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Network-based in silico drug efficacy screening

The increasing cost of drug development together with a significant drop in the number of new drug approvals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases t...

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Autores principales: Guney, Emre, Menche, Jörg, Vidal, Marc, Barábasi, Albert-László
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740350/
https://www.ncbi.nlm.nih.gov/pubmed/26831545
http://dx.doi.org/10.1038/ncomms10331
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author Guney, Emre
Menche, Jörg
Vidal, Marc
Barábasi, Albert-László
author_facet Guney, Emre
Menche, Jörg
Vidal, Marc
Barábasi, Albert-László
author_sort Guney, Emre
collection PubMed
description The increasing cost of drug development together with a significant drop in the number of new drug approvals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases to introduce a drug-disease proximity measure that quantifies the interplay between drugs targets and diseases. By correcting for the known biases of the interactome, proximity helps us uncover the therapeutic effect of drugs, as well as to distinguish palliative from effective treatments. Our analysis of 238 drugs used in 78 diseases indicates that the therapeutic effect of drugs is localized in a small network neighborhood of the disease genes and highlights efficacy issues for drugs used in Parkinson and several inflammatory disorders. Finally, network-based proximity allows us to predict novel drug-disease associations that offer unprecedented opportunities for drug repurposing and the detection of adverse effects.
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spelling pubmed-47403502016-03-04 Network-based in silico drug efficacy screening Guney, Emre Menche, Jörg Vidal, Marc Barábasi, Albert-László Nat Commun Article The increasing cost of drug development together with a significant drop in the number of new drug approvals raises the need for innovative approaches for target identification and efficacy prediction. Here, we take advantage of our increasing understanding of the network-based origins of diseases to introduce a drug-disease proximity measure that quantifies the interplay between drugs targets and diseases. By correcting for the known biases of the interactome, proximity helps us uncover the therapeutic effect of drugs, as well as to distinguish palliative from effective treatments. Our analysis of 238 drugs used in 78 diseases indicates that the therapeutic effect of drugs is localized in a small network neighborhood of the disease genes and highlights efficacy issues for drugs used in Parkinson and several inflammatory disorders. Finally, network-based proximity allows us to predict novel drug-disease associations that offer unprecedented opportunities for drug repurposing and the detection of adverse effects. Nature Publishing Group 2016-02-01 /pmc/articles/PMC4740350/ /pubmed/26831545 http://dx.doi.org/10.1038/ncomms10331 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Guney, Emre
Menche, Jörg
Vidal, Marc
Barábasi, Albert-László
Network-based in silico drug efficacy screening
title Network-based in silico drug efficacy screening
title_full Network-based in silico drug efficacy screening
title_fullStr Network-based in silico drug efficacy screening
title_full_unstemmed Network-based in silico drug efficacy screening
title_short Network-based in silico drug efficacy screening
title_sort network-based in silico drug efficacy screening
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740350/
https://www.ncbi.nlm.nih.gov/pubmed/26831545
http://dx.doi.org/10.1038/ncomms10331
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