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Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA

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Researchers at the EPA’s National Center for Computational Toxicology integrate advances in biology, chemistry, and computer science to examine the toxicity of chemicals and help prioritize chemicals for further research based on potential human health risks. The intention of this research program is to quickly evaluate thousands of chemicals for potential risk but with much reduced cost relative to historical approaches. This work involves computational and data driven approaches including high-throughput screening, modeling, text-mining and the integration of chemistry, exposure and biological data. We have developed a number of databases and applications that are delivering on the vision of developing a deeper understanding of chemicals and their effects on exposure and biological processes that are supporting a large community of scientists in their research efforts. This presentation will provide an overview of our work to bring together diverse large scale data from the chemical and biological domains, our approaches to integrate and disseminate these data, and the delivery of models supporting computational toxicology. This abstract does not reflect U.S. EPA policy.

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Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA

  1. 1. Delivering The Benefits of Chemical-Biological Integration in Computational Toxicology at the EPA Antony Williams†, Kamel Mansouri, Chris Grulke, Keith Houck, Ann Richard, Jeff Edwards, Matt Martin, John Wambaugh, Grace Patlewicz, Imran Shah, Richard Judson, Kevin Crofton and Russell Thomas National Center for Computational Toxicology U.S. Environmental Protection Agency, RTP, NC August 21-25, 2016 ACS Fall Meeting, Philadelphia, PA This work was reviewed by the U.S. EPA and approved for presentation but does not necessarily reflect official Agency policy. http://www.orcid.org/0000-0002-2668-4821
  2. 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. 3. Scientific leadership https://www.epa.gov/chemical-research/toxicity-forecasting 2
  4. 4. Our Bioassay Data https://www.epa.gov/chemical-research/downloadable-computational-toxicology-data 3
  5. 5. Our Exposure Predictions 4
  6. 6. Our Dashboard Applications 5
  7. 7. ACToR https://actor.epa.gov/actor/ • Aggregated Computational Toxicology Resource • A warehouse of publicly available chemical toxicity data • Aggregates data from >1000 public sources on >500,000 chemicals 6
  8. 8. ACToR https://actor.epa.gov/actor/ 7
  9. 9. ACToR https://actor.epa.gov/actor/ 8
  10. 10. CPCat https://actor.epa.gov/actor/ 9 Chemical and Product Categories is a database containing information mapping >43,000 chemicals to a set of terms categorizing their usage or function.
  11. 11. Toxcast Dashboard https://actor.epa.gov/dashboard/ • To interrogate chemical screening data from ToxCast and the Tox21 collaboration 10
  12. 12. Our Developing Architecture
  13. 13. Our Latest Dashboard https://comptox.epa.gov • Providing access to our “curated chemistry” • Database of chemicals, mapped to identifiers, and tens of thousands of experimental physchem properties • Predictive models and calculation details • An integration hub for NCCT applications • A link farm across 10s of EPA and Public websites 12
  14. 14. Our Latest Dashboard https://comptox.epa.gov 13 >720,000 chemicals >14 years of assembled data An Integration Hub
  15. 15. 15 years of Curated Data 14
  16. 16. Bisphenol A (Accessing DSSTox Data) 15
  17. 17. Physicochemical Properties 16
  18. 18. Data Downloads 17
  19. 19. Data Download: Excel 18
  20. 20. Predictions for >720,000 Chemicals • NCCT_Model predictions built on curated data • All chemicals in CompTox Dashboard pushed through all predictive models • Predicted data made available, with detailed MODEL REPORTS 19
  21. 21. Predicted Data 20 Calculation Result for a chemical Model Performance with full QMRF Nearest Neighbors from Training Set
  22. 22. Prediction Details and QMRF Report 21
  23. 23. External Links 22
  24. 24. Synonyms 23 Over a million synonyms, different levels of curation and validation
  25. 25. Functional Use and Composition (Integrating CPCat Data) 24
  26. 26. Bioassay Screening Data (Integrating ToxCast Data) 25
  27. 27. Bioassay Screening Data (Integrating ToxCast Data) 26
  28. 28. Exposure Data – NHANES and ExpoCast Predictions 27 Environ. Sci. Technol., 2013, 47 (15), pp 8479–8488
  29. 29. PubChem integration 28
  30. 30. Work in Progress: Environmental Fate, Transport and Toxicity 29
  31. 31. Work in Progress: Analog Identification and Similarity Search
  32. 32. Conclusions • NCCT has been delivering data, algorithms, models and software tools for a decade • A new flexible architecture to support multiple both internal and external apps • First iteration of CompTox dashboard supports chemistry based searches • Future concept… 31
  33. 33. Future Search Possibilities 32 Chemicals Products Targets Assays Literature
  34. 34. Acknowledgements Kamel Mansouri Chris Grulke Keith Houck Ann Richard Jeff Edwards Matt Martin John Wambaugh Grace Patlewicz Imran Shah Richard Judson Kevin Crofton Russell Thomas

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