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Network neighbors of drug targets contribute to drug side-effect similarity

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Item Type:Article
Title:Network neighbors of drug targets contribute to drug side-effect similarity
Creators Name:Brouwers, L. and Iskar, M. and Zeller, G. and van Noort, V. and Bork, P.
Abstract:In pharmacology, it is essential to identify the molecular mechanisms of drug action in order to understand adverse side effects. These adverse side effects have been used to infer whether two drugs share a target protein. However, side-effect similarity of drugs could also be caused by their target proteins being close in a molecular network, which as such could cause similar downstream effects. In this study, we investigated the proportion of side-effect similarities that is due to targets that are close in the network compared to shared drug targets. We found that only a minor fraction of side-effect similarities (5.8 %) are caused by drugs targeting proteins close in the network, compared to side-effect similarities caused by overlapping drug targets (64%). Moreover, these targets that cause similar side effects are more often in a linear part of the network, having two or less interactions, than drug targets in general. Based on the examples, we gained novel insight into the molecular mechanisms of side effects associated with several drug targets. Looking forward, such analyses will be extremely useful in the process of drug development to better understand adverse side effects.
Keywords:Biological Models, Drug Interactions, Pharmaceutical Preparations, Signal Transduction
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e22187
Date:13 July 2011
Official Publication:https://doi.org/10.1371/journal.pone.0022187
PubMed:View item in PubMed

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