Reconstructing subclonal composition and evolution from whole genome sequencing of tumors
This work addresses the challenge of understanding tumor heterogeneity for cancer genomics, representing an incremental improvement with a specific correction.
The authors tackled the problem of reconstructing subclonal composition and evolution in tumors from whole genome sequencing data by developing PhyloWGS, a method that incorporates a phylogenic correction for variant allele frequencies in copy number altered loci, resulting in improved reconstruction compared to existing methods.
Tumors often contain multiple subpopulations of cancerous cells defined by distinct somatic mutations. We describe a new method, PhyloWGS, that can be applied to WGS data from one or more tumor samples to reconstruct complete genotypes of these subpopulations based on variant allele frequencies (VAFs) of point mutations and population frequencies of structural variations. We introduce a principled phylogenic correction for VAFs in loci affected by copy number alterations and we show that this correction greatly improves subclonal reconstruction compared to existing methods.