PLoS Computational Biology (Oct 2023)

Refphase: Multi-sample phasing reveals haplotype-specific copy number heterogeneity.

  • Thomas B K Watkins,
  • Emma C Colliver,
  • Matthew R Huska,
  • Tom L Kaufmann,
  • Emilia L Lim,
  • Cody B Duncan,
  • Kerstin Haase,
  • Peter Van Loo,
  • Charles Swanton,
  • Nicholas McGranahan,
  • Roland F Schwarz

DOI
https://doi.org/10.1371/journal.pcbi.1011379
Journal volume & issue
Vol. 19, no. 10
p. e1011379

Abstract

Read online

Most computational methods that infer somatic copy number alterations (SCNAs) from bulk sequencing of DNA analyse tumour samples individually. However, the sequencing of multiple tumour samples from a patient's disease is an increasingly common practice. We introduce Refphase, an algorithm that leverages this multi-sampling approach to infer haplotype-specific copy numbers through multi-sample phasing. We demonstrate Refphase's ability to infer haplotype-specific SCNAs and characterise their intra-tumour heterogeneity, to uncover previously undetected allelic imbalance in low purity samples, and to identify parallel evolution in the context of whole genome doubling in a pan-cancer cohort of 336 samples from 99 tumours.