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The immunopeptidome from a genomic perspective : establishing the non-canonical landscape of MHC class I–associated peptides
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dc.contributor.author | Bedran, Georges | |
dc.contributor.author | Gasser, Hans-Christof | |
dc.contributor.author | Weke, Kenneth | |
dc.contributor.author | Wang, Tongjie | |
dc.contributor.author | Bedran, Dominika | |
dc.contributor.author | Laird, Alexander | |
dc.contributor.author | Battail, Christophe | |
dc.contributor.author | Zanzotto, Fabio Massimo | |
dc.contributor.author | Pesquita, Catia | |
dc.contributor.author | Axelson, Håkan | |
dc.contributor.author | Rajan, Ajitha | |
dc.contributor.author | Harrison, David J. | |
dc.contributor.author | Palkowski, Aleksander | |
dc.contributor.author | Pawlik, Maciej | |
dc.contributor.author | Parys, Maciej | |
dc.contributor.author | O'Neill, J Robert. | |
dc.contributor.author | Brennan, Paul M. | |
dc.contributor.author | Symeonides, Stefan N. | |
dc.contributor.author | Goodlett, David R. | |
dc.contributor.author | Litchfield, Kevin | |
dc.contributor.author | Fahraeus, Robin | |
dc.contributor.author | Hupp, Ted R. | |
dc.contributor.author | Kote, Sachin | |
dc.contributor.author | Alfaro, Javier A. | |
dc.date.accessioned | 2023-04-03T16:30:07Z | |
dc.date.available | 2023-04-03T16:30:07Z | |
dc.date.issued | 2023-06-01 | |
dc.identifier | 283970946 | |
dc.identifier | 50862a9c-47a5-4e6c-b3f8-d4fed319326a | |
dc.identifier | 85160968693 | |
dc.identifier.citation | Bedran , G , Gasser , H-C , Weke , K , Wang , T , Bedran , D , Laird , A , Battail , C , Zanzotto , F M , Pesquita , C , Axelson , H , Rajan , A , Harrison , D J , Palkowski , A , Pawlik , M , Parys , M , O'Neill , J R , Brennan , P M , Symeonides , S N , Goodlett , D R , Litchfield , K , Fahraeus , R , Hupp , T R , Kote , S & Alfaro , J A 2023 , ' The immunopeptidome from a genomic perspective : establishing the non-canonical landscape of MHC class I–associated peptides ' , Cancer Immunology Research , vol. 11 , no. 6 , pp. 747-762 . https://doi.org/10.1158/2326-6066.cir-22-0621 | en |
dc.identifier.issn | 2326-6066 | |
dc.identifier.other | Jisc: 996380 | |
dc.identifier.other | ORCID: /0000-0001-9041-9988/work/132763937 | |
dc.identifier.uri | https://hdl.handle.net/10023/27326 | |
dc.description | Funding: G.B., D.B., K.W., A.P., R.F., T.R.H., S.K., and J.A.A. received support from Fundacja na rzecz Nauki Polskiej (FNP) (grant ID: MAB/3/2017). D.R.G. received support from Genome Canada & Genome BC (grant ID: 264PRO). D.J.H. received support from NuCana plc (grant ID: SMD0-ZIUN05). H.A. received support from Swedish Cancer Foundation (grant ID: 211709). H.G. received support from United Kingdom Research and Innovation (UKRI) (grant ID: EP/S02431X/1). C.P. received support from Fundação para a Ciência e a Tecnologia (FCT) through LASIGE Research Unit (grant ID: UIDB/00408/2020 and UIDP/00408/2020). A.L. F.M.Z., C.P., A.R., A.P., and J.A.A. received support from European Union’s Horizon 2020 research and innovation programme (grant ID: 101017453). C.B. received support from Agence Nationale de la Recherche (ANR) through GRAL LabEX (grant ID: ANR-10-LABX-49-01) and CBH-EUR-GS 32 (grant ID: ANR-17-EURE0003). S.N.S. received support from Cancer Research UK (CRUK) and the Chief Scientist's Office of Scotland (CSO): Experimental Cancer Medicine Centre (ECMC) (grant ID: ECMCQQR-2022/100017). A.L. received support from Chief Scientist's Office of Scotland (CSO) NRS Career Researcher Fellowship. R.O.N. received support from CRUK Cambridge Centre Thoracic Cancer Programme (grant ID: CTRQQR-2021\100012). | en |
dc.description.abstract | Tumor antigens can emerge through multiple mechanisms, including translation of non-coding genomic regions. This non-canonical category of antigens has recently gained attention; however, our understanding of how they recur within and between cancer types is still in its infancy. Therefore, we developed a proteogenomic pipeline based on deep learning de novo mass spectrometry to enable the discovery of non-canonical MHC-associated peptides (ncMAPs) from non-coding regions. Considering that the emergence of tumor antigens can also involve post-translational modifications, we included an open search component in our pipeline. Leveraging the wealth of mass spectrometry-based immunopeptidomics, we analyzed 26 MHC class I immunopeptidomic studies of 9 different cancer types. We validated the de novo identified ncMAPs, along with the most abundant post-translational modifications, using spectral matching and controlled their false discovery rate (FDR) to 1%. Interestingly, the non-canonical presentation appeared to be 5 times enriched for the A03 HLA supertype, with a projected population coverage of 54.85%. Here, we reveal an atlas of 8,601 ncMAPs with varying levels of cancer selectivity and suggest 17 cancer-selective ncMAPs as attractive targets according to a stringent cutoff. In summary, the combination of the open-source pipeline and the atlas of ncMAPs reported herein could facilitate the identification and screening of ncMAPs as targeting agents for T-cell therapies or vaccine development. | |
dc.format.extent | 16 | |
dc.format.extent | 2357068 | |
dc.language.iso | eng | |
dc.relation.ispartof | Cancer Immunology Research | en |
dc.subject | Cancer | en |
dc.subject | Tumour antigens | en |
dc.subject | Non-canonical MHC class I-associated peptides | en |
dc.subject | Mass spectrometry | en |
dc.subject | Shared antigens | en |
dc.subject | DAS | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject | MCC | en |
dc.title | The immunopeptidome from a genomic perspective : establishing the non-canonical landscape of MHC class I–associated peptides | en |
dc.type | Journal article | en |
dc.contributor.sponsor | European Commission | en |
dc.contributor.institution | University of St Andrews. School of Medicine | en |
dc.contributor.institution | University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis | en |
dc.contributor.institution | University of St Andrews. Cellular Medicine Division | en |
dc.identifier.doi | 10.1158/2326-6066.cir-22-0621 | |
dc.description.status | Peer reviewed | en |
dc.identifier.grantnumber | 101017453 | en |
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