Adverse Outcome Pathways (AOP)

Background information and AOP Wiki

Background


An Adverse Outcome Pathway (AOP) is a conceptual framework that portrays existing knowledge concerning the linkage between the two anchor points Molecular Initiating Event (MIE) and Adverse Outcome (AO), at a level of biological organization relevant to risk assessment. The goal of an AOP is to provide the framework to describe the Key Events that lead from MIE to AO.

AOPs are important for expanding the use of mechanistic toxicological data for risk assessment and regulatory applications.  Information can be derived from in vitro, in vivo, or computational systems.  AOPs allow scientists to connect results from the use of in-vitro tools and rapid screening protocols to actual adverse outcomes.

AOP liver fibrosis

Fig.1 An example of AOP (Liver Fibrosis).

 

AOP Wiki


The wiki-based tool "AOP Wiki" provides a user-friendly and open-source interface for rapid, widely accessible, and collaborative sharing of established AOPs and building new AOPs. The goals are to structure information and to provide a shared space to facilitate collaboration.  This design will help to avoid duplicated efforts.  In addition, it will initiate scientific discussions early in order to build consensus on the evidence supporting the biological information underlying each AOP as well as the relevance of that AOP for supporting regulatory decision making. 

AOP Wiki is being developed by multiple organizations – the European Commission Joint Research Centre, the EPA Office of Research and Development, the Organization of Economic Cooperation and Development (OECD), and the international scientific community at large. Coordination among these organizations will help with international recognition and consensus. AOP Wiki is an implementation of the OECD "Guidance on Developing and Assessing AOPs", and thereby lets users both develop new AOPs and make the most of already developed AOPs. The easy-to-use tool will stimulate open crowd-sourced knowledge development capture and use.

AOP Wiki uses templates to make it easy for users to include the information needed for proper evaluation of an AOP. These templates are based on the OECD guidance on "Developing and Assessing AOPs", so that fully developed AOPs from the wiki should be suitable for use in a regulatory context. The general idea is to develop an AOP within the wiki, i.e. without first capturing it with other tools (text processing or similar).  AOP Wiki allows developing an AOP using user-friendly widgets, so users can focus on content, and IT issues (e.g. web markup tags) are largely kept in the background. This simplifies the process for scientists and users that may not have extensive experience with editing in a wiki environment.  In addition, a controlled vocabulary promotes consistent terminology, thereby avoiding unnecessary duplication of information in the wiki. 

AOP Wiki represents the initial phase in a larger effort to build a complete AOP knowledgebase (AOP KB). In addition to the AOP wiki to capture textual knowledge, the AOP KB will contain two additional modules. A graphic module will support AOP development and highlight the interconnections among AOPs via network viewing tools. This module will apply a more formal structure to the AOP definition and incorporate quantitative information to facilitate computational modelling of AOPs. An Intermediate Effects module will provide AOP information in a format acceptable for regulatory purposes (OECD Harmonised Templates). Together, these modules will form a comprehensive collection of AOP knowledge - based on internationally accepted standards.


Timeline

 

  • July, 2013 – Beta release for OECD AOP development teams
  • December, 2013 – Broader access based on OECD EAG recommendations
  • 2014 and beyond –
    • Integrate wiki with other components of the AOP KB
    • Focus on formalizing AOP information to facilitate computational modeling