Web-based access to experimental and predicted data for environmental fate, transport and toxicity data
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This document describes the CompTox Chemistry Dashboard, a publicly accessible website developed by the EPA's National Center for Computational Toxicology that provides data on over 762,000 chemicals. The dashboard contains experimental and predicted physicochemical property data, environmental fate and transport data, toxicity data, and models. It allows users to search, view detailed chemical pages, access prediction reports, perform batch searches, and will integrate additional predicted properties and data in the future. The goal is to provide a central resource for computational toxicology data to support chemical safety assessments.
Web-based access to experimental and predicted data for environmental fate, transport and toxicity data
- 1. Web-based access to experimental and predicted data for environmental fate, transport and toxicity data Antony Williams1, Todd Martin2, Valery Tkachenko3, Kamel Mansouri4 and Chris Grulke1 1) National Center for Computational Toxicology, U.S. Environmental Protection Agency, RTP, NC 2) National Risk Management Research Laboratory, U.S. Environmental Protection Agency, Cincinnati, OH 3) Science Data Software, LLC, Rockville, MD 20850 4) Integrated Laboratory Systems, Research Triangle Park, North Carolina, United States August 2018 ACS Fall Meeting, Boston 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. What is the EPA-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. • Prediction models and predicted data are some of our major outputs
- 3. The CompTox Chemistry Dashboard • A publicly accessible website delivering access: – ~762,000 chemicals with related property data – Searchable by chemical, product use, gene and assay – Experimental and predicted physicochemical property data, environmental fate and transport, and tox endpoints – “Bioactivity data” for the ToxCast/Tox21 project – plus derived models – Generalized Read-Across (GenRA) module – “Batch searching” of predicted data for thousands of chemicals 2
- 9. Property Initial file Curated Data Curated QSAR ready AOP 818 818 745 BCF 685 618 608 BioHC 175 151 150 Biowin 1265 1196 1171 BP 5890 5591 5436 HL 1829 1758 1711 KM 631 548 541 KOA 308 277 270 LogP 15809 14544 14041 MP 10051 9120 8656 PC 788 750 735 VP 3037 2840 2716 WF 5764 5076 4836 WS 2348 2046 2010 Curation to QSAR Ready Files
- 10. Detailed OPERA Prediction Reports 9
- 11. Prediction Details and QMRF Report
- 13. Physical properties in TEST Endpoint Definition Viscosity A measure of the resistance of a fluid to flow (cP) defined as the proportionality constant between shear rate and shear stress Surface tension A property of the surface of a liquid (dyn/cm) that allows it to resist an external force Water solubility The amount of a chemical (mg/L) that will dissolve in liquid water to form a homogeneous solution 12
- 14. Other Dashboard Predictions • Predictions and models expand outside of simply physicochemical and environmental fate and transport • Examples – Read-across for Toxicity Endpoints – Quantitative Structure–Use Relationship (QSUR) models – High-Throughput ToxicoKinetics (HTTK) – Models based on high throughput bioactivity data 13
- 15. Definitions: Read-Across • Known information on the property of a substance (source) is used to make a prediction of the same property for another substance (target) that is considered “similar” 14 Source chemical Target chemical Property Reliable data Missing data Predicted to be harmfulKnown to be harmful Acute fish toxicity?
- 16. GenRA (Generalised Read-Across) • Predicting toxicity as a similarity-weighted activity of nearest neighbors based on chemistry and/or bioactivity descriptors • Goal: to systematically evaluate read-across performance and uncertainty using available data • The approach enabled a performance baseline for read- across predictions of toxicity effects within specific study outcomes to be established 15
- 18. GenRA (Generalised Read-Across) Structure Similarity
- 19. GenRA (Generalised Read-Across) Data gap analysis
- 20. GenRA (Generalised Read-Across) 19 Run GenRA Target Source analogues
- 21. Batch Searching • Singleton searches are useful but we work with thousands of chemicals! • Typical questions – What are the SMILES strings for a list of 1000 chemicals? – Do any of this list of chemicals have XXX type of data? – What are the predicted logP values for a list of chemicals? – Can I get lists of predicted properties in Excel files? In SDF files? 20
- 24. Excel Output 23
- 28. API in development Prototype services available 27 https://comptox.epa.gov/dashboard/web-test/WS?smiles=CCO&method=hc
- 29. Our support for FAIR Data 28
- 31. Work in Progress • Present work in development – Development of OPERA model web services – Development of pKa and logD prediction models – Display of TEST Toxicity endpoints predicted data – Analytical Data support • Spectral searching against predicted Mass Spectra 30
- 32. pKa Prediction Model • pKa prediction models based on Open Data Set of 8000 chemicals – acidic, basic and amphoteric chemicals 31
- 33. Toxicity Endpoints in TEST Endpoint Definition 96 hour fathead minnow LC50 Concentration in mg/L that causes 50% of fathead minnow to die after 96 hours 48 hour Daphnia magna LC50 Concentration in mg/L that causes 50% of Daphnia magna to die after 48 hours 48 hour T. pyriformis IGC50 Concentration in mg/L that causes 50% growth inhibition to T. pyriformis after 48 hours Oral rat LD50 Amount of chemical in mg/kg body weight that causes 50% of rats to die after oral ingestion 32 Developmental toxicity Whether or not a chemical causes developmental toxicity effects to humans or animals Ames mutagenicity A compound is positive for mutagenicity if it induces revertant colony growth in any strain of Salmonella typhimurium
- 34. Property Data is one aspect.. • CompTox Dashboard has many applications – A central hub for lists of chemicals – A “publication” environment for our published data – to enable data transparency – The basis of other applications in development – RapidTox for rapid risk assessment using the underpinning data – Non-targeted analysis support for mass spectrometry 33
- 35. 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 34
- 36. Search Expt. vs. Predicted Spectra
- 37. Library Fragmentation Spectra (20eV) Observed Fragmentation Spectra (20eV) Match Score Predicted Mass Spectra
- 38. Conclusion • The CompTox Dashboard provides access to data for ~762,000 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 delivered • Real time prediction models expanding in number • Web services available for some physchem and toxicity endpoints 37
- 39. 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 38