Artykuł w czasopiśmie
Brak miniatury
Licencja
ClosedAccessDostęp zamknięty
 

Epistasis in genomic and survival data of cancer patients

Uproszczony widok
cris.lastimport.scopus2024-02-12T20:32:10Z
dc.abstract.enCancer aggressiveness and its effect on patient survival depends on mutations in the tumor genome. Epistatic interactions between the mutated genes may guide the choice of anticancer therapy and set predictive factors of its success. Inhibitors targeting synthetic lethal partners of genes mutated in tumors are already utilized for efficient and specific treatment in the clinic. The space of possible epistatic interactions, however, is overwhelming, and computational methods are needed to limit the experimental effort of validating the interactions for therapy and characterizing their biomarkers. Here, we introduce SurvLRT, a statistical likelihood ratio test for identifying epistatic gene pairs and triplets from cancer patient genomic and survival data. Compared to established approaches, SurvLRT performed favorable in predicting known, experimentally verified synthetic lethal partners of PARP1 from TCGA data. Our approach is the first to test for epistasis between triplets of genes to identify biomarkers of synthetic lethality-based therapy. SurvLRT proved successful in identifying the known gene TP53BP1 as the biomarker of success of the therapy targeting PARP in BRCA1 deficient tumors. Search for other biomarkers for the same interaction revealed a region whose deletion was a more significant biomarker than deletion of TP53BP1. With the ability to detect not only pairwise but twelve different types of triple epistasis, applicability of SurvLRT goes beyond cancer therapy, to the level of characterization of shapes of fitness landscapes.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorMatlak, Dariusz
dc.contributor.authorSzczurek, Ewa
dc.date.accessioned2024-01-24T22:49:43Z
dc.date.available2024-01-24T22:49:43Z
dc.date.issued2017
dc.description.financeNie dotyczy
dc.description.number7
dc.description.volume13
dc.identifier.doi10.1371/JOURNAL.PCBI.1005626
dc.identifier.issn1553-734X
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/106333
dc.identifier.weblinkhttps://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1005626
dc.languageeng
dc.pbn.affiliationcomputer and information sciences
dc.relation.ispartofPLoS Computational Biology
dc.relation.pages1-16
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enFitness epistasis
dc.subject.enBreast cancer
dc.subject.enCancers and neoplasms
dc.subject.enBiomarkers
dc.subject.enGenetic causes of cancer
dc.subject.enMalignant tumors
dc.subject.enEpistasis
dc.subject.enCancer genomics
dc.titleEpistasis in genomic and survival data of cancer patients
dc.typeJournalArticle
dspace.entity.typePublication