gene2drug: a computational tool for pathway-based rational drug repositioning

Bioinformatics. 2018 May 1;34(9):1498-1505. doi: 10.1093/bioinformatics/btx800.


Motivation: Drug repositioning has been proposed as an effective shortcut to drug discovery. The availability of large collections of transcriptional responses to drugs enables computational approaches to drug repositioning directly based on measured molecular effects.

Results: We introduce a novel computational methodology for rational drug repositioning, which exploits the transcriptional responses following treatment with small molecule. Specifically, given a therapeutic target gene, a prioritization of potential effective drugs is obtained by assessing their impact on the transcription of genes in the pathway(s) including the target. We performed in silico validation and comparison with a state-of-art technique based on similar principles. We next performed experimental validation in two different real-case drug repositioning scenarios: (i) upregulation of the glutamate-pyruvate transaminase (GPT), which has been shown to induce reduction of oxalate levels in a mouse model of primary hyperoxaluria, and (ii) activation of the transcription factor TFEB, a master regulator of lysosomal biogenesis and autophagy, whose modulation may be beneficial in neurodegenerative disorders.

Availability and implementation: A web tool for Gene2drug is freely available at An R package is under development and can be obtained from


Supplementary information: Supplementary data are available at Bioinformatics online.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Computational Biology / methods*
  • Computer Simulation*
  • Drug Discovery / methods
  • Drug Repositioning / methods*
  • Humans
  • Mice
  • Software*