GET AOP TRAINED

0
AOPs in the Wiki
0
OECD-endorsed AOPs

Adverse outcome pathways (AOPs)

The Adverse Outcome Pathway (AOP) concept was developed to address a practical need in toxicology: to be able to use the latest in vitro (non-animal) tools to predict what exposure to a chemical might do to a whole animal or population. In order to design testing strategies that sufficiently address the breadth of potential adverse possibilities, it is important to understand the underlying biology as explicitly and with as much confidence as possible. Simply stated, an AOP is an explicit description of the biology that underlies a biological pathway that can be perturbed by an external force (such as chemical exposure) – of all of the steps that occur from the original perturbation at the molecular level, through changes at the cellular, tissue, organ, organ system, individual and even population levels (Figure 1).

The OECD AOP development program

The Organization for Economic Cooperation and Development (OECD) is coordinating the AOP framework: a tool that allows compilation, organization and evaluation of biological information in a formalized way in order to facilitate the use of molecular and cellular information in decision making – whether to support weight-of-evidence evaluations, identify information needs and direct further research, or to design testing strategies to answer questions about chemical safety.  The AOP framework consists of guidance documents that aid in building and using AOPs, software for collecting and organizing the information, a program for formally assessing the information, and a training group that creates materials to train new AOP builders and users. According to the OECD, AOPs “can be viewed as a sequence of events commencing with initial interactions of a stressor with a biomolecule in a target cell or tissue (i.e., molecular initiating event), progressing through a dependent series of intermediate events and culminating with an adverse outcome. AOPs are typically represented sequentially, moving from one key event to another, as compensatory mechanisms and feedback loops are overcome” (OECD, 2018). An AOP consists of a variable number and arrangement of a few key elements: a molecular initiating event (MIE), the adverse outcome (AO) of regulatory relevance, any number of intermediate Key Events (KE) and the relationships between these elements (key event relationships or KERs). Five general principles are involved in AOP development: (1) AOPs are not chemical specific, (2) AOPs are modular (consisting of KEs and KERs) that can be shared between two or more pathways, (3) as a matter of practicality, a convention of AOP development is that each AOP is linear: one AOP consists of a mostly linear link from one MIE to one AO; (4) for most real world applications, AOP networks are the functional unit of prediction, and (5) AOPs are living documents, and, as more information is discovered, will be continuously updated and never really finished (Villeneuve et al. 2014). Diagram of an AOP

Figure 1. Diagram of an AOP.


AOP knowledgebase and Wiki

OECD is also coordinating the software necessary for collecting and evaluating AOP information, the AOP Knowledgebase (AOP-KB, Figure 2). The main element of the AOP-KB is currently the AOP Wiki (https://aopwiki.org). The AOP wiki is designed to capture all of the information about AOP elements in text form, via standardized drop-down menus (to keep a standard format and consistent ontology) and free text fields (to accommodate data, explanations and references). As of this writing, there are more than 200 AOPs and more than 1000 KEs and KERs described in the wiki linked to 340 different stressors (metrics available on the AOP Wiki). As more pathways are described, connections between KEs that are common to different pathways are identified, and in this way, biological networks, which are the basis for predicting AOs from MIEs, are discovered. The AOP Wiki also supports evaluation of the consistency, quantity and quality of the information supporting the KERs and AOP overall (OECD, 2018, Meek et al., 2014). AOPs that are published in the OECD program series are evaluated in two stages. The first review is by members of the OECD AOP program to make sure the information has been entered in compliance with OECD guidance. The second stage is an independent scientific review by a subject matter expert group that can be a combination of OECD and outside experts – this is similar to peer review of a scientific publication.

AOP-KB

Figure 2. The AOP Knowledge-Base and related projects

How do I learn more about AOPs, the OECD program, or the Wiki?

In addition to materials available from the OECD, we have developed presentations, a continuing education course lecture, and an online training course in the AOP wiki, all of which are free and linked below.

