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Structure Identification Using High Resolution Mass Spectrometry Data and the EPA CompTox Dashboard
The document discusses the development of a dashboard by the EPA's National Center for Computational Toxicology to identify chemical exposures that may disrupt biological processes. This dashboard contains over 720,000 chemical records and supports non-targeted analysis by providing detailed chemical data, curation, and searching capabilities. The presentation emphasizes the importance of data quality and future research directions for improving chemical identification and analysis.
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Structure Identification Using High Resolution Mass Spectrometry Data and the EPA CompTox Dashboard
- 1. Structure Identification UsingHigh Resolution Mass Spectrometry Data and the EPA CompTox Dashboard Antony J. Williams, Andrew McEachran, Chris Grulke, Elin Ulrich, Jennifer Smith, Jeff Edwards and Jon Sobus, November 2-3, 2016 SWEMSA 2016 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. Who is NCCT? •National Center for Computational Toxicology – part of EPA’s Office of Research and Development • Research driven by EPA’s Chemical Safety for Sustainability Research Program – Develop new approaches to evaluate the safety of chemicals – Integrate advances in biology, biotechnology, chemistry, exposure science and computer science • Goal - To identify chemical exposures that may disrupt biological processes and cause adverse outcomes. 1
- 3. Our Dashboard Applications •Some of our Web-based Applications 2
- 4. Introducing Our LatestDashboard https://comptox.epa.gov 3 • >720,000 chemicals • >14 years assembling data
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- 7. ToxCast Bioassay ScreeningData Useful Meta Data 6
- 8. Functional Use andComposition VERY Useful Meta Data 7
- 9. Dashboard: External Linksto Analytical Methods and Data 8
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- 13. Previous Work withSuspect-Screening ONE ASPECT of the dashboard is to support Non-targeted Analysis
- 14. Rank-Ordering of “Known-Unknowns” usingChemSpider 13
- 15. Some history… • 2007A Hobby Project 14
- 16. Some history… • 2007A Hobby Project • 2009 ChemSpider Acquired 15
- 17. Some history… • 2007A Hobby Project • 2009 ChemSpider Acquired • May 2015 Joined EPA – what we are showing is very new 16
- 18.
- 19. Monoisotopic Mass Search 18 Found344 results for '215.096 ± 0.005 amu'
- 20.
- 21. Download as SDFfile 20
- 22. Formula Search 21 Found 8results for 'C8H14ClN5'
- 23. Does the DashboardAdd Value? 22 721k structures
- 24. Does the DashboardAdd Value? • Remember: – Focus on high quality data and curation – Data sources include EPA data sources and a focus on environmental chemistry • No “dilution” by chemical vendors 23
- 25.
- 26. Bisphenol A asan example ChemSpider: 1564 Structures 25
- 27. Bisphenol A asan example Dashboard: 215 Structures 26
- 28. ChemSpider 6926 Results!!! 27 Tacedinaline MethylRed C.I Disperse Yellow 3
- 29. Using Meta-Data toSort Candidates 28 Anti-cancer Drug Microbiological Indicator Dye Textile/Product Dye
- 30. Same top hits– different ranking 90 hits only versus 6926 hits 29 18 17 4Tacedinaline Methyl Red C.I Disperse Yellow 3
- 31. Chemical Identification Dashboard vsChemSpider Sorted by number of references (ChemSpider) or data sources (Dashboard) Monoisotopic Mass (+/- 0.005 amu) Search Position of compound sorted Source of List # of Compounds Search Tool Mean Position Median Position #1 #2 #3 #4 #5+ McEachran et al Wastewater 34 ChemSpider 1.8 1 28 5 0 0 1 Dashboard 1.3 1 31 2 0 0 1 Misc. NTA Compounds 13 ChemSpider 2 1 7 5 0 0 1 Dashboard 1.7 1 10 2 0 0 1 Bade et al (2016) 19 ChemSpider 2.1 1 11 2 5 0 1 Dashboard 1.6 1 12 3 3 1 0 Rager et al (2016) 24 ChemSpider 2.25 1 15 2 1 2 4 Dashboard 1.08 1 22 2 0 0 0
