Machine learning prediction of Antibody-Antigen binding: dataset, method and testing

Ye, Chao; Hu, Wenxing; Gaeta, Bruno

DNA sequencing technologies are providing new insights into the immune response by allowing the large scale sequencing of rearranged immunoglobulin gene present in an individual, however the applications of this approach are limited by the lack of methods for determining the antigen(s) that an immunoglobulin encoded by a given sequence binds to. Computational methods for predicting antibody-antigen interactions that leverage structure prediction and docking have been proposed, however these methods require knowledge of the 3D structures. As a step towards the development of a machine learning method suitable for predicting antibody-antigen binding affinities from sequence data, a weighted nearest neighbor machine learning approach was applied to the problem. A prediction program was coded in Python and evaluated using cross-validation on a dataset of 600 antibodies interacting with 50 antigens. The classification predicting accuracy was around 76% for this dataset. These results provide a useful frame of reference as well as protocols and considerations for machine learning and dataset creation in this area. Both the dataset (in csv format) and the machine learning program (coded in python) are freely available for download.