Portal:AOP

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The Adverse Outcome Pathway (AOP) Portal on WikiPathways

Welcome to the Adverse Outcome Pathway Portal!

This Adverse Outcome Pathway (AOP) portal for WikiPathways is created to highlight the molecular basis of AOPs or events in AOPS. In general, AOPs start with a Molecular Initiating Event (MIE) caused by a stressor, followed by Key Events (KEs), that lead to an Adverse Outcome (AO). These AOPs are intended specifically for regulatory decision making and are typically stored in the AOP Knowledge Base (AOPKB). Because AOPs are simplified explanations of biological effects after the effect of a stressor they are not useful to describe and understand the molecular basis of the AOPs and not suited to do data analysis. Such analysis is needed especially for in silico risk analysis that is intended to lower animal use in toxicology studies. This portal was created to present the molecular level of the AOPs and getting more into detail on the biological processes involved in them. The development of these molecular AOPS is relevant for the European research projects on toxicology EU-ToxRisk and OpenRiskNet that also fundedn part of the work.


The logo of EU-ToxRisk space The logo of OpenRiskNet space The logo of the OpenPhacts Foundation space The logo of eNanoMapper

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News

2018-04-04 - Changed Featured Pathways page, now shows images of all pathways included in the portal

2017-08-14 - Proposed AOP list added to the Mission section

2017-05-19 - The first AOP based on descriptive text from aopwiki.org on liver fibrosis is added to the portal.

2017-03-29 - The first AOPs that are added into this portal on pulmonary fibrosis, are results of the eNanoMapper project.

2017-03-29 - This portal was created

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Mission

The purpose of this portal is to create a collection of AOPs on the molecular level for the AOPs that are, or will be created for the EU-ToxRisk program, in which Open PHACTS Foundation (OPF) is responsible for AOP creation. The subjects of the first AOPs are linked to the use cases of the EU-ToxRisk program, and there will be a team of experts involved in the creation of each AOP.


The proposed list of the first set of AOPs to be created, some are more defined than others:

  • Chemical-induced bile duct obstruction leads to liver failure
  • Chemical-induced bile duct obstruction leads to nephrotoxicity
  • Inhibition of N-linked glycosylation leads to liver injury
  • Mitochondrial complex inhibition leading to liver injury
  • Inhibition of mitochondrial complex I of nigra-striatal neurons leads to parkinsonian motor deficits
  • Peripheral neuropathy caused by microtubule interacting drugs
  • Oxidative reactivity leads to chemical-induced fanconi syndrome
  • Binding to complex I of the electron transport chain leading to chemical-induced Fanconi syndrome
  • Intracellular accumulation of chemicals via the megalin/cubulin system leading to tubulonephritis
  • Oxidant-induced pulmonary emphysema
  • α-diketone-induced bronchiolitis obliterans
  • HDAC inhibition leads to neural tube defects
  • Cyp17 inhibition leads to undescended testes
  • Oxidative stress-induced liver injury
  • IKK complex inhibition leads to liver failure
  • HDAC inhibition leads to impaired craniofacial development


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


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Featured Pathway

Lung fibrosis (Homo sapiens)
View all Featured Pathways for this Portal


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Support

This project has received funding from the European Union’s Horizon 2020 research and innovation programme project EU-ToxRisk under grant agreement No. 681002 and EINFRA-22-2016 programme project OpenRiskNet under grant agreement No. 731075.

The logo of the EUspaceThe logo of EU-ToxRisk space The logo of OpenRiskNet


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Contributors

The logo of MISVIK The logo of Karolinska Institutet The logo of Maastricht University

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