Statistical tests for intra-tumour clonal co-occurrence and exclusivity

Jack Kuipers, Ariane L. Moore, Katharina Jahn, Peter Schraml, Feng Wang, Kiyomi Morita, P. Andrew Futreal, Koichi Takahashi, Christian Beisel, Holger Moch, Niko Beerenwinkel

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Tumour progression is an evolutionary process in which different clones evolve over time, leading to intra-tumour heterogeneity. Interactions between clones can affect tumour evolution and hence disease progression and treatment outcome. Intra-tumoural pairs of mutations that are overrepresented in a co-occurring or clonally exclusive fashion over a cohort of patient samples may be suggestive of a synergistic effect between the different clones carrying these mutations. We therefore developed a novel statistical testing framework, called GeneAccord, to identify such gene pairs that are altered in distinct subclones of the same tumour. We analysed our framework for calibration and power. By comparing its performance to baseline methods, we demonstrate that to control type I errors, it is essential to account for the evolutionary dependencies among clones. In applying GeneAccord to the single-cell sequencing of a cohort of 123 acute myeloid leukaemia patients, we find 1 clonally co-occurring and 8 clonally exclusive gene pairs. The clonally exclusive pairs mostly involve genes of the key signalling pathways.

Original languageEnglish (US)
Article numbere1009036
JournalPLoS computational biology
Volume17
Issue number12
DOIs
StatePublished - Dec 2021

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Ecology
  • Modeling and Simulation
  • Molecular Biology
  • Genetics
  • Cellular and Molecular Neuroscience
  • Computational Theory and Mathematics

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