The CompTox Chemistry Dashboard v3.0 – New …...The CompTox Chemistry Dashboard v3.0 – New...

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)Williams.Antony@epa.govORCID: https://orcid.org/0000-0002-2668-4821

81