Interpretable bilinear attention network with domain adaptation improves drug–target prediction

• Published in: Nature machine intelligence Vol. 5; no. 2; pp. 126 - 136
• Main Authors: Bai, Peizhen, Miljković, Filip, John, Bino, Lu, Haiping
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.02.2023; Nature Publishing Group
• Subjects: 631/154/1435/2418; 639/705/117; Adaptation; Classification; Datasets; Deep learning; Domains; Drugs; Engineering; Ligands; Neural networks; Performance prediction; Proteins
• ISSN: 2522-5839; 2522-5839
• DOI: 10.1038/s42256-022-00605-1

Predicting drug–target interaction is key for drug discovery. Recent deep learning-based methods show promising performance, but two challenges remain: how to explicitly model and learn local interactions between drugs and targets for better prediction and interpretation and how to optimize generalization performance of predictions on novel drug–target pairs. Here, we present DrugBAN, a deep bilinear attention network (BAN) framework with domain adaptation to explicitly learn pairwise local interactions between drugs and targets, and adapt in response to out-of-distribution data. DrugBAN works on drug molecular graphs and target protein sequences to perform prediction, with conditional domain adversarial learning to align learned interaction representations across different distributions for better generalization on novel drug–target pairs. Experiments on three benchmark datasets under both in-domain and cross-domain settings show that DrugBAN achieves the best overall performance against five state-of-the-art baseline models. Moreover, visualizing the learned bilinear attention map provides interpretable insights from prediction results. Predicting drug–target interaction with computational models has attracted a lot of attention, but it is a difficult problem to generalize across domains to out-of-distribution data. Bai et al. present here a method that aims to model local interactions of proteins and drug molecules while being interpretable and provide cross-domain generalization.