Applications of the US EPAs CompTox Chemicals Dashboard to support - - PowerPoint PPT Presentation

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Applications of the US EPAs CompTox Chemicals Dashboard to support - - PowerPoint PPT Presentation

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http://www. orcid.org/0000-0002-2668-4821 Applications of the US EPAs CompTox Chemicals Dashboard to support structure identification and chemical forensics using mass spectrometry Antony Williams 1 and Andrew D. McEachran 2,3 1) National

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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 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

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  • 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

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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 – 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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CompTox Chemicals Dashboard

https://comptox.epa.gov/dashboard

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Search Chemicals

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Detailed Chemical Pages

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Access to Chemical Hazard Data

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In Vitro Bioassay Screening

ToxCast and Tox21

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Sources of Exposure to Chemicals

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MS-Ready Mappings

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Specific Data-Mappings “MS-Ready Structures”

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MS-Ready Publication

https://doi.org/10.1186/s13321-018-0299-2

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MS-Ready Mappings Set

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Mass and Formula Searches Supporting Mass Spectrometry

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Advanced Searches Mass Based Search

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Advanced Searches Mass Based Search

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Advanced Searches Mass Based Search

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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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Batch Searches

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Batch Searches

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Batch Searching Formula/Mass

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Excel Output

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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

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MS-Ready Structures Underpin Analysis

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MS-Ready Structures Underpin Analysis

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The Dashboard to Support MS-Analysis

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MS-Ready Structures Underpin Analysis

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MS-Ready Mappings

  • Input 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 93 Chemicals – 7 in EPAHFR

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Complexity to Simplicity 93 Chemicals – 7 in the list

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Searching batches Formula (or mass) searching

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Downloadable Data

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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
  • Generation of MS-ready structures:

– Upload file, download results – Service based generation

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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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Library Fragmentation Spectra (20eV) Observed Fragmentation Spectra (20eV) Match Score

Predicted Mass Spectra

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Search Expt. vs. Predicted Spectra

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Prototype Development

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Prototype Development

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Conclusion

  • The CompTox Chemicals Dashboard provides

access to data for ~875,000 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

  • 2 years development as a CompTox Integration Hub

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Acknowledgements

  • 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

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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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