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Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing

The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on g...

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Autores principales: Zhao, Feng, Guo, Xiaolong, Wang, Yanjie, Liu, Jie, Lee, Wen-hui, Zhang, Yun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126716/
https://www.ncbi.nlm.nih.gov/pubmed/25105297
http://dx.doi.org/10.1371/journal.pone.0104191
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author Zhao, Feng
Guo, Xiaolong
Wang, Yanjie
Liu, Jie
Lee, Wen-hui
Zhang, Yun
author_facet Zhao, Feng
Guo, Xiaolong
Wang, Yanjie
Liu, Jie
Lee, Wen-hui
Zhang, Yun
author_sort Zhao, Feng
collection PubMed
description The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research.
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spelling pubmed-41267162014-08-12 Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing Zhao, Feng Guo, Xiaolong Wang, Yanjie Liu, Jie Lee, Wen-hui Zhang, Yun PLoS One Research Article The discovery of new drugs requires the development of improved animal models for drug testing. The Chinese tree shrew is considered to be a realistic candidate model. To assess the potential of the Chinese tree shrew for pharmacological testing, we performed drug target prediction and analysis on genomic and transcriptomic scales. Using our pipeline, 3,482 proteins were predicted to be drug targets. Of these predicted targets, 446 and 1,049 proteins with the highest rank and total scores, respectively, included homologs of targets for cancer chemotherapy, depression, age-related decline and cardiovascular disease. Based on comparative analyses, more than half of drug target proteins identified from the tree shrew genome were shown to be higher similarity to human targets than in the mouse. Target validation also demonstrated that the constitutive expression of the proteinase-activated receptors of tree shrew platelets is similar to that of human platelets but differs from that of mouse platelets. We developed an effective pipeline and search strategy for drug target prediction and the evaluation of model-based target identification for drug testing. This work provides useful information for future studies of the Chinese tree shrew as a source of novel targets for drug discovery research. Public Library of Science 2014-08-08 /pmc/articles/PMC4126716/ /pubmed/25105297 http://dx.doi.org/10.1371/journal.pone.0104191 Text en © 2014 Zhao et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Zhao, Feng
Guo, Xiaolong
Wang, Yanjie
Liu, Jie
Lee, Wen-hui
Zhang, Yun
Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
title Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
title_full Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
title_fullStr Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
title_full_unstemmed Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
title_short Drug Target Mining and Analysis of the Chinese Tree Shrew for Pharmacological Testing
title_sort drug target mining and analysis of the chinese tree shrew for pharmacological testing
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4126716/
https://www.ncbi.nlm.nih.gov/pubmed/25105297
http://dx.doi.org/10.1371/journal.pone.0104191
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