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

Molecular & Cellular Proteomics : MCP
Roman MylonasMichal Bassani-Sternberg

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 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 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 man...Continue Reading

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Datasets Mentioned

BETA
PXD005231
PXD010793

Methods Mentioned

BETA
acetylation
exome sequencing

Software Mentioned

PRIDE
TagPep
R
Andromeda
MzJava
MaxQuant Comet
Ensemble
PEAKS
GibbsCluster
PEAKS Studio

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