BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes (1)
B-cells perform these functions by producing antibodies, proteins that are either secreted or expressed on the B-cell surface, and that recognize their molecular target (called antigen) by binding to a part of it (called epitope) in a highly selective manner.
B-cell epitopes can be divided into two groups. Linear epitopes are formed by linear stretches of residues in the antigen protein sequence. In contrast, discontinuous (conformational) epitopes are formed by residues far apart in the antigen sequence that are brought together in space by its folding. Even though the majority of epitopes are conformational, most contain one or few linear stretches.
Clicking on the ‘Advanced Output is Off ’ button will switch to the advanced visualization mode, in which structural predictions from NetSurfP are added.
The Gini importance values for the 5 RF models are highly consistent, confirming the robustness of the proposed model. Moreover, the figure shows that be- sides the residue type, the predicted RSA is one of the most important features contributing to the predictive power of our method. The method outperforms a baseline predictor solely based on the RSA values provided by Net-SurfP. The AUC, AUC10% and corresponding p values are displayed. To assess the highly prioritized predictions, the average positive predictive value (PPV) and true positive rate (TPR) on the 60 top-scoring residues per protein were calculated. BepiPred-2.0 achieves a significantly better PPV and a marginally better TPR when compared to the other methods.
BepiPred-2.0 has a higher performance than BepiPred-1.0 and LBtope. In par- ticular, as AUC10% focuses on the highest predictions, the gap between BepiPred-1.0 and BepiPred-2.0 for this mea- sure underlines the higher specificity of 2.0 compared to 1.0 for high scoring residues. In evaluation of linear epitope predictive power, BepiPred-2.0 out- performs BepiPred-1.0.
Four unique epitope regions are currently present in different solved structures (1BVK, 1C08, 1MLC, 4TSB). All epitope regions are included in the evaluation, BepiPred-2.0 achieves an AUC of 0.713 and AUC10% of 0.304.
