ToxTargetLinks

Extend molecular biological networks with toxic compounds.
Produces a link set for the Cytoscape CyTargetLinker App that can be used to extend molecular biological networks that contain proteins with toxic compounds that have proteins in that network as their target. These interactions can be understood to lead to molecular initiating events. The link set can also start from a network with toxic compounds and add the protein targets. Data were taken from CTD, the Comparative Toxicogenomics Database.

For end-users
For developers
Type:
Database / data source
Categories:
Toxicology, chemical properties and bioassay databases, Processing and analysis
Applicability domain:
Toxicology, Bioinformatics
Topic:
Chemical properties, Information extraction
Biological area:
Omics
Targeted industry:
Chemicals, Nanotechnology, Drugs, Cosmetics, Food, Other consumer products
Targeted users:
Risk assessors, Researchers, Students, Software Developers, Data managers, Informed public
Relevant OpenRiskNet case studies:
  • AOPLink - Identification and Linking of Data related to AOPWiki
  • DataCure - Data curation and creation of pre-reasoned datasets and searching
References and training materials:

https://f1000research.com/articles/7-743/v2


Provided by:
Maastricht University
Login required:
No
Implementation status:
Graphical user interface available
Technology readiness level:
TRL 3 – experimental proof of concept
Integration status:
Integration in progress
Service integration operations completed:
Utilises the OpenRiskNet APIs to ensure that each service is accessible to our proposed interoperability layer.
Is annotated according to the semantic interoperability layer concept using defined ontologies.
Is containerised for easy deployment in virtual environments of OpenRiskNet instances.
Has documented scientific and technical background.
Is deployed into the OpenRiskNet reference environment.
Is listed in the OpenRiskNet discovery services.
Is listed in other central repositories like eInfraCentral, bio.tools and TeSS (ELIXIR).
Provides legal and ethical statements on how the service can be used.

Resources & Training

Report
Identification and Linking of Data related to AOPs of AOP-Wiki [AOPLink]
Marvin Martens and Egon Willighagen (Maastricht University, Department of Bioinformatics - BiGCaT)
7 Oct 2019
Abstract:
The Adverse Outcome Pathway (AOP) concept has been introduced to support risk assessment (Ankley et al., 2010). An AOP is initiated upon exposure to a stressor that causes a Molecular Initiating Event (MIE), followed by a series of Key Events (KEs) on increasing levels of biological organization. Eventually, the chain of KEs ends with the Adverse Outcome (AO), which describes the phenotypic outcome, disease, or the effect on the population. In general, an AOP captures mechanistic knowledge of a sequence of toxicological responses after exposure to a stressor. While starting with molecular information, for example, the initial interaction of a chemical with a cell, the AOPs contain information of downstream responses of the tissue, organ, individual and population. Currently, AOPs are stored in the AOP-Wiki, a collaborative platform to exchange mechanistic toxicological knowledge as a part of the AOP-KB, an initiative by the OECD. Normally, AOP development starts with a thorough literature search for existing knowledge, describing the sequence of KEs that form the AOP. However, the use of AOPs for regulatory purposes also requires detailed validation and linking to existing knowledge (Knapen et al., 2015; Burgdorf et al., 2017). Part of the development of AOPs is the search for data that supports the occurrence and biological plausibility of KEs and their relationships (KERs). This type of data can be found in literature, and increasingly in public databases. The main goal of this case study is to establish the links between AOPs of the AOP-Wiki and experimental data to support a particular AOP. This will allow finding AOPs related to experimental data, and finding data related to a particular AOP.
Additional materials:
Report

