Integrating systems biology sources illuminates drug action

  • Posted on: 24 March 2016
  • By: fcoldren
TitleIntegrating systems biology sources illuminates drug action
Publication TypeJournal Article
Year of Publication2014
AuthorsGottlieb A, Altman RB
JournalClin Pharmacol Ther
Date Published2014 Jun
KeywordsAlgorithms, Databases, Factual, Drug Interactions, Drug Repositioning, Gene Regulatory Networks, Humans, Pharmacogenetics, Pharmacology, Signal Transduction, Systems Biology

There are significant gaps in our understanding of the pathways by which drugs act. This incomplete knowledge limits our ability to use mechanistic molecular information rationally to repurpose drugs, understand their side effects, and predict their interactions with other drugs. Here, we present DrugRouter, a novel method for generating drug-specific pathways of action by linking target genes, disease genes, and pharmacogenes using gene interaction networks. We construct pathways for more than a hundred drugs and show that the genes included in our pathways (i) co-occur with the query drug in the literature, (ii) significantly overlap or are adjacent to known drug-response pathways, and (iii) are adjacent to genes that are hits in genome-wide association studies assessing drug response. Finally, these computed pathways suggest novel drug-repositioning opportunities (e.g., statins for follicular thyroid cancer), gene-side effect associations, and gene-drug interactions. Thus, DrugRouter generates hypotheses about drug actions using systems biology data.

Alternate JournalClin. Pharmacol. Ther.
PubMed ID24577151
PubMed Central IDPMC4029855
Grant ListGM102365 / GM / NIGMS NIH HHS / United States
GM61374 / GM / NIGMS NIH HHS / United States
LM05652 / LM / NLM NIH HHS / United States
P50 MH094267 / MH / NIMH NIH HHS / United States
R01 GM102365 / GM / NIGMS NIH HHS / United States
R01 LM005652 / LM / NLM NIH HHS / United States
R24 GM061374 / GM / NIGMS NIH HHS / United States