GSL-DTI: Graph structure learning network for Drug-Target interaction prediction

Methods. 2024 Mar:223:136-145. doi: 10.1016/j.ymeth.2024.01.018. Epub 2024 Feb 14.

Abstract

Motivation: Drug-target interaction prediction is an important area of research to predict whether there is an interaction between a drug molecule and its target protein. It plays a critical role in drug discovery and development by facilitating the identification of potential drug candidates and expediting the overall process. Given the time-consuming, expensive, and high-risk nature of traditional drug discovery methods, the prediction of drug-target interactions has become an indispensable tool. Using machine learning and deep learning to tackle this class of problems has become a mainstream approach, and graph-based models have recently received much attention in this field. However, many current graph-based Drug-Target Interaction (DTI) prediction methods rely on manually defined rules to construct the Drug-Protein Pair (DPP) network during the DPP representation learning process. However, these methods fail to capture the true underlying relationships between drug molecules and target proteins.

Results: We propose GSL-DTI, an automatic graph structure learning model used for predicting drug-target interactions (DTIs). Initially, we integrate large-scale heterogeneous networks using a graph convolution network based on meta-paths, effectively learning the representations of drugs and target proteins. Subsequently, we construct drug-protein pairs based on these representations. In contrast to previous studies that construct DPP networks based on manual rules, our method introduces an automatic graph structure learning approach. This approach utilizes a filter gate on the affinity scores of DPPs and relies on the classification loss of downstream tasks to guide the learning of the underlying DPP network structure. Based on the learned DPP network, we transform the prediction of drug-target interactions into a node classification problem. The comprehensive experiments conducted on three public datasets have shown the superiority of GSL-DTI in the tasks of DTI prediction. Additionally, GSL-DTI provides a fresh perspective for advancing research in graph structure learning for DTI prediction.

Keywords: Drug-Protein Pair (DPP); Drug-Target Interaction; Graph Structure Learning; Heterogeneous Information Networks.

MeSH terms

  • Drug Delivery Systems*
  • Drug Discovery*
  • Machine Learning