MEDICC2: Whole-Genome Doubling Aware Copy-Number Phylogenies for Cancer Evolution

Authors

Tom L Kaufmann
Marina Petkovic
Thomas B K Watkins
Emma C Colliver
Sofya Laskina
Nisha Thapa
Darlan C Minussi
Nicholas Navin
Charles Swanton
Peter Van Loo
Kerstin Haase
Maxime Tarabichi
Roland F Schwarz

Publication Date

11-14-2022

Journal

Genome Biology

Abstract

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.

Keywords

Humans, Phylogeny, Neoplasms, DNA Copy Number Variations, Exome, Genome, Human, Aneuploidy, Cancer evolution, Chromosomal instability, Intratumor heterogeneity, Phylogenetic reconstruction, Single-cell sequencing, Somatic copy-number alterations, Whole-genome doubling

DOI

10.1186/s13059-022-02794-9

PMID

36376909

PMCID

PMC9661799

PubMedCentral® Posted Date

11-14-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes