Ab-Ligity: Identifying sequence-dissimilar antibodies that bind to the same epitope

Motivation: Solving the structure of an antibody-antigen complex gives atomic level information of the interactions between an antibody and its antigen, but such structures are expensive and hard to obtain. Alternative experimental sources include epitope mapping and binning experiments which can be used as a surrogate to identify key interacting residues. However, their resolution is usually not sufficient to identify if two antibodies have identical interactions. Computational approaches to this problem have so far been based on the premise that antibodies with similar sequences behave similarly. Such approaches will fail to identify sequence-distant antibodies that target the same epitope. Results: We present Ab-Ligity, a structure-based similarity measure tailored to antibody-antigen interfaces. Using predicted paratopes on model antibody structures, we assessed our ability to identify those antibodies that target highly similar epitopes. Most antibodies adopting similar binding modes can be identified from sequence similarity alone, using methods such as clonotyping. In the challenging subset where the antibody sequences differ significantly, Ab-Ligity is still able to predict antibodies that would bind to highly similar epitopes (area under the precision-recall curve of 0.86). We compared Ab-Ligity9s performance to an existing tool InterComp, and showed improved performance alongside a significant speed-up. These results suggest that Ab-Ligity will allow the identification of diverse (sequence-dissimilar) antibodies that bind to the same epitopes from large datasets such as immune repertoires. Availability: http://opig.stats.ox.ac.uk/resources