1. Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing.
- Author
-
Jiang Y, Qiu Y, Minn AJ, and Zhang NR
- Subjects
- Computational Biology methods, DNA Copy Number Variations genetics, Exome genetics, Genetic Heterogeneity, Humans, Internet, Mutation, Neoplasms pathology, Phylogeny, Polymorphism, Single Nucleotide, Software, Clonal Evolution genetics, Evolution, Molecular, High-Throughput Nucleotide Sequencing methods, Neoplasms genetics
- 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/., Competing Interests: The authors declare no conflict of interest.
- Published
- 2016
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