrin-3; Famesyl pyrophosphate synthase and Rho 23; Famesyl pyrophosphate synthase and Rho 23-GTPase-activating protein; Famesyl pyrophosphate synthase and Cytoskeletal Keratin 78 type II; Famesyl pyrophosphate synthase and collagen chain (VI) Alpha-3; Famesyl pyrophosphate synthase and Beta subunit of protéasome type-5; Famesyl pyrophosphate synthase and Heterogeneous nuclear ribonucleoproteins A2/BI; Famesyl pyrophosphate synthase and Histone H2B type 1-B; Famesyl pyrophosphate synthase and homolog of DnaJ subfamîly C member 13; Farnesyl pyrophosphate synthase and Beta enolase; Famesyl pyrophosphate synthase and Glutathione S-transferase P; Famesyl pyrophosphate synthase and Glutathione S-transferase Mu 3; or fragments thereof.

In another aspect, the at least one polypeptide comprises SEQ ID NO:I and SEQ ID NO:2; SEQ ID NO:1 and SEQ ID NO:3; SEQ ID NO:1 and SEQ ID NO:4; SEQ ID NO:1 and SEQ ID NO:5; SEQ ID NO:1 and SEQ ID NO:6; SEQ ID NO:1 and SEQ ID NO:7; SEQ ID NO:1 and SEQ ID NO:8; SEQ IDNO:1 and SEQ ID NO:9; SEQ IDNO:1 and SEQ IDNO: 10; SEQ ID NO:1 and SEQ ID NO:1I; SEQ IDNO:1 and SEQ IDNO: 12; SEQ ID NO:1 and SEQ ID NO: 13; SEQ ID NO:1 and SEQ ID NO: 14; SEQ ID NO:I and SEQ ID NO: 15; SEQ ID NO:1 and SEQ ID NO: 16;

SEQ ID NO:1 and SEQ ID NO: 17; SEQ ID NO:1 and SEQ ID NO; 18; SEQ ID NO:1 and SEQ ID NO: 19; SEQ ID NO:1 and SEQ ID NO:20; or fragments thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, neurofibromin or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat Shock Protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type Π, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Glyceraldehyde-3 phosphate dehydrogenase or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of neurofibromin, Protein 1 containing fibronectîn domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/BI, Histone H2B type l-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Protein 1 containing fibronectin domain type III or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Eukaryotic initiation factor 4A-I or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type 111, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein I-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, and Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, L-lactate dehydrogenase chain B or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like l, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Nuclear heterogeneous Ribonucleoprotein Al or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, polycystic kidney disease protein I-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, polycystic kidney disease protein 1-like 1 or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunît of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, heat shock protein Cognate 71 kDa or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, Ankyrin-3, Rho 23 GTPaseactivating protein, Cytoskeletal Keratin 78 type Π, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione Stransferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Ankyrin-3 or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, heat shock protein Cognate 71 kDa, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Rho 23 GTPase-activating protein or a fragment thereof, and at least one additional polypeptide selected from the group consistîng of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, beat shock protein Cognate 71 kDa, Ankyrin-3,

Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Cytoskeletal Keratin 78 type II or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type ΙΠ, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein AI, polycystic kidney disease protein 1-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone FI2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Farnesyl pyrophosphate synthase or a fragment thereof, collagen chain (VI) Alpha-3 or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein I-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Beta subunit of protéasome type-5 or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type IL collagen chain (VI) Alpha-3, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Heterogeneous nuclear ribonucleoproteins A2/BI or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein I-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Histone H2B type 1-B, homolog of DnaJ subfamiiy C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Histone H2B type 1-B or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like I, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, homolog of DnaJ subfamily C member 13 or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein 1-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Beta enolase or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, GlyceraIdehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, polycystic kidney disease protein I-like 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/BI, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

In another aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Glutathione S-transferase P or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein AI, polycystic kidney disease protein 1-like I, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase Mu 3 and a fragment thereof.

In one aspect, the at least one polypeptide comprises Famesyl pyrophosphate synthase or a fragment thereof, Glutathione S-transferase Mu 3 or a fragment thereof, and at least one additional polypeptide selected from the group consisting of neurofibromin, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein AI, polycystic kidney disease protein 1-lîke 1, heat shock protein Cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, collagen chain (VI) Alpha-3, Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:2 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide having an amino acid sequence selected from the group consisting of SEQ ID NOs:3-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:3 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2 and 4-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:4 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-3 and 5-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 5 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-4 and 6-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:6 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID N Os: 2-5 and 7-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:7 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-6 and 8-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:8 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-7 and 9-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:9 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-8 and 10-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 10 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-9 and 11-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 11 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-10 and 12-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 12 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2- l 1 and 13-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 13 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-I2 and 14-20 and a fragment thereof

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amîno acid sequence of SEQ ID NO:I or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 14 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amîno acid sequence selected from the group consisting of SEQ ID NOs:2-13 and 15-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 15 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-14 and 16-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 16 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-15 and 17-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 17 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-16 and 18-20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 18 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs:2-17 and 19-20 and a fragment thereof.

