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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135612/ https://www.ncbi.nlm.nih.gov/pubmed/21765950 http://dx.doi.org/10.1371/journal.pone.0022187 |
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author | Brouwers, Lucas Iskar, Murat Zeller, Georg van Noort, Vera Bork, Peer |
author_facet | Brouwers, Lucas Iskar, Murat Zeller, Georg van Noort, Vera Bork, Peer |
author_sort | Brouwers, Lucas |
collection | PubMed |
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 | Online Article Text |
id | pubmed-3135612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31356122011-07-15 Network Neighbors of Drug Targets Contribute to Drug Side-Effect Similarity Brouwers, Lucas Iskar, Murat Zeller, Georg van Noort, Vera Bork, Peer PLoS One Research Article 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. Public Library of Science 2011-07-13 /pmc/articles/PMC3135612/ /pubmed/21765950 http://dx.doi.org/10.1371/journal.pone.0022187 Text en Brouwers et al. https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. |
spellingShingle | Research Article Brouwers, Lucas Iskar, Murat Zeller, Georg van Noort, Vera Bork, Peer Network Neighbors of Drug Targets Contribute to Drug Side-Effect Similarity |
title | 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_short | Network Neighbors of Drug Targets Contribute to Drug Side-Effect Similarity |
title_sort | network neighbors of drug targets contribute to drug side-effect similarity |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135612/ https://www.ncbi.nlm.nih.gov/pubmed/21765950 http://dx.doi.org/10.1371/journal.pone.0022187 |
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