Methods and systems for determining somatic mutation clonality

A system for characterizing cancer cells in at least one test sample comprising nucleic acids, the system comprising:

• a sequencer for receiving nucleic acids from the test sample and providing nucleic acid sequence information of the test sample;
• a processor;
• and
• one or more computer-readable storage media having stored thereon instructions for execution on said processor to:
• (a) receive genomic sequence data obtained by sequencing nucleic acids in at least one test sample from a subject, wherein the nucleic acids are from one or more subclones of cancer cells;
• (b) determine a plurality of somatic mutation variants in the genomic sequence data;
• (c) calculate, for each somatic mutation variant, an initial cancer cell fraction (iCCF) using a VAF, wherein a cancer cell fraction is a fraction of cancer cells having the somatic mutation variant among all cancer cells, and wherein the VAF is an allele frequency of the somatic mutation variant, thereby obtaining a plurality of iCCFs for the plurality of somatic mutation variants;
• (d) cluster the plurality of iCCFs for the plurality of somatic mutation variants, thereby obtaining one or more clusters of iCCFs, each cluster corresponding to variants present in a same subclone of the one or more subclones;
• and
• (e) determine one or more final cancer cell fractions (fCCFs) for one or more somatic mutations of the plurality of somatic mutations using iCCFs of the one or more clusters.

A computer program product comprising a non-transitory machine readable medium storing program code that, when executed by one or more processors of a computer system, causes the computer system to implement a method of characterizing cancer cells in at least one test sample comprising nucleic acids, said program code comprising:

• (a) code for receiving genomic sequence data obtained by sequencing nucleic acids in at least one test sample from a subject, wherein the nucleic acids are from one or more subclones of cancer cells;
• (b) code for determining a plurality of somatic mutation variants in the genomic sequence data;
• (c) code for calculating, for each somatic mutation variant, an initial cancer cell fraction (iCCF) using a VAF, wherein a cancer cell fraction is a fraction of cancer cells having the somatic mutation variant among all cancer cells, and wherein the VAF is an allele frequency of the somatic mutation variant, thereby obtaining a plurality of iCCFs for the plurality of somatic mutation variants;
• (d) code for clustering the plurality of iCCFs for the plurality of somatic mutation variants, thereby obtaining one or more clusters of iCCFs, each cluster corresponding to variants present in a same subclone of the one or more subclones;
• and
• (e) code for determining one or more final cancer cell fractions (fCCFs) for one or more somatic mutations of the plurality of somatic mutations using iCCFs of the one or more clusters.