ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer.

Autor: Trincado JL; Josep Carreras Leukemia Research Institute, Badalona, Spain., Reixachs-Solé M; Australian National University, Canberra, Australia.; EMBL Australia Partner Laboratory Network at the Australian National University, Canberra, Australia., Pérez-Granado J; Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), Dept. of Experimental and Health Sciences, Pompeu Fabra University (UPF), Barcelona, Spain., Fugmann T; Philochem AG, Otelfingen, Switzerland., Sanz F; Research Programme on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), Dept. of Experimental and Health Sciences, Pompeu Fabra University (UPF), Barcelona, Spain., Yokota J; National Cancer Center Research Institute (NCCRI), Tokyo, Japan., Eyras E; Australian National University, Canberra, Australia.; EMBL Australia Partner Laboratory Network at the Australian National University, Canberra, Australia.; Catalan Institution for Research and Advanced Studies, Barcelona, Spain.; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain.
Jazyk: angličtina
Zdroj: PLoS computational biology [PLoS Comput Biol] 2021 Sep 16; Vol. 17 (9), pp. e1009411. Date of Electronic Publication: 2021 Sep 16 (Print Publication: 2021).
DOI: 10.1371/journal.pcbi.1009411
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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