An integrative network-based approach for drug target indication expansion.

<h4>Background</h4>The identification of a target-indication pair is regarded as the first step in a traditional drug discovery and development process. Significant investment and attrition occur during discovery and development before a molecule is shown to be safe and efficacious for t...

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Autores principales:	Yingnan Han, Clarence Wang, Katherine Klinger, Deepak K Rajpal, Cheng Zhu
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d0c087013a1340469574ab1015671ef4
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spelling	oai:doaj.org-article:d0c087013a1340469574ab1015671ef42021-12-02T20:15:33ZAn integrative network-based approach for drug target indication expansion.1932-620310.1371/journal.pone.0253614https://doaj.org/article/d0c087013a1340469574ab1015671ef42021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253614https://doaj.org/toc/1932-6203<h4>Background</h4>The identification of a target-indication pair is regarded as the first step in a traditional drug discovery and development process. Significant investment and attrition occur during discovery and development before a molecule is shown to be safe and efficacious for the selected indication and becomes an approved drug. Many drug targets are functionally pleiotropic and might be good targets for multiple indications. Methodologies that leverage years of scientific contributions on drug targets to allow systematic evaluation of other indication opportunities are critical for both patients and drug discovery and development scientists.<h4>Methods</h4>We introduced a network-based approach to systematically screen and prioritize disease indications for drug targets. The approach fundamentally integrates disease genomics data and protein interaction network. Further, the methodology allows for indication identification by leveraging state-of-art network algorithms to generate and compare the target and disease subnetworks.<h4>Results</h4>We first evaluated the performance of our method on recovering FDA approved indications for 15 randomly selected drug targets. The results showed superior performance when compared with other state-of-art approaches. Using this approach, we predicted novel indications supported by literature evidence for several highly pursued drug targets such as IL12/IL23 combination.<h4>Conclusions</h4>Our results demonstrated a potential global approach for indication expansion strategies. The proposed methodology enables rapid and systematic evaluation of both individual and combined drug targets for novel indications. Additionally, this approach provides novel insights on expanding the role of genes and pathways for developing therapeutic intervention strategies.Yingnan HanClarence WangKatherine KlingerDeepak K RajpalCheng ZhuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 7, p e0253614 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yingnan Han Clarence Wang Katherine Klinger Deepak K Rajpal Cheng Zhu An integrative network-based approach for drug target indication expansion.
description	<h4>Background</h4>The identification of a target-indication pair is regarded as the first step in a traditional drug discovery and development process. Significant investment and attrition occur during discovery and development before a molecule is shown to be safe and efficacious for the selected indication and becomes an approved drug. Many drug targets are functionally pleiotropic and might be good targets for multiple indications. Methodologies that leverage years of scientific contributions on drug targets to allow systematic evaluation of other indication opportunities are critical for both patients and drug discovery and development scientists.<h4>Methods</h4>We introduced a network-based approach to systematically screen and prioritize disease indications for drug targets. The approach fundamentally integrates disease genomics data and protein interaction network. Further, the methodology allows for indication identification by leveraging state-of-art network algorithms to generate and compare the target and disease subnetworks.<h4>Results</h4>We first evaluated the performance of our method on recovering FDA approved indications for 15 randomly selected drug targets. The results showed superior performance when compared with other state-of-art approaches. Using this approach, we predicted novel indications supported by literature evidence for several highly pursued drug targets such as IL12/IL23 combination.<h4>Conclusions</h4>Our results demonstrated a potential global approach for indication expansion strategies. The proposed methodology enables rapid and systematic evaluation of both individual and combined drug targets for novel indications. Additionally, this approach provides novel insights on expanding the role of genes and pathways for developing therapeutic intervention strategies.
format	article
author	Yingnan Han Clarence Wang Katherine Klinger Deepak K Rajpal Cheng Zhu
author_facet	Yingnan Han Clarence Wang Katherine Klinger Deepak K Rajpal Cheng Zhu
author_sort	Yingnan Han
title	An integrative network-based approach for drug target indication expansion.
title_short	An integrative network-based approach for drug target indication expansion.
title_full	An integrative network-based approach for drug target indication expansion.
title_fullStr	An integrative network-based approach for drug target indication expansion.
title_full_unstemmed	An integrative network-based approach for drug target indication expansion.
title_sort	integrative network-based approach for drug target indication expansion.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/d0c087013a1340469574ab1015671ef4
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An integrative network-based approach for drug target indication expansion.

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