Predicting viral sensitivity to antibodies using genetic sequences and antibody similarities

For genetically variable pathogens such as human immunodeficiency virus (HIV)-1, individual viral isolates can differ dramatically in their sensitivity to antibodies. The ability to predict which viruses will be sensitive and which will be resistant to a specific antibody could aid in the design of antibody therapies and help illuminate resistance evolution. Due to the enormous number of possible combinations, it is not possible to experimentally measure neutralization values for all pairs of viruses and antibodies. Here, we developed a simple and interpretable method called grouped neutralization learning (GNL) to predict neutralization values by leveraging viral genetic sequences and similarities in neutralization profiles between antibodies. The trained model is interpretable and can identify key mutations that impact viral sensitivity. Our method compares favorably to state-of-the-art approaches and is robust to model parameter assumptions. GNL can predict neutralization values for viral sequences without observed neutralization measurements, an important capability for assessing antibody coverage in populations whose viral diversity is genetically characterized. We also demonstrate that GNL can successfully transfer knowledge between independent data sets, allowing rapid estimates of viral sensitivity based on prior knowledge.