A Sticky Multinomial Mixture Model of Strand-Coordinated Mutational Processes in Cancer.
Bioinformatics
Cancer
Quantitative Genetics
Journal
iScience
ISSN: 2589-0042
Titre abrégé: iScience
Pays: United States
ID NLM: 101724038
Informations de publication
Date de publication:
27 Mar 2020
27 Mar 2020
Historique:
received:
18
12
2019
revised:
23
01
2020
accepted:
05
02
2020
pubmed:
24
2
2020
medline:
24
2
2020
entrez:
24
2
2020
Statut:
ppublish
Résumé
The characterization of mutational processes in terms of their signatures of activity relies mostly 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. It can both use known signatures or learn new ones. We show that this model provides a more accurate description of the properties of mutagenic processes than independent-mutation achieving substantially higher likelihood on held-out data. We apply this model to characterize the processivity of mutagenic processes across multiple types of cancer.
Identifiants
pubmed: 32088392
pii: S2589-0042(20)30084-5
doi: 10.1016/j.isci.2020.100900
pmc: PMC7038582
pii:
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100900Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
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