*An ongoing program, in the form of “AOPs 101” and “AOPs 201” sessions, were created Human Toxicology Project Consortium (HTPC) in partnership the Physicians Committee for Responsible Medicine (PCRM) to introduce scientists, regulators, and researchers to the OECD AOP program. The programs have been running several times a year since 2014. The HTPC has been reorganized into this AFSA Tox21 workstream and will continue the partnership with PCRM in AOP training going forward.

Training resources

Resource title

Description

Online Adverse Outcome Pathway (AOP) Wiki course

Course 1: AOP History and Overview

Course 2: AOP Wiki Tutorial

Self exam: AOP Wiki Tutorial (not working due to recent removal of support for Flash player – will be updated soon).

Download

Coursera lecture

Free short video from Module 4 of Coursera Lecture – Toxicology 21: Scientific Applications.

The Need, and Opportunity, for a New Approach to Toxicology, Including Predictive Tools (Dr Kate Willett, HSI)

SETAC 2015 CE Course

Continuing Education course presented at Society of Environmental Toxicology and Chemistry 2015.

Developing and Applying Adverse Outcome Pathways: What You Need to Know – Part 1

Developing and Applying Adverse Outcome Pathways: What You Need to Know – Part 2

The AOP Wiki

AOP Wiki

Please read guidance and/or take courses first!

OECD AOP Handbook

Guidance that describes how to use the AOP wiki, including nomenclature, conventions, a description of what information goes where, and how to evaluate the information in the KERs.

Users’ Handbook supplement to the Guidance Document for developing and assessing Adverse Outcome Pathways. OECD Series on Adverse Outcome Pathways

OECD Webinars on Adverse Outcome Pathways (AOPs)

OECD webinars on Testing and Assessment Methodologies with a focus on AOPs.

Training needs, resources and opportunities for AOPs

AOP-KB and AOP developing tips

Assembling and evaluating weight of evidence and quantitative understanding

The AOP Framework as a collaborative tool

OECD AOP development program

The OECD AOP development programme is overseen by the extended Advisory Group on Molecular Screening and Toxicogenomics (EAGMST).

OECD website that describes the program and contains valuable links

OECD IATA development program

The AOP concept can be applied as a framework to develop Integrated Approaches to Testing and Assessment (IATA).

OECD website that describes the program and contains valuable links

OECD Guidance Document for the use of AOPs in developing IATA, Series on Testing and assessment no. 260

OECD Guidance Document 260

CIAO Key Event Relationship and AOP-Wiki Training – April 2021

Training given to the CIAO COVID project – a volunteer group of experts working on Modelling the Pathogenesis of COVID-19 Using the AOP Framework.

CIAO Key Event Relationship and AOP-Wiki Training

Kristie Sullivan (PCRM)

Environmental Mutagenesis and Genomics Society webinar on AOPs – Jan 22nd 2020

Webinar given to the Environmental Mutagenesis and Genomics Society to provide training on AOPs and how they can be used in genotoxicity.

AOPs: What are they and how the EMGS can become involved?

Carole Yauk (Health Canada) and Jason O’Brien (Environment and Climate Change Canada)

IUTOX (International Union of Toxicology) 15th International Congress of Toxicology – July 16th 2019

Ancillary meeting given at IUTOX 2019 to introduce the OECD AOP framework, present a real-life case study of AOP development and application, and guide participants through an example of AOP-building in the AOP Wiki.

AOP Hands-on Training: Building the Foundation for Predictive Toxicology.

Indian AOP training program

How to build an AOP (Dr Surat Parvatam, CCMB Centre for Predictive Human Model Systems)

Society of Toxicology (SOT) 57th Annual Meeting – March 18th 2018

Ancillary meeting given at SOT 2018.

The AOP Concept, Creating and using an AOP, Evaluating the AOP evidence, and Hands-on activity.

Society for the Advancement of Adverse Outcome Pathways (SAAOP) Training videos -July 20th 2017

Introduction to Adverse Outcome Pathways and the AOP Wiki presented by the SAAOP in 2017.

back to top