The copy-number tree mixture deconvolution problem and applications to multi-sample bulk sequencing tumor data

Simone Zaccaria, Mohammed El-Kebir, Gunnar W. Klau, Benjamin J. Raphael

Research output: Chapter in Book/Report/Conference proceedingConference contribution

7 Scopus citations

Abstract

Cancer is an evolutionary process driven by somatic mutation. This process can be represented as a phylogenetic tree. Constructing such a phylogenetic tree from genome sequencing data is a challenging task due to the mutational complexity of cancer and the fact that nearly all cancer sequencing is of bulk tissue, measuring a super-position of somatic mutations present in different cells. We study the problem of reconstructing tumor phylogenies from copy number aberrations (CNAs) measured in bulk-sequencing data. We introduce the Copy-Number Tree Mixture Deconvolution (CNTMD) problem, which aims to find the phylogenetic tree with the fewest number of CNAs that explain the copy number data from multiple samples of a tumor. CNTMD generalizes two approaches that have been researched intensively in recent years: deconvolution/factorization algorithms that aim to infer the number and proportions of clones in a mixed tumor sample; and phylogenetic models of copy number evolution that model the dependencies between copy number events that affect the same genomic loci. We design an algorithm for solving the CNTMD problem and apply the algorithm to both simulated and real data. On simulated data, we find that our algorithm outperforms existing approaches that perform either deconvolution or phylogenetic tree construction under the assumption of a single tumor clone per sample. On real data, we analyze multiple samples from a prostate cancer patient, identifying clones within these samples and a phylogenetic tree that relates these clones and their differing proportions across samples. This phylogenetic tree provides a higher-resolution view of copy number evolution of this cancer than published analyses.

Original languageEnglish (US)
Title of host publicationResearch in Computational Molecular Biology - 21st Annual International Conference, RECOMB 2017, Proceedings
EditorsS.Cenk Sahinalp
PublisherSpringer Verlag
Pages318-335
Number of pages18
ISBN (Print)9783319569697
DOIs
StatePublished - 2017
Event21st Annual International Conference on Research in Computational Molecular Biology, RECOMB 2017 - Hong Kong, China
Duration: May 3 2017May 7 2017

Publication series

NameLecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics)
Volume10229 LNCS
ISSN (Print)0302-9743
ISSN (Electronic)1611-3349

Other

Other21st Annual International Conference on Research in Computational Molecular Biology, RECOMB 2017
CountryChina
CityHong Kong
Period5/3/175/7/17

All Science Journal Classification (ASJC) codes

  • Theoretical Computer Science
  • Computer Science(all)

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    Zaccaria, S., El-Kebir, M., Klau, G. W., & Raphael, B. J. (2017). The copy-number tree mixture deconvolution problem and applications to multi-sample bulk sequencing tumor data. In S. C. Sahinalp (Ed.), Research in Computational Molecular Biology - 21st Annual International Conference, RECOMB 2017, Proceedings (pp. 318-335). (Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics); Vol. 10229 LNCS). Springer Verlag. https://doi.org/10.1007/978-3-319-56970-3_20