A machine-learned computational functional genomics-based approach to drug classification

Eur J Clin Pharmacol. 2016 Dec;72(12):1449-1461. doi: 10.1007/s00228-016-2134-x. Epub 2016 Oct 1.


Objective: The public accessibility of "big data" about the molecular targets of drugs and the biological functions of genes allows novel data science-based approaches to pharmacology that link drugs directly with their effects on pathophysiologic processes. This provides a phenotypic path to drug discovery and repurposing. This paper compares the performance of a functional genomics-based criterion to the traditional drug target-based classification.

Methods: Knowledge discovery in the DrugBank and Gene Ontology databases allowed the construction of a "drug target versus biological process" matrix as a combination of "drug versus genes" and "genes versus biological processes" matrices. As a canonical example, such matrices were constructed for classical analgesic drugs. These matrices were projected onto a toroid grid of 50 × 82 artificial neurons using a self-organizing map (SOM). The distance, respectively, cluster structure of the high-dimensional feature space of the matrices was visualized on top of this SOM using a U-matrix.

Results: The cluster structure emerging on the U-matrix provided a correct classification of the analgesics into two main classes of opioid and non-opioid analgesics. The classification was flawless with both the functional genomics and the traditional target-based criterion. The functional genomics approach inherently included the drugs' modulatory effects on biological processes. The main pharmacological actions known from pharmacological science were captures, e.g., actions on lipid signaling for non-opioid analgesics that comprised many NSAIDs and actions on neuronal signal transmission for opioid analgesics.

Conclusions: Using machine-learned techniques for computational drug classification in a comparative assessment, a functional genomics-based criterion was found to be similarly suitable for drug classification as the traditional target-based criterion. This supports a utility of functional genomics-based approaches to computational system pharmacology for drug discovery and repurposing.

Keywords: Big data; Data science; Emergent self-organizing maps; Gene ontology; Machine-leraning; Pathophysiological process.

MeSH terms

  • Analgesics / classification*
  • Databases, Factual
  • Drug Discovery
  • Gene Ontology
  • Genomics*
  • Humans
  • Machine Learning
  • Pharmaceutical Preparations / classification*


  • Analgesics
  • Pharmaceutical Preparations