The Royal Society of Chemistry (RSC) is a major participant in providing access to chemistry related data via the web. As an internationally renowned society for the chemical sciences, a scientific publisher and the host of the ChemSpider database for the community, RSC continues to make dramatic strides in providing online access to data. ChemSpider provides access to over 30 million chemicals sourced from over 500 data suppliers and linked out to related information on the web. The platform is a crowdsourcing environment whereby members of the community can participate in validating and expanding the content of the database. With a set of application programming interfaces ChemSpider is used by various organizations and projects to serve up data for various purposes. These include structure identification for mass spectrometry instrument vendors, RSC databases such as the Marinlit natural products database and a European grant-based project from the Innovative Medicines Initiative fund. This presentation will provide an overview of various cheminformatics activities and projects that RSC is involved with to serve the medicinal chemistry community. This will include the Open PHACTS semantic web project, the PharmaSea project to identify new pharmaceutical leads from the ocean and the UK National Compound Collection to identify new lead compounds contained within PhD theses.

1. Serving the Medicinal Chemistry
Community with RSC
Cheminformatics Platforms
Antony Williams
Brazilian Medicinal Chemistry Conference,
November 11th 2014

2. www.slideshare.net/AntonyWilliams

3. Chemistry for the Community
• The Royal Society of Chemistry as a provider
of chemistry for the community:
• As a charity
• As a scientific publisher
• As a host of commercial databases
• As a partner in grant-based projects
• As the host of ChemSpider
• New: the RSC Data Repository for Chemistry

4. Overwhelmed with data…

5. So much online data…

6. Organizations releasing data

7. Funders encourage openness

8. We model data – then lose it
• What if we could share models and the
underlying data via a central repository?
• This is MOSTLY not a technology issue!!!

9. Pharma Companies Repeat Work
Pre-competitive Informatics:
Pharma are all accessing, processing, storing & re-processing external research data
Literature
Genbank
PubChem
Patents
Databases
Downloads
Data Integration Data Analysis
Firewalled Databases
Repeat at
each
company
x

10. Publications lock up data

11. When I finish this article…

12. The data will be locked up..

13. But what if we could navigate?
What’s the
structure?
Are they in
our file?
What’s
similar?
What’s the
Pharmacology target?
data?
Known
Pathways?
Working On
Connections Now?
to disease?
Expressed in
right cell type?
Competitors?
IP?

15. • ~30 million chemicals and growing
• Data sourced from >500 different sources
• Crowd sourced curation and annotation
• Ongoing deposition of data from our
journals and our collaborators
• Structure centric hub for web-searching
• It’s a really big dictionary!!!

16. ChemSpider

17. ChemSpider

18. Experimental/Predicted Properties

19. Literature references

20. Google Books

21. Patents references

22. RSC Databases

23. Vendors and data sources

24. With structures and names…

25. Name Searching

26. Standards for Integration

27. Structure Searching

28. What did we learn???
• Data Quality is an enormous challenge
• Crowd sourced annotation can help!

29. Crowdsourced Enhancement
• The community can clean and enhance the
database by providing Feedback and direct
curation
• Tens of thousands of edits made

30. But Software Can Help
• SRS as guidance for standardization rules

31. http://cvsp.chemspider.com

32. ChemSpider is a building block

33. …for grant-based services
• Use ChemSpider data slices and API/Web
services to support grant-based projects
• Multiple European consortium-based grants
• PharmaSea (FP7 funded)
• Open PHACTS (IMI funded)
• Support Open Drug Discovery projects

35. Over half of all drugs introduced between
1940 and 2006 were of natural origin or
inspired by natural compounds

37. http://www.pharma-sea.eu/

38. PharmaSea

39. ..as a dereplication platform

40. http://www.openphacts.org/

41. • 3-year Innovative Medicines Initiative project
• Integrating chemistry and biology data using
semantic web technologies
• Open code, open data, open standards
• Academics, Pharma Companies, Publishers…

42. The Open PHACTS community ecosystem

43. Open PHACTS http://ops.rsc.org

44. Chemistry Searching…

45. But what about Biology???

46. http://explorer.openphacts.org

47. Open PHACTS Explorer

48. Pharmacology by Compound

49. Compounds and enzymes

50. Compounds and enzymes

51. Pharmacology by Target

53. Facilitated by ChemSpider RDF

54. Open Sourcing Data and Code
• Open PHACTS data licensed as Open Data
– approx. 2 Million chemicals
• Open Source code to release to community
(from Open PHACTS github site)
• Chemical Registration Service
• Chemical Validation and Standardization Platform

55. ChemSpider as a “dictionary”
• Systematic name(s)
• Trivial Name(s)
• SMILES
• InChI Strings
• InChIKeys
• Database IDs
• Registry Number

56. Valium on ChemSpider
With strong dictionaries
connections can be made…

57. Semantic Mark-up of Articles

58. Linking Names to Structures

59. …and providing more links…
MedChemComm

60. Mark-up of MedChemComm

61. Mark-up of MedChemComm

62. Mark-up of MedChemComm

63. Links out from MedChemComm

64. Links out from MedChemComm

65. What about old publications?
• We would LOVE to bring data out of our archive
• Find chemical names and generate structures
• Find chemical images and generate structures
• Find reactions – and make a database!
• Find data (MP, BP, LogP) and host. Build models!
• Find figures and database them
• Find spectra (and link to structures)
• Validate the data algorithmically

