Abstract
B-cells can neutralize pathogenic molecules by targeting them with extreme specificity using receptors secreted or expressed on their surface (antibodies). This is achieved via molecular interactions between the paratope (i.e., the antibody residues involved in the binding) and the interacting region (epitope) of its target molecule (antigen). Discerning the rules that define this specificity would have profound implications for our understanding of humoral immunogenicity and its applications. The aim of this work is to produce improved, antibody-specific epitope predictions by exploiting features derived from the antigens and their cognate antibodies structures, and combining them using statistical and machine learning algorithms. We have identified several geometric and physicochemical features that are correlated in interacting paratopes and epitopes, used them to develop a Monte Carlo algorithm to generate putative epitopes-paratope pairs, and train a machine-learning model to score them. We show that, by including the structural and physicochemical properties of the paratope, we improve the prediction of the target of a given B-cell receptor. Moreover, we demonstrate a gain in predictive power both in terms of identifying the cognate antigen target for a given antibody and the antibody target for a given antigen, exceeding the results of other available tools.
Highlights
B-cells form an essential part of the adaptive immune system, as they are capable of providing long-term protection against pathogens and harmful molecules
We investigate if including antibody-derived features in the training leads to a better accuracy in the prediction of the correct epitope, and improves the identification of the correct target for a given antibody from a pool of antigens, and the correct target of a given antigen from a pool of antibody targets
We investigated correlations between structural and physicochemical properties of actual paratope and epitope patches
Summary
B-cells form an essential part of the adaptive immune system, as they are capable of providing long-term protection against pathogens and harmful molecules Their extremely specific B-cell receptors, named immunoglobulins or antibodies, are key components in this process. Most B-cell epitopes are discontinuous in sequence, meaning that they are composed of residues that might be far apart in sequence and are brought together in spatial proximity by the protein folding [1]. Data describing such conformational epitopes are mainly obtained from experimentally resolved 3D structures of antibodies co-crystallized with their target antigen, which allows a very precise identification of the epitope residues
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