Systematic identification of cancer-specific MHC-binding peptides with RAVEN

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dc.authoridÖzen, Özlem/0000-0002-9082-1317
dc.authoridFeuchtinger, Tobias/0000-0002-8517-9681
dc.authoridGrünewald, Thomas G. P./0000-0003-0920-7377
dc.authoridOhmura, Shunya/0000-0002-0930-5172
dc.authoridkiran, merve Meryem/0000-0003-2498-0472
dc.authoridAKATLI, AYSE NUR/0000-0002-9677-2456
dc.authoridMarchetto, Aruna/0000-0002-8873-2251
dc.authorwosidÖzen, Özlem/AAK-4468-2021
dc.authorwosidFeuchtinger, Tobias/AAS-3869-2021
dc.authorwosidGrünewald, Thomas G. P./O-2317-2013
dc.authorwosidOhmura, Shunya/HGF-1322-2022
dc.authorwosidkiran, merve Meryem/GSI-6419-2022
dc.authorwosidAKATLI, AYSE NUR/ABH-4455-2020
dc.authorwosidKnott, Maximilian/AAD-4315-2021
dc.contributor.authorBaldauf, Michaela C.
dc.contributor.authorGerke, Julia S.
dc.contributor.authorKirschner, Andreas
dc.contributor.authorBlaeschke, Franziska
dc.contributor.authorEffenberger, Manuel
dc.contributor.authorSchober, Kilian
dc.contributor.authorRubio, Rebeca Alba
dc.date.accessioned2024-08-04T20:45:21Z
dc.date.available2024-08-04T20:45:21Z
dc.date.issued2018
dc.departmentİnönü Üniversitesien_US
dc.description.abstractImmunotherapy can revolutionize anti-cancer therapy if specific targets are available. Immunogenic peptides encoded by cancer-specific genes (CSGs) may enable targeted immunotherapy, even of oligo-mutated cancers, which lack neo-antigens generated by protein-coding missense mutations. Here, we describe an algorithm and user-friendly software named RAVEN (Rich Analysis of Variable gene Expressions in Numerous tissues) that automatizes the systematic and fast identification of CSG-encoded peptides highly affine to Major Histocompatibility Complexes (MHC) starting from transcriptome data. We applied RAVEN to a dataset assembled from 2,678 simultaneously normalized gene expression microarrays comprising 50 tumor entities, with a focus on oligo-mutated pediatric cancers, and 71 normal tissue types. RAVEN performed a transcriptome-wide scan in each cancer entity for gender-specific CSGs, and identified several established CSGs, but also many novel candidates potentially suitable for targeting multiple cancer types. The specific expression of the most promising CSGs was validated in cancer cell lines and in a comprehensive tissue-microarray. Subsequently, RAVEN identified likely immunogenic CSG-encoded peptides by predicting their affinity to MHCs and excluded sequence identity to abundantly expressed proteins by interrogating the UniProt protein-database. The predicted affinity of selected peptides was validated in T2-cell peptide-binding assays in which many showed binding-kinetics like a very immunogenic influenza control peptide. Collectively, we provide an exquisitely curated catalogue of cancer-specific and highly MHC-affine peptides across 50 cancer types, and a freely available software (https://github.com/JSGerke/RAVENsoftware) to easily apply our algorithm to any gene expression dataset. We anticipate that our peptide libraries and software constitute a rich resource to advance anti-cancer immunotherapy.en_US
dc.description.sponsorshipVerein zur Forderung von Wissenschaft und Forschung an der Medizinischen Fakultat der LMU Munchen (WiFoMed); Daimler and Benz Foundation; Reinhard Frank Foundation; LMU Munich's Institutional Strategy LMUexcellent; Mehr LEBEN fur kreb-skranke Kinder - Bettina-Brau-Stiftung; Walter Schulz Foundation; Kind-Philipp Foundation; Friedrich-Baur Foundation; Fritz Thyssen Foundation [FTF-2015-01046]; Dr. Leopold and Carmen Ellinger Foundation; Wilhelm Sander-Foundation [2016.167.1]; Matthias-Lackas Foundation; Barbara und Hubertus Trettner Foundation; Deutsche Forschungsgemeinschaft [DFG 391665916]; German Cancer Aid [DKH-111886, DKH-70112257]; Deutsche Krebshilfe [70112257]en_US
dc.description.sponsorshipThe laboratory of TGPG is supported by grants from the 'Verein zur Forderung von Wissenschaft und Forschung an der Medizinischen Fakultat der LMU Munchen (WiFoMed)', the Daimler and Benz Foundation in cooperation with the Reinhard Frank Foundation, by LMU Munich's Institutional Strategy LMUexcellent within the framework of the German Excellence Initiative, the 'Mehr LEBEN fur kreb-skranke Kinder - Bettina-Brau-Stiftung', the Walter Schulz Foundation, the Kind-Philipp Foundation, the Friedrich-Baur Foundation, the Fritz Thyssen Foundation (FTF-2015-01046), the Dr. Leopold and Carmen Ellinger Foundation, the Wilhelm Sander-Foundation (2016.167.1), the Matthias-Lackas Foundation, the Barbara und Hubertus Trettner Foundation, the Deutsche Forschungsgemeinschaft (DFG 391665916) and by the German Cancer Aid (DKH-111886 and DKH-70112257). Deutsche Krebshilfe [70112257].en_US
dc.identifier.doi10.1080/2162402X.2018.1481558
dc.identifier.issn2162-402X
dc.identifier.issue9en_US
dc.identifier.pmid30228952en_US
dc.identifier.scopus2-s2.0-85050570589en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.1080/2162402X.2018.1481558
dc.identifier.urihttps://hdl.handle.net/11616/98399
dc.identifier.volume7en_US
dc.identifier.wosWOS:000443993100028en_US
dc.identifier.wosqualityQ1en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherTaylor & Francis Incen_US
dc.relation.ispartofOncoimmunologyen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectImmunotherapyen_US
dc.subjectbioinformaticsen_US
dc.subjectmicroarrayen_US
dc.subjectcancer-specific genesen_US
dc.titleSystematic identification of cancer-specific MHC-binding peptides with RAVENen_US
dc.typeArticleen_US

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