title: Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing.
abstract: Cancer is a disease driven by evolutionary selection on somatic genetic and epigenetic alterations. Here, we propose Canopy, a method for inferring the evolutionary phylogeny of a tumor using both somatic copy number alterations and single-nucleotide alterations from one or more samples derived from a single patient. Canopy is applied to bulk sequencing datasets of both longitudinal and spatial experimental designs and to a transplantable metastasis model derived from human cancer cell line MDA-MB-231. Canopy successfully identifies cell populations and infers phylogenies that are in concordance with existing knowledge and ground truth. Through simulations, we explore the effects of key parameters on deconvolution accuracy and compare against existing methods. Canopy is an open-source R package available at https://cran.r-project.org/web/packages/Canopy/.
authors: Genomics and Computational Biology Graduate Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104;
authors: Yuchao
authors: Y
authors: Jiang
authors: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute of Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Yu
authors: Y
authors: Qiu
authors: Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; Institute of Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104.
authors: Andy J
authors: AJ
authors: Minn
authors: Department of Statistics, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104; nzh@wharton.upenn.edu.
authors: Nancy R
authors: NR
authors: Zhang
mesh_terms: D060965:Clonal Evolution / Q000235:genetics*; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations / Q000235:genetics; D019143:Evolution, Molecular; D059472:Exome / Q000235:genetics; D018740:Genetic Heterogeneity; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D020407:Internet; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D012984:Software
keywords: cancer evolution; cancer genomics; clonal deconvolution; intratumor heterogeneity; phylogeny inference