Adverse Outcome Pathways (AOP)
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.
Fig.1 An example of AOP (Liver Fibrosis).
The AOP Wiki has been made available to the public on 25 September 2014: access it at https://aopkb.org
AOP Wiki represents the initial phase in a larger effort to build a complete AOP knowledge base (AOP-KB). In addition to the AOP Wiki to capture textual knowledge, the AOP KB will contain three additional modules:
- Effectopedia will be a modelling platform designed for collaborative development and utilization of AOPs. Visually expressed modular structures will capture semantically annotated knowledge and algorithms to enable both qualitative and quantitative modelling of AOPs along with all the supporting evidence. Effectopedia is currently being developed.
- The Intermediate Effects DB will host chemical-related data (following the OECD Harmonised Templates (OHT) format), derived from non-apical endpoint methods, and inform how individual compounds trigger Molecular Initiating Events (MIE) and/or Key Events (KE). Cross-referencing these empirical observations with AOP descriptions within the AOP-KB will link directly to the underlying evidence supporting the AOPs. The Intermediate Effects DB is currently being developed.
- The AOP Xplorer will be a computational tool that enables automated graphical representation of AOPs and networks among them. The Xplorer is currently being developed.
AOP-KB will offer the opportunity for third party software developers to connect to the Knowledge Base via the AOP-KB Hub. Application Programming Interfaces (API) and format standards are currently being developed.
In July 2013 a beta-testing version has been made available for testing to an initial user group comprising current contributors to the OECD's AOP Development Programme, including members of the OECD Extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST) and the WHO/IPCS Mode of Action project group. Since January 2014 and until mid-2014, parties that have submitted an AOP project proposal are capturing their AOP knowledge in the system.