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Unraveling the glycosylated immunopeptidome with HLA-Glyco

Author

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  • Georges Bedran

    (University of Gdansk
    University of Michigan)

  • Daniel A. Polasky

    (University of Michigan)

  • Yi Hsiao

    (Department of Computational Medicine and Bioinformatics)

  • Fengchao Yu

    (University of Michigan)

  • Felipe Veiga Leprevost

    (University of Michigan)

  • Javier A. Alfaro

    (University of Gdansk
    University of Victoria
    University of Edinburgh)

  • Marcin Cieslik

    (University of Michigan
    Department of Computational Medicine and Bioinformatics
    University of Michigan School of Medicine)

  • Alexey I. Nesvizhskii

    (University of Michigan
    Department of Computational Medicine and Bioinformatics)

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.

Suggested Citation

  • Georges Bedran & Daniel A. Polasky & Yi Hsiao & Fengchao Yu & Felipe Veiga Leprevost & Javier A. Alfaro & Marcin Cieslik & Alexey I. Nesvizhskii, 2023. "Unraveling the glycosylated immunopeptidome with HLA-Glyco," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39270-2
    DOI: 10.1038/s41467-023-39270-2
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