title: OncoNEM: inferring tumor evolution from single-cell sequencing data.
abstract: Single-cell sequencing promises a high-resolution view of genetic heterogeneity and clonal evolution in cancer. However, methods to infer tumor evolution from single-cell sequencing data lag behind methods developed for bulk-sequencing data. Here, we present OncoNEM, a probabilistic method for inferring intra-tumor evolutionary lineage trees from somatic single nucleotide variants of single cells. OncoNEM identifies homogeneous cellular subpopulations and infers their genotypes as well as a tree describing their evolutionary relationships. In simulation studies, we assess OncoNEM's robustness and benchmark its performance against competing methods. Finally, we show its applicability in case studies of muscle-invasive bladder cancer and essential thrombocythemia.
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK.
authors.forename: Edith M
authors.initials: EM
authors.lastname: Ross
authors.affiliation: Cancer Research UK Cambridge Institute, University of Cambridge, Robinson Way, Cambridge, UK. florian.markowetz@cruk.cam.ac.uk.
authors.forename: Florian
authors.initials: F
authors.lastname: Markowetz
mesh_terms: D000465:Algorithms; D060965:Clonal Evolution; D019295:Computational Biology / Q000379:methods*; D019143:Evolution, Molecular; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D015233:Models, Statistical; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D059010:Single-Cell Analysis / Q000379:methods*; D013921:Thrombocytopenia / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
keywords: Cancer evolution; Phylogenetic tree; Single-cell sequencing; Tumor evolution; Tumor heterogeneity