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MHC-BPS: MHC-binder prediction server for identifying peptides of flexible lengths from sequence-derived physicochemical properties

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Abstract

Major histocompatibility complex (MHC)-binding peptides are essential for antigen recognition by T-cell receptors and are being explored for vaccine design. Computational methods have been developed for predicting MHC-binding peptides of fixed lengths, based on the training of relatively few non-binders. It is desirable to introduce methods applicable for peptides of flexible lengths and trained by using more diverse sets of non-binders. MHC-BPS is a web-based MHC-binder prediction server that uses support vector machines for predicting peptide binders of flexible lengths for 18 MHC class I and 12 class II alleles from sequence-derived physicochemical properties, which were trained by using 4,208∼3,252 binders and 234,333∼168,793 non-binders, and evaluated by an independent set of 545∼476 binders and 110,564∼84,430 non-binders. The binder prediction accuracies are 86∼99% for 25 and 70∼80% for five alleles, and the non-binder accuracies are 96∼99% for 30 alleles. A screening of HIV-1 genome identifies 0.01∼5% and 5∼8% of the constituent peptides as binders for 24 and 6 alleles, respectively, including 75∼100% of the known epitopes. This method correctly predicts 73.3% of the 15 newly published epitopes in the last 4 months of 2005. MHC-BPS is available at http://bidd.cz3.nus.edu.sg/mhc/.

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Acknowledgement

This work was supported in part by grants from Singapore ARF R-151-000-031-112, Shanghai Commission for Science and Technology (04QMX1450) and the 973 National Key Basic Research Program of China (2004CB720103).

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Correspondence to Yu Zong Chen.

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Table 1

Distribution of the binding peptides of different HLA alleles with respect to peptide length in units of the number of amino acids (34,692 kb)

Table 2

Data sets and the computed binder and non-binder prediction accuracies of the SVM prediction systems for different HLA alleles developed in this work. A total of 18 MHC class I and 12 MHC class II alleles are covered. TP, TN, FP, and FN are the number of true positive (true binder), true negative (true non-binder), false positive (false binder), and false negative (false non-binder), respectively. The total number of binders and non-binders in a data set is TP + FN and TN + FP, respectively) (42,217 kb)

Table 3

List of newly reported epitopes in the last 4 months of 2005 and SVM prediction results (5,351 kb)

Table 4

Statistics of the predicted peptide binders from the HIV-1 genome (NCBI entry NC_001802) by using our method and several other web-based prediction servers (130,095 kb)

Additional data sets for evaluation

Binders and non-binders are available in MHCBN database: http://bioinformatics.uams.edu/mirror/mhcbn/) and SYFPEITHI database http://www.syfpeithi.de/

Newly reported epitopes in the last 4 months of 2005 and SVM prediction results

NC_001802, Human immunodeficiency virus 1, complete genome ssRNA; linear; length, 9,181 nt

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Cui, J., Han, L.Y., Lin, H.H. et al. MHC-BPS: MHC-binder prediction server for identifying peptides of flexible lengths from sequence-derived physicochemical properties. Immunogenetics 58, 607–613 (2006). https://doi.org/10.1007/s00251-006-0117-2

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