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Cited by 15Glycosylation and Glycoproteins Researchvaccines and immunoinformatics approachesAdvanced Proteomics Techniques and Applications

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Unraveling the glycosylated immunopeptidome with HLA-Glyco

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Bedran, Georges, Polasky, Daniel A., Hsiao, Yi, Yu, Fengchao, da Veiga Leprevost, Felipe, Alfaro, Javier A., Cieslik, Marcin, Nesvizhskii, Alexey I.·2023·Nature Communications
DOI 10.1038/s41467-023-39270-2PMC PMC10258777
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Abstract

Recent interest in targeted therapies has been sparked by the study of MHC-associated peptides (MAPs) that undergo post-translational modifications (PTMs), particularly glycosylation. In this study, we introduce a fast computational workflow that merges the MSFragger-Glyco search algorithm with a false discovery rate control for glycopeptide analysis from mass spectrometry-based immunopeptidome data. By analyzing eight large-scale publicly available studies, we find that glycosylated MAPs are predominantly presented by MHC class II. Here, we present HLA-Glyco, a comprehensive resource containing over 3,400 human leukocyte antigen (HLA) class II N-glycopeptides from 1,049 distinct protein glycosylation sites. This resource provides valuable insights, including high levels of truncated glycans, conserved HLA-binding cores, and differences in glycosylation positional specificity between HLA allele groups. We integrate the workflow within the FragPipe computational platform and provide HLA-Glyco as a free web resource. Overall, our work provides a valuable tool and resource to aid the nascent field of glyco-immunopeptidomics.

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Metadata

Authors
Bedran, G., Polasky, D. A., Hsiao, Y., Yu, F., da Veiga Leprevost, F., Alfaro, J. A., Cieslik, M., & Nesvizhskii, A. I.
Affiliations
  • University of Michigan (US)
  • University of Victoria (CA)
Corresponding author
Nesvizhskii, Alexey I.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-06-12
Volume
14
Issue
1
Pages
3461-3461
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-023-39270-2
PMC
PMC10258777
OpenAlex
W4380361693
Cited by
15
References
2
Citations by year
2026: 3 · 2025: 6 · 2024: 4 · 2023: 2
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute (U24-CA210967, U24-CA271037)
  • EC | Horizon 2020 Framework Programme (101017453)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
  • Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords
glycopeptide analysis, post-translational modification, glycosylation sites, false discovery rate control, FragPipe
MeSH terms
Algorithms, Genes, MHC Class II, Glycopeptides, Glycosylation, Humans, Protein Processing, Post-Translational

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