Drug Side-Effect Prediction Via Random Walk on the Signed Heterogeneous Drug Network

Molecules. 2019 Oct 11;24(20):3668. doi: 10.3390/molecules24203668.

Abstract

Drug side-effects have become a major public health concern as they are the underlying cause of over a million serious injuries and deaths each year. Therefore, it is of critical importance to detect side-effects as early as possible. Existing computational methods mainly utilize the drug chemical profile and the drug biological profile to predict the side-effects of a drug. In the utilized drug biological profile information, they only focus on drug-target interactions and neglect the modes of action of drugs on target proteins. In this paper, we develop a new method for predicting potential side-effects of drugs based on more comprehensive drug information in which the modes of action of drugs on target proteins are integrated. Drug information of multiple types is modeled as a signed heterogeneous information network. We propose a signed heterogeneous information network embedding framework for learning drug embeddings and predicting side-effects of drugs. We use two bias random walk procedures to obtain drug sequences and train a Skip-gram model to learn drug embeddings. We experimentally demonstrate the performance of the proposed method by comparison with state-of-the-art methods. Furthermore, the results of a case study support our hypothesis that modes of action of drugs on target proteins are meaningful in side-effect prediction.

Keywords: modes of action of drugs; random walk; side-effect prediction; signed heterogeneous information network.

MeSH terms

  • Algorithms
  • Computational Biology*
  • Drug Discovery
  • Drug Interactions
  • Drug-Related Side Effects and Adverse Reactions / prevention & control*
  • Humans
  • Molecular Targeted Therapy*
  • Proteins / antagonists & inhibitors

Substances

  • Proteins