the comptox chemistry dashboard v3.0 – new …...the comptox chemistry dashboard v3.0 – new...
TRANSCRIPT
The CompTox Chemistry Dashboard v3.0 – New Searches and Support for
Bioactivity Data
Antony WilliamsNational Center for Computational Toxicology, U.S. Environmental Protection Agency, RTP, NC
September 27th 2018Communities of Practice
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
Outline – what’s new in v3.0?
• Welcome the CompTox Portal• New name for the dashboard• User interface overhaul – easier navigation• New search capabilities• Enhanced support for bioactivity data• New data and new lists added• Work in progress
1
The CompTox Portalhttps://comptox.epa.gov/
2
Watch for our newshttps://comptox.epa.gov/dashboard/news_info
3
Release Noteshttps://comptox.epa.gov/dashboard/comptox_release_notes.pdf
• A detailed list of new functionality and fixes
4
Staying up with the Dashboardhttps://comptox.epa.gov/dashboard/news_info
5
CompTox Chemicals Dashboardhttps://comptox.epa.gov/dashboard
6
CompTox DashboardChemicals
7
CompTox DashboardProducts and Use Categories
8
CompTox DashboardAssays and Genes
9
Detailed Chemical PagesNew User Interface Design
10
Access to Chemical Hazard Data
11
Hazard Data from “ToxVal_DB”Lots of new data added - ECOTOX
• ToxVal Database contains following data:– 30,050 chemicals– 772,721 toxicity values– 29 sources of data– 21,507 sub-sources– 4585 journals cited– 69,833 literature citations
12
Sources of Exposure to Chemicals
13
What chemicals in what product and use categories?
14
What chemicals in what product and use categories?
15
Remember home page searchesSearching for “eye”…
16
In Vitro Bioassay Screening ToxCast and Tox21
17
In Vitro Bioassay Screening ToxCast and Tox21
18
Earlier Dashboard Applications
19
In Vitro Bioassay Screening ToxCast and Tox21
20
Assay Modal Details
21
In Vitro Bioassay Screening ToxCast and Tox21
22
In Vitro Bioassay Screening Multi-chart Display
23
In Vitro Bioassay Screening ToxCast and Tox21
24
Assay Modal Details
25
List of Chemicals for an Assay
26
Choose Display Details
27
Tile/Table ModeMore flexibility in table display
28
In Vitro Bioassay Screening ToxCast and Tox21
29
Access to Analytical QC Data
30
Access to Analytical QC Data
31
GenRA (Generalised Read-Across)
32
GenRA (Generalised Read-Across)
Structure Similarity
Select and Review Analogs
GenRA (Generalised Read-Across)
Review Available Data Fingerprint indicating available dataSelect and Review Analogs
GenRA (Generalised Read-Across)
35
Run GenRATarget
Source analogues
Red : Toxicity effects. Blue: No Toxicity effectsGrey : Absence of data
Related Substancese.g. Transformation Products
36
UVCB Chemicals
37
Related Substances for Markush
38
Identifiers to Support Searches
39
Literature Searches and Links
40
Abstract Sifter – PubMed Integration searching >28 million abstracts
41
External Links to ~80 websitesGrowing list of out links -
42
Mass and Formula SearchesSupporting Mass Spectrometry
43
Advanced SearchesMass Based Search
44
Advanced SearchesMass Based Search
45
MS-Ready Structureshttps://jcheminf.biomedcentral.com/articles/10.1186/s13321-018-0299-2
46
MS-Ready Structures
47
MS-Ready Mappings
48
MS-Ready Mappings Set
49
Batch Searching
• Singleton searches are useful but we work with thousands of chemicals!
• Typical questions– What chemicals can I get for 5000 CAS Numbers?– Can I get predicted properties for 1000 chemicals?– 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?
50
Batch Searching
51
Batch Searching
52
Excel Output
53
How can be curate our data?
• Crowdsourcing is well proven nowadays• Comments can be added at a record level
• Submitted comments are reviewed by administrators and responded to
54
Public Crowdsourced Commentshttps://comptox.epa.gov/dashboard/comments/public_index
55
Comments to date
• The majority of comments to date:– Structure and names/CASRN do not match– Add additional synonyms– Request to add specific property data– Structure layout/depiction needs improving
56
Crowdsourcing CommentsSingle Cell Commenting added
• Highlight an alphanumeric text string
57
Crowdsourcing Comments
58
Lists of Lists
• Lists of chemicals – ca. 100 lists• List of ToxCast/Tox21 assays
59
11 PFAS Listshttp://comptox-prod.epa.gov/dashboard/chemical_lists
60
The OECD List of PFAShttp://www.oecd.org/chemicalsafety/portal-perfluorinated-chemicals/
61
The OECD List of PFAShttp://www.oecd.org/chemicalsafety/portal-perfluorinated-chemicals/
62
Want data for a list???
• Simply send to Batch and choose data…
63
List of Assays
64
Select an Assay to NavigateTile View
65
Select an Assay to NavigateTable View
66
Real-Time Predictions
67
Real-Time Predictions
68
Work in Progress
• CFM-ID– Viewing and Downloading pre-predicted spectra– Search spectra against the database
• Structure/substructure/similarity search• pKa prediction
69
Predicted Mass Spectrahttp://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
70
Library Fragmentation Spectra (20eV)
Observed Fragmentation Spectra (20eV)
Match Score
Predicted Mass Spectra
Search Expt. vs. Predicted Spectra
Prototype Development
73
Prototype Development
74
pKa Prediction Model
• pKa prediction models based on Open Data Set of 8000 chemicals – acidic, basic and amphoteric chemicals
75
NCCT “InvitroDB_v3”
• The last public release of ToxCast data (invitroDB_v2) was in 3rd Quarter of 2015
• The next release invitroDB_v3 is Fall 2018• Data includes new assays, new chemicals,
new pipelining, results of data curation• Data will also release via CompTox Dashboard• Data will be available at https://www.epa.gov/chemical-
research/exploring-toxcast-data-downloadable-data
76
Downloadable Data Being Updated
77
Conclusion
• The CompTox Chemistry Dashboard provides access to data for ~765,000 chemicals
• An expanding list of data types and sources has been integrated
• New searches based on Product Use and Categories and Assay and Gene
• The chemical lists of interest grows with each release
• Next release scheduled for Fall 2018 with InvitroDB_v3 data – more chemicals, more assays
78
How is it built?https://jcheminf.springeropen.com/articles/10.1186/s13321-017-0247-6
79
Acknowledgments
• Our NCCT CompTox Chemical Dashboard Development and IT Team
• The NCCT Team of Scientists• NERL scientists - Mass Spectrometry• Kamel Mansouri – OPERA models• Todd Martin – TEST predictions
80
Contact
Antony WilliamsUS EPA Office of Research and DevelopmentNational Center for Computational Toxicology (NCCT)[email protected]: https://orcid.org/0000-0002-2668-4821
81