The Francis Crick Institute
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MEDICC2: whole-genome doubling aware copy-number phylogenies for cancer evolution.

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journal contribution
posted on 2022-11-21, 11:05 authored by Tom L Kaufmann, Marina Petkovic, Thomas BK 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
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.


Crick (Grant ID: 10169, Grant title: Swanton FC001169) Crick (Grant ID: 10202, Grant title: Van Loo FC001202)