Pervasive conditional selection of driver mutations and modular epistasis networks in cancer

23 Pág. Centro de Biotecnología y Genómica de Plantas

Detalles Bibliográficos
Autores: Iranzo, Jaime, Gruenhagen, George, Calle-Espinosa, Jorge, Koonin, Eugene V.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/296715
Acceso en línea:http://hdl.handle.net/10261/296715
https://api.elsevier.com/content/abstract/scopus_id/85136282543
Access Level:acceso abierto
Palabra clave:CP
Cancer
Cancer genomics
Cancer subtypes
Co-occurrence
Conditional selection
Driver mutation
Epistasis
Mutational landscape
Mutual exclusivity
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spelling Pervasive conditional selection of driver mutations and modular epistasis networks in cancerIranzo, JaimeGruenhagen, GeorgeCalle-Espinosa, JorgeKoonin, Eugene V.CPCancerCancer genomicsCancer subtypesCo-occurrenceConditional selectionDriver mutationEpistasisMutational landscapeMutual exclusivity23 Pág. Centro de Biotecnología y Genómica de PlantasCancer driver mutations often display mutual exclusion or co-occurrence, underscoring the key role of epistasis in carcinogenesis. However, estimating the magnitude of epistasis and quantifying its effect on tumor evolution remains a challenge. We develop a method (Coselens) to quantify conditional selection on the excess of nonsynonymous substitutions in cancer genes. Coselens infers the number of drivers per gene in different partitions of a cancer genomics dataset using covariance-based mutation models and determines whether coding mutations in a gene affect selection for drivers in any other gene. Using Coselens, we identify 296 conditionally selected gene pairs across 16 cancer types in the TCGA dataset. Conditional selection affects 25%-50% of driver substitutions in tumors with >2 drivers. Conditionally co-selected genes form modular networks, whose structures challenge the traditional interpretation of within-pathway mutual exclusivity and across-pathway synergy, suggesting a more complex scenario where gene-specific across-pathway epistasis shapes differentiated cancer subtypes.J.I. is supported by the Ramón y Cajal Program of the Spanish Ministry of Science (grant no. RYC-2017-22524), the Agencia Estatal de Investigación of Spain (grant no. PID2019-106618GA-I00), and the Severo Ochoa Program for Centers of Excellence in R&D of the Agencia Estatal de Investigación of Spain (grant no. SEV-2016-0672 [2017–2021] to the CBGP). G.G. is supported by the DHHS/PHS/National Institutes of Health (grant no. 2R01DE019637-10, “Patterning the vertebrate dentition through replacement and repair”). J.C.-E. is supported by the Youth Employment Initiative of the European Social Fund through a junior postdoctoral contract from Comunidad de Madrid (grant no. PEJD-2019-POST/BIO-16377). E.V.K. is supported by intramural research program funds of the National Institutes of Health (National Library of Medicine).Peer reviewedElsevier BVMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)National Institutes of Health (US)European CommissionComunidad de MadridIranzo, Jaime [0000-0002-4538-7726]Gruenhagen, George [0000-0001-6713-5370]Calle-Espinosa, Jorge [0000-0003-2090-2768]Koonin, Eugene V. [0000-0003-3943-8299]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232022info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/296715https://api.elsevier.com/content/abstract/scopus_id/85136282543reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MICINN//RYC-2017-22524info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106618GA-I00info:eu-repo/grantAgreement/AEI//SEV-2016-0672S2019/16377/POST-BIOCell reportshttps://doi.org/10.1016/j.celrep.2022.111272Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2967152026-05-22T06:33:51Z
dc.title.none.fl_str_mv Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
title Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
spellingShingle Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
Iranzo, Jaime
CP
Cancer
Cancer genomics
Cancer subtypes
Co-occurrence
Conditional selection
Driver mutation
Epistasis
Mutational landscape
Mutual exclusivity
title_short Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
title_full Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
title_fullStr Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
title_full_unstemmed Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
title_sort Pervasive conditional selection of driver mutations and modular epistasis networks in cancer
dc.creator.none.fl_str_mv Iranzo, Jaime
Gruenhagen, George
Calle-Espinosa, Jorge
Koonin, Eugene V.
author Iranzo, Jaime
author_facet Iranzo, Jaime
Gruenhagen, George
Calle-Espinosa, Jorge
Koonin, Eugene V.
author_role author
author2 Gruenhagen, George
Calle-Espinosa, Jorge
Koonin, Eugene V.
author2_role author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Agencia Estatal de Investigación (España)
National Institutes of Health (US)
European Commission
Comunidad de Madrid
Iranzo, Jaime [0000-0002-4538-7726]
Gruenhagen, George [0000-0001-6713-5370]
Calle-Espinosa, Jorge [0000-0003-2090-2768]
Koonin, Eugene V. [0000-0003-3943-8299]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv CP
Cancer
Cancer genomics
Cancer subtypes
Co-occurrence
Conditional selection
Driver mutation
Epistasis
Mutational landscape
Mutual exclusivity
topic CP
Cancer
Cancer genomics
Cancer subtypes
Co-occurrence
Conditional selection
Driver mutation
Epistasis
Mutational landscape
Mutual exclusivity
description 23 Pág. Centro de Biotecnología y Genómica de Plantas
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/296715
https://api.elsevier.com/content/abstract/scopus_id/85136282543
url http://hdl.handle.net/10261/296715
https://api.elsevier.com/content/abstract/scopus_id/85136282543
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MICINN//RYC-2017-22524
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PID2019-106618GA-I00
info:eu-repo/grantAgreement/AEI//SEV-2016-0672
S2019/16377/POST-BIO
Cell reports
https://doi.org/10.1016/j.celrep.2022.111272
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Elsevier BV
publisher.none.fl_str_mv Elsevier BV
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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