Predicting unseen antibodies’ neutralizability via adaptive graph neural networks

Most natural and synthetic antibodies are ‘unseen’. That is, the demonstration of their neutralization effects with any antigen requires laborious and costly wet-lab experiments. The existing methods that learn antibody representations from known antibody–antigen interactions are unsuitable for unseen antibodies owing to the absence of interaction instances. The DeepAAI method proposed herein learns unseen antibody representations by constructing two adaptive relation graphs among antibodies and antigens and applying Laplacian smoothing between unseen and seen antibodies’ representations. Rather than using static protein descriptors, DeepAAI learns representations and relation graphs ‘dynamically’, optimized towards the downstream tasks of neutralization prediction and 50% inhibition concentration estimation. The performance of DeepAAI is demonstrated on human immunodeficiency virus, severe acute respiratory syndrome coronavirus 2, influenza and dengue. Moreover, the relation graphs have rich interpretability. The antibody relation graph implies similarity in antibody neutralization reactions, and the antigen relation graph indicates the relation among a virus’s different variants. We accordingly recommend probable broad-spectrum antibodies against new variants of these viruses.