SERMACS 2012

SERMACS 2012

Chemical Validation and Standardization Platform (CVSP)

Kenneth Karapetyan, Colin Batchelor, Valery Tkachenko, Antony Williams

A quality chemical record

Correct file format (SDF, MOL, CDX, etc.)

“Valid” chemical structure Valid atoms (not query atoms) Valid bonds Valid valences Valid charges Stereo (defined/unknown/undefined)

Synonyms Names (name to structure) SMILES, InChIs (SMILES/InChI to structure)

XRefs

“Quality-conscious” databases

Not just for storage but shares responsibility for the data Understands that bad data will eventually propagate to

others Uses deposition system with strong validation rules

Warns users when conflicts are detected and when records are ambiguous

Stops user from depositing when critical chemical errors are suspected

Help depositors to “self-curate” their own data

A Vision of a Validation System

Validation rules are transparent to community

Validation rules can be revised by users for their particular purpose

Free to the community

Accessible in batch mode by Web GUI and Web service

Could be integrated to any chemical deposition system

Rules are based on SMARTS/SMILES for finding offending patterns in molecules. Non-standard INCHI is used for determining unknown/undefined stereo descriptors

Standardization

Who is concerned with standardization? Database maintainers Chemists that prepare data for property calculations Scientists investigating structure-activity relationships

They all can have different business rules in mind

CVSP is an open and flexible platform for different flavors of standardization

Rules are based on SMIRKS transformations

CVSP: select rule set

CVSP: Acid-Base competitive ionization

CVSP: define rule variables

CVSP: result of processing

DrugBank dataset (6516 records)

Marked as Errors (arbitrary)

2 records with query bonds 3 records with invalid atoms (asterisk in polymers) Unusual valence: ~70 (oxygen 3, sulfur 3 and 5, Mg 4, B 5, etc.)

Warnings INCHI not matching structure (100+) SMILES not matching structure (100+)

DrugBank ID: DB00755 InChI=1S/C20H28O2/c1-15(8-6-9-16(2)14-19(21)22)11-12-18-

17(3)10-7-13-20(18,4)5/h6,8-9,11-12,14H,7,10,13H2,1-5H3,(H,21,22)/b9-6+,12-11+,15-8+,16-14+

DrugBank ID: DB00614

Lessons

Don’t bury a depositor with tons of validation messages. Rank them by chemical severity

Bring the depositors attention to records with the highest warning count Records that have inconsistent InChI and

SMILES and NAMES certainly have issues

Only bring the most ambiguous records to a depositors’ attention – let them “self-curate”. Raise records that are suspected to have critical chemical errors to the top

Where will we use CVSP? For external projects we are involved with – for example,

Open PHACTS where we are responsible for hosting chemistry data mapped to biology data

Made available to RSC authors to check their chemical compounds prior to submitting articles

To be integrated to the ChemSpider deposition system to validate and standardize new data

For validating and standardizing existing data in ChemSpider and other RSC compound databases

Thanks

We would appreciate some feedback on CVSP.Please email us to request access.

Also if you would like us to run some datasets through CVSP and give you the results back please email us.

Email: karapetyank@rsc.org