In another aspect, the at least one polypeptide comprises a polypeptide with at least about

70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 19 or a fragment thereof, and at least one additional polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence 10 selected from the group consisting of SEQ ID NOs:2-18 and 20 and a fragment thereof.

In one aspect, the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof, and a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:20 or a fragment thereof, and at least one additional 15 polypeptide having at least about 70% sequence identity to a polypeptide an amino acid sequence selected from the group consisting of SEQ ID NOs :2-19 and a fragment thereof.

In a further aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow.

ln one aspect, the method also includes administering a treatment to the subject. In an additional aspect, the treatment is surgery, radiation, chemotherapy, targeted therapy and/or immunotherapy.

The tenu treatment is used interchangeably herein with the term therapeutic method and refers to both 1 ) therapeutic treatments or measures that cure, slow down, lessen symptoms of, 25 and/or hait progression of a diagnosed pathologie conditions or disorder, and 2) and prophylactic/ preventative measures. Those in need of treatment may include individuals already having a particular medical disorder as well as those who may ultimately acquire the disorder (i.e., those needing préventive measures).

The tenus “therapeutîcally effective amount”, “effective dose,” “therapeutîcally effective 30 dose , effective amount,” or the like refer to that amount of the subject compound that will elicit the biological or medical response of a tissue, System, animal or human that is being sought by the researcher, veterinarian, medical doctor or other clinicîan.

The ternis “administration of’ and or “administering” should be understood to mean providing a pharmaceutical composition in a therapeutically effective amount to the subject in need of treatment. Administration routes can be enterai, topical or parentéral. As such, administration routes include but are not limited to intracutaneous, subcutaneous, intravenous, intraperitoneal, intraarterial, intrathecal, întracapsular, intraorbital, intracardiac, intradermal, transdermal, transtracheal, subcuticular, intraarticulare, subcapsular, subarachnoid, intraspinal and intrastemal, oral, sublingual buccal, rectal, vaginal, nasal ocular administrations, as well infusion, inhalation, and nebulization. The phrases “parentéral administration” and “administered parenterally” as used herein means modes of administration other than enterai and topical administration. The pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration. Suitable unit dosage forms, include, but are not limited to powders, tablets, pills, capsules, lozenges, suppositories, patches, nasal sprays, injectables, implantable sustained-release formulations, lipid complexes, etc.

The biomarkers and polypeptides disclosed herein are useful for the diagnosis of cervical cancer. As used herein, the term “diagnosis” refers to any method of detecting or detennining that a subject has cervical cancer.

In another embodiment, the présent invention provides a method of diagnosing cervical cancer in a subject by detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Farnesyl pyrophosphate synthase, neurofibromin 1, Glyceraldehyde-3 phosphate dehydrogenase, Protein l containing fibronectin domain type III, Eukaryotic initiation factor 4A-1, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock protein cognate protein 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog ofDnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-147 or a fragment thereof; and diagnosing cervical cancer based on the détection of at least one polypeptide. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ÏD NOs: 1-20 or a fragment thereof.

In one aspect, the sample is blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospinal fluid (CSF), tear, vaginal fluid, feces, skin, and haîr. In certain aspects, the sample is a blood sample and the subject is human.

In an additional aspect, the at least one polypeptide is selected is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Cognate thermal shock protein 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In a further aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having an amino acid sequence selected from SEQ ID NOs:2-20 or a fragment there of.

In another aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow. In one aspect, the method also includes admînistering a treatment to the subject. In certain aspects, the treatment is surgery, radiation, chemotherapy, targeted therapy and/or îmmunotherapy.

In some embodiments, diagnosing, predicting, and/or monitoring the status or outcome of a cancer may comprise determining a therapeutic regîmen. Detennining a therapeutic regimen may comprise admînistering an anti-cancer therapeutic. Alternatively, detennining the treatment for the cancer may comprise modifying a therapeutic regimen. Modifyîng a therapeutic regimen may comprise increasing, decreasîng, or terminating a therapeutic regimen.

Treatment options for cervical cancer include surgery, radiation, chemotherapy, targeted therapy, and îmmunotherapy.

Surgical Treatment for cervical cancer dépends on the type and stage of cervical cancer. For precancerous lésion surgical interventions include ablation and excision surgery. Surgical intervention for advanced cervical cancer include hysterectomy (simple or radical) and Trachelectomy.

