Network target for screening synergistic drug combinations with application to traditional Chinese medicine

BACKGROUND: Multicomponent therapeutics offer bright prospects for the control of complex diseases in a synergistic manner. However, finding ways to screen the synergistic combinations from numerous pharmacological agents is still an ongoing challenge. RESULTS: In this work, we proposed for the firs...

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Autores principales: Li, Shao, Zhang, Bo, Zhang, Ningbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121110/
https://www.ncbi.nlm.nih.gov/pubmed/21689469
http://dx.doi.org/10.1186/1752-0509-5-S1-S10
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author Li, Shao
Zhang, Bo
Zhang, Ningbo
author_facet Li, Shao
Zhang, Bo
Zhang, Ningbo
author_sort Li, Shao
collection PubMed
description BACKGROUND: Multicomponent therapeutics offer bright prospects for the control of complex diseases in a synergistic manner. However, finding ways to screen the synergistic combinations from numerous pharmacological agents is still an ongoing challenge. RESULTS: In this work, we proposed for the first time a “network target”-based paradigm instead of the traditional "single target"-based paradigm for virtual screening and established an algorithm termed NIMS (Network target-based Identification of Multicomponent Synergy) to prioritize synergistic agent combinations in a high throughput way. NIMS treats a disease-specific biological network as a therapeutic target and assumes that the relationship among agents can be transferred to network interactions among the molecular level entities (targets or responsive gene products) of agents. Then, two parameters in NIMS, Topology Score and Agent Score, are created to evaluate the synergistic relationship between each given agent combinations. Taking the empirical multicomponent system traditional Chinese medicine (TCM) as an illustrative case, we applied NIMS to prioritize synergistic agent pairs from 63 agents on a pathological process instanced by angiogenesis. The NIMS outputs can not only recover five known synergistic agent pairs, but also obtain experimental verification for synergistic candidates combined with, for example, a herbal ingredient Sinomenine, which outperforms the meet/min method. The robustness of NIMS was also showed regarding the background networks, agent genes and topological parameters, respectively. Finally, we characterized the potential mechanisms of multicomponent synergy from a network target perspective. CONCLUSIONS: NIMS is a first-step computational approach towards identification of synergistic drug combinations at the molecular level. The network target-based approaches may adjust current virtual screen mode and provide a systematic paradigm for facilitating the development of multicomponent therapeutics as well as the modernization of TCM.
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spelling pubmed-31211102011-06-23 Network target for screening synergistic drug combinations with application to traditional Chinese medicine Li, Shao Zhang, Bo Zhang, Ningbo BMC Syst Biol Report BACKGROUND: Multicomponent therapeutics offer bright prospects for the control of complex diseases in a synergistic manner. However, finding ways to screen the synergistic combinations from numerous pharmacological agents is still an ongoing challenge. RESULTS: In this work, we proposed for the first time a “network target”-based paradigm instead of the traditional "single target"-based paradigm for virtual screening and established an algorithm termed NIMS (Network target-based Identification of Multicomponent Synergy) to prioritize synergistic agent combinations in a high throughput way. NIMS treats a disease-specific biological network as a therapeutic target and assumes that the relationship among agents can be transferred to network interactions among the molecular level entities (targets or responsive gene products) of agents. Then, two parameters in NIMS, Topology Score and Agent Score, are created to evaluate the synergistic relationship between each given agent combinations. Taking the empirical multicomponent system traditional Chinese medicine (TCM) as an illustrative case, we applied NIMS to prioritize synergistic agent pairs from 63 agents on a pathological process instanced by angiogenesis. The NIMS outputs can not only recover five known synergistic agent pairs, but also obtain experimental verification for synergistic candidates combined with, for example, a herbal ingredient Sinomenine, which outperforms the meet/min method. The robustness of NIMS was also showed regarding the background networks, agent genes and topological parameters, respectively. Finally, we characterized the potential mechanisms of multicomponent synergy from a network target perspective. CONCLUSIONS: NIMS is a first-step computational approach towards identification of synergistic drug combinations at the molecular level. The network target-based approaches may adjust current virtual screen mode and provide a systematic paradigm for facilitating the development of multicomponent therapeutics as well as the modernization of TCM. BioMed Central 2011-06-20 /pmc/articles/PMC3121110/ /pubmed/21689469 http://dx.doi.org/10.1186/1752-0509-5-S1-S10 Text en Copyright ©2011 Li et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Report
Li, Shao
Zhang, Bo
Zhang, Ningbo
Network target for screening synergistic drug combinations with application to traditional Chinese medicine
title Network target for screening synergistic drug combinations with application to traditional Chinese medicine
title_full Network target for screening synergistic drug combinations with application to traditional Chinese medicine
title_fullStr Network target for screening synergistic drug combinations with application to traditional Chinese medicine
title_full_unstemmed Network target for screening synergistic drug combinations with application to traditional Chinese medicine
title_short Network target for screening synergistic drug combinations with application to traditional Chinese medicine
title_sort network target for screening synergistic drug combinations with application to traditional chinese medicine
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3121110/
https://www.ncbi.nlm.nih.gov/pubmed/21689469
http://dx.doi.org/10.1186/1752-0509-5-S1-S10
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