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ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer
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ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer
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Journal Article
ISOTOPE: ISOform-guided prediction of epiTOPEs in cancer
2021
Overview
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 .
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
Alternative Splicing - genetics
/ Alternative Splicing - immunology
/ Breast Neoplasms - immunology
/ Cancer
/ Carcinoma, Small Cell - genetics
/ Carcinoma, Small Cell - immunology
/ Epitopes
/ Female
/ Genes
/ Histocompatibility Antigens Class I - genetics
/ Histocompatibility Antigens Class I - immunology
/ Humans
/ Identification and classification
/ Major histocompatibility complex
/ Male
/ Medicine and Health Sciences
/ Mutation
/ Patients
/ Peptides
/ Protein Isoforms - immunology
/ Proteins
/ RNA-Seq
/ Splicing
/ Tumors
