Predicting peptides that bind to MHC molecules using supervised learning of hidden Markov models.
The binding of a major histocompatibility complex (MHC) molecule to a peptide originating in an antigen is essential to recognizing antigens in immune systems, and it has proved to be important to use computers to predict the peptides that will bind to an MHC molecule. The purpose of this paper is twofold: First, we propose to apply supervised learning of hidden Markov models (HMMs) to this problem, which can surpass existing methods for the problem of predicting MHC-binding peptides. Second, we generate peptides that have high probabilities to bind to a certain MHC molecule, based on our proposed method using peptides binding to MHC molecules as a set of training data. From our experiments, in a type of cross-validation test, the discrimination accuracy of our supervised learning method is usually approximately 2-15% better than those of other methods, including backpropagation neural networks, which have been regarded as the most effective approach to this problem. Furthermore, using an HMM trained for HLA-A2, we present new peptide sequences that are provided with high binding probabilities by the HMM and that are thus expected to bind to HLA-A2 proteins. Peptide sequences not shown in this paper but with rather high binding probabilities can be obtained from the author.
Mamitsuka
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C&C Media Research Laboratories, NEC Corporation, Kawasaki, Kanagawa, Japan. mami@ccm.cl.nec.co.jp
D000465:Algorithms; D016208:Databases, Factual; D006680:HLA Antigens / Q000378:metabolism*; D015789:HLA-A2 Antigen / Q000378:metabolism; D015798:HLA-DR1 Antigen / Q000378:metabolism; D015804:HLA-DR4 Antigen / Q000378:metabolism; D006801:Humans; D008285:Major Histocompatibility Complex; D008390:Markov Chains; D016571:Neural Networks, Computer; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
D006680:HLA Antigens; D015789:HLA-A2 Antigen; D015798:HLA-DR1 Antigen; D015804:HLA-DR4 Antigen; D010455:Peptides