Journal
GENOME BIOLOGY
Volume 23, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13059-022-02794-9
Keywords
Somatic copy-number alterations; Chromosomal instability; Aneuploidy; Whole-genome doubling; Intratumor heterogeneity; Cancer evolution; Phylogenetic reconstruction; Single-cell sequencing
Funding
- Helmholtz Association (Germany)
- German Ministry for Education and Research [01IS18025A, 01IS18037A]
- Foulkes Foundation
- Royal Society Research Professorships Enhancement Award [RP/EA/180007]
- Ministry of Culture and Science of the State of North Rhine-Westphalia
- Breast Cancer Research Foundation (BCRF)
- Marie Curie ITN Project PLOIDYNET (FP7-PEOPLE-2013) [607722]
- Francis Crick Institute from Cancer Research UK [FC001169, FC001202]
- Francis Crick Institute from UK Medical Research Council [FC001169, FC001202]
- Francis Crick Institute from Wellcome Trust [FC001169, FC001202]
- Royal Society [RP150154]
- F.R.S.-FNRS
- Medical Research Council [MR/L016311/1]
- CPRIT grant support [RR210006]
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This study presents a new method called MEDICC2, which utilizes somatic copy-number alterations to accurately infer evolutionary trees and whole-genome doubling in cancer cells.
Aneuploidy, chromosomal instability, somatic copy-number alterations, and whole-genome doubling (WGD) play key roles in cancer evolution and provide information for the complex task of phylogenetic inference. We present MEDICC2, a method for inferring evolutionary trees and WGD using haplotype-specific somatic copy-number alterations from single-cell or bulk data. MEDICC2 eschews simplifications such as the infinite sites assumption, allowing multiple mutations and parallel evolution, and does not treat adjacent loci as independent, allowing overlapping copy-number events. Using simulations and multiple data types from 2780 tumors, we use MEDICC2 to demonstrate accurate inference of phylogenies, clonal and subclonal WGD, and ancestral copy-number states.
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