title: ddClone: joint statistical inference of clonal populations from single cell and bulk tumour sequencing data.
abstract: Next-generation sequencing (NGS) of bulk tumour tissue can identify constituent cell populations in cancers and measure their abundance. This requires computational deconvolution of allelic counts from somatic mutations, which may be incapable of fully resolving the underlying population structure. Single cell sequencing (SCS) is a more direct method, although its replacement of NGS is impeded by technical noise and sampling limitations. We propose ddClone, which analytically integrates NGS and SCS data, leveraging their complementary attributes through joint statistical inference. We show on real and simulated datasets that ddClone produces more accurate results than can be achieved by either method alone.
authors.affiliation: Bioinformatics Graduate Program, University of British Columbia, 570 West 7th Avenue, Vancouver, V5Z 4S6, BC, Canada.
authors.forename: Sohrab
authors.identifier: 0000-0001-6402-523X
authors.initials: S
authors.lastname: Salehi
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 2B5, BC, Canada.|Department of Molecular Oncology, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, V5Z 1L3, BC, Canada.
authors.forename: Adi
authors.initials: A
authors.lastname: Steif
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 2B5, BC, Canada.|Department of Molecular Oncology, British Columbia Cancer Agency, 675 West 10th Avenue, Vancouver, V5Z 1L3, BC, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Roth
authors.affiliation: Bioinformatics Graduate Program, University of British Columbia, 570 West 7th Avenue, Vancouver, V5Z 4S6, BC, Canada.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 2B5, BC, Canada.
authors.forename: Samuel
authors.initials: S
authors.lastname: Aparicio
authors.affiliation: Department of Statistics, University of British Columbia, 2207 Main Mall, Vancouver, V6T 1Z4, BC, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bouchard-Côté
authors.affiliation: Bioinformatics Graduate Program, University of British Columbia, 570 West 7th Avenue, Vancouver, V5Z 4S6, BC, Canada. sshah@bccrc.ca.|Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, V6T 2B5, BC, Canada. sshah@bccrc.ca.
authors.forename: Sohrab P
authors.initials: SP
authors.lastname: Shah
mesh_terms: D000483:Alleles; D000818:Animals; D002999:Clone Cells / Q000378:metabolism*; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D064593:Heterografts; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D015233:Models, Statistical; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA; D059010:Single-Cell Analysis / Q000379:methods; D064726:Triple Negative Breast Neoplasms / Q000235:genetics / Q000473:pathology; D057188:Workflow
keywords: Chinese restaurant process; Clonal evolution; Distance dependent; Intra-tumour heterogeneity; Joint probabilistic model; Next-generation sequencing; Single cell sequencing