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dc.contributor.authorVasicek, Jakub
dc.contributor.authorSkiadopoulou, Dafni
dc.contributor.authorKuznetsova, Ksenia
dc.contributor.authorWen, Bo
dc.contributor.authorJohansson, Stefan
dc.contributor.authorNjølstad, Pål Rasmus
dc.contributor.authorBruckner, Stefan
dc.contributor.authorKäll, Lukas
dc.contributor.authorVaudel, Marc
dc.description.abstractBackground The nonrandom distribution of alleles of common genomic variants produces haplotypes, which are fundamental in medical and population genetic studies. Consequently, protein-coding genes with different co-occurring sets of alleles can encode different amino acid sequences: protein haplotypes. These protein haplotypes are present in biological samples and detectable by mass spectrometry, but they are not accounted for in proteomic searches. Consequently, the impact of haplotypic variation on the results of proteomic searches and the discoverability of peptides specific to haplotypes remain unknown. Findings Here, we study how common genetic haplotypes influence the proteomic search space and investigate the possibility to match peptides containing multiple amino acid substitutions to a publicly available data set of mass spectra. We found that for 12.42% of the discoverable amino acid substitutions encoded by common haplotypes, 2 or more substitutions may co-occur in the same peptide after tryptic digestion of the protein haplotypes. We identified 352 spectra that matched to such multivariant peptides, and out of the 4,582 amino acid substitutions identified, 6.37% were covered by multivariant peptides. However, the evaluation of the reliability of these matches remains challenging, suggesting that refined error rate estimation procedures are needed for such complex proteomic searches. Conclusions As these procedures become available and the ability to analyze protein haplotypes increases, we anticipate that proteomics will provide new information on the consequences of common variation, across tissues and time.en_US
dc.publisherOxford University Pressen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.titleFinding haplotypic signatures in proteinsen_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.rights.holderCopyright 2023 The Author(s)en_US
dc.relation.projectNorges forskningsråd: 301178en_US
dc.identifier.citationGigaScience. 2023, 12, giad093.en_US

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Navngivelse 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse 4.0 Internasjonal