Human mirnas for use in diagnosis, prognosis, and therapy of human conditions and diseases

Abstract

Disclosed herein are novel compositions, methods, and systems for determining whether a subject has, or is at risk of developing, or is at a given stage of a condition afflicting a tissue of interest, or determining the tissue or cell provenance of a biological sample, based on expression level of one or more of the novel miRNA and isomiR sequences disclosed herein. The compositions, methods, and systems described herein can be used to diagnose a disease or disorder, or prognose a given stage and/or progression of the disease or disorder, or determine the identity of the tissue or cell in a sample. In some embodiments, the compositions, methods, and systems described herein can be used to develop a treatment for the disease or disorder. For example, in some embodiments, the novel miRNAs can be used as therapeutics for treatment of a disease or disorder.

1 . A method of determining whether a subject has, or is at risk of developing, or is at
 a given stage of a condition afflicting a tissue of interest, comprising measuring in a biological sample from the tissue of interest expression level of one or more of the miRNAs, wherein the miRNAs comprise a sequence selected from SEQ ID NO: 1 to SEQ ID NO: 47,972, wherein the alteration of the level of said one or more miRNAs as compared to the level of the same one or more miRNA in a reference sample is indicative of the subject either having, or being at risk of developing, or is at a given stage of the condition.   
     
     
         2 . The method of  claim 1 , wherein isoforms of the miRNAs are used. 
     
     
         3 . The method of  claim 1 , wherein the reference sample represents a normal condition of the tissue. 
     
     
         4 . The method of  claim 1 , wherein the reference sample represents a recognizable stage of an abnormal condition of the tissue. 
     
     
         5 . The method of  claim 1 , wherein the tissue of interest is breast. 
     
     
         6 . The method of  claim 1 , wherein the tissue of interest is pancreas. 
     
     
         7 . The method of  claim 1 , wherein the tissue of interest. is blood. 
     
     
         8 . The method of  claim 1 , wherein the tissue of interest is prostate. 
     
     
         9 . The method of  claim 1 , wherein the tissue of interest is colon. 
     
     
         10 . The method of  claim 1 , wherein the tissue of interest is lung. 
     
     
         11 . The method of  claim 1 , wherein the tissue of interest is skin. 
     
     
         12 . The method of  claim 1 , wherein the tissue of interest is brain. 
     
     
         13 . The method of  claim 1 , wherein the tissue of interest is liver. 
     
     
         14 . The method of  claim 1 , wherein the tissue of interest is heart. 
     
     
         15 . The method of  claim 1 , wherein the tissue of interest is muscle. 
     
     
         16 . The method of  claim 1 , wherein the tissue of interest is ovary. 
     
     
         17 . The method of  claim 1 , wherein the tissue of interest is testicle. 
     
     
         18 . The method of  claim 1 , wherein the tissue of interest is bone marrow. 
     
     
         19 . The method of  claim 5 , wherein the condition of interest is ductal in situ carcinoma (breast carcinoma). 
     
     
         20 . The method of  claim 5 , wherein the condition of interest is lobular in situ carcinoma. 
     
     
         21 . The method of  claim 5 , wherein the condition of interest is invasive breast cancer. 
     
     
         22 . The method of  claim 6 , wherein the condition of interest is early stage cancer of the pancreas. 
     
     
         23 . The method of  claim 6 , wherein the condition of interest is late stage cancer of the pancreas. 
     
     
         24 . The method of  claim 7 , wherein the condition of interest is leukemia. 
     
     
         25 . The method of  claim 8 , wherein the condition of interest is cancer of the prostate. 
     
     
         26 . The method of  claim 9 , wherein the condition of interest is cancer or the colon. 
     
     
         27 . The method of  claim 10 , wherein the condition of interest is cancer of the lung. 
     
     
         28 . The method of  claim 11 , wherein the condition of interest is melanoma. 
     
     
         29 . The method of  claim 11 , wherein the condition of interest is psoriasis. 
     
     
         30 . The method of  claim 12 , wherein the condition of interest is Alzheimer's disease. 
     
     
         31 . The method of  claim 12 , wherein the condition of interest is Parkinson's disease. 
     
     
         32 . The method of  claim 12 , wherein the condition of interest is cancer of the brain. 
     
     
         33 . The method of  claim 13 , wherein the condition of interest is cancer of the liver. 
     
     
         34 . The method of  claim 14 , wherein the condition of interest is cardiomyopathy. 
     
     
         35 . The method of  claim 15 , wherein the condition of interest is a muscle disorder. 
     
     
         36 . The method of  claim 16 , wherein the condition of interest is ovarian cancer. 
     
     
         37 . The method of  claim 17 , wherein the condition of interest is testicular cancer. 
     
     
         38 . The method of  claim 18 , wherein the condition of interest is myelodysplastic syndrome (MDS) or myeloproliferative disorders (MPD).