TY - JOUR
T1 - Unraveling the glycosylated immunopeptidome with HLA-Glyco
AU - Bedran, Georges
AU - Polasky, Daniel A.
AU - Hsiao, Yi
AU - Yu, Fengchao
AU - da Veiga Leprevost, Felipe
AU - Alfaro, Javier A.
AU - Cieslik, Marcin
AU - Nesvizhskii, Alexey I.
N1 - This work was funded by NIH grants R01-GM-094231, U24-CA210967, U24-CA271037 received by G.B., D.P., Y.H., F.Y., F.L., M.C., A.N. This work was supported by the International Centre for Cancer Vaccine Science (Fundacja na rzecz Nauki Polskiej: MAB/3/2017) project is carried out within the International Research Agendas program of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund (received by G.B. and J.A.). This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No 101017453 (received by J.A.).
PY - 2023/6/12
Y1 - 2023/6/12
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-39270-2
DO - 10.1038/s41467-023-39270-2
M3 - Article
SN - 2041-1723
VL - 14
SP - 1
EP - 12
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3461
ER -