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2014 ; 95
(6
): 663-9
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Integrating systems biology sources illuminates drug action
#MMPMID24577151
Gottlieb A
; Altman RB
Clin Pharmacol Ther
2014[Jun]; 95
(6
): 663-9
PMID24577151
show ga
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.