Gene

Biology

Ploidy

Somatic cell

Copy-number variation

Somatic evolution in cancer

Coalescent theory

Computational biology

Evolutionary biology

Copy number analysis

Genetics

Phylogenetic tree

Genome

Genome instability

Phylogenetics

DNA damage

Aneuploidy

Chromosome

Genome biology

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.

MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution