Antibody Specific B-Cell Epitope Predictions: Leveraging Information From Antibody-Antigen Protein Complexes.
Jespersen, M. C., Mahajan, S., Peters, B., Nielsen, M. and Marcatili, P.
Department of Bio and Health Informatics, Technical University of Denmark, Kongens Lyngby, Denmark.
La Jolla Institute for Allergy and Immunology, Center for Infectious Disease, Allergy and Asthma Research, La Jolla, CA, United States.
Instituto de Investigaciones Biotecnologicas, Universidad Nacional de San Martin, Buenos Aires, Argentina.
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.
Frontiers in Immunology 10: 298 (2019)