Portal:AOP/Mission

From WikiPathways

Current revision

Purpose

The purpose of this portal is to create a collection of AOPs on the molecular level and facilitating the use of high-throughput transcriptomic data in the AOP framework. The subjects of the first AOPs are linked to the use cases of the EU-ToxRisk program, based on [aopwiki.org AOP-Wiki] entries, and the CIAO project on COVID-19 AOPs.

List of molecular AOPs present in this portal (some are more defined than others):

• Mitochondrial Complex I inhibition leads to liver injury
• Mitochondrial Complex I inhibition leads to parkinsonian motor deficits
• Mitochondrial Complex I inhibition leads to Fanconi syndrome
• Protein alkylation leads to liver fibrosis
• Interaction with lung resident cell membrane components leads to lung fibrosis
• Multiple MIEs lead to liver steatosis
• ACE2 inhibition leads to increased mortality

Basic strategies and principles for general AOPs are described in this paper:

Villeneuve et al. (2014). Adverse Outcome Pathway (AOP) Development I: Strategies and Principles. Toxicological Sciences PubMed

The list of Featured Pathways is not static and can be updated at any time. If you know of a pathway that should be added, please contact Marvin Martens.

Creating molecular AOPs

Molecular AOPs are developed as so-called meta-pathways, in which the overall layout of the AOP is preserved as in literature or AOP-Wiki in terms of Key Events. These exist as new "Event" type datanodes containing AOP-Wiki identifiers, and are connected with basic directed interactions. Next, molecular pathways of processes described in Key Events (existing in WikiPathways database or newly developed) are connected with the Event nodes with basic interactions. This structure allows use of the AOP's modular nature to generate AOP networks and extend with molecular entities such as genes, proteins and metabolites using Cytoscape and the apps of WikiPathways and CyTargetLinker.