Integration of Computational Toxicology, Toxicogenomics Data Mining, and Omics Techniques to Unveil Toxicity Pathways

doi:10.1021/acssuschemeng.0c09196

CORC > 烟台海岸带研究所 > 中国科学院烟台海岸带研究所 > 中科院海岸带环境过程与生态修复重点实验室

	Integration of Computational Toxicology, Toxicogenomics Data Mining, and Omics Techniques to Unveil Toxicity Pathways
	Wang, Xiaoqing 2,3,4; Li, Fei 2,3; Chen, Jingwen 5; Ji, Chenglong 1,2,3; Wu, Huifeng 1,2,3
刊名	ACS SUSTAINABLE CHEMISTRY & ENGINEERING
	2021-03-22
卷号	9 期号:11 页码:4130-4138
关键词	Adverse outcome pathway (AOP) Comparative toxicogenomics database (CTD) Triphenyl phosphate (TPP) Molecular dynamics (MD) Transcriptome analyses
ISSN号	2168-0485
DOI	10.1021/acssuschemeng.0c09196
通讯作者	Li, Fei(fli@yic.ac.cn) ; Wu, Huifeng(hfwu@yic.ac.cn)
英文摘要	Growing numbers of synthetic chemicals have potential endocrine-disrupting effects and cause potential ecological and health risks. However, the primary toxicity pathways and mechanisms of endocrine disruption are poorly understood and the existing risk assessment relies heavily on animal testing. Database mining, omics technology, and computer simulation can serve as an alternative approach to explore the mechanisms by building adverse outcome pathways (AOPs). The present study took a case of thyroid interference with triphenyl phosphate (TPP) to explain the potential toxic effects at levels from submolecules to cells utilizing the AOP framework developed by multiple techniques. This study retrieved the data from a comparative toxicogenomics database (CTD) and screened out the core gene. Molecular dynamics (MD) analysis was used to explore configuration changes and confirm the molecular initiating event (MIE). The transcriptomic analysis was further utilized to supplement the relationships between MIEs and key events (KEs) of the AOP. The thyroid hormone receptor beta (THRB) was identified as the core gene at submolecular levels. MD analysis found that the configuration changes of C-terminal helix 12 (H12) of thyroid hormone receptor beta (TR beta) were discovered as the MIE. The transcriptomic analysis extended the related KE1 at the subcellular level, such as changes in gene expression levels for coding cycle regulation (CCND1), inflammatory response (IL1A and IL6), and cell proliferation and apoptosis (BAD, TP53, and CASP9). Then, the KE2 at cellular levels such as apoptosis, cell cycle control, and cell proliferation were influenced accordingly. As a result, these alterations led to thyroid disorder as adverse outcomes. This study provided an efficient way to facilitate the complement of possible AOPs and brought new insights into understanding the toxic mechanisms of emerging synthetic chemicals.
资助项目	Yantai Science and Technology Development Plan[2020MSGY060] ; National Natural Science Foundation of China[21677173] ; National Natural Science Foundation of China[41530642] ; Youth Innovation Promotion Association CAS[2017255]
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Engineering
语种	英语
WOS记录号	WOS:000636758600018
资助机构	Yantai Science and Technology Development Plan ; National Natural Science Foundation of China ; Youth Innovation Promotion Association CAS
内容类型	期刊论文
源URL	[http://ir.yic.ac.cn/handle/133337/27232]
专题	烟台海岸带研究所_中科院海岸带环境过程与生态修复重点实验室烟台海岸带研究所_近岸生态与环境实验室
通讯作者	Li, Fei; Wu, Huifeng
作者单位	1.Chinese Acad Sci, Ctr Ocean Megasci, Qingdao 266071, Peoples R China 2.YICCAS, Shandong Key Lab Coastal Environm Proc, Yantai 264003, Peoples R China 3.Chinese Acad Sci, Yantai Inst Coastal Zone Res YIC, CAS Key Lab Coastal Environm Proc & Ecol Remediat, Beijing, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 5.Dalian Univ Technol, Sch Environm Sci & Technol, Key Lab Ind Ecol & Environm Engn MOE, Dalian 116024, Peoples R China
推荐引用方式 GB/T 7714	Wang, Xiaoqing,Li, Fei,Chen, Jingwen,et al. Integration of Computational Toxicology, Toxicogenomics Data Mining, and Omics Techniques to Unveil Toxicity Pathways[J]. ACS SUSTAINABLE CHEMISTRY & ENGINEERING,2021,9(11):4130-4138.
APA	Wang, Xiaoqing,Li, Fei,Chen, Jingwen,Ji, Chenglong,&Wu, Huifeng.(2021).Integration of Computational Toxicology, Toxicogenomics Data Mining, and Omics Techniques to Unveil Toxicity Pathways.ACS SUSTAINABLE CHEMISTRY & ENGINEERING,9(11),4130-4138.
MLA	Wang, Xiaoqing,et al."Integration of Computational Toxicology, Toxicogenomics Data Mining, and Omics Techniques to Unveil Toxicity Pathways".ACS SUSTAINABLE CHEMISTRY & ENGINEERING 9.11(2021):4130-4138.