MassIVE MSV000084442

Partial Public PXD015761

Patient datasets for: A large peptidome dataset improves HLA class I epitope prediction across most of the human population

Description

Sarkizova S, Klaeger S, Le PM, Li LW, Oliveira G, Keshishian H, Hartigan CH, Zhang W, Braun DA, Ligon KL, Bachireddy P, Zervantonakis IK, Rosenbluth JM, Ouspenskaia T, Law T, Justeson S, Stevens J, Lane WJ, Eisenhaure T, Zhang GL, Clauser KR, Hacohen N, Carr SA, Wu CJ, Keskin DB. Nature Biotechnology 2019. Prediction of HLA epitopes is important for the development of cancer immunotherapies and vaccines. However, current prediction algorithms have limited predictive power, in part because they were not trained on high-quality epitope datasets covering a broad range of HLA alleles. To enable prediction of endogenous HLA class I-associated peptides across a large fraction of the human population, we used mass spectrometry to profile >185,000 peptides eluted from 95 HLA-A, -B, -C and -G mono-allelic cell lines. We identified canonical peptide motifs per HLA allele, unique and shared binding submotifs across alleles and distinct motifs associated with different peptide lengths. By integrating these data with transcript abundance and peptide processing, we developed HLAthena, providing allele-and-length-specific and pan-allele-pan-length prediction models for endogenous peptide presentation. These models predicted endogenous HLA class I-associated ligands with 1.5-fold improvement in positive predictive value compared with existing tools and correctly identified >75% of HLA-bound peptides that were observed experimentally in 11 patient-derived tumor cell lines. [doi:10.25345/C5ZW9K] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: HLA class I ; immunopeptidome

Contact

Principal Investigators:
(in alphabetical order)
Steven A. Carr, Broad Institute of MIT and Harvard, United States
Submitting User: clauser
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Experimental Design
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Identification Results
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Quantification Results
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Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

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Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

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Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

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Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

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