US-EPA Comptox Chemicals Dashboard to support mass spectrometry - - PowerPoint PPT Presentation

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US-EPA Comptox Chemicals Dashboard to support mass spectrometry - - PowerPoint PPT Presentation

Mar 29, 2024 148 likes •805 views

http://www. orcid.org/0000-0002-2668-4821 US-EPA Comptox Chemicals Dashboard to support mass spectrometry targeted and non-targeted analysis Antony Williams 1 , Alex Chao 2 , Tom Transue 3 , Tommy Cathey 3 , Elin Ulrich 4 and Jon Sobus 4 1)

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US-EPA Comptox Chemicals Dashboard to support mass spectrometry targeted and non-targeted analysis

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

August 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

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CompTox Chemicals Dashboard

https://comptox.epa.gov/dashboard

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875k Chemical Substances

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Detailed Chemical Pages

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Sources of Exposure to Chemicals

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Physicochemical properties and environmental fate and transport

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CompTox Chemicals Dashboard

  • Can provide access to toxicity, environmental

fate and transport and metabolism data

  • Individual chemicals can map to degradation

products and metabolites

  • Advanced searches support mass and formula

searches

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Link farm to public resources

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

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Toxicity Estimation Software Tool (TEST) Real Time Predictions

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Mass & Formula Searching

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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”

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

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MS-Ready Mappings

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MS-Ready Mappings Set

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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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Candidate ranking

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Data Source Ranking of “known unknowns”

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  • Mass and/or formula is for an

unknown chemical but contained within a reference database

  • Most likely candidate chemicals

have the most associated data sources, most associated lit. articles or both

C14H22N2O3 266.16304 Chemical Reference Database Sorted candidate structures

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Is a bigger database better?

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  • ChemSpider was 26 million chemicals then
  • Much BIGGER today
  • Is bigger better??
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Using Metadata for Ranking

  • Use available metadata to rank candidates

– Associated data sources

  • Associated lists in the underlying database
  • Associated data sources in PubChem
  • Specific types (e.g. water, surfactants, pesticides etc.)

– Number of associated literature articles (Pubmed) – Chemicals in the environment – the number of products/categories containing the chemical is a very important source of data

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Identification ranks for 1783 chemicals using multiple data streams

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DS: Data Sources PC: PubChem PM: PubMed STOFF: DB KEMI: DB

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Comparing Search Performance

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  • Dashboard content was 720k chemicals
  • Only 3% of ChemSpider size
  • What was the comparison in performance?
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SAME dataset for comparison

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How did performance compare?

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For the same 162 chemicals, Dashboard outperforms ChemSpider

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How did performance compare?

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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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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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Batch Searching Formula/Mass

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

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Related Searches to Support Mass Spectrometry

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Find me “related structures” Formula-Based Search

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Select Chemicals of Interest

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Find me “related structures” Based on Structure Similarity

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Find me “related structures” Based on Structure Similarity

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Find me “related structures” Structure Similarity – sort on mass

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Chemical lists

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Chemical Lists

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EPAHFR: Hydraulic Fracturing

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List of Opioids – Presence in Lists?

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Batch Search Names

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Excel Download

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Batch Search in specific lists

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API services and Open Data

  • Available API and web services
  • Open Data available for download

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Web Services https://actorws.epa.gov/actorws/

  • Dozens of web services to provide access

to data

  • Data in UI, JSON and XML format

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Example: InChIKey to DTXCIDs

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https://actorws.epa.gov/actorws/dsstox/v02/msready?identifier =UVOFGKIRTCCNKG-UHFFFAOYSA-N

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MassBank mapping to Dashboard

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Benefits of Open Data

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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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In Progress

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Work in Progress

  • Predicted Spectra for candidate ranking

– Viewing and Downloading pre-predicted spectra – Search spectra against the database

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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 >800,000

structures, to be accessible via Dashboard

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Search Expt. vs. Predicted Spectra

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  • Predictions generated and stored for >700,000 structures
  • Python code to score experimental vs predicted spectra
  • Cosine dot product match score calculation

August 26, 2019 Nontargeted screening of wastewater for water reuse using mass spectrometry Current Advances in Water Analysis 59

CFM-ID Predicted Library Available

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Prototype Development Structure/substructure search

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Conclusion

  • Dashboard access to data for ~875,000 chemicals
  • MS-Ready data facilitates structure identification
  • Related metadata facilitates candidate ranking

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  • Relationship mappings and

chemical lists of great utility

  • Dashboard and contents

are one part of the solution

  • New API and Web Services

are in development

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Acknowledgements

  • NCCT IT development team
  • Tommy Cathey, ACTOR Web Services
  • Nancy Baker, Abstract Sifter
  • Todd Martin & Valery Tkachenko,

WebTEST

  • Kathie Dionisio & Kristin Isaacs, CPDat
  • Thanks to Emma Schymanski, University
  • f Luxembourg, for coordinating all efforts

with the NORMAN Network for curation of lists on the Suspect Exchange

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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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