In recent years, in parallel with the general broad trend of information proliferation, many tens of public chemical databases have been created and made available using internet technologies. In many cases fluent data exchange has occurred between these various databases as they source information from one another. While this has the advantages of linking together multiple data sources the results also include the proliferation of errors across the various databases. The lack of a public authority to resolve such errors significantly affects the quality of freely accessible chemical information. While ChemSpider has previously allowed a crowdsourcing approach to curation efforts have now migrated to addressing this problem using a "federated resolver" approach. This presentation will report on our work in this area.

1. ChemSpider as a Chemical
Term Resolver
Antony Williams, Valery Tkachenko,
Sean Ekins and Andy Fant
ACS San Diego March 2012

2. The Web of Chemistry – VERY BIG!

3. Online Databases are “Linking”

4. It is so difficult to navigate…
IP?
What’s the
structure?
Are they in
our file?
What’s
similar?
What’s the
Pharmacology target?
data?
Known
Pathways?
Competitors?
Working On
Connections Now?
to disease?
Expressed in
right cell type?

5. Open PHACTS Project
 Develop a set of robust standards…
 Implement the standards in a semantic integration hub
 Deliver services to support drug discovery programs in
pharma and public domain
 22 partners, 8 pharmaceutical companies, 3 biotechs
 36 months project
Guiding principle is open access, open usage, open source
- Key to standards adoption -

7. What is the Structure of Vitamin K?

8. MeSH
 A lipid cofactor that is required for normal blood
clotting.
 Several forms of vitamin K have been identified:
 VITAMIN K 1 (phytomenadione) derived from
plants,
 VITAMIN K 2 (menaquinone) from bacteria, and
synthetic naphthoquinone provitamins,
 VITAMIN K 3 (menadione).

9. What is the Structure of Vitamin K1?

12. Create an Online “Resolver” as a
path to chemistry
 Search all forms of structure IDs
 Systematic name(s)
 Trivial Name(s)
 SMILES
 InChI Strings
 InChIKeys
 Database IDs
 Registry Number

13. ChemSpider

14. Available Information…
 Linked to vendors, safety data, toxicity, metabolism

15. Available Information….

16. Vitamin K1 Names

17. Vitamin K1 on ChemSpider CORRECT

18. Resolving Names for QUALITY
 Searching chemical identifiers should resolve to
the correct chemical as much as possible

19. Validated Name-Structure Dictionaries
 Chemical name dictionaries are used for:
 Text-mining (publications, patents)
 Used to index PubMed and link to Google Patents
 Linking to other databases – think Biology!
 When structures are not available drug names link
 Searching the web
 Names link to structures link to InChIs

20. I want to know about “Vincristine”

21. Vincristine: Identifiers

22. Vincristine: Patents
Linked by Name

23. Many Names, One Structure

24. Top 200 Drugs on Wikipedia
http://en.wikipedia.org/wiki/List_of_bestselling_drugs

25. The Project Challenge PART ONE
 Agree on the set of chemical names to work with
 Independently create an SDF file in each “lab”
 Compare differences and agree on final structures
 Issue “Gold Standard” SDF file to team

26. RSC Process

27. Relative accuracy of groups against
final master list

28. The Project Challenge PART TWO
 Use Gold Standard SDF File to investigate data
quality on these compounds in Internet Databases
 Two checks
 Search chemical name – does it return the
correct compound. If not correct, how is it
different?
 Search “structure” – SMILES, Molfile,
InChIString or InChIKey

29. “The First 10”

30. Performance on 150 Drug Names

32. NPC Browser Set

33. Standardize
 Use the SRS as a guidance document for
standardization
 Adjust as necessary to our needs

34. Nitro groups

35. Salt and Ionic Bonds

36. One dictionary look up is never enough…
 ChemSpider does not contain all chemistry
 We are not the only ones curating data
 New chemistry expands daily and goes online

37. One dictionary look up is never enough…
 Federation is key….
 Check ChemSpider first, if not found then
 Check PubChem
 Check NCI resolver
 Check ChEBI
 Check ….the “network” of open interfaces
 Each resolver will have its own “quantitative
confidence”.

38. Chemical Identifier Resolver (CIR)
Converts a given
structure identifier into
another representation
or structure identifier.
Resolve names,
identifiers etc
http://cactus.nci.nih.gov/chemical/structure

39. What can become a resolver?

40. We are building….
 A central federated resolver utilizing available
services
 Dictionary lookups, systematic name conversions
(multiple tools – ACD/Labs, Lexichem, OPSIN)
 “Consensus” decisions and guidance BUT
 Chemicals have timelines!!!

41. ORIGINAL FINAL

42. Thank you
Email: williamsa@rsc.org
Twitter: ChemConnector
Personal Blog: www.chemconnector.com
SLIDES: www.slideshare.net/AntonyWilliams