GENNDTI: Drug-Target Interaction Prediction Using Graph Neural Network Enhanced by Router Nodes

Identifying drug-target interactions (DTI) is crucial in drug discovery and repurposing, and in silico techniques for DTI predictions are becoming increasingly important for reducing time and cost. Most interaction-based DTI models rely on the guilt-by-association principle that “similar drugs can interact with similar targets”. However, such methods utilize precomputed similarity matrices and cannot dynamically discover intricate correlations. Meanwhile, some methods enrich DTI networks by incorporating additional networks like DDI and PPI networks, enriching biological signals to enhance DTI prediction. While these approaches have achieved promising performance in DTI prediction, such coarse-grained association data do not explain the specific biological mechanisms underlying DTIs. In this work, we propose GENNDTI, which constructs biologically meaningful routers to represent and integrate the salient properties of drugs and targets. Similar drugs or targets connect to more same router nodes, capturing property sharing. In addition, heterogeneous encoders are designed to distinguish different types of interactions, modeling both real and constructed interactions. This strategy enriches graph topology and enhances prediction efficiency as well. We evaluate the proposed method on benchmark datasets, demonstrating comparative performance over existing methods. We specifically analyze router nodes to validate their efficacy in improving predictions and providing biological explanations.