Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing

Yuchao Jiang, Yu Qiu, Andy J. Minn, Nancy R. Zhang
2016 Proceedings of the National Academy of Sciences of the United States of America  
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
more » ... 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/. intratumor heterogeneity | cancer evolution | clonal deconvolution | cancer genomics | phylogeny inference Author contributions: Y.J. and N.R.Z. formulated the model; Y.J. developed the algorithm and methods; Y.J. and N.R.Z. planned and executed the simulations studies and the analysis of the human breast cancer xenograft dataset; Y.J., Y.Q., A.J.M., and N.R.Z. generated and analyzed the breast cancer cell line dataset; and Y.J. and N.R.Z. wrote the paper. The authors declare no conflict of interest. This article is a PNAS Direct Submission. Freely available online through the PNAS open access option. Data deposition: The whole-exome sequencing data of the transplantable metastasis model derived from MDA-MB-231 have been deposited in the BioProject database, www.ncbi.nlm.nih.gov/bioproject (accession no. PRJNA315318).
doi:10.1073/pnas.1522203113 pmid:27573852 pmcid:PMC5027458 fatcat:wge7d574pnazvcwnhcoyrxxipe