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


  • T.L. Kaufmann
  • M. Petkovic
  • T.B.K. Watkins
  • E.C. Colliver
  • S. Laskina
  • N. Thapa
  • D.C. Minussi
  • N. Navin
  • C. Swanton
  • P. Van Loo
  • K. Haase
  • M. Tarabichi
  • R.F. Schwarz


  • Genome Biology


  • Genome Biol 23 (1): 241


  • 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.