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

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.

SUBMITTER: Watkins TBK

PROVIDER: S-EPMC10621967 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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

Watkins Thomas B K TBK Colliver Emma C EC Huska Matthew R MR Kaufmann Tom L TL Lim Emilia L EL Duncan Cody B CB Haase Kerstin K Van Loo Peter P Swanton Charles C McGranahan Nicholas N Schwarz Roland F RF

PLoS computational biology 20231023 10

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 int ...[more]

PMID: 37871126

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