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A Sticky Multinomial Mixture Model of Strand-Coordinated Mutational Processes in Cancer

  • Itay Sason
  • Damian Wojtowicz
  • Welles Robinson
  • Mark D. M. Leiserson
  • Teresa M. Przytycka
  • Roded SharanEmail author
Conference paper
Part of the Lecture Notes in Computer Science book series (LNCS, volume 11467)

Abstract

The characterization of mutational processes in terms of their signatures of activity relies, to the most part, on the assumption that mutations in a given cancer genome are independent of one another. Recently, it was discovered that certain segments of mutations, termed processive groups, occur on the same DNA strand and are generated by a single process or signature. Here we provide a first probabilistic model of mutational signatures that accounts for their observed stickiness and strand-coordination. The model conditions on the observed strand for each mutation, and allows the same signature to generate a run of mutations. We show that this model provides a more accurate description of the properties of mutagenic processes than independent-mutation models or strand oblivous models, achieving substantially higher likelihood on held-out data. We apply this model to characterize the processivity of mutagenic processes across multiple types of cancer in terms of replication and transcriptional strand-coordination.

Notes

Acknowledgements

This study was supported in part by a fellowship from the Edmond J. Safra Center for Bioinformatics at Tel-Aviv University. DW and TMP are supported by the Intramural Research Programs of the National Library of Medicine (NLM), National Institutes of Health, USA. RS was supported by Len Blavatnik and the Blavatnik Family foundation. We thank Mark Keller for his help in processing mutation datasets.

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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Itay Sason
    • 1
  • Damian Wojtowicz
    • 2
  • Welles Robinson
    • 3
  • Mark D. M. Leiserson
    • 3
  • Teresa M. Przytycka
    • 2
  • Roded Sharan
    • 1
    Email author
  1. 1.School of Computer ScienceTel Aviv UniversityTel AvivIsrael
  2. 2.National Center for Biotechnology Information, National Library of MedicineNational Institutes of HealthBethesdaUSA
  3. 3.Center for Bioinformatics and Computational BiologyUniversity of MarylandCollege ParkUSA

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