This document discusses the CompTox Chemistry Dashboard, a publicly accessible website developed by the US EPA's National Center for Computational Toxicology. The dashboard provides data on over 760,000 chemicals, including physicochemical properties, bioactivity data, and links to other resources. It supports applications in structure identification and chemical forensics using mass spectrometry through features like batch searching by formula or mass, MS-ready chemical mappings, and predicted mass spectra. The dashboard is being expanded to include additional prediction models and web services to further enable non-targeted analysis using mass spectrometry data.

1. Applications of the US EPA’s CompTox
Dashboard to support structure
identification and chemical forensics
using mass spectrometry
Antony Williams1, Andrew D. McEachran2,
Jon R. Sobus3 and Emma Schymanski4
1) National Center for Computational Toxicology, U.S. Environmental Protection Agency, RTP, NC
2) Oak Ridge Institute of Science and Education (ORISE) Research Participant, RTP, NC
3) National Exposure Research Laboratory, U.S. Environmental Protection Agency, RTP, NC
4) Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Campus Belval, Luxembourg
August 2018
ACS Fall Meeting, Boston
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

2. • National Center for Computational Toxicology
established in 2005 to integrate:
– High-throughput and high-content technologies
– Modern molecular biology
– Data mining and statistical modeling
– Computational biology and chemistry
• Researching computational approaches to
quickly evaluate the safety of chemicals for
potential risk.
• Outputs: a lot of data, models, algorithms and
software applications
National Center for
Computational Toxicology

3. The CompTox Chemistry Dashboard
• A publicly accessible website delivering access:
– New entry portal for all NCCT dashboards
– ~762,000 chemicals with related property data
– Searchable by chemical, product use, gene and assay
(ToxCast)
– Experimental and predicted physicochemical property data
– “Bioactivity data” for the ToxCast/Tox21 project
– Generalized Read-Across (GenRA) module
– Links to other agency websites and public data resources
– “Literature” searches for chemicals using public resources
– “Batch searching” for thousands of chemicals
– DOWNLOADABLE Open Data for reuse and repurposing
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4. CompTox Dashboard
https://comptox.epa.gov/dashboard
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5. CompTox Dashboard
Chemicals
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6. Detailed Chemical Pages
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7. Access to Chemical Hazard Data
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8. In Vitro Bioassay Screening
ToxCast and Tox21
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9. Sources of Exposure to Chemicals
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10. External Links to ~80 websites
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11. MS-Ready Mappings
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12. MS-Ready Mappings Set
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13. Mass and Formula Searches
Supporting Mass Spectrometry
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14. Advanced Searches
Mass Based Search
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15. Advanced Searches
Mass Based Search
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16. Batch Searching
• Singleton searches are useful but we work
with thousands of chemicals!
• Typical questions
– 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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17. Batch Searching
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18. Batch Searching
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19. Excel Output
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20. Suspect Screening and Non-Targeted
Analysis Workflow
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DSSTox Chemical Database
“Molecular Features”
Extracted Samples
Raw Samples
Raw Features
Matched Formulas
Mapped Structures
Prioritized Structures
(using ToxPi)
Confirmed Structures
(using ToxCast standards)
Processed Features
Prioritized Features
Predicted Formulas
Candidate Structures
Sorted Structures
Predicted Retention Times
Predicted/Observed Functional Use
Top Candidate Structure(s)
Suspect Screening Non-Targeted Analysis
Predicted Concentrations
Predicted/Observed Media Occurrence
Predicted Mass Spectra
Methodological Concordance
Red = Analytical Chemistry
Blue = Data Processing & Analysis
Green = Informatics & Web Services
Purple = Mathematical & QSPR Modeling
Color Key
Content from J. Sobus, US-EPA-NERL

21. The Dashboard to Support
MS-Analysis
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MS-Ready
Structures
Underpin
Analysis

22. Specific Data-Mappings
“MS-Ready Structures”
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23. MS-Ready Mappings
• Input Formula: C10H16N2O8
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24. MS-Ready Mappings
• Same Input Formula: C10H16N2O8
• MS Ready Formula Search: 93 Chemicals
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25. MS-Ready Mappings
• 93 chemicals returned in total
– Only 7 of the 93 are single component chemicals
– Only 4 of the 93 are non-isotope-labeled
– 3 are neutral compounds and 1 is charged
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26. Complexity to Simplicity
93 Chemicals – 7 in EPAHFR
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27. Complexity to Simplicity
93 Chemicals – 7 in the list
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28. Searching batches
Formula (or mass) searching
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29. Downloadable Data
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30. Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
• Retention Time Index Prediction
• Structure/substructure/similarity search
• Generation of MS-ready structures:
– Upload file, download results
– Service based generation
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31. Predicted Mass Spectra
http://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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32. Library Fragmentation
Spectra (20eV)
Observed Fragmentation
Spectra (20eV)
Match
Score
Predicted Mass Spectra

33. Search Expt. vs. Predicted Spectra

34. Prototype Development
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35. Prototype Development
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36. Conclusion
• The CompTox Chemistry Dashboard provides access
to data for ~760,000 chemicals
• Multiple prediction models available for data gap
filling
– OPERA models and TEST models – PhysChem and Tox endpoints
– Models based on in vitro data – classification models
– Generalized Read-Across development in progress
• Real time prediction models rollout has started
• Web services available for some physchem and
toxicity endpoints
• 2 years development as a CompTox Integration Hub
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37. Contact
Antony Williams
US EPA Office of Research and Development
National Center for Computational Toxicology (NCCT)
Williams.Antony@epa.gov
ORCID: https://orcid.org/0000-0002-2668-4821
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