High resolution mass spectrometry (HRMS) and non-targeted analysis (NTA) are of increasing interest in chemical forensics for the identification of emerging contaminants and chemical signatures of interest. At the US Environmental Protection Agency, our research using HRMS for non-targeted and suspect screening analyses utilizes databases and cheminformatics approaches that are applicable to chemical forensics. The CompTox Chemicals Dashboard is an open chemistry resource and web-based application containing data for ~900,000 substances. Basic functionality for searching through the data is provided through identifier searches, such as systematic name, trade names and CAS Registry Numbers. Advanced Search capabilities supporting mass spectrometry include mass and formula-based searches, combined substructure-mass searches and searching experimental mass spectral data against predicted fragmentation spectra. A specific type of data mapping in the underpinning database, using “MS-Ready” structures, has proven to be a valuable approach for structure identification that links structures that can be identified via HRMS with related substances in the form of salts, and other multi-component mixtures that are available in commerce. These MS-Ready structures have been used as an input set for computational MS-fragmentation to provide a database against which to search experimental data for spectral matching. This presentation will provide an overview of how the CompTox Chemicals Dashboard supports structure identification and non-targeted analysis in chemical forensics. This abstract does not necessarily represent the views or policies of the U.S. Environmental Protection Agency.

1. The EPA CompTox Chemicals Dashboard to
support structure identification and chemical
forensics using mass spectrometry
Fall 2019
ACS Fall Meeting, San Diego
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
Antony Williams1, Alex Chao2, Tom Transue3, Tommy Cathey3,
Elin Ulrich4 and Jon Sobus4
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) General Dynamics Information Technology, RTP, NC
4) National Exposure Research Laboratory, U.S. Environmental Protection Agency, RTP, NC

2. Overview
• The CompTox Chemicals Dashboard - web-
based database of 875k substances
• Associated data including:
– Experimental and predicted physicochemical data
– In vivo hazard data
– In vitro bioactivity screening data
– Link farm to tens of public resources
• Integrated modules – read-across, lit search
• Data mappings and searches supporting
Mass Spectrometry & structure identification
1

3. CompTox Chemicals Dashboard
https://comptox.epa.gov/dashboard
2

4. BASIC Search
3

5. Detailed Chemical Pages
4

6. Sources of Exposure to Chemicals
5

7. Identifiers to Support Searches
6

8. Link Access
7

9. NIST WebBook
https://webbook.nist.gov/chemistry/
8

10. MassBank of North America
https://mona.fiehnlab.ucdavis.edu
9

11. Batch
Searching
10

12. Aggregate data for a list of chemicals
11

13. Batch Search Names
12
Excel
Download

14. Add Other Data of Interest
13

15. Chemical Lists of
Interest…
14

16. Chemical Lists
15

17. PFAS lists of Chemicals
16

18. Batch Search in specific lists
17

19. “MS-ready”
Structures
18

20. 19

21. “MS-Ready Structures”
https://doi.org/10.1186/s13321-018-0299-2
20

22. MS-Ready Mappings
21

23. MS-Ready Mappings Set
22

24. Mass and Formula
Searching
23

25. Advanced Searches
Mass Search
24

26. Advanced Searches
Mass Search
25

27. MS-Ready Structures for
Formula Search
26

28. MS-Ready Structures
Batch Searches
27

29. MS-Ready Mappings
• EXACT Formula: C10H16N2O8: 3 Hits
28

30. MS-Ready Mappings
• Same Input Formula: C10H16N2O8
• MS Ready Formula Search: 125 Chemicals
29

31. 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
30

32. 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?
31

33. Batch Searching Formula/Mass
32

34. Searching batches using MS-Ready
Formula (or mass) searching
33

35. Additional
Mass-Spec
Functionality
34

36. Formula-Based Search
35

37. Select Chemicals of Interest
36

38. Prune to list of interest
37

39. Literature Searching
38

40. Literature Searching
39

41. Literature Searching
40

42. Work in
Progress
41

43. List Registration Activities
• Registering and curating numerous lists
– NIST library of chemicals
– United States Geological Survey chemicals in water
– Scientific Working Group for the Analysis of Seized Drugs
– Synthetic Cannabinoids
– Mycotoxins
42

44. Work in Progress
• CFM-ID
– Viewing and Downloading pre-predicted spectra
– Search spectra against the database
• Structure/substructure/similarity search
• Access to API and web services
43

45. 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
44

46. Search Expt. vs. Predicted Spectra

47. Search Expt. vs. Predicted Spectra

48. Spectral Viewer Comparison
47

49. Presented at this meeting
48

50. Example match
49

51. Predicted Data Already Public
Publication and Data Files
50
https://epa.figshare.com/articles/CFM-ID_Paper_Data/7776212/1

52. Prototype Development
51

53. Prototype Development
52

54. API services and Open Data
• Web Services https://actorws.epa.gov/actorws/
• Data sets also available for download..
53

55. Web Services
https://actorws.epa.gov/actorws/
• Data in UI, JSON and XML format
54

56. InChIKey to DTXCIDs
55
https://actorws.epa.gov/actorws/dsstox/v02/msready?identifier
=UVOFGKIRTCCNKG-UHFFFAOYSA-N

57. MassBank mapping to Dashboard
56

58. When data is
openly shared…
57

59. NORMAN Suspect List Exchange
https://www.norman-network.com/?q=node/236
58

60. Conclusion
• Dashboard access to data for ~875,000 chemicals
• MS-Ready data facilitates structure identification
• Related metadata facilitates candidate ranking
59
• Relationship mappings and
chemical lists of great utility
• Curation and mutual
sharing of chemical lists is
important (e.g. NORMAN)

61. Acknowledgements
• An enormous team of contributors
from NCCT, especially the IT
software development team
• Our curation team for their care
and focus on data quality
• Many public domain databases
and open data contributors
• Emma Schymanski, University of
Luxembourg for coordinating
curation of NORMAN lists
• Jerry Zweigenbaum and Andrew
McEachran, Agilent Inc., for
example spectra to test CFM-ID
matching

62. Contact
Antony Williams
NCCT, US EPA Office of Research and Development,
Williams.Antony@epa.gov
ORCID: https://orcid.org/0000-0002-2668-4821
61
https://doi.org/10.1186/s13321-017-0247-6