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H-RACS: a handy tool to rank anti-cancer synergistic drugs

Though promising, identifying synergistic combinations from a large pool of candidate drugs remains challenging for cancer treatment. Due to unclear mechanism and limited confirmed cases, only a few computational algorithms are able to predict drug synergy. Yet they normally require the drug-cell tr...

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Autores principales: Yan, Xinmiao, Yang, Yiyan, Chen, Zikun, Yin, Zuojing, Deng, Zeliang, Qiu, Tianyi, Tang, Kailin, Cao, Zhiwei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695372/
https://www.ncbi.nlm.nih.gov/pubmed/33173014
http://dx.doi.org/10.18632/aging.103925
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author Yan, Xinmiao
Yang, Yiyan
Chen, Zikun
Yin, Zuojing
Deng, Zeliang
Qiu, Tianyi
Tang, Kailin
Cao, Zhiwei
author_facet Yan, Xinmiao
Yang, Yiyan
Chen, Zikun
Yin, Zuojing
Deng, Zeliang
Qiu, Tianyi
Tang, Kailin
Cao, Zhiwei
author_sort Yan, Xinmiao
collection PubMed
description Though promising, identifying synergistic combinations from a large pool of candidate drugs remains challenging for cancer treatment. Due to unclear mechanism and limited confirmed cases, only a few computational algorithms are able to predict drug synergy. Yet they normally require the drug-cell treatment results as an essential input, thus exclude the possibility to pre-screen those unexplored drugs without cell treatment profiling. Based on the largest dataset of 33,574 combinational scenarios, we proposed a handy webserver, H-RACS, to overcome the above problems. Being loaded with chemical structures and target information, H-RACS can recommend potential synergistic pairs between candidate drugs on 928 cell lines of 24 prevalent cancer types. A high model performance was achieved with AUC of 0.89 on independent combinational scenarios. On the second independent validation of DREAM dataset, H-RACS obtained precision of 67% among its top 5% ranking list. When being tested on new combinations and new cell lines, H-RACS showed strong extendibility with AUC of 0.84 and 0.81 respectively. As the first online server freely accessible at http://www.badd-cao.net/h-racs, H-RACS may promote the pre-screening of synergistic combinations for new chemical drugs on unexplored cancers.
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spelling pubmed-76953722020-12-04 H-RACS: a handy tool to rank anti-cancer synergistic drugs Yan, Xinmiao Yang, Yiyan Chen, Zikun Yin, Zuojing Deng, Zeliang Qiu, Tianyi Tang, Kailin Cao, Zhiwei Aging (Albany NY) Research Paper Though promising, identifying synergistic combinations from a large pool of candidate drugs remains challenging for cancer treatment. Due to unclear mechanism and limited confirmed cases, only a few computational algorithms are able to predict drug synergy. Yet they normally require the drug-cell treatment results as an essential input, thus exclude the possibility to pre-screen those unexplored drugs without cell treatment profiling. Based on the largest dataset of 33,574 combinational scenarios, we proposed a handy webserver, H-RACS, to overcome the above problems. Being loaded with chemical structures and target information, H-RACS can recommend potential synergistic pairs between candidate drugs on 928 cell lines of 24 prevalent cancer types. A high model performance was achieved with AUC of 0.89 on independent combinational scenarios. On the second independent validation of DREAM dataset, H-RACS obtained precision of 67% among its top 5% ranking list. When being tested on new combinations and new cell lines, H-RACS showed strong extendibility with AUC of 0.84 and 0.81 respectively. As the first online server freely accessible at http://www.badd-cao.net/h-racs, H-RACS may promote the pre-screening of synergistic combinations for new chemical drugs on unexplored cancers. Impact Journals 2020-11-10 /pmc/articles/PMC7695372/ /pubmed/33173014 http://dx.doi.org/10.18632/aging.103925 Text en Copyright: © 2020 Yan et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Yan, Xinmiao
Yang, Yiyan
Chen, Zikun
Yin, Zuojing
Deng, Zeliang
Qiu, Tianyi
Tang, Kailin
Cao, Zhiwei
H-RACS: a handy tool to rank anti-cancer synergistic drugs
title H-RACS: a handy tool to rank anti-cancer synergistic drugs
title_full H-RACS: a handy tool to rank anti-cancer synergistic drugs
title_fullStr H-RACS: a handy tool to rank anti-cancer synergistic drugs
title_full_unstemmed H-RACS: a handy tool to rank anti-cancer synergistic drugs
title_short H-RACS: a handy tool to rank anti-cancer synergistic drugs
title_sort h-racs: a handy tool to rank anti-cancer synergistic drugs
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695372/
https://www.ncbi.nlm.nih.gov/pubmed/33173014
http://dx.doi.org/10.18632/aging.103925
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