PMID- 35386688
OWN - NLM
STAT- MEDLINE
DCOM- 20220408
LR  - 20220703
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Unsupervised Mining of HLA-I Peptidomes Reveals New Binding Motifs and Potential 
      False Positives in the Community Database.
PG  - 847756
LID - 10.3389/fimmu.2022.847756 [doi]
LID - 847756
AB  - Modern vaccine designs and studies of human leukocyte antigen (HLA)-mediated 
      immune responses rely heavily on the knowledge of HLA allele-specific binding 
      motifs and computational prediction of HLA-peptide binding affinity. 
      Breakthroughs in HLA peptidomics have considerably expanded the databases of 
      natural HLA ligands and enabled detailed characterizations of HLA-peptide binding 
      specificity. However, cautions must be made when analyzing HLA peptidomics data 
      because identified peptides may be contaminants in mass spectrometry or may 
      weakly bind to the HLA molecules. Here, a hybrid de novo peptide sequencing 
      approach was applied to large-scale mono-allelic HLA peptidomics datasets to 
      uncover new ligands and refine current knowledge of HLA binding motifs. Up to 
      12-40% of the peptidomics data were low-binding affinity peptides with an 
      arginine or a lysine at the C-terminus and likely to be tryptic peptide 
      contaminants. Thousands of these peptides have been reported in a community 
      database as legitimate ligands and might be erroneously used for training 
      prediction models. Furthermore, unsupervised clustering of identified ligands 
      revealed additional binding motifs for several HLA class I alleles and 
      effectively isolated outliers that were experimentally confirmed to be false 
      positives. Overall, our findings expanded the knowledge of HLA binding 
      specificity and advocated for more rigorous interpretation of HLA peptidomics 
      data that will ensure the high validity of community HLA ligandome databases.
CI  - Copyright (c) 2022 Sricharoensuk, Boonchalermvichien, Muanwien, Somparn, Pisitkun 
      and Sriswasdi.
FAU - Sricharoensuk, Chatchapon
AU  - Sricharoensuk C
AD  - Center of Excellence in Computational Molecular Biology, Faculty of Medicine, 
      Chulalongkorn University, Bangkok, Thailand.
FAU - Boonchalermvichien, Tanupat
AU  - Boonchalermvichien T
AD  - Center of Excellence in Computational Molecular Biology, Faculty of Medicine, 
      Chulalongkorn University, Bangkok, Thailand.
FAU - Muanwien, Phijitra
AU  - Muanwien P
AD  - Medical Sciences, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand.
FAU - Somparn, Poorichaya
AU  - Somparn P
AD  - Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn 
      University, Bangkok, Thailand.
FAU - Pisitkun, Trairak
AU  - Pisitkun T
AD  - Center of Excellence in Systems Biology, Faculty of Medicine, Chulalongkorn 
      University, Bangkok, Thailand.
AD  - Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand.
FAU - Sriswasdi, Sira
AU  - Sriswasdi S
AD  - Center of Excellence in Computational Molecular Biology, Faculty of Medicine, 
      Chulalongkorn University, Bangkok, Thailand.
AD  - Research Affairs, Faculty of Medicine, Chulalongkorn University, Bangkok, 
      Thailand.
LA  - eng
SI  - figshare/10.6084/m9.figshare.16025226
SI  - figshare/10.6084/m9.figshare.19207386
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220321
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (HLA Antigens)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - 0 (Histocompatibility Antigens Class II)
RN  - 0 (Ligands)
RN  - 0 (Peptides)
SB  - IM
MH  - *HLA Antigens/genetics/metabolism
MH  - *Histocompatibility Antigens Class I
MH  - Histocompatibility Antigens Class II/metabolism
MH  - Humans
MH  - Ligands
MH  - Peptides
MH  - Protein Binding
PMC - PMC8977642
OTO - NOTNLM
OT  - De novo peptide sequencing
OT  - HLA binding motifs
OT  - HLA class I
OT  - HLA peptidomics
OT  - IEDB
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/04/08 06:00
MHDA- 2022/04/09 06:00
PMCR- 2022/01/01
CRDT- 2022/04/07 05:16
PHST- 2022/01/03 00:00 [received]
PHST- 2022/02/25 00:00 [accepted]
PHST- 2022/04/07 05:16 [entrez]
PHST- 2022/04/08 06:00 [pubmed]
PHST- 2022/04/09 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.847756 [doi]
PST - epublish
SO  - Front Immunol. 2022 Mar 21;13:847756. doi: 10.3389/fimmu.2022.847756. eCollection 
      2022.