Radiation is used to treat cervical cancer and to treat cervical cancer récurrence. There are two types of radiation typically used for treating cervical cancer, extemal beam radiation and brachytherapy. Extemal beam radiation therapy (EBRT) aims x-rays at the cancer from a machine outside the body. Treatment is much like gettîng a regular x-ray, but the radiation dose is stronger.

When EBRT is used as the main treatment for cervical cancer, it is usually combined with chemotherapy. Brachytherapy, or internai radiation therapy, puts a source of radiation in or near the cancer. Brachytherapy is mainly used in addition to EBRT as a part of the main treatment for cervical cancer.

Chemotherapy is also used to treat cervical cancer, wither alone or in combination with 10 another method. Chemotherapy may include Cîsplatin, Carboplatin, Paclitaxel (Taxol), Topotecan, docetaxel (Taxotere), ifosfamide (Ifex), 5-fluorouracil (5-FU), irinotecan (Camptosar), gemcitabine (Gemzar)and mitomycin. Targeted therapy for the treatment of cervical cancer includes Bevacizumab. Immunotherapy for the treatment of cervical cancer includes Pembrolizumab (PD-1 inhibitor).

In an additional embodiment, the présent invention provides a method of treating cervical cancer in a subject in need thereof, the method is detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear 20 heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteîns A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a 25 polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NOs; 1-147 or a fragment thereof; dîagnosing cervical cancer based on the détection of the at least one polypeptide; and administering a treatment to the subject. In one aspect, the sample is a blood sample. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the 30 amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof.

In an additional aspect, the at least one polypeptide is Famesyl pyrophosphate synthase and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-1, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, I-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPaseactivating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione Stransferase Mu 3 or a fragment thereof. In a further embodiment, the at least one polypeptides is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide with an amino acid sequence selected from SEQ ID N Os: 220 or a fragment thereof.

In another aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, micro fluidic device, latéral flow assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow assay. In an additional aspect, the treatment is selected from the group consisting of surgery, radiation, chemotherapy, targeted therapy and immunotherapy. In a further aspect, the chemotherapy is Cisplatin, Carboplatin, Paclitaxel, Topotecan, docetaxel, ifosfamide, 5fluorouracil, irinotecan, gemcitabine or mitomycin. In certain aspects, the targeted therapy is bevacizumab and the immunotherapy is pembrolizumab.

The biomarkers of the présent invention can be used to predict response to treatment for cervical cancer.

In a further embodiment, the présent invention provides methods of predicting a response to treatment for a subject having cervical cancer by detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofibromin I, GlyceraIdehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-Iactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1 -like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having amino acid sequence selected from SEQ ID NOs: 1-147 or a fragment thereof; and predicting a response to treatment based on the détection of the at least one polypeptide. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof.

In one aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In another aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In an additional aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microiluidic device, latéral flow assay, vertical flow or immunoassay. In a further aspect, the detecting is by latéral flow assay. In certain aspects, the treatment is surgery, radiation, chemotherapy, targeted therapy and immunotherapy.

The biomarkers of the présent application are useful for detennining the stage of cervical cancer. Cervical cancer can be classified on different scales. The Papanicolau System classifies the lésions in degrees of severity, from grade I that corresponds to normal cytology, to grade V that corresponds to invasive squamous cancer of the cervix. The Richart classification System classifies the results of a cytology into: Négative, Reactive or not classifiable squamous atypical, HPV infection, Cervical intraepithélial neoplasia (CIN) grades I, Il and III, carcinoma in situ and invasive squamous cancer of the cervix . Fînally, the Bethesda nomenclature classifies the results of a cytology as: Négative, ASCUS-ASCH, low-grade intraepithélial lésions, high-grade intraepithélial lésions and invasive squamous cancer of the cervix.

The FIGO (International Fédération of Gynecology and Obstetrics) staging System is used most often for cancers of the female reproductive organs, including cervical cancer. For cervical cancer, the clinical stage is used and is based on the results of the doctor's physical exam, biopsies, imaging tests, and a few other tests that are done in some cases, such as cystoscopy and proctoscopy.

Table 2

FIGO Stage	Stage description
I
	IA	The cancer cells hâve grown from the surface of the cervix into deeper tissues of the cervix. Cancer has not spread to nearby lymph nodes. Cancer has not spread to distant sites. It has not spread to distant sites.
	IA1	The area of cancer can only bc seen with a microscope and is less than 3 mm (about 1/8inch) deep. It has not spread to nearby lymph nodes. It has not spread to distant sites.
	IA2	The area of cancer can only be seen with a microscope and is between 3 mm and 5 mm (about l/5-inch) deep. It not has not spread to nearby lymph nodes. It has not spread to distant sites.
	IB	This includes stage I cancer that has spread deeper than 5 mm (about 1/5 inch) but is still limited to the cervix. It has not spread to nearby lymph nodes. It has not spread to distant sites.
	IB1	The cancer is deeper than 5 mm (about 1/5-inch) but not more than 2 cm (about 4/5-inch) in size. It has not spread to nearby lymph nodes. It has not spread to distant sites.
	1B2	The cancer is at least 2 cm in size but not larger than 4 cm. It has not spread to nearby lymph nodes. It has not spread to distant sites.
	IB3	The cancer is at least 4 cm in size and limited to the cervix. It has not spread to nearby lymph nodes. It has not spread to distant sites.

