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.
Funder
Cancer Research UK
UK Medical Research Council
Wellcome Trust
Royal Society Research Professorship
CRUK Cancer Immunotherapy Catalyst Network
CRUK Lung Cancer Centre of Excellence
Rosetrees
Novo Nordisk Foundation
Royal Society Professor Enhancement Award
National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre
Cancer Research UK–University College London Centre
Experimental Cancer Medicine Centre
Breast Cancer Research Foundation
Mark Foundation For Cancer Research
European Research Council
Stand Up To Cancer
NIHR BRC at University College London Hospitals
CRUK University College London Experimental Cancer Medicine Centre
Winton Charitable Foundation
CPRIT
Ministerium für Innovation, Wissenschaft und Forschung des Landes Nordrhein-Westfalen
Helmholtz Association
Bundesministerium für Bildung und Forschung
Publisher
Public Library of Science (PLoS)
Subject
Computational Theory and Mathematics,Cellular and Molecular Neuroscience,Genetics,Molecular Biology,Ecology,Modeling and Simulation,Ecology, Evolution, Behavior and Systematics
Cited by
3 articles.
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