Learning Multi-Scale Heterogeneous Representations and Global Topology for Drug-Target Interaction Prediction

IEEE J Biomed Health Inform. 2022 Apr;26(4):1891-1902. doi: 10.1109/JBHI.2021.3121798. Epub 2022 Apr 14.

Abstract

Identification of interactions between drugs and target proteins plays a critical role not only in drug discovery but also in drug repositioning. Deep integration of inter-connections and intra-similarities between heterogeneous multi-source data about drugs and targets, however, is a challenging issue. We propose a drug-target interaction (DTI) prediction model by learning from drug and protein related multi-scale attributes and global topology formed by heterogeneous connections. A drug-protein-disease heterogeneous network (RPD-Net) is firstly constructed to associate diverse similarities, interactions and associations across nodes. Secondly, we propose a multi-scale pairwise deep representation learning module consisting of a new embedding strategy to integrate diverse inter-relations and intra-relations, and dilation convolutions for multi-scale deep representation extraction. A global topology learning module is proposed which is composed of strategy based on non-negative matrix factorization (NMF) to extract topology from RPD-Net, and a new relational-level attention mechanism for discriminative topology embedding. Experimental results using public dataset demonstrate improved performance over state-of-the-art methods and contributions of our major innovations. Evaluation results by top k recall rates and case studies on five drugs further show the effectiveness of our method in retrieving potential target candidates for drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms*
  • Drug Development / methods
  • Drug Repositioning
  • Humans
  • Neural Networks, Computer*
  • Proteins

Substances

  • Proteins