Systems and methods for identifying somatic mutations

Abstract

Systems and method for identifying somatic mutations can receive first and second sequence information, determine if a variant present in the first sequencing information is also present in the second sequence information, and identify variants present in the first sequence information are somatic mutations when the variant is either not present in the second sequence information or the presence of the variant in the second sequence information is likely due to a sequencing error.

1 .- 22 . (canceled) 
     
     
         23 . A method of identifying a somatic mutation in nucleic acid sequence reads generated by a nucleic acid sequence analysis device, wherein a first sequence information represents the nucleic acid sequencing reads generated from a first sample and a second sequence information represents the nucleic acid sequencing reads generated from a second sample, the method comprising:
 receiving the first and second sequence information at a processor;   identifying a variant in the first sequence information;   determining if the variant is present in the second sequence information;   determining, when the variant is present in the second sequence information, whether the variant in the second sequence information is due to sequencing error;   determining first and second coverage levels of a position corresponding to the variant in the first and second sequence information;   and   identifying the variant as a somatic mutation when the variant in the second sequence information is due to sequencing error and the first and second coverage levels are above a coverage threshold.   
     
     
         24 . The method of  claim 23 , further comprising identifying the variant as a somatic mutation when the variant is not present in the second sequence information and when the first and second coverage levels are not less than the coverage threshold. 
     
     
         25 . The method of  claim 23 , further comprising identifying the variant as a low confidence somatic mutation when the variant is not present in the second sequence information and when the second coverage level is less than the coverage threshold. 
     
     
         26 . The method of  claim 23 , further comprising identifying the variant as a low confidence somatic mutation when the first coverage level is less than the coverage threshold. 
     
     
         27 . The method of  claim 23 , further comprising identifying the variant as a low confidence somatic mutation when the second coverage level is less than the coverage threshold. 
     
     
         28 . The method of  claim 23 , wherein the variant identified in the first sequence information is a low frequency variant. 
     
     
         29 . The method of  claim 23 , the variant identified in the second sequence information has a low stringency. 
     
     
         30 . A computer program product, comprising a computer-readable storage medium whose contents include a program with instructions to be executed on a processor, wherein the processor is configured to receive a first sequence information and a second sequence information, wherein the first and second sequence information represent nucleic acid sequencing reads generated for first and second samples by a nucleic acid sequence analysis device, the instructions comprising:
 instructions to identify a variant in the first sequence information;   instructions to determine if the variant is present in the second sequence information;   instructions to determine, when the variant is present in the second sequence information, whether the variant in the second sequence information is due to sequencing error ;   instructions to determine first and second coverage levels of a position corresponding to the variant in the first and second sequence information; and   instructions to identify the variant as a somatic mutation when the variant in the second sequence information is due to sequencing error and the first and second coverage levels are above a coverage threshold.   
     
     
         31 . The computer program product of  claim 30 , further comprising instructions to identify the variant as a somatic mutation when the variant is not present in the second sequence information and when the first and second coverage levels are not less than the coverage threshold. 
     
     
         32 . The computer program product of  claim 30 , further comprising instructions to identify the variant as a low confidence somatic mutation when the variant is not present in the second sequence information and when the second coverage level is less than the coverage threshold. 
     
     
         33 . The computer program product of  claim 30 , further comprising instructions to identify the variant as a low confidence somatic mutation when the first coverage level is less than the coverage threshold. 
     
     
         34 . The computer program product of  claim 30 , further comprising instructions to identify the variant as a low confidence somatic mutation when the second coverage level is less than the coverage threshold. 
     
     
         35 . A system for identifying a somatic mutation in nucleic acid sequence reads generated by a nucleic acid sequence analysis device, wherein a first sequence information represents the nucleic acid sequencing reads generated from a first sample and a second sequence information represents the nucleic acid sequencing reads generated from a second sample, comprising:
 a processor configured to:
 receive the first sequence information and the second sequence information; 
 identify a variant in the first sequence information; 
 determine if the variant is present in the second sequence information; 
 determine, when the variant is present in the second sequence information, whether the variant in the second sequence information is due to sequencing error; 
 determine first and second coverage levels of a position corresponding to the variant in the first and second sequence information; and 
 identify the variant as a somatic mutation when the variant in the second sequence information is due to sequencing error and the first and second coverage levels are above a coverage threshold. 
   
     
     
         36 . The system of  claim 35 , wherein the first sample comprises a tumor sample and the second sample comprises a non-tumor sample. 
     
     
         37 . The system of  claim 35 , wherein the processor is further configured to identify the variant as a somatic mutation when the variant is not present in the second sequence information and when the first and second coverage levels are not less than the coverage threshold. 
     
     
         38 . The system of  claim 35 , wherein the processor is further configured to identify the variant as a low confidence somatic mutation when the variant is not present in the second sequence information and when the second coverage level is less than the coverage threshold. 
     
     
         39 . The system of  claim 35 , wherein the processor is further configured to identify the variant as a low confidence somatic mutation when the first coverage level is less than the coverage threshold. 
     
     
         40 . The system of  claim 35 , wherein the processor is further configured to identify the variant as a low confidence somatic mutation when the second coverage level is less than the coverage threshold. 
     
     
         41 . The system of  claim 35 , wherein the variant identified in the first sequence information is a low frequency variant. 
     
     
         42 . The system of  claim 35 , wherein the variant identified in the second sequence information has a low stringency.