II		The cancer has grown beyond the cervix and utérus, but hasrit spread to the walls of the pelvis or the lower part of the vagina. It has not spread to nearby lymph nodes. It has not spread to distant sites.
	IIA	The cancer has grown beyond the cervix and utérus but has not spread into the tissues next to the cervix (called the parametria). It has not spread to nearby lymph nodes. It has not spread to distant sites.
	II AI	The cancer is not larger than 4 cm (about 1 3/5 inches). It not has not spread to nearby lymph nodes. It has not spread to distant sites.
	IIA2	The cancer is 4 cm or larger. It has not spread to nearby lymph nodes, It has not spread to distant sites.
	1IB	The cancer has grown beyond the cervix and utérus and has spread into the tissues next to the cervix (the parametria). It has not spread to nearby lymph nodes. It has not spread to distant sites.
III		The cancer has spread to the lower part of the vagina or the walls of the pelvis. The cancer may be blocking the ureters (tubes that carry urine from the kîdneys to the bladder), It might or might not hâve not spread to nearby lymph nodes. It has not spread to distant sites.
	IIIA	The cancer has spread to the lower part of the vagina but not the walls of the pelvis. It has not spread to nearby lymph nodes. It has not spread to distant sites.
	ΠΙΒ	The cancer has grown into the walls of the pelvis and/or is blocking one or both ureters caustng kidney problems (called hydronephrosis). It has not spread to nearby lymph nodes, It has not spread to distant sites.
	me	The cancer can be any size. Imaging tests or a biopsy show the cancer has spread to nearby pelvic lymph nodes (IIIC1) or para-aortic lymph nodes (II1C2). It has not spread to distant sites.
IV		The cancer has grown into the bladder or rectum or to far away organs like the lungs or bones.

	IVA	The cancer has spread to the bladder or rectum or it is growing out of the pelvis.
	1VB	The cancer has spread to distant organs outside the pelvic area, such as distant lymph nodes, lungs or boues.

In another embodiment, the présent invention provides methods for determining the stage of cervical cancer in a subject in need thereof by detecting at least one polypeptide in a sample from the subject; wherein the at least one polypeptide is selected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-147 or a fragment thereof; and determining the stage of cervical cancer in the subject based on the détection of the at least one polypeptide. In one aspect, the at least one polypeptide is a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof.

In one aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-1, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In another aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 or a fragment thereof and at least one polypeptide with at least about

70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In an additional aspect, the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow assay or immunoassay. In a spécifie aspect, the detecting is by latéral flow assay. In a further aspect, the method also includes admînistering a treatment to the subject. In certain aspects, the treatment is surgery, radiation, chemotherapy, targeted therapy or îmmunotherapy. In one aspect, the cervical cancer is stage I, stage II, stage III or stage IV.

In one embodiment, the présent invention provides a kit with a sample collection unit; a latéral flow device; and instructions for using the latéral flow device.

Sample collection device is any device that can be used to collect a sample. The sample blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospinal fluid (CSF), tear, vaginal fluid, feces, skin, and hair.

A latéral flow device is a simple to use diagnostic device used to confirm the presence or absence of a target analyte, such as pathogens or biomark ers in a sample. The most commonly known type of latéral flow rapid test strip is the pregnancy test.

Typically latéral flow assays use a device comprises several pads (made of a sériés of capillary beds, capable of transporting a fluid): a sample pad to receive the iiquid sample; a conjugale pad, including réactivé molécules used to visualize positive control, a positive line and a test line.

For the détection of a target protein, the conjugale pad includes antibodies spécifie for the target protein conjugated to a détectable tag; a positive line (positive control) is generated comprising fixed anti- anti- target protein antibodies (for example anti IgG antibodies), and a test line was generated comprising fixed anti- target protein antibodies. When the sample pad is contacted with a sample containing the target protein, the target protein reacts with the anti- target protein antibodies conjugated to a détectable tag in the conjugale pad. As the Iiquid flows to the test and positive lines, the target protein présent in the sample, conjugated with the labeled antibodies reacted with the fixed anti-target protein antibodies on the test line, and anti- target protein antibodies conjugated to the détectable tag but not conjugated to the target protein reacts with the fixed anti-Ig antibodies on the positive line. Both reactions générale a positive reading on the test line, and on the positive line.

