Estimation of Carcinogenicity Using Molecular Fragments Tree

doi:10.1021/ci300266p

CORC > 上海药物研究所 > 中国科学院上海药物研究所 > 药物发现与设计中心

	Estimation of Carcinogenicity Using Molecular Fragments Tree
	Wang, Yong 2; Lu, Jing 2; Wang, Fei 2; Shen, Qiancheng 2; Zheng, Mingyue2 ; Luo, Xiaomin2 ; Zhu, Weiliang2 ; Jiang, Hualiang1,2 ; Chen, Kaixian2
刊名	JOURNAL OF CHEMICAL INFORMATION AND MODELING
	2012-08
卷号	52 期号:8 页码:1994-2003
ISSN号	1549-9596
DOI	10.1021/ci300266p
文献子类	Article
英文摘要	Carcinogenicity is an important toxicological endpoint that poses high concern to drug discovery. In this study, we developed a method to extract structural alerts (SAs) and Modulating factors of carcinogens on the basis of statistical analyses. First, the Gaston algorithm, a frequent subgraph mining method, was used to detect substructures that occurred at least six times. Then, a molecular fragments tree was built and pruned to select high-quality SAs. The p-value of the parent node in the tree and that of its children nodes were compared, and the nodes that had a higher statistical significance in binomial tests were retained. Finally, modulating factors that suppressed the toxic effects of SAs were extracted by three self defining rules. The accuracy of the 77 SAs plus four SA/modulating factor pairs model for the training set, and the test set was 0.70 and 0.65, respectively. Our model has higher predictive ability than Benigni's model, especially in the test set. The results highlight that this method is preferable in terms of prediction accuracy, and the selected SAs are useful for prediction as well as interpretation. Moreover, our method is convenient to users in that it can extract SAs from a database using an automated and unbiased manner that does not rely on a priori knowledge of mechanism of action.
资助项目	Hi-TECH Research and Development Program of China[2012AA020308] ; National ST Major Project[2012ZX09301-001-002] ; National Natural Science Foundation of China[21021063] ; State Key Program of Basic Research of China[2009CB918502]
WOS关键词	SALMONELLA MUTAGENICITY ; STRUCTURAL ALERTS ; PREDICTION
WOS研究方向	Pharmacology & Pharmacy ; Chemistry ; Computer Science
语种	英语
出版者	AMER CHEMICAL SOC
WOS记录号	WOS:000308254200010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277990]
专题	药物发现与设计中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Zheng, Mingyue
作者单位	1.E China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China 2.Chinese Acad Sci, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Wang, Yong,Lu, Jing,Wang, Fei,et al. Estimation of Carcinogenicity Using Molecular Fragments Tree[J]. JOURNAL OF CHEMICAL INFORMATION AND MODELING,2012,52(8):1994-2003.
APA	Wang, Yong.,Lu, Jing.,Wang, Fei.,Shen, Qiancheng.,Zheng, Mingyue.,...&Chen, Kaixian.(2012).Estimation of Carcinogenicity Using Molecular Fragments Tree.JOURNAL OF CHEMICAL INFORMATION AND MODELING,52(8),1994-2003.
MLA	Wang, Yong,et al."Estimation of Carcinogenicity Using Molecular Fragments Tree".JOURNAL OF CHEMICAL INFORMATION AND MODELING 52.8(2012):1994-2003.