Connecting Adverse Outcome Pathways, knowledge …...2019/07/15 · Connecting Adverse Outcome Pathways, knowledge and data with AOPLink workﬂows Marvin Martens - Maastricht University

www.openrisknet.org

OpenRiskNet: Open e-Infrastructure to Support Data Sharing, Knowledge Integration and in silico Analysis and Modelling in Risk Assessment

Project Number 731075

Connecting Adverse Outcome Pathways, knowledge and data with AOPLink workflows

Marvin Martens - Maastricht University15-July-2019

www.openrisknet.org

OpenRiskNet webinars series

Topic Date & Time

Past events

Introduction sessions to the OpenRiskNet e-infrastructure

Webinar recordings:● Session 1 (24 Sep 2018)● Session 2 (27 Sep 2018)● Session 3 (4 Oct 2018)● Session 4 (30 Oct 2018)

Learn how to deploy the OpenRiskNet virtual research environment Webinar recordings (25 Feb 2019)

Demonstration on data curation and creation of pre-reasoned datasets in the OpenRiskNet framework Webinar recordings (18 Mar 2019)

Identification and linking of data related to AOPWiki (an OpenRiskNet case study) Webinar recordings (26 March 2019)

The Adverse Outcome Pathway Database (AOP-DB) Webinar recordings (8 April 2019)

How to describe OpenRiskNet services and their functionality by semantic annotation Webinar recordings (13 May 2019)

Use of Nextflow tool for toxicogenomics-based prediction and mechanism identification in OpenRiskNet e-infrastructure Webinar recordings (27 May 2019)

Demonstration on OpenRiskNet approach on modelling for prediction or read across (ModelRX case study) Webinar recordings (11 June 2019)

Combining neXtProt and WikiPathways strengths using SPARQL federated queries Webinar recordings (12 June 2019)

Deploying Applications to an OpenRiskNet Virtual Environment Webinar recordings (24 June 2019)

Current event Connecting Adverse Outcome Pathways, knowledge and data with AOPLink workflows Monday, 15 July 2019, 16:00 CESTRegistration: https://openrisknet.org/events/70/

Future events Final OpenRiskNet F2F Workshop 23-24 Oct 2019 (Amsterdam, The Netherlands)https://openrisknet.org/events/74/

https://openrisknet.org/events/

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Adverse Outcome Pathways

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Adverse Outcome Pathways (AOPs) bridge the gap between scientists and regulators

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AOPs are chains of biological events

Framework that captures mechanistic knowledge of toxicological processes to support decision making in risk assessments

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AOPs support knowledge-based decision-making in risk assessmentsAid Integrated Approaches to Testing and Assessment (IATA)

Allow re-use of knowledge

● Predictive value● Reduce animal testing● Identify knowledge gaps● Faster, more efficient● Cost-effective

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OpenRiskNet case study: AOPLink

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AOPLink: two main research questions

Q1: For an AOP, which experimental data is available to support the AOP?

Q2: Can this experimental data support an existing AOP?

Experimental data Adverse Outcome Pathways

AOPLink

www.openrisknet.org 9Berggren et al. https://doi.org/10.1016/j.comtox.2017.10.001

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AOP-Wiki: Central repository in AOPLink

● The main qualitative AOP repository of the AOP-KB● Joint effort between EC-JRC and US EPA

Element Number

Adverse Outcome Pathways 262

Key Events 1261

Key Event Relationships 1592

Stressors 497

https://aopwiki.org

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AOP-Wiki website

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AOPs in AOP-Wiki contain diverse types of info

https://aopwiki.org/aops/38

www.openrisknet.org 13

Adverse Outcome Pathway:- Abstract- Background- Applicability- Key Events- Key Event Relationships- Stressors- Assessment

Stressor:- Chemical - CAS - DSStox - InchiKey - Names- Evidence- Description

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Stressor:- Chemical - CAS - DSStox - InchiKey - Names- Evidence- Description Key Event:

- Description- Method- Key Event components - Biological process - Biological object - Biological action- Applicability - Taxonomy - Life stage - Sex

Key Event:- Description- Method- Key Event components - Biological process - Biological object - Biological action- Applicability - Taxonomy - Life stage - Sex

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Key Event Relationship:- Description- Biological plausibility- Empirical evidence- Uncertainties- Quantitative understanding- Applicability - Taxonomy - Life stage - Sex

Stressor:- Chemical - CAS - DSStox - InchiKey - Names- Evidence- Description Key Event:

- Description- Method- Key Event components - Biological process - Biological object - Biological action- Applicability - Taxonomy - Life stage - Sex

