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

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...

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Autores principales:	Lucas Brouwers, Murat Iskar, Georg Zeller, Vera van Noort, Peer Bork
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/606aaf2812694a1fbfa39c3ac67814eb
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spelling	oai:doaj.org-article:606aaf2812694a1fbfa39c3ac67814eb2021-11-18T06:50:20ZNetwork neighbors of drug targets contribute to drug side-effect similarity.1932-620310.1371/journal.pone.0022187https://doaj.org/article/606aaf2812694a1fbfa39c3ac67814eb2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21765950/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203In 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.Lucas BrouwersMurat IskarMurat IskarGeorg ZellerVera van NoortPeer BorkPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22187 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Lucas Brouwers Murat Iskar Murat Iskar Georg Zeller Vera van Noort Peer Bork Network neighbors of drug targets contribute to drug side-effect similarity.
description	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.
format	article
author	Lucas Brouwers Murat Iskar Murat Iskar Georg Zeller Vera van Noort Peer Bork
author_facet	Lucas Brouwers Murat Iskar Murat Iskar Georg Zeller Vera van Noort Peer Bork
author_sort	Lucas Brouwers
title	Network neighbors of drug targets contribute to drug side-effect similarity.
title_short	Network neighbors of drug targets contribute to drug side-effect similarity.
title_full	Network neighbors of drug targets contribute to drug side-effect similarity.
title_fullStr	Network neighbors of drug targets contribute to drug side-effect similarity.
title_full_unstemmed	Network neighbors of drug targets contribute to drug side-effect similarity.
title_sort	network neighbors of drug targets contribute to drug side-effect similarity.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/606aaf2812694a1fbfa39c3ac67814eb
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Network neighbors of drug targets contribute to drug side-effect similarity.

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