1.
Applications of the US EPA’s CompTox
Chemicals Dashboard to support
structure identification and chemical
forensics using mass spectrometry
Antony Williams1 and Andrew D. McEachran2,3
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) Present Address: Agilent Inc., Santa Clara, CA
March 18th 2019
Pittcon, Philadelphia
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.
CompTox Chemicals Dashboard
• A publicly accessible website delivering access:
– ~875,000 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
– 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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3.
CompTox Chemicals Dashboard
https://comptox.epa.gov/dashboard
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4.
BASIC Search
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5.
Detailed Chemical Pages
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6.
Access to Chemical Hazard Data
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7.
In Vitro Bioassay Screening
ToxCast and Tox21
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8.
Sources of Exposure to Chemicals
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Identifiers to Support Searches
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10.
Literature Searches and Links
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11.
Link Access
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12.
NIST WebBook
https://webbook.nist.gov/chemistry/
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13.
MassBank of North America
https://mona.fiehnlab.ucdavis.edu
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14.
m/z CLOUD
https://www.mzcloud.org/
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15.
SIMPLE
APPLICATIONS
FOR MASS SPEC.
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16.
Find me “opioids like Morphine”
Structure Similarity
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Find me “opioids like Morphine”
Structure Similarity
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Find me “opioids like Morphine”
Structure Similarity – sort on mass
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Find me “opioids like Morphine”
Formula-Based Search
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Select Chemicals of Interest
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Prune to list of interest
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Sort for “morphine” by string
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Literature Searching
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Literature Searching
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Literature Searching
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FOCUSED
CHEMICAL LISTS
OF INTEREST
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Chemical Lists
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PFAS lists of Chemicals
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EPAHFR: Hydraulic Fracturing
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Aggregate data for a list of chemicals
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Batch Search Names
30
Excel
Download

32.
Add Other Data of Interest
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Batch Search in specific lists
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MASS AND
FORMULA
SEARCHING
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Advanced Searches
Mass and Formula Based Search
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Advanced Searches
Mass and Formula Based Search
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Batch Searching
• Singleton searches are useful but we work
with thousands of masses and formulae!
• 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?
– Can I include properties in the download file?
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38.
Batch Searching Formula/Mass
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39.
DO WE REALLY
NEED ANOTHER
DATABASE?
38

40.
Is a bigger database better?
39
• ChemSpider was 26 million chemicals then
• Much BIGGER today
• Is bigger better??

41.
Comparing Search Performance
40
• Dashboard content was 720k chemicals
• Only 3% of ChemSpider size
• What was the comparison in performance?

42.
SAME dataset for comparison
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How did performance compare?
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Data Quality is important
• Data quality in free web-based databases!
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Will the correct Microcystin LR Stand Up?
ChemSpider Skeleton Search
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Comparing ChemSpider Structures
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Comparing ChemSpider Structures
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Other Searches
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Delivering a Better Database
• An ideal database would provide:
– Curated CAS Number-Name mappings with “correct”
chemical structures
• We have full time curators checking data
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Names to CASRN Mappings
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Subtleties
50
E/Z-stereochemistry E-stereochemistry
“4-Decene”

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CAS Registry Numbers
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Alternative Synonyms
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SPECIFIC
APPLICATIONS
TO MASS SPEC.
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Mass Spec Focused Applications
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Mass Spec Focused Applications
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“MS-Ready Structures”
https://doi.org/10.1186/s13321-018-0299-2
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Specific Data-Mappings
“MS-Ready Structures”
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MS-Ready Mappings
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MS-Ready Mappings Set
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Advanced Searches
Mass Search
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Advanced Searches
Mass Search
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MS-Ready Structures for
Formula Search
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MS-Ready Structures
Batch Searches
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MS-Ready Mappings
• EXACT Formula: C10H16N2O8: 3 Hits
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MS-Ready Mappings
• Same Input Formula: C10H16N2O8
• MS Ready Formula Search: 125 Chemicals
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MS-Ready Mappings
• 125 chemicals returned in total
– 8 of the 125 are single component chemicals
– 3 of the 8 are isotope-labeled
– 3 are neutral compounds and 2 are charged
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Complexity to Simplicity - Use Lists
125 Chemicals – 7 in EPAHFR
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Complexity to Simplicity
125 Chemicals – 7 in the list
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Searching batches using MS-Ready
Formula (or mass) searching
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72.
UVCB
CHEMICAL
SUBSTANCES
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UVCB Chemicals
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Many Hydraulic Fracturing
Chemicals are “Complex”
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“Markush Structures”
https://en.wikipedia.org/wiki/Markush_structure
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UVCB: Complex Surfactants
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UVCB: Complex Surfactants
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UVCB: Complex Surfactants
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WORK IN
PROGRESS
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80.
Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
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81.
Predicted Mass Spectra
http://cfmid.wishartlab.com/
• MS/MS spectra prediction for ESI+, ESI-, and EI
• Predictions generated and stored for >800,000
structures, to be accessible via Dashboard
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Search Expt. vs. Predicted Spectra

83.
Search Expt. vs. Predicted Spectra

84.
Spectral Viewer Comparison
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Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
• Retention Time Index Prediction
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Retention Time Prediction for Ranking
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Moving to Relative Retention Times
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Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
• Retention Time Index Prediction
• Structure/substructure/similarity search
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Prototype Development
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Prototype Development
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Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
• Retention Time Index Prediction
• Structure/substructure/similarity search
• Integration of predicted ion mobility data
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Collision Cross Section Prediction
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Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
• Retention Time Index Prediction
• Structure/substructure/similarity search
• Integration of predicted ion mobility data
• Access to API and web services for
programmatic access
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API services and Open Data
• Groups waiting on our API and web services
• Mass Spec companies instrument integration
• Release will be in iterations but for now our
data are available
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SIDE EFFECTS
OF SHARING
OPEN DATA
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96.
NORMAN Suspect List Exchange
https://www.norman-network.com/?q=node/236
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Integration to MetFrag in place
https://jcheminf.biomedcentral.com/articles/10.1186/s13321-018-0299-2
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Conclusion
• Dashboard access to data for ~875,000 chemicals
• MS-Ready data facilitates structure identification
• Related metadata facilitates candidate ranking
97
• Relationship mappings and
chemical lists of great utility
• Dashboard and contents
are one part of the solution
• Future releases will offer
even more utility
• We are committed to open
API development with time..

99.
Acknowledgements
• THANK YOU for the invitation!
• IT Development team – especially Jeff
Edwards and Jeremy Dunne
• Chris Grulke for the ChemReg system
• NERL colleagues – Jon Sobus, Elin Ulrich,
Mark Strynar, Seth Newton
• Emma Schymanski, LCSB, Luxembourg
• The NORMAN Network and all contributors
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100.
Contact
Antony Williams
US EPA Office of Research and Development
National Center for Computational Toxicology
EMAIL: Williams.Antony@epa.gov
ORCID: https://orcid.org/0000-0002-2668-4821
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