Systems and Methods for Protecting Nucleic Acid Molecules

Abstract

Processes and materials to protect nucleic acid molecules are described. Processes and materials to detect neoplasms from a biopsy are described. Processes and materials to build a sequencing library are described. Cell-free nucleic acids can be sequenced and the sequencing result can be utilized to detect sequences derived from a neoplasm.

1 . A composition comprising (i) a nucleic acid molecule and (ii) a heterologous antioxidant moiety comprising a sulfinic acid group. 
     
     
         2 . The composition of  claim 1 , wherein the heterologous antioxidant moiety has the structure: 
       
         
           
           
               
               
           
         
       
       wherein R1 is C1-C6 alkylamine. 
     
     
         3 . The composition of  claim 1 , wherein the heterologous antioxidant moiety is hypotaurine. 
     
     
         4 .- 6 . (canceled) 
     
     
         7 . The composition of  claim 1 , wherein the heterologous antioxidant moiety reduces transversion of one or more nucleotides of the nucleic acid molecule. 
     
     
         8 . The composition of  claim 7 , wherein the transversion comprises a purine to pyrimidine point mutation. 
     
     
         9 .- 10 . (canceled) 
     
     
         11 . The composition of  claim 1 , wherein a concentration of the heterologous antioxidant moiety in the composition is between about 0.1 millimolar and about 100 millimolar. 
     
     
         12 .- 13 . (canceled) 
     
     
         14 . The composition of  claim 1 , wherein a concentration of a population of nucleic acid molecules comprising the nucleic acid molecule in the composition is between about 10 nanomolar and about 10 micromolar. 
     
     
         15 .- 18 . (canceled) 
     
     
         19 . The composition of  claim 1 , comprising a nucleic acid analysis sample, wherein the nucleic acid analysis sample comprises the nucleic acid molecule. 
     
     
         20 . The composition of  claim 19 , further comprising one or more nucleic acid probes designed to capture the nucleic acid molecule from a pool of nucleic acid molecules. 
     
     
         21 . (canceled) 
     
     
         22 . The composition of  claim 1 , wherein the nucleic acid molecule is a cell-free nucleic acid molecule. 
     
     
         23 . (canceled) 
     
     
         24 . The composition of  claim 1 , wherein the nucleic acid molecule is from a biological sample from a subject. 
     
     
         25 .- 26 . (canceled) 
     
     
         27 . A method comprising mixing (i) a nucleic acid molecule and (ii) a heterologous antioxidant moiety comprising a sulfinic acid group. 
     
     
         28 . The method of  claim 27 , wherein the heterologous antioxidant moiety has the structure: 
       
         
           
           
               
               
           
         
       
       wherein R1 is C1-C6 alkylamine. 
     
     
         29 . The method of  claim 27 , wherein the heterologous antioxidant moiety is hypotaurine. 
     
     
         30 .- 35 . (canceled) 
     
     
         36 . The method of  claim 27 , wherein, upon subjecting a mixture comprising the nucleic acid molecule and the heterologous antioxidant moiety to at about 47° C. for about 8 hours, the mixture experiences reduced transversions of one or more nucleotides of the nucleic molecule by at least about 20%, 30%, 40%, 50%, or more as compared to a corresponding control composition that lacks the heterologous antioxidant moiety. 
     
     
         37 .- 44 . (canceled) 
     
     
         45 . The method of  claim 27 , wherein the nucleic acid molecule is a cell-free nucleic acid molecule. 
     
     
         46 . (canceled) 
     
     
         47 . The method of  claim 27 , wherein the nucleic acid molecule is from a biological sample from a subject. 
     
     
         48 . The method of  claim 47 , wherein the subject is a human subject. 
     
     
         49 .- 50 . (canceled) 
     
     
         51 . The method of  claim 27 , further comprising capturing the nucleic acid molecule via one or more nucleic acid probes prior to, concurrent with, or subsequent to the mixing. 
     
     
         52 . The method of  claim 27 , further comprising, subsequent to the mixing, sequencing at least a portion of the nucleic acid molecule. 
     
     
         53 .- 56 . (canceled)