- 32. Dashboard vs ChemSpider RankingSummary Mass-based Searching Formula Based Searching Dashboard ChemSpider Dashboard ChemSpider Cumulative Average Position 1.3 2.2 1.2 1.4 % in #1 Position 85% 70% 88% 80% • Selected peer-reviewed publications • 162 total individual chemicals in search
- 33. The Confusion ofChemicals… Valid CAS-substance? Monoisotopic Mass Formula Parent structure (no stereo, desalted) Resolve CAS-structure mappings for accurate data mapping Collapse sphere to collect all data at parent structure-formula level DSSTox_v2 Database & Cheminformatics Layer many:1 • Deleted CAS • Invalid CAS • Salt forms • Complex forms • Hydrate forms • Approx mappings to mixtures • Approx mappings to ill- defined substances • Stereoisomers • Unresolved tautomers CAS2 ? CAS5 ? CAS3 ? CAS1 ? CAS4 ?NOCAS? Data1 Data2 Data3 Data4 Data5 Data6 Data7 Data8 Data9 CAS-Structure “Sphere of Confusion”
- 34. DSSTox List CurationTool Conflicts binned to facilitate curation
- 35. Helping to CurateData • We are helping to Curate Data (prior to linking from our dashboard) • Our discussions with Thomas and team – “We all agree it is hard!” 34
- 36. Helping to CurateData • We are helping to Curate Data (prior to linking from our dashboard) • Our discussions with Thomas and team – “We all agree it is hard!” • Approx. 80% of STOFF-IDENT is done… 35
- 37. Helping to CurateData • We are helping to Curate Data (prior to linking from our dashboard) • Our discussions with Thomas and team – “We all agree it is hard!” • Approx. 80% of STOFF-IDENT is done… 36
- 38. Curating on CASRNsis DIFFICULT • 36861-47-9 : SI00004220 • 38102-62-4 : SI00008957 37
- 39. Collisions in CASNumbers 38
- 40. Active and DeletedCASRN 39
- 41. But there areMANY CASRNs! • http://web.stanford.edu/group/swain/cinf/c asreg/snumber.html 40
- 42. How Bad CanIt Get?? 41
- 43. How Bad CanIt Get? This one is 316 Deleted CASRN 42
- 44. Helping to CurateData • We are missing 159 CAS Numbers listed in STOFF-IDENT • Work on curating and mapping MASSBANK is underway. Much bigger!! Way more work
- 45. Our OPEN Datais available… • Various types of data at FTP download site: ftp://newftp.epa.gov/COMPTOX/Sustainable_Chemistry_ Data/Chemistry_Dashboard 44
- 46. Data Availability • Thedata are now available in METLIN • Available in MetFrag (alpha) and in testing. 45
- 47. Coming December 2016 BatchSearching Names/CASRNs • What are these chemicals? 46
- 48. Coming December 2016 BatchSearching… 47
- 49. Coming December 2016 Downloadto Excel 48
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- 51. Metadata included forRanking 50
- 52. Need for “MS-ReadyStructures” 51
- 53. “QSAR-Ready Structures” • Forthe purpose of building QSAR Models we already “standardize” structures – Desalt/Neutralize – Desolvate – Remove stereochemistry • Some minor tweaks gets us “MS-ready Structures”. ALREADY in our database. 52
- 54. “QSAR-Ready Structures” • Massand Formula-based searches will be based on MS-ready structures but connected to the original chemical (with name, CAS, rank ordering) • MS-ready structures and substance mappings will be available as Open Data 53
- 55. Rank-Ordering – incl.PubChem 54
- 56. Future Work • Continueto research rank-ordering approaches • Working on “retention time prediction” • Search for adducts (+Na, +K, +NH4) and handle decarboxylation, loss of water etc • Additional links to methods – CDC NIOSH • Expand link outs to Mass Spec databases – Thermo’s mzCloud, Massbank, etc. • Predicting metabolites and degradants • Optimize web services for the community 55
- 57. Conclusions • Only 1aspect of the dashboard is focused on MS – to support the EPA NTA Trial underway • We should work on data curation TOGETHER! • We are “part” of the solution. Our Open Data and Open Services should be of value. 56
- 58. Acknowledgements EPA NCCT Chris Grulke JeffEdwards Ann Richard Jennifer Smith Andrew McEachran* EPA NERL Jon Sobus Seth Newton Elin Ulrich * = ORISE Participant
Editor's Notes
- #32 For example- Rager was actually 33 confirmed; Bade was 25