ISOTOPE : ISOform-guided prediction of epiTOPEs in cancer
Trincado Alonso, Juan Luis, 1987- (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Reixachs Solé, Marina (EMBL Australia Partner Laboratory Network at the Australian National University)
Pérez Granado, Judith (Hospital del Mar (Barcelona, Catalunya))
Fugmann, Tim (Philochem AG)
Sanz, Ferran (Hospital del Mar (Barcelona, Catalunya))
Yokota, Jun (National Cancer Center Research Institute (NCCRI))
Eyras, Eduardo (Institut Hospital del Mar d'Investigacions Mèdiques)

Date:	2021
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.
Grants:	Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-1020 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-00519 Agencia Estatal de Investigación BIO2017-85364-R Agencia Estatal de Investigación CEX2018-000782-M Instituto de Salud Carlos III FI18/00034 Instituto de Salud Carlos III PT17/0009/0014
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Published in:	PLoS computational biology, Vol. 17 Núm. 9 (september 2021) , p. e1009411, ISSN 1553-7358

DOI: 10.1371/journal.pcbi.1009411
PMID: 34529669

22 p, 2.3 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Josep Carreras Leukaemia Research Institute
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Articles > Published articles