1. ChemSpider -Connecting and Curating
Online Chemistry Resources
Antony Williams
EBI, November 30th
2010

2. Chemistry on the Internet
 100s of websites serving up chemistry data, SDF
files of structures and data
 Some primary resources : PubChem, ChEBI,
DrugBank, ChemIDPlus, Wikipedia
 ChemSpider “links” chemistry on the internet
 Almost 25 million compounds, 400 data sources
 Allows community deposition, curation, annotation
 Integrating properties, publications, patents, media
 Text, structure, substructure (in testing) searching

3. www.chemspider.com

4. Search for a Chemical

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

6. We Have Delivered the Vision
“Build a Structure Centric Community to
Serve Chemists”
 Integrate chemical structure data on the web
 Create a “structure-based hub” to information,
data and algorithmic predictions
 Let chemists contribute their own data
 Allow the community to curate/correct data

7. How Did We Build It?
 We deal in Molfiles or SDF files – including
coordinates
 We do rudimentary filtering – valence checking,
charge imbalance – prior to deposition
 We have our own “business logic” to standardize
 We use InChI to “aggregate tautomers” to one
record
 Link out to external sites where possible using IDs

8. Inherited Errors
 We have inherited errors from every database…
all public compound databases, including ours,
have errors
 “Incorrect” structures – assertions, timelines etc
 “Incorrect” names associated with structures
 Properties
 Links
 Publications
 ENORMOUS CHALLENGE

9. What is the Structure of Vitamin K?

10. 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). Vitamin K 3 provitamins,
after being alkylated in vivo, exhibit the
antifibrinolytic activity of vitamin K. Green leafy
vegetables, liver, cheese, butter, and egg yolk are
good sources of vitamin K

11. What is the Structure of Vitamin K1?

12. What is the Structure of Vitamin K1?

13. CAS’s Common Chemistry

14. Wikipedia

17. ChEBI – Manual Curation

20. PubChem

22. “2-methyl-3-(3,7,11,15-tetramethylhexadec-2-
enyl)naphthalene-1,4-dione”
 Variants of systematic names on PubChem
 2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7S,11R)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7R,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,7S,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E,11S)-3,7,11,15-tetramethyl
 2-methyl-3-[(E)-3,7,11,15-tetramethyl
 2-methyl-3-(3,7,11,15-tetramethyl
 2-methyl-3-[(E)-3,7,11,15-tetramethyl

23. Public Domain Chemistry Databases
 Our databases are a mess…
 Non-curated databases are proliferating errors
 We source and deposit data between databases
 Original sources of errors hard to determine
 Curation is time-consuming, challenging and
exacting
 An examination of quality in databases – inter/intra
lab comparison of processes for 150 drugs

25. Vytorin: Ezetimibe/Simvastatin

26. Vytorin: Ezetimibe/Simvastatin

27. Vytorin: Ezetimibe/Simvastatin

28. Vytorin: Ezetimibe/Simvastatin

29. Vytorin: Ezetimibe/Simvastatin

30. Symbicort: Budesonide + Formoterol

31. Symbicort: Budesonide + Formoterol
ChemIDPlus
Wikipedia

32. DrugBank: Search Symbicort…

33. Symbicort: Budesonide + Formoterol
 PubChem
 8 structures called Budesonide. 1 “correct”
 6 structures called Formoterol. 1 “correct”
 Search on “Symbicort” gives 1 structure.

34. Taxol: Paclitaxel 44 structures

35. Taxol: Paclitaxel Bioassay Data

36. Taxol: Paclitaxel Bioassay Data
 Most Bioassay data associated with structure
with one ambiguous stereocenter

37. Data on the Web – Good or Bad??
Taken from: Rafael Sidis’ Blog

38. Data on the Registry

39. Data on the Registry

40. Data on the Registry

41. How are data handled in Pharma?
 Algorithms for “collapsing” data? Skeletons only?
 Processing structure-name pairs?
 Manual curation?
 Does it matter relative to the noise in the
measurements?
 Do correct structure representations matter, and
to who?????

42. EPA’s DailyMed

43. EPA’s DailyMed

44. EPA’s DailyMed

45.  Consider searching each of these
chemical databases by chemical
name (systematic name, trade
name or synonym). Please mark
each online resource according to
how much you generally trust the
results.

47. Drug Name Generic Name ChEBI ChemSpider
CAS Com.
Chem ChemIDPlus DailyMed DrugBank PubChem Wikipedia
Spiriva
Tiotropium
Bromide
No Hits  No Hits    4/0 
Depakote
Valproate
semisodium
       No
Structure
Basen Voglibose   No Hits  No Hits  2/1 
Symbicort 1) Budesonide       8/1 
Symbicort 2) Formoterol WRONG  No Hits    6/1 
Vytorin 1) Ezetimibe   No Hits     
Vytorin 2) Simvastatin       2/1 
Taxol Paclitaxel       44/1 
Thalidomid Thalidomide No Hits       
Zocor Simvastatin       2/1 
Crestor Rosuvastatin   No Hits    2/1 

48. Why Curated Dictionaries Matter

49. Success Depends on Dictionaries

50. Online Curation
 Online databases generally do NOT allow
curation or annotation
 If you find errors they stay there!
 ChemSpider allows immediate curation

51. Crowdsourcing Works
 Over 100 people have deposited data (structures,
spectra, etc) and participated in data curation
 Different level curators check each others work
 Wikipedia is the modern primary example
 Some curators are “madmen”…

52. Crowdsourcing Works
 Over 100 people have deposited data (structures,
spectra, etc) and participated in data curation
 Different level curators check each others work
 Wikipedia is the modern primary example
 Some curators are “madmen”…
 The Oxford English Dictionary

53. Collaborative Data Curation
 How can we COLLECTIVELY clean online data?
 ChemSpider has inherited junk from >400 data
sources. Some of this has proliferated into
PubChem. We should deprecate it.
 We need to develop a way to share curation actions
back to original data sources
 A mindset of bigger is better is problematic. How
many “real chemicals” are in the public databases?

54. ChemSpider
 ChemSpider is free to use.
 Multiple web services are available.
 New data added daily.
 Curation and data validation ongoing everyday.
 Provided by the RSC.
www.chemspider.com

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