Key Event:- Description- Method- Key Event components - Biological process - Biological object - Biological action- Applicability - Taxonomy - Life stage - Sex

Key Event Relationship:- Description- Biological plausibility- Empirical evidence- Uncertainties- Quantitative understanding- Applicability - Taxonomy - Life stage - Sex

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Problem:● AOP-Wiki pages contain text, tables, and identifiers

Goals:● Extract specific information (accessibility)● Harmonize with other databases (interoperability)

Solution: ● Semantic modeling of the database, including ontological annotations

and persistent identifiers

From full-page descriptions to semantic modelling

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AOP-Wiki RDF

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Resource Description Framework (RDF)

● Standard to describe information in web resources

● Information stored in triples

● Generally used in databases

● Large number of libraries and tools

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Conversion to RDF

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Connectivity in existing AOP-Wiki

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Underlying database has eleven main subjects

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All subjects are connected by identifiers (IDs)

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Adding semantic meaning to predicates

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Simplified overview of AOP-Wiki subjects

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How to access the AOP-Wiki RDF

Through the REST API

http://grlc.io/api/marvinm2/AOPWikiQueries

Through the SPARQL endpoint

http://aopwiki-rdf.prod.openrisknet.org/sparql/

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Example #1: Methods of an AOP

Question:

For AOP 38 (Protein Alkylation leading to Liver Fibrosis), print:

● KE IDs● KE names● Measurement methods text

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SPARQL endpoint grlc REST API

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Example #2: Find AOPs by CAS-RN

By single CAS-RN: 107-18-6:

By list of CAS-RN: 107-18-6, 103-90-2, 83-79-4 (no limit)

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Additional identifiers to the AOP-Wiki RDF (e.g. Chemicals)

For CAS-RN 107-18-6, external identifiers for ChEBI, HMDB, ChemSpider, etc.

Example #3: Find AOPs by ChEBI ID

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Example #3: Find AOPs by ChEBI ID

Find AOPs with one of the ChEBI IDs found earlier: CHEBI:16605

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Example #4: Query multiple AOPs at onceQuery all chemical names that lead to a particular AO: Learning and memory impairment (KE ID 341)

Query all AOs that can be the result of a particular MIE: AhR activation (KE ID 18)

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grlc facilitates the use of AOP-Wiki RDF

● No need to learn SPARQL

● Use of an interface● Parameters

○ Free-text○ Pre-defined

● Allows direct requests○ From command line○ URL with query string

■ http://grlc.io/api/marvinm2/AOPWikiQueries/get-methods-for-aop?aopfilter=38

● GitHub: https://github.com/marvinm2/AOPWikiQueries for requests35

SELECT ?AopLabel ?KeyEventID ?KeyEventURL ?AssayText WHERE { ?KeyEventURL a aopo:KeyEvent ; rdfs:label ?KeyEventID ; dcterms:isPartOf ?aop; mmo:0000000 ?AssayText . ?aop rdfs:label ?AopLabel .VALUES ?aop {aop:38}}

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Jupyter workflow

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Integration in risk assessment workflowQuestion

● Does the AOP-Wiki contain AOPs relevant to nanomaterial toxicity?

Approach

● Extracting all chemicals from AOP-Wiki and using the ChEBI Ontology● Text matching for AOPs, Key Events, and Stressors

Result

● No nanomaterials found through the chemical identifiers● 10 AOPs linked to nanomaterial toxicity through text mapping

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Intermediate poll

Q: Which kind of data or knowledge would be beneficial to AOPs that should be integrated in Jupyter notebooks that is not yet presented?

a. Disease/phenotype databasesb. Chemical/chemical reaction databasesc. Gene variantd. Population geneticse. Molecular pathway databases (e.g. WikiPathways)

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AOPLink in broader perspective

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AOPLink connected to OpenRiskNet case studies

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Ongoing work

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Integration of the AOP-DBWinners of the OpenRiskNet implementation challenge

Database of AOPs linked to external data sources for:

● Chemicals● Genes● Pathways● ToxCast assays● Diseases

AOP-DB is being converted into RDF

Will be exposed as a SPARQL endpoint

AOP-DB webinar: https://openrisknet.org/events/60/42

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Integration of PathVisioRPC

Available for a variety of preferred programming languages

PathVisio functionalities withoutneeding to install the software

Visualise and analyse expression data on molecular pathways from WikiPathways

https://doi.org/10.1186/s12859-015-0708-8 43

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Acknowledgements

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.

Connecting Adverse Outcome Pathways, knowledge …...2019/07/15 · Connecting Adverse Outcome Pathways, knowledge and data with AOPLink workﬂows Marvin Martens - Maastricht University

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