Environmental Laboratory, U.S. Army Engineer Research and Development Center, Vicksburg, MS, USA.
Institute for Genomics, Biocomputing & Biotechnology, Mississippi State University, Starkville, MS, USA.
ALTEX. 2020;37(1):64-74. doi: 10.14573/altex.1906201. Epub 2019 Aug 26.
New approaches, like the Adverse Outcome Pathway (AOP) framework, have been developed to describe how chemicals cause toxicity by linking in vitro assays to adverse health outcomes. However, approaches, tools and resources for development of AOPs have not been well described. Here we review information resources for AOP development and define a streamlined process for linking a chemical to an existing AOP. We propose a four step process to facilitate AOP development: link the uncharacterized chemical directly to Molecular Initiating Events, Key Events, or Adverse Outcomes; identify analogs with toxicological information for the uncharacterized chemical; link the characterized chemical (initial chemical if characterized, a characterized analog if initial chemical is not) to Molecular Initiating Events, Key Events, or Adverse Outcomes; and identify AOPs that contain the Molecular Initiating Events, Key Events, or Adverse Outcomes that were found in Steps 1 and 3. The process and library of informational resources proposed and tested here served as the foundation for an informational online tool (AOPERA) that helps practitioners identify their current-state knowledge gaps, navigate the four-step process, and connect to relevant resources. AOPERA can be found at https://igbb.github.io/AOPERA_HTML. Additionally, we anticipate that by simplifying and standardizing the process of linking a chemical to a known AOP, we will lower the barrier to entry for this objective and increase its accessibility to new practitioners. In turn, this may increase the demand for new or improved AOPs to which practitioners can link chemicals, thereby contributing to the expansion of the library of known AOPs.
新方法，如不良结局路径（AOP）框架，已经被开发出来，通过将体外检测与不良健康结局联系起来，来描述化学物质如何引起毒性。然而，AOP 的开发方法、工具和资源并没有得到很好的描述。在这里，我们回顾了 AOP 开发的信息资源，并定义了一个将化学物质与现有 AOP 联系起来的简化流程。我们提出了一个四步流程来促进 AOP 的发展：将未表征的化学物质直接与分子起始事件、关键事件或不良结局联系起来；为未表征的化学物质识别具有毒理学信息的类似物；将表征的化学物质（如果已表征，则为初始化学物质的类似物，如果初始化学物质未被表征）与分子起始事件、关键事件或不良结局联系起来；并识别包含在步骤 1 和 3 中发现的分子起始事件、关键事件或不良结局的 AOP。这里提出和测试的流程和信息资源库为信息在线工具（AOPERA）奠定了基础，该工具帮助从业者识别他们当前的知识差距，导航四步流程，并连接到相关资源。AOPERA 可在 https://igbb.github.io/AOPERA_HTML 找到。此外，我们预计，通过简化和标准化将化学物质与已知 AOP 联系起来的过程，我们将降低实现这一目标的门槛，并增加其对新从业者的可及性。反过来，这可能会增加对新的或改进的 AOP 的需求，从业者可以将化学物质与之联系起来，从而有助于扩大已知 AOP 的库。
