RT Journal Article
SR Electronic
T1 HLAProphet: Personalized allele-level quantification of the HLA proteins
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2023.01.29.526142
DO 10.1101/2023.01.29.526142
A1 Michael B. Mumphrey
A1 Ginny Xiaohe Li
A1 Noshad Hosseini
A1 Alexey Nesvizhskii
A1 Marcin Cieslik
YR 2023
UL http://biorxiv.org/content/early/2023/01/31/2023.01.29.526142.abstract
AB Loss of HLA expression in tumor cells is a commonly observed phenotype that is known to be associated with T-cell evasion. Proteogenomic characterizations of the molecular mechanisms underpinning this loss of HLA expression are hindered by the polymorphic nature of the HLA proteins, with most individuals having germline HLA sequences that are highly divergent from the sequences found in standard reference databases. To address this issue, we have developed HLAProphet, an algorithm that utilizes HLA types from paired DNA sequencing data to provide personalized allele-level quantification of the HLA proteins from TMT mass spectrometry data. We show that HLAProphet triples the number of tryptic peptide identifications made by standard reference based approaches, and produces protein expression values that have high concordance with RNA expression and known loss of heterozygosity events.Competing Interest StatementThe authors have declared no competing interest.