The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment.
The Role of Omics in the Application of Adverse Outcome Pathways for Chemical Risk Assessment.
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DOI：
10.1093/toxsci/kfx097
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发表时间：
2017-08-01
期刊：
影响因子：
--
通讯作者：
Falciani F
中科院分区：
文献类型：
--
作者：
Brockmeier EK;Hodges G;Hutchinson TH;Butler E;Hecker M;Tollefsen KE;Garcia-Reyero N;Kille P;Becker D;Chipman K;Colbourne J;Collette TW;Cossins A;Cronin M;Graystock P;Gutsell S;Knapen D;Katsiadaki I;Lange A;Marshall S;Owen SF;Perkins EJ;Plaistow S;Schroeder A;Taylor D;Viant M;Ankley G;Falciani F
结合2014年9月在利物浦大学（联合王国）举行的第二次国际环境组学专题讨论会，举办了一次讲习班，汇集了来自学术界、政府和工业界的毒理学和监管科学专家。研讨会的目的是审查高内容组学数据集（例如，转录组学，代谢组学，脂质组学和蛋白质组学）在不良结果途径（AOP）框架内支持生态和人类健康风险评估的具体作用。鉴于在生态风险评估中应用组学数据的例子越来越多，我们考虑了组学数据集如何继续支持AOP框架。特别是，组学的作用，确定潜在的AOP分子启动事件，并提供支持性证据的关键事件在不同层次的生物组织和跨分类组进行了讨论。还讨论了具有短期和中期突破潜力的领域，例如提供机械证据以支持化学交叉，为行动方式分配提供证据信息的权重，了解生物网络，以及开发物种敏感性的稳健外推。会议审议了需要应对的关键挑战，包括需要对实验设计采取连贯一致的办法，缺乏一个相互商定的框架来将基因和途径与关键事件定量联系起来，以及需要在分子一级更好地解释化学诱导的变化。这篇文章的开发提供了一个生态风险评估过程的概述和高内容的分子水平的数据集如何通过AOP框架可以支持未来的评估程序的观点。
In conjunction with the second International Environmental Omics Symposium (iEOS) conference, held at the University of Liverpool (United Kingdom) in September 2014, a workshop was held to bring together experts in toxicology and regulatory science from academia, government and industry. The purpose of the workshop was to review the specific roles that high-content omics datasets (eg, transcriptomics, metabolomics, lipidomics, and proteomics) can hold within the adverse outcome pathway (AOP) framework for supporting ecological and human health risk assessments. In light of the growing number of examples of the application of omics data in the context of ecological risk assessment, we considered how omics datasets might continue to support the AOP framework. In particular, the role of omics in identifying potential AOP molecular initiating events and providing supportive evidence of key events at different levels of biological organization and across taxonomic groups was discussed. Areas with potential for short and medium-term breakthroughs were also discussed, such as providing mechanistic evidence to support chemical read-across, providing weight of evidence information for mode of action assignment, understanding biological networks, and developing robust extrapolations of species-sensitivity. Key challenges that need to be addressed were considered, including the need for a cohesive approach towards experimental design, the lack of a mutually agreed framework to quantitatively link genes and pathways to key events, and the need for better interpretation of chemically induced changes at the molecular level. This article was developed to provide an overview of ecological risk assessment process and a perspective on how high content molecular-level datasets can support the future of assessment procedures through the AOP framework.
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