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HLAProphet: Personalized allele-level quantification of the HLA proteins

View ORCID ProfileMichael B. Mumphrey, Ginny Xiaohe Li, Noshad Hosseini, Alexey Nesvizhskii, Marcin Cieslik
doi: https://doi.org/10.1101/2023.01.29.526142
Michael B. Mumphrey
1Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI USA
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Ginny Xiaohe Li
2Department of Pathology, University of Michigan, Ann Arbor, MI USA
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Noshad Hosseini
1Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI USA
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Alexey Nesvizhskii
1Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI USA
2Department of Pathology, University of Michigan, Ann Arbor, MI USA
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Marcin Cieslik
1Department of Computational Medicine & Bioinformatics, University of Michigan, Ann Arbor, MI USA
2Department of Pathology, University of Michigan, Ann Arbor, MI USA
3Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI USA
4University of Michigan Rogel Cancer Center, Ann Arbor, MI USA
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  • For correspondence: mcieslik@umich.edu
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Abstract

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 Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted January 31, 2023.
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HLAProphet: Personalized allele-level quantification of the HLA proteins
Michael B. Mumphrey, Ginny Xiaohe Li, Noshad Hosseini, Alexey Nesvizhskii, Marcin Cieslik
bioRxiv 2023.01.29.526142; doi: https://doi.org/10.1101/2023.01.29.526142
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HLAProphet: Personalized allele-level quantification of the HLA proteins
Michael B. Mumphrey, Ginny Xiaohe Li, Noshad Hosseini, Alexey Nesvizhskii, Marcin Cieslik
bioRxiv 2023.01.29.526142; doi: https://doi.org/10.1101/2023.01.29.526142

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