The document discusses building a structure-centric community for chemists using crowd-sourcing. It describes ChemSpider, a free online database of over 20 million chemical structures that allows users to search, deposit, and curate chemical data. ChemSpider aims to connect structured chemical information to other resources and enable collaborative authoring and discovery. Challenges include maintaining data quality at scale and integrating with established authorities through an open community effort.

1. Crowd-Sourcing to Build a Structure
Centric Community for Chemists
Antony Williams
Whitney Symposium 2008 - Networks

2. Social Networking for Chemists
Building a Structure Centric Community for Chemists

3. Network Drug Discovery Tools
www.curehunter.com
Building a Structure Centric Community for Chemists

4. Beware the Networks!
Building a Structure Centric Community for Chemists

5. Collaborative Authoring in Academia
 Group level collaboration via Wikis
Building a Structure Centric Community for Chemists

6. Collaborative Authoring for Drug Discovery
 Pfizerpedia
Building a Structure Centric Community for Chemists

7. Collaborative Knowledge Management
for Chemists – Wikipedia, Built by a Network
Building a Structure Centric Community for Chemists

8. and biologists…WikiProteins
Building a Structure Centric Community for Chemists

9. WikiProteins
What
Is
Tegafur?
Building a Structure Centric Community for Chemists

10. Commonly Lacking…
 Approaches generally lack “structural intelligence”
 Structures have properties (Mw, MF, exp. & pred. properties)
 Collections of structures need to be searchable by structure
 Most data collections are “self-contained” and rarely
connecting to other resources via “structure”
Building a Structure Centric Community for Chemists

11. A Search Engine for Chemists
 Questions a chemist might ask…
 What is the melting point of n-butanol?
 What is the chemical structure of Xanax?
 Chemically, what is viagra?
 What are the stereocenters of cholesterol?
 Where can I find publications about Taxol?
 What are the different trade names for Ketoconazole?
 What is the NMR spectrum of Aspirin?
 What are the safety handling issues for Thymol Blue?
 ChemSpider can answer all of these questions
Building a Structure Centric Community for Chemists

12. ChemSpider Data Content
 Over 20 million unique chemical structures :
 Online Databases –PubChem, Drugbank, HMDB, Wikipedia
 Chemical Vendors – over 40 different vendors and growing
 Personal Depositions – individual contributions
 Journal Publishers
 Content database vendors
 Analytical data collections
 Patents (9 MILLION Structures to search patents)
 Web scraping
Content is linked back to the original data sources
Building a Structure Centric Community for Chemists

13. A Structure Centric Community for Chemists
 A FREE ACCESS platform for deposition,
management, curation, annotation and extension of
information associated with chemical structures
 Semantically connect to other sites providing access to
knowledge, data and information of determined quality
 Search by alphanumeric text, chemical structure and
substructure and combination searches
 Predict properties for submitted structures
Building a Structure Centric Community for Chemists

14. Tell me about Aspirin
Building a Structure Centric Community for Chemists

15. Tell me about Aspirin
Building a Structure Centric Community for Chemists

16. Links out to KEGG
Kyoto Encyclopedia of Genes and Genomes
Building a Structure Centric Community for Chemists

17. Tell me about Aspirin
Building a Structure Centric Community for Chemists

18. Tell me About Aspirin
Building a Structure Centric Community for Chemists

19. Tell me about Aspirin
Building a Structure Centric Community for Chemists

20. Tell me about Aspirin
Building a Structure Centric Community for Chemists

21. Abstract Compounds?
 Is there any information about “Quesnoin”?
 Type in the name (and there may be many) or other
identifier
 Paste a chemical structure
 Draw the structure
Building a Structure Centric Community for Chemists

22. Example Search
Building a Structure Centric Community for Chemists

23. Example Search
Building a Structure Centric Community for Chemists

24. Example Search 2
 What compounds have a mass of 300+/-0.001?
 or search a combination of intrinsic/predicted properties
Building a Structure Centric Community for Chemists

25. Example Search 2
Building a Structure Centric Community for Chemists

26. Complex Search
Building a Structure Centric Community for Chemists

27. Search Open Access Journals – ChemSpider
Building a Structure Centric Community for Chemists

28. Search PubMed – ChemSpider
Building a Structure Centric Community for Chemists

29. The Quality of Data Online…
 Aggregating data opens up quality issues
 Structure-identifier associations are “dirty”
 Structures are COMMONLY incorrect – stereochem issues
 Manual curation of small databases is enough work – what
about millions of structures?
 Structures are far from perfect. What is a “correct structure”?
 Full stereochemistry?
 Historical timeline of structure?
 Who is the authority?
Building a Structure Centric Community for Chemists

