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

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:

  • Reduced mitochondrial activity leads to cholestasis
  • Liver fibrosis
  • Unfolded protein response-mediated liver toxicity
  • Mitotoxicity-mediated hepatotoxicity
  • 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
  • Oxidative reactivity leads to acceleration of chronic kidney disease
  • Compound accumulation via Megalin/Cubilin uptake leads to acute and chronic kidney disease
  • Renal proximal tubular uptake via organic cation transporters leads to...
  • Oxidant-induced pulmonary emphysema
  • α-diketone-induced bronchiolitis obliterans
  • HDAC inhibition leads to neural tube defects
  • Cyt p450 inhibition leads to Feminization and Masculinization
  • Estrogen/androgen ...
  • Oxidative stress-induced hepatoxicity
  • Inflammatory cytokine-induced cell death
  • 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

Gastric ulcer formation (Homo sapiens)
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Status:1
Message:Exception in thread "main" java.lang.NullPointerException at org.pathvisio.core.Engine.getPathwayImporters(Unknown Source) at org.pathvisio.core.Engine.importPathway(Unknown Source) at org.pathvisio.core.util.Converter.main(Unknown Source)


Command:java -Xmx1024M -jar /var/www/wikipathways/wpi/bin/pathvisio_core.jar "/var/www/wikipathways" "/var/www/wikipathways/images/c/ca/WP4026_92275.svg" 2>&1
' in /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php:1168 Stack trace:

  1. 0 /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php(1143): Pathway::convert(false, '/var/www/wikipa...')
  2. 1 /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php(1058): Pathway->saveConvertedCache('svg')
  3. 2 /var/www/wikipathways/wpi/extensions/Pathways/Pathway.php(1070): Pathway->updateCache('svg')
  4. 3 /var/www/wikipathways/wpi/extensions/pathwayThumb.php(129): Pathway->getImage()
  5. 4 /var/www/wikipathways/wpi/extensions/pathwayThumb.php(53): makeThumbLinkObj(Object(Pathway), 'Gastric ulcer f...', 'https://www.wik...', 'Gastric ulcer f...', 'center', 'pwthumb', '300')
  6. 5 [internal function]: renderPathwayImage(Object(Parser), 'Pathway:WP4026', '300', 'center', 'Gastric ulcer f...', 'pathway', 'Gastric ulcer f...')
  7. 6 /var/www/wikipathways/includes/parser/Parser.php(2860): call_user_func_array('renderPathwayIm...', Array)
  8. 7 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(915): Parser->braceSubstitution(Array, Object(PPTemplateFrame_DOM))
  9. 8 /var/www/wikipathways/includes/parser/Parser.php(2986): PPFrame_DOM->expand(Object(PPNode_DOM))
  10. 9 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(915): Parser->braceSubstitution(Array, Object(PPFrame_DOM))
  11. 10 /var/www/wikipathways/includes/parser/Parser.php(2678): PPFrame_DOM->expand(Object(PPNode_DOM), 0)
  12. 11 /var/www/wikipathways/includes/parser/Parser.php(966): Parser->replaceVariables('{{Template:Toda...')
  13. 12 /var/www/wikipathways/includes/parser/Parser.php(439): Parser->internalParse('{{Template:Toda...')
  14. 13 /var/www/wikipathways/wpi/extensions/PathwayOfTheDay/PathwayOfTheDay.php(60): Parser->recursiveTagParse('{{Template:Toda...')
  15. 14 [internal function]: getPathwayOfTheDay(Object(Parser), 'Thursday 23 Nov...', 'Portal:AOP/Feat...')
  16. 15 /var/www/wikipathways/includes/parser/Parser.php(2860): call_user_func_array('getPathwayOfThe...', Array)
  17. 16 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(915): Parser->braceSubstitution(Array, Object(PPTemplateFrame_DOM))
  18. 17 /var/www/wikipathways/includes/parser/Parser.php(2981): PPFrame_DOM->expand(Object(PPNode_DOM))
  19. 18 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(915): Parser->braceSubstitution(Array, Object(PPTemplateFrame_DOM))
  20. 19 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(1239): PPFrame_DOM->expand(Object(DOMElement), 4)
  21. 20 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(1247): PPTemplateFrame_DOM->getNamedArgument('contents')
  22. 21 /var/www/wikipathways/includes/parser/Parser.php(3201): PPTemplateFrame_DOM->getArgument('contents')
  23. 22 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(934): Parser->argSubstitution(Array, Object(PPTemplateFrame_DOM))
  24. 23 /var/www/wikipathways/includes/parser/Parser.php(2986): PPFrame_DOM->expand(Object(PPNode_DOM))
  25. 24 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(915): Parser->braceSubstitution(Array, Object(PPTemplateFrame_DOM))
  26. 25 /var/www/wikipathways/includes/parser/Parser.php(2986): PPFrame_DOM->expand(Object(PPNode_DOM))
  27. 26 /var/www/wikipathways/includes/parser/Preprocessor_DOM.php(915): Parser->braceSubstitution(Array, Object(PPFrame_DOM))
  28. 27 /var/www/wikipathways/includes/parser/Parser.php(2678): PPFrame_DOM->expand(Object(PPNode_DOM), 0)
  29. 28 /var/www/wikipathways/includes/parser/Parser.php(966): Parser->replaceVariables('{{{{FULLPAGENAM...')
  30. 29 /var/www/wikipathways/includes/parser/Parser.php(321): Parser->internalParse('{{{{FULLPAGENAM...')
  31. 30 /var/www/wikipathways/includes/Article.php(3406): Parser->parse('{{{{FULLPAGENAM...', Object(Title), Object(ParserOptions), true, true, 92275)
  32. 31 /var/www/wikipathways/includes/Article.php(875): Article->outputWikiText('{{{{FULLPAGENAM...', false)
  33. 32 /var/www/wikipathways/includes/Wiki.php(437): Article->view()
  34. 33 /var/www/wikipathways/includes/Wiki.php(59): MediaWiki->performAction(Object(OutputPage), Object(Article), Object(Title), Object(User), Object(WebRequest))
  35. 34 /var/www/wikipathways/index.php(93): MediaWiki->initialize(Object(Title), Object(Article), Object(OutputPage), Object(User), Object(WebRequest))
  36. 35 {main}
View all Featured Pathways for this Portal


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Support

The EU-ToxRisk and OpenRiskNet projects are funded by the EU, CORDIS Project IDs 681002 and 731075 respectively.

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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