PT  - JOURNAL ARTICLE
AU  - Michael B. Mumphrey
AU  - Ginny Xiaohe Li
AU  - Noshad Hosseini
AU  - Alexey Nesvizhskii
AU  - Marcin Cieslik
TI  - HLAProphet: Personalized allele-level quantification of the HLA proteins
AID  - 10.1101/2023.01.29.526142
DP  - 2023 Jan 01
TA  - bioRxiv
PG  - 2023.01.29.526142
4099  - http://biorxiv.org/content/early/2023/01/31/2023.01.29.526142.short
4100  - http://biorxiv.org/content/early/2023/01/31/2023.01.29.526142.full
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.