A Large Peptidome Dataset Improves HLA Class I Epitope Prediction Across Most of the Human Population
View/ Open
Manuscript - clean.pdf (480.6Kb)
Access Status
Full text of the requested work is not available in DASH at this time ("restricted access"). For more information on restricted deposits, see our FAQ.Author
Le, Phuong M
Li, Letitia W
Oliveira, Giacomo
Keshishian, Hasmik
Hartigan, Christina R
Zhang, Wandi
Bachireddy, Pavan
Ouspenskaia, Tamara
Law, Travis
Justesen, Sune
Stevens, Jonathan
Eisenhaure, Thomas
Zhang, Guang Lan
Klauser, Karl R
Hacohen, Nir
Carr, Steven A
Klaeger, Susan
Published Version
https://doi.org/10.1038/s41587-019-0322-9Metadata
Show full item recordCitation
Le, Phuong M, Letitia W Li, Giacomo Oliveira, Hasmik Keshishian, Christina R Hartigan, Wandi Zhang, Pavan Bachireddy et al. "A Large Peptidome Dataset Improves HLA Class I Epitope Prediction Across Most of the Human Population." Nat Biotechnol 38, no. 2 (2019): 199-209. DOI: 10.1038/s41587-019-0322-9Abstract
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.Other Sources
http://pubmed.ncbi.nlm.nih.gov/31844290/Citable link to this page
https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37370468
Collections
- HMS Scholarly Articles [18278]
Contact administrator regarding this item (to report mistakes or request changes)