The CompTox Chemistry Dashboard v3.0 – New Searches and Support for

Bioactivity Data

Antony WilliamsNational Center for Computational Toxicology, U.S. Environmental Protection Agency, RTP, NC

September 27th 2018Communities of Practice

http://www.orcid.org/0000-0002-2668-4821

The views expressed in this presentation are those of the author and do not necessarily reflect the views or policies of the U.S. EPA

Outline – what’s new in v3.0?

• Welcome the CompTox Portal• New name for the dashboard• User interface overhaul – easier navigation• New search capabilities• Enhanced support for bioactivity data• New data and new lists added• Work in progress

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The CompTox Portalhttps://comptox.epa.gov/

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Watch for our newshttps://comptox.epa.gov/dashboard/news_info

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Release Noteshttps://comptox.epa.gov/dashboard/comptox_release_notes.pdf

• A detailed list of new functionality and fixes

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Staying up with the Dashboardhttps://comptox.epa.gov/dashboard/news_info

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CompTox Chemicals Dashboardhttps://comptox.epa.gov/dashboard

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CompTox DashboardChemicals

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CompTox DashboardProducts and Use Categories

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CompTox DashboardAssays and Genes

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Detailed Chemical PagesNew User Interface Design

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Access to Chemical Hazard Data

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Hazard Data from “ToxVal_DB”Lots of new data added - ECOTOX

• ToxVal Database contains following data:– 30,050 chemicals– 772,721 toxicity values– 29 sources of data– 21,507 sub-sources– 4585 journals cited– 69,833 literature citations

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Sources of Exposure to Chemicals

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What chemicals in what product and use categories?

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What chemicals in what product and use categories?

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Remember home page searchesSearching for “eye”…

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In Vitro Bioassay Screening ToxCast and Tox21

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In Vitro Bioassay Screening ToxCast and Tox21

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Earlier Dashboard Applications

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In Vitro Bioassay Screening ToxCast and Tox21

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Assay Modal Details

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In Vitro Bioassay Screening ToxCast and Tox21

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In Vitro Bioassay Screening Multi-chart Display

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In Vitro Bioassay Screening ToxCast and Tox21

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Assay Modal Details

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List of Chemicals for an Assay

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Choose Display Details

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Tile/Table ModeMore flexibility in table display

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In Vitro Bioassay Screening ToxCast and Tox21

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Access to Analytical QC Data

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Access to Analytical QC Data

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GenRA (Generalised Read-Across)

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GenRA (Generalised Read-Across)

Structure Similarity

Select and Review Analogs

GenRA (Generalised Read-Across)

Review Available Data Fingerprint indicating available dataSelect and Review Analogs

GenRA (Generalised Read-Across)

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Run GenRATarget

Source analogues

Red : Toxicity effects. Blue: No Toxicity effectsGrey : Absence of data

Related Substancese.g. Transformation Products

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UVCB Chemicals

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Related Substances for Markush

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Identifiers to Support Searches

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Literature Searches and Links

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Abstract Sifter – PubMed Integration searching >28 million abstracts

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External Links to ~80 websitesGrowing list of out links -

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Mass and Formula SearchesSupporting Mass Spectrometry

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Advanced SearchesMass Based Search

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Advanced SearchesMass Based Search

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MS-Ready Structureshttps://jcheminf.biomedcentral.com/articles/10.1186/s13321-018-0299-2

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MS-Ready Structures

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MS-Ready Mappings

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MS-Ready Mappings Set

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Batch Searching

• Singleton searches are useful but we work with thousands of chemicals!

• Typical questions– What chemicals can I get for 5000 CAS Numbers?– Can I get predicted properties for 1000 chemicals?– What is the list of chemicals for the formula CxHyOz ?– What is the list of chemicals for a mass +/- error ?– Can I get chemical lists in Excel files? In SDF files?

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Batch Searching

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Batch Searching

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Excel Output

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How can be curate our data?

• Crowdsourcing is well proven nowadays• Comments can be added at a record level

• Submitted comments are reviewed by administrators and responded to

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Public Crowdsourced Commentshttps://comptox.epa.gov/dashboard/comments/public_index

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Comments to date

• The majority of comments to date:– Structure and names/CASRN do not match– Add additional synonyms– Request to add specific property data– Structure layout/depiction needs improving

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Crowdsourcing CommentsSingle Cell Commenting added

• Highlight an alphanumeric text string

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Crowdsourcing Comments

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Lists of Lists

• Lists of chemicals – ca. 100 lists• List of ToxCast/Tox21 assays

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11 PFAS Listshttp://comptox-prod.epa.gov/dashboard/chemical_lists

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The OECD List of PFAShttp://www.oecd.org/chemicalsafety/portal-perfluorinated-chemicals/

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The OECD List of PFAShttp://www.oecd.org/chemicalsafety/portal-perfluorinated-chemicals/

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Want data for a list???

• Simply send to Batch and choose data…

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List of Assays

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Select an Assay to NavigateTile View

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Select an Assay to NavigateTable View

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Real-Time Predictions

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Real-Time Predictions

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Work in Progress

• CFM-ID– Viewing and Downloading pre-predicted spectra– Search spectra against the database

• Structure/substructure/similarity search• pKa prediction

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Predicted Mass Spectrahttp://cfmid.wishartlab.com/

• MS/MS spectra prediction for ESI+, ESI-, and EI• Predictions generated and stored for >700,000

structures, to be accessible via Dashboard

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Library Fragmentation Spectra (20eV)

Observed Fragmentation Spectra (20eV)

Match Score

Predicted Mass Spectra

Search Expt. vs. Predicted Spectra

Prototype Development

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Prototype Development

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pKa Prediction Model

• pKa prediction models based on Open Data Set of 8000 chemicals – acidic, basic and amphoteric chemicals

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NCCT “InvitroDB_v3”

• The last public release of ToxCast data (invitroDB_v2) was in 3rd Quarter of 2015

• The next release invitroDB_v3 is Fall 2018• Data includes new assays, new chemicals,

new pipelining, results of data curation• Data will also release via CompTox Dashboard• Data will be available at https://www.epa.gov/chemical-

research/exploring-toxcast-data-downloadable-data

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Downloadable Data Being Updated

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Conclusion

• The CompTox Chemistry Dashboard provides access to data for ~765,000 chemicals

• An expanding list of data types and sources has been integrated

• New searches based on Product Use and Categories and Assay and Gene

• The chemical lists of interest grows with each release

• Next release scheduled for Fall 2018 with InvitroDB_v3 data – more chemicals, more assays

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How is it built?https://jcheminf.springeropen.com/articles/10.1186/s13321-017-0247-6

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Acknowledgments

• Our NCCT CompTox Chemical Dashboard Development and IT Team

• The NCCT Team of Scientists• NERL scientists - Mass Spectrometry• Kamel Mansouri – OPERA models• Todd Martin – TEST predictions

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Contact

Antony WilliamsUS EPA Office of Research and DevelopmentNational Center for Computational Toxicology (NCCT)Williams.Antony@epa.govORCID: https://orcid.org/0000-0002-2668-4821

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