In one aspect, the latéral flow device detects at least one polypeptide seiected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein I polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence seiected from SEQ ID NOs: 1-147 or a fragment thereof. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence seiected from SEQ ID NOs: 1-20 or a fragment thereof.

In an additional aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide seiected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPaseactivating protein, Cytoskeletal Keratin 78 type II, Alph-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione Stransferase Mu 3 or a fragment thereof. In a further aspect, the at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO:1 or a fragment thereof and at least one polypeptide seiected from a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence seiected from SEQ ID NO:2-20 or a fragment thereof.

In another aspect, the latéral flow device detects the at least one polypeptide by an immunoassay. In one aspect, the sample collection unit collecta a blood sample.

In an additional embodiment, the présent invention provides a use of the détection of at least one polypeptide for the diagnosis of cervical cancer in a subject in need thereof, wherein the at least one polypeptide is seiected from Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous

Ribonucleoprotein Al, 1 -like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-147 or a fragment thereof. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs: 1-20 or a fragment thereof.

In a further aspect, the at least one polypeptide is detected in a sample from the subject and the sample is a blood sample. In another aspect, the at least one polypeptide is Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaiyotîc initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1 -like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alph-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof. In one aspect, the at least one polypeptide is a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from SEQ ID NOs:2-20 or a fragment thereof.

In another aspect, the detecting is by protein mîcroarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow assay or immunoassay. In certain aspects, the detecting is by latéral flow assay.

The following examples are provided to further illustrate the embodiments of the présent invention, but are not intended to limit the scope of the invention. While they are typical of those that might be used, other procedures, méthodologies, or techniques known to those skilled in the art may altematively be used.

EXAMPLES

EXAMPLE 1

SECRETOME ANALYSIS OF CERVICAL CANCER CELL LINES

In order to identify cervical cancer biomarkers, a secretome analysis of cervical cancer cells was performed using cervical cancer cell line HeLa (cervical adenocarcinoma, positive for HPV18), SiHa cells (grade II, squamous cell cervical carcinoma, positive for HPV16), and C-33A (cervical carcinoma, négative for HPV) and the HaCaT cell line as a négative control. These Unes were selected because they represent the most frequent histological types and viral génotypes in cervical intraepithélial lésions and in CC; and were either cultured (in vitro secretome), or inoculated into mice (ex vivo secretome).

HeLa and SiHa cells were cultured in serum-free Advanced RPMI 1640 supplemented with 2 mM L-glutamine and Penicillin-Streptomycin at 1 % v / v, at 37 ° C and with 5% CO2 until a 70-80% confluence was reached. The cells were washed three times with stérile physiological solution (0.9% NaCl (w / v)). As illustrâted in Figure 2, there was no significant growth différences between the cells at day 6, when the cells reached 70% confluence.

For in vitro secretome analysis, the cells were then incubated in serum-free RPMI 1640 without phénol red (Gibco, Invitrogen) for 20 hours, and the medium collected and centrifuged at 1,500 g for 5 minutes. The supematant was passed through a 0.22 μηι size PVDF membrane (Millex, Millipore) and stored at -70 ° C until further use (see Figure 1).

For the ex vivo secretome analysis, the secreted proteins were collected from tumors collected on female Nu ! Nu mice (4-6 weeks) inoculated with 10 HeLa or SiHa cells. After 30, 45 and 50 days after inoculation, the tumors were collected (triplicate) and washed 3 times with 50 mL of physiological solution and then incubated for 20 hours with sérum free RMPI medium without phénol red. The medium was removed and centrifuged at 1,500 x g for 5 minutes, the supernatant was passed through a 0.22 μιη pore size membrane PVDF membrane (Millex, Millipore) and stored at -70 ° C until further use (see Figure 1). The secreted proteins collected in vitro and ex vivo were lyophilized and resuspended in 1 mL of ultrapure water. Protein isolation was performed by phénol extraction.

To identify the proteins secreted by the different cell lines, the proteins were separated by electrophoresis on an SDS-PAGE matrix and stained with bright Coomassie blue (see Figure 3A). Each lane containing 30 μg protein was eut into 20 lines throughout the column, the proteins contained were extracted and digested with trypsin. The generated peptides were analyzed in a nano LC-MS / MS System (Q-TOF Synapt G2 MS; Waters). The identification of peptides and proteins was performed using the MASCOT search engine through the MASCOT Distiller interface (Matrix Science). The databases consulted were Swiss-Prot and NCBI.