30. Who holds THE Quality Authority?
 Chemical Abstracts Service is the structural authority
today. 1400 (?) employees, world standard in chemistry
information
 101 years of knowledge, process and expertise.
MANUAL curation is key. Robotic curation is enabling
 How can an online, free access system peacefully co-
exist with the authority?
Building a Structure Centric Community for Chemists

31. Quality is a Major Issue- Search Butanol
Building a Structure Centric Community for Chemists

32. Crowd-sourcing Database Compilation
Building a Structure Centric Community for Chemists

33. Wikipedia – Crowdsourcing Chemistry
Building a Structure Centric Community for Chemists

34. Wikipedia Chemistry Curation project
 Only ca. 5000 organic structures, 7000 total structures
 MONTHS of work so far for a team of 6 people
 Many errors removed in the process. Curation process
is a daily event for users/depositors
 Slow and torturous process for stereo molecules.
Building a Structure Centric Community for Chemists

35. Thymol Blue on ChemSpider
 Data online includes:
 UV-vis spectrum
 Measured experimental properties
 Link to Wikipedia article
 Links to chromatography details
 Multiple identifiers/trade names etc.
 Links to vendors/suppliers/other databases
 Safety information
Building a Structure Centric Community for Chemists

36. Differences between ChemSpider/Wikipedia
ChemSpider Wikipedia
>20 million unique structures ~5000 organics, 2000 others
Complex queries – Properties, Text
Text, structure/substructure, OA
publishers, Data Sources, …
Prediction of properties No
Analytical Data No
Active depositors/curators – 30 Active editors – about 50 (?)
5000 people/day; 1100 registered ????
Compound monographs linked Detailed compound monographs
Building a Structure Centric Community for Chemists

37. Differences between Wikipedia/ChemSpider
Wikipedia ChemSpider
Supported by tried and tested Primarily Microsoft .NET
Media-Wiki platform. technologies with OS components
Established infrastructure and “Out of a basement” on three
Wikipedia Foundation Team servers and 5 volunteers
Chemistry is a subset of the ‘Pedia Chemistry is the focus of ‘Spider
GFL licensing for everything Mixed “licensing”
Strong team of WP:Chem Growing team of WP:Chem
advocates, curators and admins advocates, curators and admins
Worldwide reputation as quality Growing reputation as focused on
source quality
Building a Structure Centric Community for Chemists

38. Crowd-sourcing Curation
 How to curate data for millions of structures?
 Robot processes can clean up depositions
 Search for Chloride and check molecular formula for Cl
 Check for stereochemistry and remove names with stereo
 Provide a simple-to-use platform to curate, annotate
and tag data
 Provide curator administration to prevent vandalism
(Veropedia)
Building a Structure Centric Community for Chemists

39. Multi-level Curation and Approval
Building a Structure Centric Community for Chemists

40. Post Comments
 Anyone can “Post Comments” associated with a
structure. To curate data we require login to track
Building a Structure Centric Community for Chemists

41. Crowd-sourcing Chemistry
 Crowd-sourced curation: identify and tag errors, edit
names, synonyms, identify records for deprecation
 ALSO
 Crowd-sourced deposition: anyone can deposit data
(structures, text, images, analytical data)
Building a Structure Centric Community for Chemists

42. But, when registered and logged in…
 Ability to curate and add to the database
 Add structures
 “Clean” structures
 Add data (spectra, CIFs, images)
 Add links to other pages (URLs)
 Add publication details
Building a Structure Centric Community for Chemists

43. Adding to the Database - Structure
Building a Structure Centric Community for Chemists

44. Adding New Text Data
Add Publication Add URL
Add Identifier
Building a Structure Centric Community for Chemists

45. Adding Supplementary Info to a Structure
Building a Structure Centric Community for Chemists

46. Can ChemSpider Enable Discovery?
 Yes, chemists can search by text, structure, substructure or
properties to look at relationships and probe drug discovery
Building a Structure Centric Community for Chemists

