W528 Nucleic Acids Research, 2012, Vol. 40, Web Server issue Figure 1. Screenshot of the peptide:MHC-I binding predictive tool results page generated using the ‘IEDB recommended’ option. The ﬁrst high- lighted area at the top indicates a checkbox with which the user can expand the table to display method-speciﬁc predictions. The second highlighted area at the bottom allows the user to download the prediction results as a text ﬁle. change as we perform larger benchmarks of newly de- veloped methods on blind datasets to determine an accurate assessment of prediction quality. For example, recent evaluations suggested that NetMHCpan is actually superior in performance to all allele-speciﬁc pre- dictors unless there is a very large amount of data avail- able for the particular allele (10). If this result can be conﬁrmed on new binding datasets, the IEDB recommen- dation will change. B-cell epitope prediction A new addition to IEDB-AR since its last publication is the ElliPro tool (23). ElliPro predicts linear and discon- tinuous epitopes for a protein structure or sequence provided by the user; for sequences, the structure is modeled using MODELLER (24). ElliPro is based on the geometrical properties of protein structure and does not require training. Tested on a benchmark dataset of discontinuous epitopes inferred from 3D structures of antibody–protein complexes (25), ElliPro has an AUC of 0.73 when the most signiﬁcant prediction was con- sidered for each protein. Since the rank of the best predic- tion was at most in the top three for >70% of proteins and never exceeded ﬁve, ElliPro can be considered a useful research tool for identifying antibody epitopes in protein antigens. Details on the comparison of ElliPro with other structure-based epitope prediction methods can be found in (23). It would also be interesting to compare the method against sequence-based approaches as well (26). Epitope analysis: Homology mapping tool The homology mapping tool enables analysis of an epitope’s location in the 3D structure of its source protein. For a given epitope, linear or discontinuous, from IEDB or submitted by a user, the tool searches for known 3D protein structures in the Protein Data Bank (PDB) (27) that are homologous to the epitope source sequence. The output page (Figure 2) provides mapping of the epitope to the source sequence, the PDB hits that contain the epitope regions, secondary structures and solvent accessibilities for each residue, presented in the format of either pairwise or multiple sequence alignment for the selected PDB hits, obtained using ClustalW2 (28,29). Residues in the alignment are colored by relative solvent accessibility; coloring can be modiﬁed according to the user-speciﬁed cutoffs on relative solvent accessi- bility of all atoms or side chain atoms only. PDB struc- tures with mapped epitopes can be visualized using EpitopeViewer (30). The 3D viewer feature uses java webstart technology, which does not appear to be smoothly integrated into Google chrome browsers. To use the feature, we recommend using Firefox. In addition to maintaining the homology mapping tool, IEDB-AR is open to incorporating tools developed by external groups. One such type of tools that is of much interest would address the problem of choosing an optimal set of epitopes given various constraints for vaccine design (31,32). IEDB application programming interface (IEDB-API) for peptide:MHC binding predictive tools A frequent user request has been to enable integration of IEDB-AR tools into external applications. For example, the Los Alamos HIV Immunology Database (33) wanted to utilize the IEDB-AR MHC binding predic- tion for their Epitope Location Finder tool (ELF: www .hiv.lanl.gov/content/sequence/ELF/epitope_analyzer. html). To address this general need, an application programming interface (IEDB-API) for tools predictive of MHC binding has been implemented. IEDB-API has been implemented using a simple (RESTful) interface that allows a user to send a prediction request via a simple HTTP POST request to the IEDB-AR