Identifying protein antigenic epitopes that are recognizable by antibodies is a key step in immunologic research. This type of research has broad medical applications, such as new immunodiagnostic reagent discovery, vaccine design, and antibody design. However, due to the countless possibilities of potential epitopes, the experimental search through trial and error would be too costly and time-consuming to be practical. To facilitate this process and improve its efficiency, computational methods were developed to predict both linear epitopes and discontinuous antigenic epitopes. For linear B-cell epitope prediction, many methods were developed, including PREDITOP, PEOPLE, BEPITOPE, BepiPred, COBEpro, ABCpred, AAP, BCPred, BayesB, BEOracle/BROracle, BEST, LBEEP, DRREP, iBCE-EL, SVMTriP, etc. For the more challenging yet important task of discontinuous epitope prediction, methods were also developed, including CEP, DiscoTope, PEPITO, ElliPro, SEPPA, EPITOPIA, PEASE, EpiPred, SEPIa, EPCES, EPSVR, etc. In this chapter, we will discuss computational methods for B-cell epitope predictions of both linear and discontinuous epitopes. SVMTriP and EPCES/EPCSVR, the most successful among the methods for each type of the predictions, will be used as model methods to detail the standard protocols. For linear epitope prediction, SVMTriP was reported to achieve a sensitivity of 80.1% and a precision of 55.2% with a fivefold cross-validation based on a large dataset, yielding an AUC of 0.702. For discontinuous or conformational B-cell epitope prediction, EPCES and EPCSVR were both benchmarked by a curated independent test dataset in which all antigens had no complex structures with the antibody. The identified epitopes by these methods were later independently validated by various biochemical experiments. For these three model methods, webservers and all datasets are publicly available at http://sysbio.unl.edu/SVMTriP , http://sysbio.unl.edu/EPCES/ , and http://sysbio.unl.edu/EPSVR/ .
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