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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
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Delivering an online service for validating and standardizing chemical structure files using the ChemSpider platform
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
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
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.
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
What we want to avoid
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
What are the common errors?
• Records without a structure
• Incorrect valences
• Atom labels
What are the common errors?
• Unbalanced charge– Name-structure errors
• Salts
• Polymers/Organometallics
• Missing stereochemistry
Side Effects of InChI on ChemSpider: Sort of helpful
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
Substance Registry System
• How do you decide your standardisation rules?• Avoid standards in isolation
http://www.fda.gov/downloads/ForIndustry/DataStandards/SubstanceRegistrationSystem-UniqueIngredientIdentifierUNII/ucm127743.pdf
• Note: This document is only a starting point
Salt and Ionic Bonds
Nitro groups
Ammonium salts
Validation rules
In XML:
Code generated dynamically from rule set.Indigo API used behind the scenes.
Standardization rules
Corrections stored in database:
SMIRKS-based corrections and also proximity-based metal–non-metal reconnection.
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.
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
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
Incorporating CVSP into data processing platforms: Knime
• The workflow includes:– SDF reader– Indigo nodes– calls for ChemSpider
validation Web services
Incorporating CVSP into data processing platforms: Knime
• Warning is returned as a result of processing
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….