47. ChemSpider – Research in Progress
 Supporting Open Notebook Science as a repository –
JC Bradley at Drexel University
 For the purpose of online virtual screening
 Applying descriptors of various types to filter a
database of 20 million compounds
 In progress:
 Utilizing SimBioSys’ LASSO Descriptor
 Collaboration based on NISS’ ChemModLab
Building a Structure Centric Community for Chemists

48. LASSO
Ligand Activity by Surface Similarity Order
Building a Structure Centric Community for Chemists

49. LASSO Descriptors on ChemSpider
SEMANTIC WEB in action
Building a Structure Centric Community for Chemists

50. LASSO Searching Method 1
 Ask the question “What are the top 1000 molecules
with similar LASSO descriptors to the actives for the
Estrogen Receptor”
Building a Structure Centric Community for Chemists

51. It WORKS - Enrichment Plot
 60% of the actives were recovered in the top 1% of the database.
 “Environmental binders” are weak binders
 The top ranked compounds may well be active ER binders
 Likely candidates for experimental investigation
Building a Structure Centric Community for Chemists

52. Tipping Point
 Tipping point - the point at
which a slow gradual change
becomes irreversible and then
proceeds with gathering pace
Building a Structure Centric Community for Chemists

53. ChemSpider Forums/Blogs
 Forum.chemspider.com
 www.chemspider.com/blog
Building a Structure Centric Community for Chemists

54. ChemSpider TouchGraph
Building a Structure Centric Community for Chemists

55. What would we most like to do?
 Enable “Collaborative Science”. What would that look
like?
 Access to chemical supplies when people need them
 Awareness of available literature, patents, databases of
curated content – whether Open Access or not.
Transaction fees (or not) are between user and provider
 Host Open Notebook Science exchanges
Building a Structure Centric Community for Chemists

56. “ChemSpider Inside”
 Instrument vendors integrated ChemSpider to their
metabolism ID project – ChemSpider linked to all Mass
Spec Intruments doing Metabolite ID?
 Wikipedia roundtrip linking to ChemSpider
 Google indexing ChemSpider at “fixed rate”
 Integration to desktop drawing packages
 Members of Microsoft BioIT Alliance
 Discussions on Taverna’s Workflow Sourceforge group
 Hosting Open Access articles shortly…
Building a Structure Centric Community for Chemists

57. Where to from here? Short term
 Integrated text and structure/substructure searching of the
Open Access literature is in development
 Web-based scraping of structure-based information –
examples in place
 Enhanced web services layer to integrate searches
 Deposit updated Patent Database (9 million structures)
 Reaction handling and deposition
Building a Structure Centric Community for Chemists

58. Where to from here? Mid-term
 Spidering for Chemistry – extract data from articles,
webpages and data sources AND stay within copyright
 WiChempedia project – wiki-layers on top of
ChemSpider, alongside Wikipedia curation project.
 Deeper integration to text-based searching and
conversion of chemical names to structures for online
structure searching:
 Improved integration with NCBI Entrez system
 Deliver “dedicated websites” for specific publishers
Building a Structure Centric Community for Chemists

59. Where to from here? Mid-Term
 An extensible datamodel “on the fly” allows us to
easily expand to integrate abstract data to structures
 Data mine and curate “parameters” – physicochemical
and physiological parameters to enable QSAR
analysis, data modeling and provision of models
online (UNC-Chapel Hill, NISS)
Building a Structure Centric Community for Chemists

60. Our Challenges
 There are “no employees”
 ChemSpider is non-funded
 System is hyper-dependent
on ISP, power and limited
compute power
 We are upsetting a lot of
people – evangelists,
cheminformatics system
vendors, publishers, data
content providers
Building a Structure Centric Community for Chemists

61. Acknowledgments
 The ChemSpider team of volunteer developers
 ChemSpider Advisory Group
 Our curators, depositors and users
 Suppliers of commercial software – Microsoft,
ACD/Labs, OpenEye, ChemAxon, SimBioSys
 SureChem – Structure Based Online Patent Searching
Building a Structure Centric Community for Chemists

62. Further reading
 www.chemspider.com/blog
 Internet-based tools for communication and
collaboration in chemistry, Drug Discovery Today,
Volume 13, Numbers 11/12, June 2008 502-506,
doi:10.1016/j.drudis.2008.03.015
 A perspective of publicly accessible/open-access
chemistry databases, Drug Discovery Today, Volume
13, Numbers 11/12, June 2008, 495-501,
doi:10.1016/j.drudis.2008.03.017
Building a Structure Centric Community for Chemists