Methods and systems of using exosomes for determining phenotypes

Abstract

Exosomes can be used for detecting biomarkers for diagnostic, therapy-related or prognostic methods to identify phenotypes, such as a condition or disease, for example, the stage or progression of a disease. Cell-of-origin exosomes can be used in profiling of physiological states or determining phenotypes. Biomarkers or markers from cell-of-origin specific exosomes can be used to determine treatment regimens for diseases, conditions, disease stages, and stages of a condition, and can also be used to determine treatment efficacy. Markers from cell-of-origin specific exosomes can also be used to identify conditions of diseases of unknown origin.

1 . A method for determining a theranosis in a subject comprising:
 (a) assessing a bio-signature for a microvesicle present in a biological sample from a subject suffering a disorder, wherein said assessing comprises assaying two or more polypeptides associated with said microvesicle; and   (b) determining whether said subject may respond to a selected treatment based on said assessing in (a), thereby determining a theranosis for said subject.   
   
   
       2 . The method of  claim 1 , wherein said disorder is a cancer, an autoimmune disorder or a cardiac disorder. 
   
   
       3 . The method of  claim 2 , wherein said cancer is lung cancer, breast cancer, or colon cancer. 
   
   
       4 . The method of  claim 1 , wherein said assessing comprises contacting said sample with at least three antibodies specific for three different analytes. 
   
   
       5 . The method of  claim 1 , wherein said microvesicle is assessed with respect to at least one nucleic acid. 
   
   
       6 . The method of  claim 5 , wherein said nucleic acid is DNA, mRNA, microRNA, snoRNA, snRNA, rRNAs, tRNAs, siRNA, hnRNA, or shRNA. 
   
   
       7 . The method of  claim 5 , wherein said nucleic acid is one or more of miR-21, miR-205, miR-92, miR-147 or miR-574. 
   
   
       8 . The method of  claim 1 , wherein said assessing comprises multiplexed analysis of said microvesicle surface biomarkers. 
   
   
       9 . The method of  claim 8 , wherein said assessing comprises identifying at least one nucleic acid, peptide, protein, lipid, antigen, carbohydrate, proteoglycan or a combination thereof. 
   
   
       10 . The method of  claim 1 , wherein said determining comprises obtaining a measure for an amount of said microvesicle. 
   
   
       11 . The method of  claim 8 , wherein said assessing further comprises multiplexed analysis of a plurality of nucleic acids in said microvesicle. 
   
   
       12 . The method of  claim 11 , wherein said plurality comprises at least one microRNA in  FIGS. 3-6 ,  19 - 24 ,  26 - 30 ,  32 ,  33 ,  36 ,  40 - 42 ,  47 ,  51 ,  53 - 57 , and  60 . 
   
   
       13 . The method of  claim 6 , wherein said microRNA is selected from miR-21, miR-205, miR-92, miR-147 or miR-574. 
   
   
       14 . The method of  claim 1 , wherein said disorder is lung cancer. 
   
   
       15 . The method of  claim 14 , wherein said bio-signature comprises at least one microRNA selected from miR-21, miR-205, miR-92, miR-147 or miR-574. 
   
   
       16 . A method for determining biomarkers of a disorder in a subject comprising:
 (a) assessing a bio-signature for a microvesicle present in a biological sample from a subject suffering a disorder, wherein said assessing comprises assaying two or more polypeptides associated with said microvesicle;   (b) determining whether one or more biomarkers are present in said microvesicle;   (c) comparing said one or more biomarkers in said sample to a reference; and   (d) determining biomarkers of said disorder based on said comparison.   
   
   
       17 . The method of  claim 16 , wherein said disorder is a cancer, an autoimmune disorder or a cardiac disorder. 
   
   
       18 . The method of  claim 17 , wherein said cancer is lung cancer, breast cancer, or colon cancer 
   
   
       19 . The method of  claim 16 , wherein said assessing comprises contacting said sample with at least three antibodies specific for three different analytes. 
   
   
       20 . The method of  claim 16 , wherein said one or biomarker is a nucleic acid, peptide, protein, lipid, antigen, carbohydrate, proteoglycan or a combination thereof. 
   
   
       21 . The method of  claim 20 , wherein said nucleic acid is DNA, mRNA, microRNA, snoRNA, snRNA, rRNAs, tRNAs, siRNA, hnRNA, or shRNA. 
   
   
       22 . The method of  claim 20 , wherein the nucleic acid is one or more of miR-21, miR-205, miR-92, miR-147 or miR-574. 
   
   
       23 . The method of  claim 16 , wherein said assessing comprises multiplexed analysis of surface markers of said microvesicle. 
   
   
       24 . The method of  claim 20 , wherein said one or more biomarker comprises at least one polypeptide and at least one nucleic acid. 
   
   
       25 . The method of  claim 16 , wherein said determining comprises obtaining a measure for an amount of said microvesicle. 
   
   
       26 . The method of  claim 23 , wherein said assessing further comprises multiplexed analysis of a plurality of nucleic acids in said microvesicle. 
   
   
       27 . The method of  claim 26 , wherein said plurality comprises at least one microRNA in  FIGS. 3-6 ,  19 - 24 ,  26 - 30 ,  32 ,  33 ,  36 ,  40 - 42 ,  47 ,  51 ,  53 - 57 , and  60 . 
   
   
       28 . The method of  claim 27 , wherein said microRNA is selected from miR-21, miR-205, miR-92, miR-147 or miR-574. 
   
   
       29 . The method of  claim 16 , wherein said disorder is lung cancer. 
   
   
       30 . The method of  claim 29 , wherein said bio-signature comprises at least one microRNA selected from miR-21, miR-205, miR-92, miR-147 or miR-574.