1662 secretome proteins were identified (see Figure 3B). As illustrated in the Venn diagram of Figure 3C, showing the intersection between the shared proteins of the CC cell lines and 5 their négative control, 20 proteins were shared in the 3 CC cell lines and absent in the négative control (see Table 3). These proteins were candidates for use in a rapid diagnostic test. In addition to the qualitative study, a quantitative analysis of 200 secreted proteins was performed using the labelfree quantification (LFQ) technique. As shown in Figure 4A, 92 proteins were found over-expressed in the 3 CC cell lines according to their Log2 value (CC cell lines vs. HaCaT). For HeLa: 45 over10 expressed proteins, SiHa: 35 over-expressed proteins, C-33A: 12 over-expressed proteins. As shown in Figures 4B, 6 secreted proteins: Glyceraldehyde-3-phosphate dehydrogenase, cognate heat shock protein 71 kDa, L-lactate dehydrogenase chain B, beta subunit of protéasome type-5 and nuclear ribonucleoproteins heterogeneous A2 / B1 were found over expressed in the 3 CC cell lines compared to its négative control. Further, and as shown in Figure 4C (which represents the Heat 15 map of proteins expressed in cell lines, where the complété lînkage hierarchical grouping shows the values in Log2 (protein expression / HSP71) on a color scale), the hierarchy analysis by cluster in the heat map revealed a simîlarity in protein expression between the FIPV positive cell lines (SiHa and HeLa). These analyzes allowed obtaining a set of common over-expressed proteins for the HPV and CC lines.

Table 3

Gene	Protein	Name
NFI	NF1_HUMAN	Neurofibromin
GAPDH	G3P_HUMAN	Glyceraldehyde-3 phosphate dehydrogenase
FNDC1	FNDCI_HUMAN	Protein 1 containing fibronectin domain type III
EIF4A1	IF4A1JHUMAN	Eukaryotic initiation factor 4A-I
LDHB	LDHB_HUMAN	L-lactate dehydrogenase chain B
HNRNPA1	ROAl_HUMAN	Nuclear heterogeneous Ribonucleoprotein Al
PKD1L1	PK1L1-HUMAN	Polycystic kidney disease protein 1 -like 1
FDPS	FPPS_HUMAN	Famesyl pyrophosphate synthase
HSPA8	HSP7C-HUMAN	Heat Shock Protein Cognate 71 kDa
ANK3	ANK3_HUMAN	Ankirin-3
ARHGAP23	ARHG23_HUMAN	Rho 23 GTPase-activating protein
KRT78	K2C78_HUMAN	Cytoskeletal Keratin 78 type II
COL6A3	CO6A3_HUMAN	Alpha-3 collagen chain (VI)
PSMB5	PSB5_HUMAN	Beta subunit of protéasome type-5
HNRNPA2B1	R0A2_HUMAN	Heterogeneous nuclear ribonucleoproteins A2/B1
HIST1H2BB	H2B1B-HUMAN	Histone H2B type 1-B

RME8	DNAJC13	homolog of DnaJ subfamily C member 13
ENO3	ENOB_HUMAN	Beta enolase
GSTP1	GSTP1 HUMAN	Glutathione S-transferase P
GSTM3	GSTM3_HUMAN	Glutathione S-transferase Mu 3

EXAMPLE 2

DETECTION OF CERVICAL TUMORS

To evaluate if ihe proteins identifïed in the in vitro secretome analysis could be used as 5 biomarkers for the détection of cervical tumors, female mice were inoculated with DC cells to develop tumors, and secreted proteins were measured in the sérum ofthe animais (see Figure 5 A).

A cohort of 9 mice was generated, with 3 different cell lines and their Controls established at 3 different times of the PT (tumor progression). The mice were inoculated with 10⁷ cells DC tumor cell lines (either HeLa or SiHa cells), and the sera were collected 30, 45 and 50 days post 10 inoculation. Sera were subjected to a Western blot with 20 pg protein per sample. The tests were performed in triplicate and were presented as means (± standard déviation). A statîstical Student's ttest was perfonned.

As illustrated in Figure 5B, illustrating the example of the détection of one of the protein of the secretome identifïed in Example 1; it was found by Western blot that the famesyl 15 pyrophosphate synthase protein was détectable in the sera of the mice inoculated with HeLa and SiHa (sera from uninoculated mice were used as Controls). The protein was found expressed in ail sera of the tumor-bearing mice, an as detailed in Figure 5C, the level of expression was found to încrease levels over time in the sera of the mice inoculated with SiHa.

