NASNet-DTI: accurate drug–target interaction prediction using heterogeneous graphs and node adaptation

Abstract Drug–target interactions (DTIs) play a key role in drug development, and accurate prediction can significantly improve the efficiency of this process. Traditional experimental methods are reliable but time-consuming and laborious. With the rapid development of deep learning, many DTI prediction methods have emerged. However, most of these methods only focus on the intrinsic features of drugs and targets, while ignoring the relational features between them. In addition, existing graph-based DTI prediction methods often face the challenge of over-smoothing in graph neural networks (GNNs), which limits their prediction accuracy. To address these issues, we propose NASNet-DTI (Drug–target Interactions Based on Node Adaptation and Similarity Networks), a new framework designed to overcome these limitations. NASNet-DTI uses graph convolutional network to extract features from drug molecules and targets separately, and constructs heterogeneous networks to represent two types of nodes: drugs and targets. The edges in the network describe their multiple relationships: drug–drug, target–target, and drug–target. In the feature learning stage, NASNet-DTI adopts a node adaptive learning strategy to dynamically determine the optimal aggregation depth for each node. This ensures that each node can learn the most discriminative features, which effectively alleviates the over-smoothing problem and improves prediction accuracy. Experimental results show that NASNet-DTI significantly outperforms existing methods on multiple datasets, demonstrating its effectiveness and potential as a powerful tool to advance drug discovery and development.