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

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

in Accuracy / Aneuploidy / Animal Genetics and Genomics / Bioinformatics / Biomedical and Life Sciences / Cancer / Cancer evolution / Chromosomal instability / Chromosomes / DNA Copy Number Variations / Evolution / Evolutionary Biology / Exome / Gene loci / genome / Genome, Human / Genomes / Genomic instability / Haplotypes / Human Genetics / Humans / Intratumor heterogeneity / Life Sciences / Method / Microbial Genetics and Genomics / Mutation / Neoplasms - genetics / Neoplasms - pathology / parallel evolution / Phylogenetics / Phylogeny / Plant Genetics and Genomics / Somatic copy-number alterations / Trees / Tumors / Whole-genome doubling

2022

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2022

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2022

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Journal Article

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

Petkovic, Marina,

Laskina, Sofya,

Swanton, Charles,

Thapa, Nisha,

Kaufmann, Tom L.,

Haase, Kerstin,

Navin, Nicholas,

Schwarz, Roland F.,

Watkins, Thomas B. K.,

Van Loo, Peter,

Colliver, Emma C.,

Minussi, Darlan C.,

Tarabichi, Maxime

2022

Overview

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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Publisher

BioMed Central,Springer Nature B.V,BMC

Subject

Accuracy

/ Aneuploidy

/ Animal Genetics and Genomics

/ Bioinformatics

/ Biomedical and Life Sciences

/ Cancer

/ Cancer evolution