US 12,456,541 B2
Analysis of genetic variants
James Xin Sun, Newton, MA (US); and Roman Yelensky, Newton, MA (US)
Assigned to Foundation Medicine, Inc., Boston, MA (US)
Filed by Foundation Medicine, Inc., Cambridge, MA (US)
Filed on Oct. 22, 2020, as Appl. No. 17/077,967.
Application 17/077,967 is a continuation of application No. 15/708,475, filed on Sep. 19, 2017, granted, now 10,847,249.
Application 15/708,475 is a continuation of application No. 14/274,525, filed on May 9, 2014, granted, now 9,792,403, issued on Oct. 17, 2017.
Claims priority of provisional application 61/939,936, filed on Feb. 14, 2014.
Claims priority of provisional application 61/821,920, filed on May 10, 2013.
Prior Publication US 2021/0043274 A1, Feb. 11, 2021
Int. Cl. G16B 20/20 (2019.01); G16B 20/00 (2019.01); G16B 20/10 (2019.01)
CPC G16B 20/20 (2019.02) [G16B 20/00 (2019.02); G16B 20/10 (2019.02)] 30 Claims
 
1. A system for classifying a variant in a tumor sample from a subject, comprising:
at least one processor operatively connected to a memory that stores one or more program instructions that, when executed by the at least one processor, are configured to:
cause the at least one processor to receive a sequence coverage input for the tumor sample, a SNP allele frequency input for the tumor sample, and a variant allele frequency for the variant in the tumor sample, wherein the sequence coverage input, the SNP allele frequency input, and the variant allele frequency were determined without using a sample-matched normal control;
fit a genome-wide copy number model for the tumor sample to the sequence coverage input and the SNP allele frequency input;
based on the genome-wide copy number model, determine a tumor purity, a total copy number for each of a plurality of genomic segments, and a minor allele copy number for each of the plurality of genomic segments, wherein at least one genomic segment of the plurality of genomic segments includes the variant; and
classify the variant as germline, somatic, subclonal, or ambiguous using the tumor purity, the total copy number for the genomic segment, the minor allele copy number for the genomic segment, and the variant allele frequency for the variant in the tumor sample.