The validation of the protein Famesyl pyrophosphate synthase as a biomarker in sera was 20 further performed in sérum obtaîn from patients with CC:

The sérum of 10 patients with CC and 10 négative Controls for CC were tested, and the expression of Farnesyl pyrophosphate synthase was assessed by western blot. As illustrated in Figures 6A and 6B, ali the patients analyzed presented Famesyl pyrophosphate synthase expression, and no expression of Famesyl pyrophosphate synthase was found in the sera of the contrais. It was 25 also observed that the level of expression was variable among patients (see Figure 6C). As further illustrated in Figures 7A-7C, Ankyrin-3 was also demonstrated as a promising biomarker that can be used to detect cervical cancer in the sérum of patient, by presenting with a significantly higher level of expression as compared to the sérum of control patients. The proteome analysis of the secretome, identifïed 20 proteins présent in CC cells and absent in négative control; and among the 6 overexpressed proteins Famesyl pyrophosphate synthase and Ankyrin-3, used an a proof-ofprincîple were used to demonstrate that its level of expression (i.e., overexpression) could be analyzed in the sérum of patient, showing that these proteins may be a useful promising candidate in the identification of this disease.

EXAMPLE 3

DETECTION OF PRE-CANCEROUS CERVICAL LESIONS

To évaluaie if the proteins identified in the in vitro secretome analysis could be used as biomarkers to detect pre-cancerous cervical lésions, the sérum of patient presenting pre-cancerous cervical lésions were assessed for the détection of the biomarkers by western blot.

The sérum of patients with pre-neoplasic lésions, with cervical cancer or with no lésions (control) were collected and analyzed for the expression of Ankyrin-3, Rho 23 GTPase-activating protein, Alpha-3 collagen chain (IV), Beta enolase, Famesyl pyrophosphate synthase, Histone H2B type 1-BB, Heterogeneous nuclear ribonucleoproteins A2/B1, Heat shock protein cognate 71 kDa, Cytoskeletal Keratin 7S type II, Beta subunit of protéasome type-5 and homolog of DnaJ subfamily C member 13.

As îllustrated in Figures 8A-8C, it was demonstrated that Famesyl pyrophosphate synthase was détectable in the sérum of patient having pre-cancerous cervical lésions LI and L2, as compared to control sera. Specifically, it was found that Famesyl pyrophosphate synthase expression was 12-tîmes higher in the sérum of patient with pre-cancerous lésions as compared to control (see Figure 8D), demonstrating that pre-cancerous lésions, as well as cancerous (see exampie 2) can be detected in the sérum of patient, by detecting the expression of Famesyl pyrophosphate synthase in the sérum, which can be used as a biomarker for the détection of precancerous cervical lésions.

As îllustrated in Figures 9A-9C, it was demonstrated that Ankyrin-3was détectable in the sérum of patient having pre-cancerous cervical lésions LI and L2, as compared to control sera. Specifically, it was found that Ankirin-3 expression was 10-times higher in the sérum of patient with pre-cancerous lésions as compared to control (see Figure 9D), demonstrating that pre-cancerous lésions, as well as cancerous (see example 2) can be detected in the sérum of patient, by detecting the expression of Ankyrin-3 in the sérum, which can be used as a biomarker for the détection of precancerous cervical lésions.

Similar results were obtained when the quantification of the proteins was intended by ELISA instead of by Western blot.

EXAMPLE 4

LATERAL FLOW ASSAY FOR THE DETECTION OF CERVICAL TUMOR AND PRECANCEROUS LESIONS

For latéral flow assay, strip containing dried spot antibodies for test lines and positive lines were prepared, and samples collected from patients were tested for the détection of Farnesyl pyrophosphate synthase.

Blood samples collected from patients were either directly diluted in Chase buffer at a 1/5 dilution rate (for sérum sample), or further absorbed onto blood separator pad (for whole blood sample) prior to being diluted in Chase buffer. 70 ul of diluted sample were used for each test.

The strip was assembled by removing the membrane section of the protective cover and apply CN-95 membrane. Two pièces of protective cover were reinoved from sections above where the nitrocellulose was placed. A 21 mm wick pad was then applied by aligning the top of the wick pad with the top of the backing card edge, and the excess backing card below the membrane, was eut off, leaving just the membrane and wick pad. The strips were eut to 5.0 mm width using Kinematic Guillotine and package in pouch with desîccant.

The test and positive lines were then prepared on the strip by spot drying antibodies. 1.0 pL of test line antibody was applied around 9 mm from the bottom of the nitrocellulose on 20 precut test strips; and 1 pL of control line antibody was applied around 15 mm up from the bottom of the nitrocellulose on each pre-cut and spotted test strip. The strips were tapped down on piece of paper and place in 40C oven for 1-hour. Once dried, the strips were packaged with desiccant. The antibodies were previously conjugated with gold (using colloïdal gold) or biotinylated.

For the assay, each conjugale were diluted to 0.02% solids using 50mM borate, 0.5% casein, 1% tween. S pL of conjugate were pipetted înto glass tube, fotlowed by 10 pL of sérum. Half of the strip was place in glass tube, with bottom of nitro submerged in the testing solution to allow conjugate/serum solution to nin up strip. 50 pL of Ix PBS, 1% tween20 were then added to glass tube to chase sample.

