LAUSR

B-cell epitope prediction (BCEP) is the original subject of immunoinformatics (i.e., bioinformatics applied to immunology). This began with protein sequence analysis to identify hydrophilic peptide fragments bound by antibodies that recognize whole proteins (1), to enable the earlier proposed development of synthetic peptide-based vaccines for inducing protective antibody-mediated immunity (2). BCEP was thus initially “prediction of protein antigenic determinants,” with each antigenic determinant being a B-cell epitope (BCE): a structural feature (e.g., sequence segment) recognized by a paratope (i.e., antigen-binding site of an immunoglobulin such as an antibody) (3, 4). Now understood as the computational identification of putative BCEs, BCEP has since grown to comprise much more sophisticated methods for analyzing both sequence (5–9) and higher-order structure (10, 11) on ever larger scales (e.g., applying genomics and proteomics for vaccine design (12, 13)). However, the full potential of BCEP for peptide-based vaccine design remains to be realized, for which reason the utility of BCEP as such has been called into question (14–17). Nevertheless, BCEP can support the development of vaccines and immunodiagnostics provided that its limitations are adequately comprehended and addressed.