1. How can the International Chemical
Identifier (InChI) be extended to non-
trivial chemicals?
of the pillars of a
V. Tkachenko, A.J. Williams,
Y. Borodina, F. Switzer, T. Peryea, L. Callahan
ACS Philly August 2012

2. What is InChI

3. InChI Examples
CH3CH2OH
InChI=1S/C2H6O/c1-2-3/h3H,2H2,1H3
ethanol
InChI=1S/C6H8O6/c7-1-2(8)5-
L-ascorbic acid 3(9)4(10)6(11)12-5/h2,5,7-8,10-
11H,1H2/t2-,5+/m0/s1

4. InChI Structure

5. InChIKey
 The condensed, 27 character standard InChIKey is a hashed version of the full standard InChI (using the
SHA-256 algorithm)
 Designed to allow for easy web searches of chemical compounds
 InChIKeys consist of
 14 characters resulting from a hash of the connectivity information of the InChI
 followed by 9 characters resulting from a hash of the remaining layers of the InChI
 followed by a single character indication the version of InChI used
 followed by single checksum character
 InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2-5,10-
11,13,16,19-20H,6-8H2,1H3/t10-,11+,13-,16-,17-/m0/s1
 BQJCRHHNABKAKU-KBQPJGBKSA-N
 Unlike InChI, InChIKey  CT only by lookup

6. Proliferation of InChI

7. Search by InChI

8. ChemSpider Google Search
http://www.chemspider.com/google/

9. What’s the catch?
 InChI has limitations
 InChI is ideal for
 Simple
 Static
 Well-defined graphs
 Real chemical substances can only be
approximated by such graphs

10. Limitations
 Non-trivial stereo (e.g. axial, planar)
 Non-trivial tautomers (e.g. ring-chain)
 Mixtures – full stereo is rarely known
 Polymers
 Markush structures
 Organometalics
 Inorganics
 Materials
 Reactions
 Etc

11. Chemical data complexity

12. Work in progress
 InChI Extensions: Under the guidance of IUPAC, several sub-teams are now
working on expanding InChI to new areas of chemical representation:
 Reaction InChI (RInChI): the reaction working group has completed its
recommendations, and work is ready to begin.
 Polymers/Mixtures: The polymers/mixtures working group also has
submitted its recommendations, and work to incorporate the new
representations should begin once version 1.04 is released.
 Markush: This project is the most complex undertaken to date. The initial
recommendations have been submitted, but financing of the work still
needs to be sorted out.
 But what do we do NOW???

13. Data
Validation
Standardization
Filtering
Componentization
Deposition Process
Deduplication
Mapping
data
Non-
redundant

14. ChemSpider Data Model

15. Organometallics

16. Mixtures or unknown stereo

17. Accelrys Enhanced Stereo

18. MOL V3000

19. Enhanced stereo and InChI…
 Unfortunately not supported
 Is it important?
 Now real-world examples…

20. FDA Substance Registration System

21. Stoichiometric and non-stoichiometric mixtures
Moiety 1:
Substance:
Moiety 2:

22. Substance: Moiety 1:
Moiety 2:
Moiety 3:
Moiety 4:

23. Substance: Moiety 1:
Moiety 2:
(undefined)

24. Moiety 1:
Substance:
(A)
Moiety 2:
(B)

25. D-glucose

26. SRS standardization approach
 Substance description
 Standardization module
 Moieties generator
 Normalization
 InChI[Key] generator
 Hash function f(InChIKeys, moieties)
 Unique ID
 Standard description

27. SRS TBD
 Markush
 Polymers
 Proteins
 Inorganics
 Materials

28. OpenPHACTS
 Open PHACTS is an Innovative Medicines Initiative
(IMI) – 3 years project
 To reduce the barriers to drug discovery in industry,
academia and for small businesses
 To build an open platform, integrating chemistry and
biology data from public domain resources
 Semantic web platform
 Open Standards, Open Data and Open Source

31. OpenPHACTS specifics
 Active/inactive ingredient
 Parent/child
 Sample/substance
 Misreferences (!!!)

32. ChemSpider Reactions

34. ChemSpider Reaction Challenges
 Deduplication
 Identification
 Deposition

35. Conclusions
 InChI is The Identifier
 InChI has its limitations
 InChI is work in progress
 InChI deficiencies can be hot-fixed

36. Acknowledgements
 RSC Cheminformatics group
 FDA SRS group
 OpenPHACTS consortium
 Software: InChI, GGA Software

37. Thank you
Email: tkachenkov@rsc.org
Blog: www.chemspider.com/blog
SLIDES:
http://www.slideshare.net/valerytkachenko16