DOI: 10.1093/bioinformatics/btad451 ISSN: 1367-4811

iGRLDTI: an improved graph representation learning method for predicting drug–target interactions over heterogeneous biological information network

Bo-Wei Zhao, Xiao-Rui Su, Peng-Wei Hu, Yu-An Huang, Zhu-Hong You, Lun Hu
  • Computational Mathematics
  • Computational Theory and Mathematics
  • Computer Science Applications
  • Molecular Biology
  • Biochemistry
  • Statistics and Probability



The task of predicting drug–target interactions (DTIs) plays a significant role in facilitating the development of novel drug discovery. Compared with laboratory-based approaches, computational methods proposed for DTI prediction are preferred due to their high-efficiency and low-cost advantages. Recently, much attention has been attracted to apply different graph neural network (GNN) models to discover underlying DTIs from heterogeneous biological information network (HBIN). Although GNN-based prediction methods achieve better performance, they are prone to encounter the over-smoothing simulation when learning the latent representations of drugs and targets with their rich neighborhood information in HBIN, and thereby reduce the discriminative ability in DTI prediction.


In this work, an improved graph representation learning method, namely iGRLDTI, is proposed to address the above issue by better capturing more discriminative representations of drugs and targets in a latent feature space. Specifically, iGRLDTI first constructs an HBIN by integrating the biological knowledge of drugs and targets with their interactions. After that, it adopts a node-dependent local smoothing strategy to adaptively decide the propagation depth of each biomolecule in HBIN, thus significantly alleviating over-smoothing by enhancing the discriminative ability of feature representations of drugs and targets. Finally, a Gradient Boosting Decision Tree classifier is used by iGRLDTI to predict novel DTIs. Experimental results demonstrate that iGRLDTI yields better performance that several state-of-the-art computational methods on the benchmark dataset. Besides, our case study indicates that iGRLDTI can successfully identify novel DTIs with more distinguishable features of drugs and targets.

Availability and implementation

Python codes and dataset are available at

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