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Synergy evaluation by a pathway-pathway interaction network: a new way to predict drug combination
Chen, Di1; Zhang, Huamin2; Lu, Peng1; Liu, Xianli3; Cao, Hongxin4; Cao Hongxin
Source PublicationMOLECULAR BIOSYSTEMS
2016
Volume12Issue:2Pages:614-623
SubtypeArticle
AbstractDrug combinations have been widely applied to treat complex diseases, like cancer, HIV and cardiovascular diseases. One of the most important characteristics for drug combinations is the synergistic effects among different drugs, that is to say, the combination effects are larger than the sum of individual effects. Although quantitative methods can be utilized to evaluate the synergistic effects based on experimental dose-response data, it is both time and resource consuming to screen all possible combinations by experimental trials. This problem makes it a formidable challenge to recognize synergistic combinations. Various attempts have been made to predict drug synergy by network biology, however, most of them are limited to estimating target associations on the PPI network. Here, we proposed a novel "pathway-pathway interaction" network-based synergy evaluation method to predict the potential synergistic drug combinations. Comparison with previous target-based methods shows that inclusion of systematic pathway-pathway interactions makes this novel method outperform others in predicting drug synergy. Moreover, it can also help to interpret how different drugs in a combination cooperate with each other to implement synergistic therapeutic effects. In general, drugs acting on the same pathway through different targets or drugs regulating a relatively small number of highly-connected pathways are more likely to produce synergistic effects.
KeywordDrug Synergy Pathway Interaction
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
DOI10.1039/c5mb00599j
WOS KeywordNF-KAPPA-B ; SEQUENCE-BASED PREDICTOR ; NECROSIS-FACTOR-ALPHA ; CELLULAR NETWORKING ; MODELS ; TARGET ; QUANTIFICATION ; EXPLORATION ; RECEPTORS ; PROTEINS
Indexed BySCI
Language英语
Funding OrganizationNational Natural Science Foundation of China(81303152) ; State Key Program of National Natural Science Foundation of China(81330086)
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemistry & Molecular Biology
WOS IDWOS:000368858900031
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Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/11334
Collection综合信息系统研究中心
Corresponding AuthorLu, Peng; Cao Hongxin
Affiliation1.Chinese Acad Sci, Inst Automat, Beijing 100190, Peoples R China
2.China Acad Chinese Med Sci, Inst Informat TCM, Beijing 100700, Peoples R China
3.China Acad Chinese Med Sci, Inst Basic Theory TCM, Beijing 100700, Peoples R China
4.State Adm Tradit Chinese Med Peoples Republ China, Beijing 100027, Peoples R China
Recommended Citation
GB/T 7714
Chen, Di,Zhang, Huamin,Lu, Peng,et al. Synergy evaluation by a pathway-pathway interaction network: a new way to predict drug combination[J]. MOLECULAR BIOSYSTEMS,2016,12(2):614-623.
APA Chen, Di,Zhang, Huamin,Lu, Peng,Liu, Xianli,Cao, Hongxin,&Cao Hongxin.(2016).Synergy evaluation by a pathway-pathway interaction network: a new way to predict drug combination.MOLECULAR BIOSYSTEMS,12(2),614-623.
MLA Chen, Di,et al."Synergy evaluation by a pathway-pathway interaction network: a new way to predict drug combination".MOLECULAR BIOSYSTEMS 12.2(2016):614-623.
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