Publisher: OpenRiskNet
Target audience: Risk assessors, Researchers, Students, Nanosafety community, Data modellers, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: UM
Report
Poster
OpenRiskNet Part II: Predictive Toxicology based on Adverse Outcome Pathways and Biological Pathway Analysis
Marvin Martens, Thomas Exner, Nofisat Oki, Danyel Jennen, Jumamurat Bayjanov, Chris Evelo, Tim Dudgeon, Egon Willighagen
28 Aug 2019
Abstract:
The OpenRiskNet project (https://openrisknet.org/) is funded by the H2020-EINFRA-22-2016 Programme. Here we present how the concept of Adverse Outcome Pathways (AOPs), which captures mechanistic knowledge from a chemical exposure causing a Molecular Initiating Event (MIE), through Key Events (KEs) towards an Adverse Outcome (AO), can be extended with additional knowledge by using tools and data available through the OpenRiskNet e-Infrastructure. This poster describes how the case study of AOPLink, together with DataCure, TGX, and SysGroup, can utilize the AOP framework for knowledge and data integration to support risk assessments. AOPLink involves the integration of knowledge captured in AOPs with additional data sources and experimental data from DataCure. TGX feeds this integration with prediction models of the MIE of such AOPs using either gene expression data or knowledge about stress response pathways. This is complemented by SysGroup, which is about the grouping of chemical compounds based on structural similarity and mode of action based on omics data. Therefore, the combination of these case studies extends the AOP knowledge and allows biological pathway analysis in the context of AOPs, by combining experimental data and the molecular knowledge that is captured in KEs of AOPs.
Related services:
ToxTargetLinks

Target audience: Risk assessors, Researchers, Students, Nanosafety community, Regulators, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: EwC, UM, IM
Poster
Webinar recording
Connecting Adverse Outcome Pathways, knowledge and data with AOPLink workflows
Marvin Martens (Department of Bioinformatics, Maastricht University, The Netherlands)
16 Jul 2019

Target audience: Risk assessors, Researchers, Students, Nanosafety community, Regulators, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: UM
Webinar recording
Presentation
Connecting Adverse Outcome Pathways, knowledge and data with AOPLink workflows
Marvin Martens (Department of Bioinformatics, Maastricht University, The Netherlands)
15 Jul 2019
Additional materials:
Slides

Target audience: Risk assessors, Researchers, Students, Nanosafety community, Data modellers, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: UM
Presentation
Presentation
AOP-Wiki Resource Description Framework
Marvin Martens (Maastricht University)
4 Jul 2019
Additional materials:
Slides

Target audience: Nanosafety community
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: UM
Presentation
Webinar recording
AOP-DB: The Adverse Outcome Pathway Database
Holly Mortensen, Ph.D. (US EPA), Phillip Langley (ORAU-SSC) and Trevor Levey (ORAU-SSC)
16 Apr 2019

Target audience: Risk assessors, Researchers, Students, Developers, OpenRiskNet stakeholders, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: EwC, UM
Webinar recording
Presentation
AOPLink - Linking experimental data to Adverse Outcome Pathways
Marvin Martens, Egon Willighagen, Chris Evelo (Department of Bioinformatics, Maastricht University, The Netherlands)
27 Mar 2019
Additional materials:
Slides

Publisher: OpenRiskNet
Target audience: Risk assessors, Researchers, Students, Data modellers, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: UM
Presentation
Webinar recording
Identification and linking of data related to AOPWiki
Marvin Martens and Egon Willighagen (Department of Bioinformatics, Maastricht University, The Netherlands), Thomas Exner (Edelweiss Connect GmbH, Switzerland)
27 Mar 2019

