In:
PLOS Computational Biology, Public Library of Science (PLoS), Vol. 17, No. 9 ( 2021-9-16), p. e1009411-
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 .
Type of Medium:
Online Resource
ISSN:
1553-7358
DOI:
10.1371/journal.pcbi.1009411
DOI:
10.1371/journal.pcbi.1009411.g001
DOI:
10.1371/journal.pcbi.1009411.g002
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10.1371/journal.pcbi.1009411.g003
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10.1371/journal.pcbi.1009411.g004
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10.1371/journal.pcbi.1009411.g005
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10.1371/journal.pcbi.1009411.g006
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10.1371/journal.pcbi.1009411.s001
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10.1371/journal.pcbi.1009411.s002
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10.1371/journal.pcbi.1009411.s003
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10.1371/journal.pcbi.1009411.s004
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10.1371/journal.pcbi.1009411.s005
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10.1371/journal.pcbi.1009411.s006
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10.1371/journal.pcbi.1009411.s007
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10.1371/journal.pcbi.1009411.s008
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10.1371/journal.pcbi.1009411.s009
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10.1371/journal.pcbi.1009411.s010
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10.1371/journal.pcbi.1009411.s011
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10.1371/journal.pcbi.1009411.s012
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10.1371/journal.pcbi.1009411.s013
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10.1371/journal.pcbi.1009411.s014
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10.1371/journal.pcbi.1009411.s015
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10.1371/journal.pcbi.1009411.s016
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10.1371/journal.pcbi.1009411.s017
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10.1371/journal.pcbi.1009411.s018
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10.1371/journal.pcbi.1009411.s019
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10.1371/journal.pcbi.1009411.s020
DOI:
10.1371/journal.pcbi.1009411.s021
DOI:
10.1371/journal.pcbi.1009411.r001
DOI:
10.1371/journal.pcbi.1009411.r002
DOI:
10.1371/journal.pcbi.1009411.r003
DOI:
10.1371/journal.pcbi.1009411.r004
DOI:
10.1371/journal.pcbi.1009411.r005
DOI:
10.1371/journal.pcbi.1009411.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2193340-6
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