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Methods for Prediction of Peptide Binding to MHC Molecules: A Comparative Study

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Abstract

Background

A variety of methods for prediction of peptide binding to major histocompatibility complex (MHC) have been proposed. These methods are based on binding motifs, binding matrices, hidden Markov models (HMM), or artificial neural networks (ANN). There has been little prior work on the comparative analysis of these methods.

Materials and Methods

We performed a comparison of the performance of six methods applied to the prediction of two human MHC class I molecules, including binding matrices and motifs, ANNs, and HMMs.

Results

The selection of the optimal prediction method depends on the amount of available data (the number of peptides of known binding affinity to the MHC molecule of interest), the biases in the data set and the intended purpose of the prediction (screening of a single protein versus mass screening). When little or no peptide data are available, binding motifs are the most useful alternative to random guessing or use of a complete overlapping set of peptides for selection of candidate binders. As the number of known peptide binders increases, binding matrices and HMM become more useful predictors. ANN and HMM are the predictive methods of choice for MHC alleles with more than 100 known binding peptides.

Conclusion

The ability of bioinformatic methods to reliably predict MHC binding peptides, and thereby potential T-cell epitopes, has major implications for clinical immunology, particularly in the area of vaccine design.

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Acknowledgments

N.P. is supported by a grant from the Canberra Hospital Salaried Specialists Private Practice Fund.

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Author notes

  1. Christian Schönbach

    Present address: Presently at Genomic Sciences Center RIKEN, Tsurumi-ku, Yokohama-shi, Kanagawa-ken, Japan

Authors and Affiliations

  1. BIC-KRDL, Kent Ridge Digital Labs, 21 Heng Mui Keng Terrace, Singapore, 119613, Singapore

    Kun Yu, Christian Schönbach, Judice L. Y. Koh & Vladimir Brusic

  2. National Bioinformatics Centre, University of Canberra, The Canberra Hospital, Woden, Australia

    Nikolai Petrovsky

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Yu, K., Petrovsky, N., Schönbach, C. et al. Methods for Prediction of Peptide Binding to MHC Molecules: A Comparative Study. Mol Med 8, 137–148 (2002). https://doi.org/10.1007/BF03402006

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  • DOI: https://doi.org/10.1007/BF03402006

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