AOP-Anchored Transcriptome Analysis Catalogue Accelerates the Discovery of Environmental Toxicants in Zebrafish

斑马鱼 转录组 计算生物学 生物 计算机科学 万维网 数据科学 化学 环境科学 遗传学 基因 基因表达
作者
Jierong Chen,Congcong Wang,Wenqing Tu,Kun Zhang,Karl Fent,Jiayin Dai,Markus Hecker,John P. Giesy,Yanbin Zhao
出处
期刊:Environmental Science & Technology [American Chemical Society]
标识
DOI:10.1021/acs.est.4c03100
摘要

Current toxicity screening approaches to evaluate the vast number of environmental chemicals that require assessment are hampered due to their significant costs, time requirements, and reliance on live animal testing. The aim of the present study was to develop an adverse outcome pathway (AOP)-anchored transcriptome analysis (AATA) catalogue to expedite the discovery of environmental toxicants. 437 AOPs from the AOPwiki (https://aopwiki.org/) and 2280 transcriptomics data sets from NCBI Gene Expression Omnibus (GEO) and EMBL-EBI ArrayExpress (AE) repositories were comprehensively reviewed and analyzed. By using the differentially expressed molecular key event (mKE) genes as connection nodes, we created a large-scale environmental substance─target gene (mKE)─predicted adverse outcomes (SGAs) network that included 78 substances, 1099 genes, and 354 adverse outcomes (AOs). To validate the reliability of the network, comprehensive literature verification was conducted. We demonstrated that 164 of the 354 AOs identified have been previously characterized in the literature. The results for 136 of these AOs were consistent with the predictions of the AATA catalogue, representing an accuracy rate of 82.9%. Besides, distinct patterns in molecular KEs and AOs among categories of substances, such as biocides and metals, were demonstrated. Some representative substances, including atrazine and copper, pose significant risks to fish at various levels of biological organization. Moreover, experimental verification of the AATA predictions was conducted, including exposures of zebrafish to perfluorooctanesulfonate, cresyl diphenyl phosphate, and lanthanum. Results demonstrated consistency with predictions of the AATA catalogue, with an accuracy rate of 92.3%. Collectively, the present findings support the AATA catalogue as an efficient and promising platform for identifying environmental toxicants to fish and thereby provide novel insights into the understanding of potential risks of environmental contaminants.
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