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….

Thank you

Email: chemspider@rsc.orgTwitter: ChemSpiderhttp://www.chemspider.comhttp://cssp.chemspider.com/