A toxicity pathway-oriented approach to develop adverse outcome pathway: AHR activation as a case study
| Autor: | Dianke Yu, Qianwen Zhao, Daochuan Li, Chuanhai Li, Meiyao Feng, Yuan Jin, Lin Xu, Xinmei Li, Guangshuai Qi, Ying Wang, Jiao Luo, Yuxin Zheng, Jing Chen, Yufei Hou, Yanjie Zhao, Mengyue Xie, Lidan Jiang, Wanli Ma, Yanhong Wei |
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| Rok vydání: | 2020 |
| Předmět: |
010504 meteorology & atmospheric sciences
Databases Factual Computer science Health Toxicology and Mutagenesis media_common.quotation_subject Systems biology Computational biology 010501 environmental sciences Toxicology 01 natural sciences Risk Assessment Toxicogenetics Human health Ingenuity Adverse Outcome Pathway Humans 0105 earth and related environmental sciences media_common Adverse Outcome Pathways Mechanism (biology) General Medicine Pathway analysis Pollution Phenotype Liver Toxicity Toxicogenomics |
| Zdroj: | Environmental pollution (Barking, Essex : 1987). 268 |
| ISSN: | 1873-6424 |
| Popis: | With numerous new chemicals introduced into the environment everyday, identification of their potential hazards to the environment and human health is a considerable challenge. Developing adverse outcome pathway (AOP) framework is promising in helping to achieve this goal as it can bring In Vitro testing into toxicity measurement and understanding. To explore the toxic mechanism underlying environmental chemicals via the AOP approach, an integration of adequate experimental data with systems biology understanding is preferred. Here, we describe a novel method to develop reliable and sensible AOPs that relies on chemical-gene interactions, toxicity pathways, molecular regulations, phenotypes, and outcomes information obtained from comparative toxicogenomics database (CTD) and Ingenuity Pathway Analysis (IPA). Using Benzo(a)pyrene (BaP), a highly studied chemical as a stressor, we identified the pivotal IPA toxicity pathways, the molecular initiating event (MIE), and candidate key events (KEs) to structure AOPs in the liver and lung, respectively. Further, we used the corresponding CTD information of multiple typical AHR-ligands, including 2,3,7,8-tetrachlorodibenzoparadioxin (TCDD), valproic acid, quercetin, and particulate matter, to validate our AOP networks. Our approach is likely to speed up AOP development as providing a time- and cost-efficient way to collect all fragmented bioinformation in published studies. It also facilitates a better understanding of the toxic mechanism of environmental chemicals, and potentially brings new insights into the screening of critical paths in the AOP network. |
| Databáze: | OpenAIRE |
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