Publisher: OpenRiskNet
Target audience: Risk assessors, Researchers, Students, Data modellers, Bioinformaticians
Open access: yes
Licence: Attribution-ShareAlike 4.0 International (CC BY-SA 4.0)
Organisations involved: EwC, UM
Webinar recording
Poster
Expanding Adverse Outcome Pathway knowledge by creating AOP-Wiki RDF with semantic annotations to facilitate risk assessment of chemicals.
Marvin Martens, Chris Evelo, Egon Willighagen
19 Feb 2019
Abstract:
1. Introduction With the ever-growing number of chemicals that require toxicological risk assessment, there is a need for faster, more efficient use of existing data to assemble effective assessment strategies [1]. Therefore, the concept of Adverse Outcome Pathways (AOPs) was introduced [2], a framework to organize existing mechanistic information about toxicological processes into a chain of smaller pieces of knowledge, called Key Events (KEs). These allow the structuring of toxicological knowledge and reduce the effort needed to capture all information before performing risk assessment [2, 3]. In order to facilitate a community effort in gathering toxicological knowledge, the AOP-Wiki was created by the European Commission JRC and the US EPA. To integrate this knowledge base more easily with other resources, we explored the use of semantic web technologies to link AOP-Wiki with other chemical and biological databases. 2. Approach The AOP-Wiki provides quarterly permanent downloads for the full database XML (https://aopwiki.org/downloads/). We parsed the AOP-Wiki knowledge with Python 3.5 and the ElementTree XML API and converted it into a semantic web RDF format, which allows for accurate description with ontological annotations, including the AOPO, CHEMINF, and Dublin Core. Chemical compounds are identified in the AOP-Wiki with CAS numbers and biological processes with a variety of ontologies, e.g. GO, Mammalian Phenotype Ontology, and Molecular Interactions ontology. These annotations are used to create Internationalized Resource Identifiers. To integrate and test the RDF, a variety of federated SPARQL queries were written and executed in Blazegraph (build version 2.1.4). 3. Results We created an AOP-Wiki RDF scheme and converted the XML into Turtle syntax. The RDF was tested with a variety of SPARQL queries to answer biological question relevant to risk assessment, such as: - What measurement / test-method information is available for a given AOP? - Which of the stressor chemicals on the AOP-Wiki can be linked molecular pathways on WikiPathways? 4. Discussion The RDF transformation of AOP-Wiki content can assist in the accessibility and expansion of toxicological knowledge by allowing semantic interoperability. The created RDF of the AOP-Wiki allows the querying and providing of additional information for stressor chemicals, genes, and proteins involved in KEs, the underlying molecular pathways, but also for the applicability of AOPs by cell types or species. This semantic approach allows novel ways to explore the rapidly growing AOP knowledge with every new publication related to toxicological studies. There is work in progress on a Virtuoso SPARQL endpoint Docker image to simplify the use of the data, and integrate the database in the OpenRiskNet e-infrastructure to provide AOP knowledge useful for automated risk assessment workflows. Funding This project has received funding from the European Union’s Horizon 2020 (EU 2020) research and innovation program under grant agreement no. 681002 (EU-ToxRisk) and EINFRA-22-2016 program under grant agreement no. 731075 (OpenRiskNet).

Target audience: Risk assessors, Researchers, Data managers, Data owners, OpenRiskNet stakeholders, Regulators, Bioinformaticians, Software developers, Data providers
Open access: yes
Licence: Attribution 4.0 International (CC BY 4.0)
Organisations involved: UM
Poster
Poster
Introducing WikiPathways to support Adverse Outcome Pathways for regulatory risk assessment
Marvin Martens, Tim Verbruggen, Penny Nymark, Roland Grafström, Lyle Burgoon, Hristo Aladjov, Fernando Torres Andón, Chris T Evelo, Egon Willighagen
7 Sep 2018
Abstract:
In the last decade, omics-based approaches such as transcriptomics, proteomics and metabolomics have become valuable tools in toxicological research, and are finding their way into regulatory toxicity. A promising framework to bridge the gap between the molecular-level measurements and risk assessment is the concept of Adverse Outcome Pathways (AOPs). These pathways comprise mechanistic knowledge and connect biological events from a molecular level towards an adverse effect after exposure to a chemical or nanomaterial. However, the implementation of omics-based approaches in the AOPs and acceptance by the risk assessment community is still a challenge. Therefore, tools are required for omics-based data analysis and visualization, and to link the data to the traditional AOPs. Here we show how WikiPathways, an open science pathway database, can serve as a viable tool for this purpose. Therefore, an AOP Portal (aop.wikipathways.org)has been created with a rapidly growing collection of molecular-level AOPs on which omics datasets can be mapped an analyzed, currently consisting of 15 pathways by 14 authors that are structured in various ways. Besides that, we are making WikiPathways more interoperable with aopwiki.org, the main knowledge-base that collects and stores AOPs. The open and collaborative nature makes WikiPathways a fast growing platform that is applicable in a wide range of biomedical research fields in which omics-based approaches are used. Also, its use of ontologies, OpenAPI documentation and FAIR (Findable, Accessible, Interoperable, Reusable) approaches makes WikiPathways interoperable with many other data sources. By introducing AOPs in WikiPathways and linking these with the AOPs in aopwiki.org, we aimed to make WikiPathways a useful tool for the regulatory toxicity community and for toxicological research in general. Eventually this could lead to implementation of WikiPathways as a data-source for decision-making in REACH (Registration, Evaluation, Authorization, and restriction of Chemicals) dossiers for risk assessment of chemicals. 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.
Related services:
ToxTargetLinks

Target audience: Risk assessors, Researchers, Students, Developers, Data managers, Data owners, Regulators, Bioinformaticians, Software developers, Data providers
Open access: yes
Licence: Attribution 4.0 International (CC BY 4.0)
Organisations involved: UM
Poster