66. RSC Archive – since 1841

67. SO MANY reactions!

68. Text Mining
The N-(β-hydroxyethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-
thiadiazol-5-yl)urea prepared in Example 6 , thionyl chloride ( 5
ml ) and benzene ( 50 ml ) were charged into a glass reaction
vessel equipped with a mechanical stirrer , thermometer and
reflux condenser .
The reaction mixture was heated at reflux with stirring , for a
period of about one-half hour .
After this time the benzene and unreacted thionyl chloride
were stripped from the reaction mixture under reduced
pressure to yield the desired product N-(β-chloroethyl)-N-methyl-
N'-(2-trifluoromethyl-1,3,4-thiaidazol-5-yl)urea as a solid
residue

69. Text Mining
The N-(β-hydroxyethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-
thiadiazol-5-yl)urea prepared in Example 6 , thionyl chloride ( 5
ml ) and benzene ( 50 ml ) were charged into a glass reaction
vessel equipped with a mechanical stirrer , thermometer and
reflux condenser .
The reaction mixture was heated at reflux with stirring , for a
period of about one-half hour .
After this time the benzene and unreacted thionyl chloride
were stripped from the reaction mixture under reduced
pressure to yield the desired product N-(β-chloroethyl)-N-methyl-
N'-(2-trifluoromethyl-1,3,4-thiaidazol-5-yl)urea as a solid
residue

70. But names = structures
• Systematic names can be generated FROM
chemical structures algorithmically

71. ..and Context Gives Reactions
The N-(β-hydroxyethyl)-N-methyl-N'-(2-trifluoromethyl-1,3,4-
thiadiazol-5-yl)urea prepared in Example 6 , thionyl chloride ( 5
ml ) and benzene ( 50 ml ) were charged into a glass reaction
vessel equipped with a mechanical stirrer , thermometer and
reflux condenser .
The reaction mixture was heated at reflux with stirring , for a
period of about one-half hour .
After this time the benzene and unreacted thionyl chloride
were stripped from the reaction mixture under reduced
pressure to yield the desired product N-(β-chloroethyl)-N-methyl-
N'-(2-trifluoromethyl-1,3,4-thiaidazol-5-yl)urea as a solid
residue

72. ChemSpider Reactions

73. Text spectra?
• 13C NMR (CDCl3, 100 MHz): δ = 14.12 (CH3),
30.11 (CH, benzylic methane), 30.77 (CH,
benzylic methane), 66.12 (CH2), 68.49 (CH2),
117.72, 118.19, 120.29, 122.67, 123.37,
125.69, 125.84, 129.03, 130.00, 130.53
(ArCH), 99.42, 123.60, 134.69, 139.23,
147.21, 147.61, 149.41, 152.62, 154.88 (ArC)

74. 1H NMR (CDCl3, 400 MHz):
δ = 2.57 (m, 4H, Me, C(5a)H), 4.24 (d, 1H, J = 4.8 Hz,
C(11b)H), 4.35 (t, 1H, Jb = 10.8 Hz, C(6)H), 4.47 (m, 2H,
C(5)H), 4.57 (dd, 1H, J = 2.8 Hz, C(6)H), 6.95 (d, 1H, J =
8.4 Hz, ArH), 7.18–7.94 (m, 11H, ArH)

75. Turn “Figures” Into Data
FIGURE
EXTRACTED

76. Models published from data

77. Text-mining Data to compare
Presently extracting
property data from
Google Patents as test

78. National Compound Collection
• Unlock chemistry data in PhD theses
• Discover novel molecules for biosciences
• Working together with industry and the
academic community
• Build the data into RSC online platforms
• Perform virtual screening/modeling and access
physical samples to screen

79. We should make sure
thesis data are available
in consumable formats –
compounds, reactions,
analytical data etc.

80. What are we building?
• We are building the “RSC Data Repository”
• Containers for compounds, reactions, analytical
data, tabular data
• Algorithms for data validation and standardization
• Flexible indexing and search technologies
• A platform for modeling data and hosting existing
models and predictive algorithms
• Chemistry RESEARCH DATA MANAGEMENT

81. Compounds

82. Reactions

83. Analytical data

84. Crystallography data

85. With data in hand maybe it’s time
What’s the
structure?
Are they in
our file?
What’s
similar?
What’s the
Pharmacology target?
data?
Known
Pathways?
Working On
Connections Now?
to disease?
Expressed in
right cell type?
Competitors?
IP?

86. Conclusions
• We are building platforms that can support
multiple communities, including MedChem
• We are working hard to extend our data and
improve quality of online data
• Opening APIs to the platforms and data
provides a powerful building block
• We are Open Sourcing components of our
platforms to the community

87. Thank you
Email: williamsa@rsc.org
ORCID: 0000-0002-2668-4821
Twitter: @ChemConnector
Personal Blog: www.chemconnector.com
SLIDES: www.slideshare.net/AntonyWilliams