a systematic assessment of mhc class ii peptide binding predictions and evaluation of a consensus approach系统评估mhc ii级肽结合的预测和评价的共识.pdfVIP
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a systematic assessment of mhc class ii peptide binding predictions and evaluation of a consensus approach系统评估mhc ii级肽结合的预测和评价的共识
A Systematic Assessment of MHC Class II Peptide Binding
Predictions and Evaluation of a Consensus Approach
1 1 1,2 ´ 2 1 1
Peng Wang , John Sidney , Courtney Dow , Bianca Mothe , Alessandro Sette , Bjoern Peters *
1 La Jolla Institute for Allergy and Immunology, La Jolla, California, United States of America, 2 Department of Biological Sciences, California State University-San Marcos,
San Marcos, California, United States of America
Abstract
The identification of MHC class II restricted peptide epitopes is an important goal in immunological research. A number of
computational tools have been developed for this purpose, but there is a lack of large-scale systematic evaluation of their
performance. Herein, we used a comprehensive dataset consisting of more than 10,000 previously unpublished MHC-
peptide binding affinities, 29 peptide/MHC crystal structures, and 664 peptides experimentally tested for CD4+ T cell
responses to systematically evaluate the performances of publicly available MHC class II binding prediction tools. While in
selected instances the best tools were associated with AUC values up to 0.86, in general, class II predictions did not perform
as well as historically noted for class I predictions. It appears that the ability of MHC class II molecules to bind variable length
peptides, which requires the correct assignment of peptide binding cores, is a critical factor limiting the performance of
existing prediction tools. To improve performance, we implemented a consensus prediction approach that combines
methods with top performances. We show that this consensus approach achieved best overall performance. Finally, we
make the large datasets used public
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