Reconstructing subclonal composition and evolution from whole genome sequencing of tumors

TL;DR

This paper introduces PhyloWGS, a novel method for reconstructing tumor subclonal composition and evolution from whole genome sequencing data, improving accuracy by correcting for copy number alterations.

Contribution

The paper presents PhyloWGS, a new approach that accurately reconstructs tumor subclones and their evolutionary relationships using VAFs and structural variation data, with a novel correction for copy number effects.

Findings

Improved subclonal reconstruction accuracy over existing methods.

Effective correction for copy number alterations enhances phylogenetic analysis.

Applicable to multiple tumor samples for comprehensive tumor evolution insights.

Abstract

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.