DEVOLUTION—A method for phylogenetic reconstruction of aneuploid cancers based on multiregional genotyping data
Open Access
- 20 September 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 4 (1), 1-14
- https://doi.org/10.1038/s42003-021-02637-6
Abstract
Phylogenetic reconstruction of cancer cell populations remains challenging. There is a particular lack of tools that deconvolve clones based on copy number aberration analyses of multiple tumor biopsies separated in time and space from the same patient. This has hampered investigations of tumors rich in aneuploidy but few point mutations, as in many childhood cancers and high-risk adult cancer. Here, we present DEVOLUTION, an algorithm for subclonal deconvolution followed by phylogenetic reconstruction from bulk genotyping data. It integrates copy number and sequencing information across multiple tumor regions throughout the inference process, provided that the mutated clone fraction for each mutation is known. We validate DEVOLUTION on data from 56 pediatric tumors comprising 253 tumor biopsies and show a robust performance on simulations of bulk genotyping data. We also benchmark DEVOLUTION to similar bioinformatic tools using an external dataset. DEVOLUTION holds the potential to facilitate insights into the development, progression, and response to treatment, particularly in tumors with high burden of chromosomal copy number alterations.Keywords
Funding Information
- Cancerfonden (CAN2018-379)
- Barncancerfonden (PR2019-0015)
- Vetenskapsrådet (2020-01033)
This publication has 51 references indexed in Scilit:
- TrAp: a tree approach for fingerprinting subclonal tumor compositionNucleic Acids Research, 2013
- THetA: inferring intra-tumor heterogeneity from high-throughput DNA sequencing dataGenome Biology, 2013
- Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancerNature, 2012
- Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion SequencingThe New England Journal of Medicine, 2012
- Fitness Conferred by BCR-ABL Kinase Domain Mutations Determines the Risk of Pre-Existing Resistance in Chronic Myeloid LeukemiaPLOS ONE, 2011
- phangorn: phylogenetic analysis in RBioinformatics, 2010
- Generation of trisomies in cancer cells by multipolar mitosis and incomplete cytokinesisProceedings of the National Academy of Sciences of the United States of America, 2010
- Analysis of the copy number profiles of several tumor samples from the same patient reveals the successive steps in tumorigenesisGenome Biology, 2010
- Segmentation-based detection of allelic imbalance and loss-of-heterozygosity in cancer cells using whole genome SNP arraysGenome Biology, 2008
- Evolutionary trees from DNA sequences: A maximum likelihood approachJournal of Molecular Evolution, 1981