|Publication Type||Journal Article|
|Year of Publication||2019|
|Authors||Sarkizova, S, Klaeger, S, Le, PM, Li, LW, Oliveira, G, Keshishian, H, Hartigan, CR, Zhang, W, Braun, DA, Ligon, KL, Bachireddy, P, Zervantonakis, IK, Rosenbluth, JM, Ouspenskaia, T, Law, T, Justesen, S, Stevens, J, Lane, WJ, Eisenhaure, T, Zhang, GLan, Clauser, KR, Hacohen, N, Carr, SA, Wu, CJ, Keskin, DB|
|Date Published||2019 Dec 16|
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.
|Alternate Journal||Nat. Biotechnol.|
|Grant List||T32HG002295 / / U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) /|