The production of valid and appropriate chemical structure representations which are appropriate for deposition into chemical structure databases and for inclusion into scientific publications requires adoption of a set of pre-processing filters and standardization procedures. As part of our ongoing effort to improve the quality of data for deposition into the RSC ChemSpider database, to provide a manner by which to validate and prepare data for publication and to provide a valuable service to the chemistry community, we have delivered the ChemValidator online service. This website provides access to an intuitive user interface for the upload of chemical compounds in various formats, pre-processing and standardization relative to a defined set of standards and validation checking of the chemicals according to a number of rules including hypervalency, absence of stereochemistry and charge balance. This presentation will report on the development of ChemValidator. This presentation was given by David Sharpe at the ACS Fall Meeting in 2012

1. Delivering an online service for validating and
standardizing chemical structure files using
the ChemSpider platform

2. Overview
• Introduction
– Why do we need to
validate/standardise data
– Examples of problems in general
– Examples of Problems in
ChemSpider
– Why InChI is not enough
– FDA rules

3. What are we trying to achieve?
• Everyone wants high quality data
• The ChemSpider team is building a reputation on
data quality
• Many datasources have errors
• We need to identify:
– Errors
– Inconsistencies
– Data duplication/Inappropriate separation of data
• Requires a process of validation and
standardization

4. What do we mean by Validation and
Standardisation?
• Validated
– Check for hypervalency, charge balance, missing
stereo
– Name-Structure relationships, etc.
• Standardized
– Use standard rules to “standardize” compounds;
Nitro groups, O-Metal bonds, tautomers, etc.

5. Where will CVSP be useful
• Currently, a standalone system
• In the future; Validation/standardisation routines
will be used:
– Built in to our deposition system
– At registration for new compounds
– To improve existing data in ChemSpider – pass through
the ChemSpider backfile
• Potential to offer optional checking service to
authors

6. What we want to avoid

7. What do we do now?
• Currently, ChemSpider uses structures (as
InChI’s) as the database key
• Need structures for depositions
• 2 Steps:
– Pre-processing prior to deposition
– InChI algorithm; provides standardisation and
mapping

8. What are the common errors?
• Records without a structure
• Incorrect valences
• Atom labels

9. What are the common errors?
• Unbalanced charge
– Name-structure errors
• Salts
• Polymers/Organometallics
• Missing stereochemistry

10. Side Effects of InChI on ChemSpider:
Sort of helpful

11. Side Effects of InChI on ChemSpider
• Advantages and disadvantages
– The depictions are meant to represent the same molecule
– Not easy to pick out “bad” representations

12. Substance Registry System
• How do you decide your standardisation rules?
• Avoid standards in isolation
http://www.fda.gov/downloads/ForIndustry/DataStandards/SubstanceRegistrationSyste
m-UniqueIngredientIdentifierUNII/ucm127743.pdf
• Note: This document is only a starting point

13. Salt and Ionic Bonds

14. Nitro groups

15. Ammonium salts

16. Validation rules
In XML:
Code generated dynamically from rule set.
Indigo API used behind the scenes.

17. Standardization rules
Corrections stored in database:
SMIRKS-based corrections and also proximity-
based metal–non-metal reconnection.

18. Case study: DrugBank
• DrugBank (http://www.drugbank.ca/)
maintained by David Wishart
• Database contains 6711 structures
• Widely regarded as a well curated, high
quality dataset
DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V,
Jewison T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R,
Guo AC, Wishart DS., Nucleic Acids Res., 2011, 39, Jan, D1035-41.

20. 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

21. CVSP as a Flexible System
• There will be various rules sets
– Rigid pre-defined rules: e.g. Meeting FDA
specifications as written, Open PHACTS modified
rules set, etc.
– Flexible user-defined rules: users upload their
rules in our custom format (XML)
– The Open PHACTS rule set will be open to the
community to reuse

22. Incorporating CVSP into data
processing platforms: Knime
• The workflow
includes:
– SDF reader
– Indigo nodes
– calls for
ChemSpider
validation Web
services

23. Incorporating CVSP into data
processing platforms: Knime
• Warning is returned as a result of processing

24. Summary
• Will release back results of DrugBank
• Alpha version of CVSP available:
http://cv.beta.rsc-us.org/Batches.aspx
• Will be a resource for the Community
• Will improve ChemSpider
• Still a long way to go….

25. Thank you
Email: chemspider@rsc.org
Twitter: ChemSpider
http://www.chemspider.com
http://cssp.chemspider.com/