title: Clonality Inference from Single Tumor Samples Using Low-Coverage Sequence Data.
abstract: Inference of intra-tumor heterogeneity can provide valuable insight into cancer evolution. Somatic mutations detected by sequencing can help estimate the purity of a tumor sample and reconstruct its subclonal composition. Although several methods have been developed to infer intra-tumor heterogeneity, the majority of these tools rely on variant allele frequencies as estimated via ultra-deep sequencing from multiple samples of the same tumor. In practice, obtaining sequencing data from a large number of samples per patient is only feasible in a few cancer types such as liquid tumors, or in rare cases involving solid tumors selected for research. We introduce CTPsingle, which aims at inferring the subclonal composition by using low-coverage sequencing data from a single tumor sample. We show that CTPsingle is able to infer the purity and the clonality of single-sample tumors with high accuracy, even restricted to a coverage depth of ∼30 × .
authors.affiliation: 1 School of Computing Science, Simon Fraser University , Burnaby, Canada .|2 Vancouver Prostate Centre , Vancouver, Canada .
authors.forename: Nilgun
authors.initials: N
authors.lastname: Donmez
authors.affiliation: 1 School of Computing Science, Simon Fraser University , Burnaby, Canada .|2 Vancouver Prostate Centre , Vancouver, Canada .
authors.forename: Salem
authors.initials: S
authors.lastname: Malikic
authors.affiliation: 2 Vancouver Prostate Centre , Vancouver, Canada .|3 Department of Urologic Sciences, University of British Columbia , Vancouver, Canada .
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Wyatt
authors.affiliation: 2 Vancouver Prostate Centre , Vancouver, Canada .
authors.forename: Martin E
authors.initials: ME
authors.lastname: Gleave
authors.affiliation: 2 Vancouver Prostate Centre , Vancouver, Canada .|3 Department of Urologic Sciences, University of British Columbia , Vancouver, Canada .
authors.forename: Colin C
authors.initials: CC
authors.lastname: Collins
authors.affiliation: 1 School of Computing Science, Simon Fraser University , Burnaby, Canada .|2 Vancouver Prostate Centre , Vancouver, Canada .|4 School of Informatics and Computing, Indiana University , Bloomington, Indiana.
authors.forename: S Cenk
authors.initials: SC
authors.lastname: Sahinalp
mesh_terms: D000465:Algorithms; D060965:Clonal Evolution; D019295:Computational Biology / Q000379:methods*; D056915:DNA Copy Number Variations; D005787:Gene Frequency; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics*; D010363:Pattern Recognition, Automated / Q000379:methods; D059010:Single-Cell Analysis / Q000379:methods*; D012984:Software
keywords: DNA sequencing; cancer progression; intra-tumor heterogeneity