Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity

Authors

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

Publication Date

10-1-2023

Journal

PLOS Computational Biology

DOI

10.1371/journal.pcbi.1011379

PMID

37871126

PMCID

PMC10621967

PubMedCentral® Posted Date

October 2023

PubMedCentral® Full Text Version

Post-print

Abstract

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.

Keywords

Humans, DNA Copy Number Variations, Haplotypes, Neoplasms, Algorithms

Published Open-Access

yes

Recommended Citation

Watkins, Thomas B K; Colliver, Emma C; Huska, Matthew R; et al., "Refphase: Multi-Sample Phasing Reveals Haplotype-Specific Copy Number Heterogeneity" (2023). Faculty, Staff and Student Publications. 2233.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/2233