ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer
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- dc.contributor.author Trincado Alonso, Juan Luis, 1987-
- dc.contributor.author Reixachs i Solé, Marina
- dc.contributor.author Pérez-Granado, Judith
- dc.contributor.author Fugmann, Tim
- dc.contributor.author Sanz, Ferran
- dc.contributor.author Yokota, Jun
- dc.contributor.author Eyras Jiménez, Eduardo
- dc.date.accessioned 2022-03-18T10:53:07Z
- dc.date.available 2022-03-18T10:53:07Z
- dc.date.issued 2021
- dc.description.abstract Immunotherapies provide effective treatments for previously untreatable tumors and identifying tumor-specific epitopes can help elucidate the molecular determinants of therapy response. Here, we describe a pipeline, ISOTOPE (ISOform-guided prediction of epiTOPEs In Cancer), for the comprehensive identification of tumor-specific splicing-derived epitopes. Using RNA sequencing and mass spectrometry for MHC-I associated proteins, ISOTOPE identified neoepitopes from tumor-specific splicing events that are potentially presented by MHC-I complexes. Analysis of multiple samples indicates that splicing alterations may affect the production of self-epitopes and generate more candidate neoepitopes than somatic mutations. Although there was no difference in the number of splicing-derived neoepitopes between responders and non-responders to immune therapy, higher MHC-I binding affinity was associated with a positive response. Our analyses highlight the diversity of the immunogenic impacts of tumor-specific splicing alterations and the importance of studying splicing alterations to fully characterize tumors in the context of immunotherapies. ISOTOPE is available at https://github.com/comprna/ISOTOPE.es
- dc.description.sponsorship Funding: This work was supported by the Spanish Government and European Regional Development Fund (FEDER) with grant BIO2017-85364-R (F.S., E.E.), by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR, Generalitat de Catalunya) with grants SGR2017-1020 (E.E) and 2017 SGR 00519 (F.S), by the Instituto de Salud Carlos III (ISCIII and FEDER) with grants FI18/00034 (J.P-G) and PT17/0009/0014 (F.S), and by the AEI with CEX2018-000782-M (F.S). The Research Programme on Biomedical Informatics (GRIB) is a member of the Spanish National Bioinformatics Institute (INB) supported by ISCIII and FEDER (PT17/0009/0014). The DCEXS is a ‘Unidad de Excelencia María de Maeztu’ supported by the AEI (CEX2018-000782-M)en
- dc.format.mimetype application/pdf
- dc.identifier.citation Trincado JL, Reixachs-Solé M, Pérez-Granado J, Fugmann T, Sanz F, Yokota J et al. ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer. PLoS Comput Biol. 2021 Sep 16;17(9):e1009411. DOI: 10.1371/journal.pcbi.1009411
- dc.identifier.doi http://dx.doi.org/10.1371/journal.pcbi.1009411
- dc.identifier.issn 1553-734X
- dc.identifier.uri http://hdl.handle.net/10230/52718
- dc.language.iso eng
- dc.publisher Public Library of Science (PLoS)
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BIO2017-85364-R
- dc.rights © 2021 Trincado et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri http://creativecommons.org/licenses/by/4.0/
- dc.subject.other Càncerca
- dc.subject.other Immunoteràpiaca
- dc.subject.other Identificacióca
- dc.title ISOTOPE: ISOform-guided prediction of epiTOPEs in canceren
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion