Systematic Identification of Molecular Targets and Pathways Related to Human Organ Level Toxicity.
Systematic Identification of Molecular Targets and Pathways Related to Human Organ Level Toxicity.
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DOI：
10.1021/acs.chemrestox.0c00305
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发表时间：
2021-02-15
影响因子：
4.1
通讯作者：
Huang, Ruili
中科院分区：
文献类型：
--
作者：
Xu, Tuan;Wu, Leihong;Xia, Menghang;Simeonov, Anton;Huang, Ruili
Mechanisms leading to organ level toxicities are poorly understood. In this study we applied an integrated approach to deduce molecular targets and biological pathways involved in chemically-induced toxicity for eight common human organ level toxicity endpoints (carcinogenicity, cardiotoxicity, developmental toxicity, hepatotoxicity, nephrotoxicity, neurotoxicity, reproductive toxicity, and skin toxicity). Integrated analysis of in vitro assay data, molecular target and pathway annotations from the literature, and toxicity-molecular target associations derived from text mining, combined with machine learning techniques, were used to generate molecular targets for each of the organ level toxicity endpoints. A total of 1,516 toxicity-related genes were identified and subsequently analyzed for biological pathway coverage resulting in 206 significant pathways (p-value < 0.05), ranging from 3 (e.g., developmental toxicity) to 101 (e.g., skin toxicity) for each toxicity endpoint. This study presents a systematic and comprehensive analysis of molecular targets and pathways related to various in vivo toxicity endpoints. These molecular targets and pathways could aid in understanding the biological mechanisms of toxicity and serve as a guide for the design of suitable in vitro assays for more efficient toxicity testing. In addition, these results are complementary to the existing adverse outcome pathway (AOP) framework and can be used to aid the development of novel AOPs. Our results provide abundant testable hypotheses for further experimental validation.
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影响因子：
64.8
作者：
Hollenstein, Kaspar;Kean, James;Marshall, Fiona H.
通讯作者：
Marshall, Fiona H.
DOI：
10.1007/978-1-4939-6346-1_12
发表时间：
2016-01-01
期刊：
HIGH-THROUGHPUT SCREENING ASSAYS IN TOXICOLOGY
影响因子：
--
作者：
Huang, Ruili
通讯作者：
Huang, Ruili
影响因子：
5.4
作者：
Han Y;Sun X;Kuang D;Tong P;Lu C;Wang W;Li N;Chen Y;Wang X;Dai J;Zhang H
通讯作者：
Zhang H
DOI：
10.1016/j.scitotenv.2018.02.015
发表时间：
2018-07-01
期刊：
The Science of the total environment
影响因子：
--
作者：
Carusi A;Davies MR;De Grandis G;Escher BI;Hodges G;Leung KMY;Whelan M;Willett C;Ankley GT
通讯作者：
Ankley GT
影响因子：
10.4
作者：
Huang R;Xia M;Cho MH;Sakamuru S;Shinn P;Houck KA;Dix DJ;Judson RS;Witt KL;Kavlock RJ;Tice RR;Austin CP
通讯作者：
Austin CP