Estimating the Contribution of Proteasomal Spliced Peptides to the HLA-I Ligandome.

Details

Serval ID
serval:BIB_A79DB078A6D8
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Estimating the Contribution of Proteasomal Spliced Peptides to the HLA-I Ligandome.
Journal
Molecular & cellular proteomics
Author(s)
Mylonas R., Beer I., Iseli C., Chong C., Pak H.S., Gfeller D., Coukos G., Xenarios I., Müller M., Bassani-Sternberg M.
ISSN
1535-9484 (Electronic)
ISSN-L
1535-9476
Publication state
Published
Issued date
12/2018
Peer-reviewed
Oui
Volume
17
Number
12
Pages
2347-2357
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Spliced peptides are short protein fragments spliced together in the proteasome by peptide bond formation. True estimation of the contribution of proteasome-spliced peptides (PSPs) to the global human leukocyte antigen (HLA) ligandome is critical. A recent study suggested that PSPs contribute up to 30% of the HLA ligandome. We performed a thorough reanalysis of the reported results using multiple computational tools and various validation steps and concluded that only a fraction of the proposed PSPs passes the quality filters. To better estimate the actual number of PSPs, we present an alternative workflow. We performed <i>de novo</i> sequencing of the HLA-peptide spectra and discarded all <i>de novo</i> sequences found in the UniProt database. We checked whether the remaining <i>de novo</i> sequences could match spliced peptides from human proteins. The spliced sequences were appended to the UniProt fasta file, which was searched by two search tools at a false discovery rate (FDR) of 1%. We find that 2-6% of the HLA ligandome could be explained as spliced protein fragments. The majority of these potential PSPs have good peptide-spectrum match properties and are predicted to bind the respective HLA molecules. However, it remains to be shown how many of these potential PSPs actually originate from proteasomal splicing events.
Keywords
Bioinformatics searching, De novo sequencing, Human Leukocyte Antigen, Immunology, Immunopeptidomics, Mass Spectrometry, Peptidomics, Proteasome-spliced peptides
Pubmed
Web of science
Open Access
Yes
Create date
24/12/2018 11:53
Last modification date
20/08/2019 16:12
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