The InChI, the International Chemical Identifier, has been the basis of both indexing and deduplication of the ChemSpider database since the inception of the platform. When the InChI was adopted we envisaged a future whereby the identifier would proliferate across journals, databases and the internet in general providing us a basis for “structure searching the internet”. This presentation will provide an overview of how the InChI has facilitated the integration of ChemSpider to chemistry on the internet, some of the surprising findings that have resulted from this work and extrapolate the influence of InChIs into the future for a chemically enabled web.

1. Great promise of navigating the
internet using InChIs
Antony J Williams
ACS San Diego March 2012

2. Openness and Quality Issues
Williams and Ekins, DDT, 16: 747-750 (2011)
Science Translational Medicine 2011

3. Warning…
 This talk is not about Quality…it’s about quantity

4. Warning…
 This talk is not about Quality…it’s about quantity
Drugbank was here

5. Data quality is a known issue

6. We ALL have issues!!!

7. It’s about what’s out there…

8. How to Link it…

9. And getting out of overwhelm…

10. So what is Yohimbine?

11. Of course it is out there…
Drugbox: 3001/5080 with InChIs
Chembox:5436/7690 with InChIs

12. Tell me more…
 Where can I find the molfile for Yohimbine?
 Papers/Patents about Yohimbine?
 What are the side effects of Yohimbine?
 Where can I order Yohimbine?
 What are the physicochemical properties?
 Metabolic pathways?
 Different synonyms of Yohimbine?
 Synthesis of Yohimbine?
 Side effects of Yohimbine?
 Etc….

13. Quantity!

14. Yohimbine on ChemSpider..Quality?

15. How do we build it?
 We deal in Molfiles or SDF files – with coordinates
 Deposit anything that has an InChI – we support
what InChI can handle, good and bad
 Standardization based on “InChI standardization”
 InChIs aggregate (certain) tautomers
 We link out to external sites using their IDs

16. Downsides of InChI
 InChI was a moving target (multi versions) but
overall worked as planned.
 Good for small molecules – but no polymers,
issues with inorganics, organometallics, imperfect
stereochemistry. ChemSpider is “small molecules”
 InChI used as the “deduplicator” – FIRST version
of a compound into the database becomes THE
structure to deduplicate against…

17. Side Effects of InChI Usage

18. SMILES by comparison…

19. Side Effects of InChI Usage

20. Standardization Issues
Depiction based on molfile

21. Downsides of Overall Approach
 Meshing data together based on InChIs worked
for simple molecules
 2D layout errors inherited or limited by algorithm
 Complex molecules that are meant to be the
same thing were NOT deduplicated. Compounds
differing by one stereocenter, named the same,
meant to be the same, are not the same

22. Yohimbine on ChemSpider..Quality?

23. So where can we travel???

24. So where can we travel???

26. InChI String Search via Google
Give me InChIKeys…

27. And where can we travel???

28.  ChemSpider
 BRENDA
 Wikipedia
 ChEMBL
 ChEBI
 DrugBank

29.  Aggregator
 Enzymes
 Encyclopedia
 Pharmacology
 Curated Chemicals
 Drug-Drug Target

30. Recognizing Compound Dilution
 So much chemistry on the web….
 And so much dilution – “structural uniqueness”
versus “accidental ambiguity”
 InChI as an easy skeleton search

31. Vancomycin – Search the Internet

32. Vancomycin
Search Molecular Search Full Molecule
SKELETON

33. Full Skeleton Search

34. All aggegators suffer dilution!

35. Many Problems Can be Solved…
 Clean up databases – structure validation,
structure standardization
 Warn about
 Valency, charge balance, depiction issues,
bond types, absent stereo, and another 100
rules (or so…)
 Standardize
 Agree community rules to “Standardize”

36. Structure Validation

37. Structure Validation - Fixed

38. What needs to happen?
 If we could validate
 Catch errors in databases (and clean)
 Proactively catch errors in publications/patents
 Reduce junk in the ether – improve QUALITY!
 If we standardized
 Interlinking should improve

40. NPC Browser Set

41. Download, Deposit, Reprocess

42. Substructure # of # of No Incomplete Complete but
Hits Correct stereochemistry Stereochemistry incorrect
Hits stereochemistry
Gonane 34 5 8 21 0
Gon-4-ene 55 12 3 33 7
Gon-1,4-diene 60 17 10 23 10

43. Structure-Name Validation
H3C
NH2
O
I I
O O CH3
H3C OH
O CH3
O
CH3
O H
HN
CH3 I OH
OH
O
O HO
O O
O
Choladine
O
CH3
Taxol
Cl
H3C N
N
CH3 CH3
CH3 H
Cholane
H H
Chlotrimazole

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

45. Nitro groups

46. Salt and Ionic Bonds

47. Ammonium salts

48. Millions of structures? Lots of Issues

49. ChemSpider Standardization
 Entire ChemSpider database will be standardized
using modified FDA rule set
 Original Molfiles will be standardized and all
properties (predicted properties, SMILES, InChIs,
Names) will all be regenerated
 Standardization procedures automatically applied
to all future depositions

50. Identifier Dictionaries
 Reciprocal curation processes…share curation
with each other.
 If a database has a compound already then use
InChiKeys to match “suggested” validation
against the compound.
 A series of “added” and “removed” synonyms
against InChIKeys for matching.

51. Proof of Concept Data Curation Sharing
Who wants to work with us?

52. Structure Validation using feed
 Look for approved synonyms
 Compare feed InChIKey with database InChIKey
 If different, flag for inspection

53. 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?

54. 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 -

56. Chemistry in Open PHACTS
 Selected data slices of ChemSpider carrying
pharmacological links into the “linked data cache”
 ChemSpiderIDs and InChIs/InChIKeys will be in
Open PHACTS and available for linking
 A structure ID standard to enable further linking
across the semantic web of science

57. ChemSpider and InChI
Internet Data
Small organic molecules Commercial Software
Undefined materials Pre-competitive Data
Organometallics Open Science
Nanomaterials Open Data
Polymers Publishers
Minerals Educators
Particle bound Open Databases
Links to Biologicals Chemical Vendors

58. The great promise should be obvious
 InChIs are here to stay
 They will evolve, they will encompass, we will
adopt and adapt
 Public and private databases will federate &
build a linked environment of validated data!
 Data validation and standardization is
needed
 Open Data will continue to proliferate
 InChIs are in the “Semantic Web” already

59. If InChI never existed or went away..
 ChemSpider would never have been built
 Database linking would suffer dramatically
 The web would not be “structure searchable”
 Cheminformatics tools would likely not be linking
to public domain databases in the same way
 And we would not have the pleasure of today…

60. Acknowledgments
 The inspiration of the InChI Masters – Steve H.,
Steve S., Alan, Dmitrii, Igor
 IUPAC, NIST, all adopters, supporters,
challengers and users
 The InChI Trust and its supporters for funding
continued development
 Al Gore –enabling us to search InChIs on the web

61. Steve Heller

62. Steve Heller

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