Methods and Processes for Non-Invasive Assessment of Genetic Variations

Abstract

Technology provided herein relates in part to methods, processes and apparatuses for non-invasive assessment of genetic variations.

1 . (canceled) 
     
     
         2 . A method for detecting cancer nucleic acid from a biological sample comprising cancer cells from a subject, wherein the sample nucleic acid comprises cancer nucleic acid and normal nucleic acid:
 (a) contacting a cell-free circulating sample nucleic acid from a biological sample from a subject with an agent that specifically binds to a histone associated with normal nucleic acid, wherein the histone is an H1 histone; which sample nucleic acid comprises a normal nucleic acid and a tumor-derived nucleic acid, wherein the histone H1 is H1.0 or H1b, and   
       separating the histone associated normal nucleic acid from the sample nucleic acid to produce a separation product, and detecting the cancer nucleic acid that is in the separation product; or
 (b) contacting the cell-free circulating sample nucleic acid with an agent that specifically binds to a histone associated with the cancer nucleic acid, wherein the histone is H3.1, and detecting the cancer nucleic acid associated with the histone. 
 
     
     
         3 . The method of  claim 2 , wherein the method further comprises selecting from the separation product from step (a) or the cancer nucleic acid associated with H3.1 from step (b) nucleic acid fragments having lengths of 150 bp or less. 
     
     
         4 . The method of  claim 2 , wherein the biological sample comprises cancer and non-cancer cells. 
     
     
         5 . The method of  claim 2 , comprising (c) performing an assay to analyze nucleic acid in the separation product. 
     
     
         6 . The method of  claim 2 , wherein step a) further comprises i) isolating cell free nucleic acids that are not bound to the agent that specifically binds to the H1 histone, wherein the histone H1 is H1.0 or H1b; and ii) contacting the isolated cell free nucleic acids from i) with an agent that specifically binds to H3.1. 
     
     
         7 . The method of  claim 2 , wherein the agent is an antibody. 
     
     
         8 . The method of  claim 2 , wherein the a) contacting the sample nucleic acid with the agent involves immunoprecipitation. 
     
     
         9 . The method of  claim 2 , wherein the biological sample comprises a blood sample, a serum sample, or a plasma sample. 
     
     
         10 . The method of  claim 2 , wherein obtaining the sample nucleic acid comprises subjecting the biological sample to an in vitro process that isolates the sample nucleic acid from other sample components. 
     
     
         11 . The method of  claim 2 , wherein the separation product comprises about 50% or greater second histone-associated nucleic acid. 
     
     
         12 . The method of  claim 5 , wherein the assay for analyzing nucleic acid in the separation product comprises use of a sequencing process. 
     
     
         13 . The method of  claim 5 , wherein the assay detects the presence or absence of a genetic variation according to the assay performed in (c). 
     
     
         14 . The method of  claim 4 , wherein the cancer cells are from a cancer selected from the group consisting of a breast cancer, a colorectal cancer, a gastrointestinal cancer, a hepatocellular cancer, a lung cancer, melanoma, non-Hodgkin lymphoma, leukemia, multiple myeloma, a bladder cancer, hepatoma, a cervical cancer, an esophageal cancer, a pancreatic cancer, or a prostate cancer. 
     
     
         15 . A method for detecting cancer nucleic acid from a biological sample comprising cancer cells from a subject,
 (a) contacting a cell-free circulating sample nucleic acid from a biological sample from a subject with a first agent that specifically binds to a histone associated with normal nucleic acid,
 wherein the histone is an H1 histone, wherein the histone H1 is H1.0 or H1b; 
   (b) separating the normal nucleic acid that is bound to the agent away from the sample nucleic acid, thereby producing a separation product,
 wherein the separation product is enriched with second histone-associated nucleic acid; 
   (c) contacting the separation product with a second agent that specifically binds to a histone associated with the second histone-associated nucleic acid, wherein the histone is an H3.1 histone, and   (d) detecting cancer nucleic acid associated with H3.1 histone.   
     
     
         16 . A method for detecting viral infection in a subject, the method comprises obtaining a biological sample from the subject, wherein the biological sample comprises a nucleic acid from healthy cells and a nucleic acid from viral-infected cells:
 (a) contacting a cell-free circulating sample nucleic acid from a biological sample from a subject with an agent that specifically binds to a histone associated with normal nucleic acid species, wherein the histone is an H1 histone; which sample nucleic acid comprises a normal nucleic acid species and a tumor-derived nucleic acid species, wherein the histone H1 is H1.0 or H1b, and separating the histone associated normal nucleic acid species from the sample nucleic acid to produce a separation product, thereby detecting the nucleic acid from the viral infected cells that is in the separation product that is enriched for viral nucleic acid in the sample nucleic acid; or   b) contacting the cell-free circulating sample nucleic acid with an agent that specifically binds to a histone associated with the nucleic acid from the viral-infected cells, wherein the histone is H3.1, and detecting the viral nucleic acid associated with the H3.1 histone.