The Francis Crick Institute
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Refphase: Multi-sample phasing reveals haplotype-specific copy number heterogeneity.

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journal contribution
posted on 2023-11-09, 14:38 authored by Thomas BK 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
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.


Crick (Grant ID: CC2041, Grant title: Swanton CC2041) Crick (Grant ID: CC2008, Grant title: Van Loo CC2008) Novo Nordisk UK Research Foundation (Grant ID: NNF15OC0016584, Grant title: NovoNordisk Foundation 16584) European Research Council (Grant ID: 835297 - PROTEUS, Grant title: ERC 835297 - PROTEUS)