MassIVE MSV000086452

Imported Reanalysis Dataset Public PXD010793

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

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Description

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 de-novo sequencing of the HLA-peptide spectra and discarded all de-novo sequences found in the UniProt database. We checked whether the remaining de-novo 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 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. [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Immunopeptidomics ; HLA-I peptides ; LC-MSMS ; Proteasomal splicing

Contact

Principal Investigators:
(in alphabetical order) 		Michal Bassani-Sternberg, Center of experimental therapeutics Department of oncology UNIL CHUV Ludwig Institute for Cancer Research Lausanne Biop�le 3 Chemin des Boveresses 155, CH-1066 Lausanne, N/A
Submitting User: ccms

Publications

Mylonas R, Beer I, Iseli C, Chong C, Pak HS, Gfeller D, Coukos G, Xenarios I, Müller M, Bassani-Sternberg M.
Estimating the Contribution of Proteasomal Spliced Peptides to the HLA-I Ligandome.
Mol Cell Proteomics. 2018 Dec;17(12):2347-2357. Epub 2018 Aug 31.

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