Portal:AOP/Mission

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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 [http://www.eu-toxrisk.eu/ EU-ToxRisk] program, in which [http://www.openphactsfoundation.org/ 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.
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== Purpose ==
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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.  
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List of molecular AOPs present in this portal (some are more defined than others):
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The proposed list of the first set of AOPs to be created, some are more defined than others:
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* Mitochondrial Complex I inhibition leads to liver injury
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* Mitochondrial Complex I inhibition leads to parkinsonian motor deficits
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* Decrease of lysosomal phospholipase activity leads to phospholipidosis
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* Mitochondrial Complex I inhibition leads to Fanconi syndrome
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* Immune-mediated liver injury
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* Protein alkylation leads to liver fibrosis
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* Reduced mitochondrial activity leads to cholestasis
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* Interaction with lung resident cell membrane components leads to lung fibrosis
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* Liver fibrosis
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* Multiple MIEs lead to liver steatosis
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* Unfolded protein response-mediated liver toxicity
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* ACE2 inhibition leads to increased mortality
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* Increased ROS levels lead to hepatotoxicity
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* Inhibition of mitochondrial complex I of nigra-striatal neurons leads to parkinsonian motor deficits
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* Decreased ATP production leads to neurodegeneration
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* Peripheral neuropathy caused by microtubule interacting drugs
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* Oxidative reactivity leads to chemical-induced fanconi syndrome
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* Oxidative reactivity leads to acceleration of chronic kidney disease
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* Compound accumulation via Megalin/Cubilin uptake leads to acute and chronic kidney disease
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* Renal proximal tubular uptake via organic cation transporters leads to...
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* Oxidative stress leads to COPD
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* Activation of Smad signaling leads to pulmonary fibrosis
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* Impaired HDAC leads to limbosacral spina bifida
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* HDAC inhibition leads to neural tube defects
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* Cyt p450 inhibition leads to Feminization and Masculinization
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* Estrogen/androgen ...
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* Bone malformation
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* Oxidative stress-induced hepatoxicity
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* Inflammatory cytokine-induced cell death
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* HDAC inhibition leads to impaired craniofacial development
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Villeneuve ''et al.'' (2014). Adverse Outcome Pathway (AOP) Development I: Strategies and Principles. ''Toxicological Sciences'' [https://www.ncbi.nlm.nih.gov/pubmed/25466378 PubMed]
Villeneuve ''et al.'' (2014). Adverse Outcome Pathway (AOP) Development I: Strategies and Principles. ''Toxicological Sciences'' [https://www.ncbi.nlm.nih.gov/pubmed/25466378 PubMed]
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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 [mailto:[email protected] contact Marvin Martens].
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== Creating molecular AOPs ==
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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.

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.

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