Pathways of Toxicity
Pathways of Toxicity
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DOI：
10.14573/altex.1309261
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发表时间：
2014-01-01
影响因子：
5.6
通讯作者：
Hartung, Thomas
中科院分区：
文献类型：
--
作者：
Kleensang, Andre;Maertens, Alexandra;Hartung, Thomas
尽管广泛的共识，需要改变毒理学和风险评估，以跟上技术和计算的变化，彻底改变了生命科学的步伐，仍然有很多工作要做，以实现毒理学的基础上的一个机制的基础上的愿景。组织了一次研讨会，探讨这一转变的一个关键方面，即开发毒性途径，作为基于系统生物学的危险识别的一个关键工具。研讨会上深入讨论了几个问题：第一个是正式定义PoT概念的挑战，PoT与其他毒理学途径概念（如作用方式）不同，但又是其补充。该研讨会提出了PoT的初步定义，即“介导有毒物质不良后果的细胞过程的分子定义”。进一步认识到，存在维持稳态的正常生理途径，并且这些生理途径在充分扰动的情况下可以成为PoT。其次，研讨会试图为PoT信息定义足够的公共和商业资源，包括数据，可视化，分析，工具和用例，以及创建此类资源所需的各种努力。第三，研讨会探讨了系统生物学方法可以为途径注释提供信息的方式，以及需要哪些资源和可用资源可以为不同的用户社区提供相关的PoT信息。
Despite wide-spread consensus on the need to transform toxicology and risk assessment in order to keep pace with technological and computational changes that have revolutionized the life sciences, there remains much work to be done to achieve the vision of toxicology based on a mechanistic foundation. A workshop was organized to explore one key aspect of this transformation the development of Pathways of Toxicity (PoT) as a key tool for hazard identification based on systems biology. Several issues were discussed in depth in the workshop: The first was the challenge of formally defining the concept of a PoT as distinct from, but complementary to, other toxicological pathway concepts such as mode of action (MoA). The workshop came up with a preliminary definition of PoT as "A molecular definition of cellular processes shown to mediate adverse outcomes of toxicants". It is further recognized that normal physiological pathways exist that maintain homeostasis and these, sufficiently perturbed, can become PoT. Second, the workshop sought to define the adequate public and commercial resources for PoT information, including data, visualization, analyses, tools, and use-cases, as well as the kinds of efforts that will be necessary to enable the creation of such a resource. Third, the workshop explored ways in which systems biology approaches could inform pathway annotation, and which resources are needed and available that can provide relevant PoT information to the diverse user communities.