Using the FLI assay described herein, it was demonstrated that Famesyl pyrophosphate synthase expression level could be determîned a liquid sample collected from a patient, such as the sérum, and that therefore pre-cancerous lésions of low and high grade, as well as cancerous cervical lésions could be detected using the device.

Although the invention has been described with référencé to the above examples, it will be understood that modifications and variations are encompassed within the spirit and scope of the invention. Accordingly, the invention is limited only by the following daims.

Claims (15)

1. An ex vivo or in vitro method comprising:

a) detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide is selected from the group consistîng of :

i) Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type 111, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, Heat shock Protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type Π, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P and Glutathione S-transferase Mu 3 and a fragment thereof; or ii) a polypeptide having the amino acid sequence with at least about 70% sequence identity to SEQ ID NOs: 1-20 or a fragment thereof; and

b) diagnosing cervical cancer based on the détection of the at least one polypeptide.

2. An ex vivo or in vitro method ofpredicting a response to treatment for a subject having cervical cancer comprising:

a) detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide comprises:

i) Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 or a fragment thereof; or ii) a polypeptide with at least about 70% sequence identity to a polypeptide having amino acid sequence selected from the group consistîng of SEQ ID NOs: 1-20 or a fragment thereof; and

b) predicting a response to treatment based on the détection of the at least one polypeptide.

B?

3. An ex vivo or in vitro method for detennining the stage of cervical cancer in a subject in need thereof, comprising:

a) detecting at least one polypeptide in a sample from a subject; wherein the at least one polypeptide comprises:

i) Famesyl pyrophosphate synthase, neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein 1 polycystic kidney disease, heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPaseactivating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type 1-B, homolog of DnaJ subfamily C member 13, Beta enolase, Glutathione S-transferase P, Glutathione Stransferase Mu 3 or a fragment thereof; or ii) a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NOs: 1-20 or a fragment thereof; and

b) detennining the stage of cervical cancer in the subject based on the détection of the at least one polypeptide.

4. The method of claim 3, wherein the cervical cancer is stage I, stage II, stage III or stage IV.

5. The method of any of daims 1-3, wherein the sample is selected from the group consisting of blood, plasma, urine, saliva, sweat, organ biopsy, cerebrospînal fluid (CSF), tear, vaginal fluid, feces, skin, and hair.

6. The method of claim 5, wherein the sample is a blood sample.

7. The method of any of daims 1-3, wherein the subject is human.

8. The method of any one of daims I- 7, wherein the at least one polypeptide comprises

Famesyl pyrophosphate synthase or a fragment thereof and at least one polypeptide selected from the group consisting of neurofibromin I, Glyceraldehyde-3 phosphate dehydrogenase, Protein 1 containing fibronectin domain type III, Eukaryotic initiation factor 4A-I, L-lactate dehydrogenase chain B, Nuclear heterogeneous Ribonucleoprotein Al, 1-like protein I polycystic kidney disease, Heat shock protein cognate 71 kDa, Ankyrin-3, Rho 23 GTPase-activating protein, Cytoskeletal Keratin 78 type II, Alpha-3 collagen chain (VI), Beta subunit of protéasome type-5, Heterogeneous nuclear ribonucleoproteins A2/B1, Histone H2B type I -B, homolog of DnaJ subfamily C member

820891

13, Beta enolase, Glutathione S-transferase P, Glutathione S-transferase Mu 3 and a fragment thereof.

9. The method of any one of claims 1 -7, wherein the at least one polypeptide comprises a polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence of SEQ ID NO: 1 or a fragment thereof and at least one polypeptide with at least about 70% sequence identity to a polypeptide having the amino acid sequence selected from the group consisting of SEQ ID NOs:2-20 and a fragment thereof.

10. The method of any one of claims I -9, wherein the detecting is by protein microarray, fluorescence détection, flow cytometry, microfluidic device, latéral flow assay, vertical flow or immunoassay,

11. The method of claim 10, whereby the detecting is by latéral flow assay.

12. The method of any of daims 1-3, further comprising detennining a treatment to be administered to the subject, wherein the treatment is selected from the group consisting of surgery, radiation, chemotherapy, targeted therapy and immunotherapy.

13. The method of claim 12, wherein the chemotherapy is selected from the group consisting of Cisplatin, Carboplatin, Paclitaxel, Topotecan, docetaxel, ifosfamide, 5-fluorouracil, irinotecan, gemcitabine and mitomycin.

14. The method of daim 12, wherein the targeted therapy is bevacizumab.

15. The method of daim 12, wherein the immunotherapy is pembrolizumab.