Antony Williams 5th Meeting on U.S. Government Chemical Databases and Open Chemistry August 2011

ChemSpider – A Crowdsourcing Environment for Hosting and Validating Chemistry Resources (and lessons from President Bush)

Antony Williams5th Meeting on U.S. Government Chemical Databases and Open Chemistry

August 2011

I want to know about “Vincristine”

Vincristine: Identifiers and Properties

Vincristine: Vendors and Sources

Vincristine: Patents

Vincristine: Articles

Vincristine: RSC Databases

Searches: The INTERNET

Validated Names for Searching…

And InChIs…

ChemSpider

The Free Chemical Database

A central hub for chemists to source information >26 million unique chemical records Aggregated from >400 data sources Chemicals, spectra, CIF files, movies, images,

podcasts, links to patents, publications, predictions

A central hub for chemists to deposit & curate data

Essential aspects of ChemSpider

ChemSpider is a BIG database..and growing

Our focus has increasingly become QUALITY over quantity

Data curation and validation is our strength – crowdsourcing is contributing, more is required

Validated data has enabled linking of the internet

There are NO errors in ChemSpider

There are NO errors in ChemSpider

“All That Glisters is Not Gold”What is the structure of Discodermolide?

How to distinguish…who’s wrong?

Neither is wrong

Data Curation…long torturous task

Data curation – JUST structure-name validation is a long, torturous, iterative task.

How about validating “data” – PhysChem data such as logP data, boiling points, melting points (J.C.Bradley’s talk), spectra

Hand on my heart….

Hand on my heart

No offence meant by what follows! We ALL have quality issues!

PHYSPROP Database

The freely downloadable database under the EPI Suite prediction software

Very Basic filters suggest data quality issues

The Stereochemistry challenge.12500 chemicals with “missed” stereo

NIST Webbook

EPA’s DailyMed

EPA’s DailyMed

EPA’s DailyMed

PubChem

Linking

Patents

Patents

WYSIWYG compounds

WYSIWYG compounds

Data Curation…long torturous task

Data curation – JUST structure-name validation is a long, torturous, iterative task.

How about validating “data” – PhysChem data such as logP data, boiling points, melting points (J.C.Bradley’s talk), spectra

The crowd in crowdsourcing is …generally small

Which of the large databases are doing careful curation. How can we share the workload? Hmm..

Consider searching each of these chemical databases by chemical name (systematic name, trade name or synonym). Please mark each online resource according to how much you generally trust the results.

Drug Name Generic Name ChEBI ChemSpiderCAS Com.

Chem ChemIDPlus DailyMed DrugBank PubChem Wikipedia

SpirivaTiotropium Bromide

No Hits No Hits 4/0

DepakoteValproate semisodium No

Structure

Basen Voglibose No Hits No Hits 2/1 Symbicort 1) Budesonide 8/1 Symbicort 2) Formoterol WRONG No Hits 6/1 Vytorin 1) Ezetimibe No Hits Vytorin 2) Simvastatin 2/1 Taxol Paclitaxel 44/1 Thalidomid Thalidomide No Hits Zocor Simvastatin 2/1 Crestor Rosuvastatin No Hits 2/1

Who does the Curation?

ChemSpider can “do it” for us

ChemSpider has built a curation interface used by the community and ourselves for curating.

All curation activities are available for review, online immediately, iteratively checked.

Curators have different abilities based on their profile: There are only a few “Master Curators”.

Can we “share” the curation workload?

Proof of Concept Data Curation Sharing

Identifier Dictionaries

Reciprocal curation processes…share curation with each other.

If a database has a compound already then use InChiKeys to match “suggested” validation against the compound.

A series of “added” and “removed” synonyms against InChIKeys for matching.

Who will participate???

Proof of Concept Data Curation Sharing

Lessons Learned : Big vs Good!

15 compounds called Yohimbine54 Skeletons for Yohimbine

Aggegators suffer dilution…

User Understanding of Data

Users searching “Yohimbine” expect to find it…not labeled versions of it, not ambiguous stereochemistries, not partial stereochemistries.

Data “aggregation” into a meaningful form is a major challenge. e.g. Assays for radiolabeled compounds linked to actual drugs.

Data curation efforts such as ChEMBL are essential!

SciMobileApps.com

SciDBs.com (Coming soon)

Open PHACTS : partnership between European Community and EFPIA

Freely accessible for knowledge discovery and verification. Data on small molecules Pharmacological profiles Pharmacokinetics ADMET data Biological targets and pathways Proprietary and public data sources.

Standardization and Quality

Our initial approaches to standardization were imperfect. We are revisiting to support OpenPHACTS.

Highly dependent on InChI and not enough standardization prior to InChI generation.

InChI is excellent and acknowledged imperfect. Way better than SMILES for linking the internet!

Conclusions

ChemSpider is one of many important chemistry resources on the internet

We have assumed an important role of curating and validating data – specifically name-structure dictionaries are of high importance but data validation is also key

We are a part of the federation of internet databases serving chemistry. MORE collaboration can serve us all better…how?

A Plea to Gov’t DBs…

Please improve gov’t DB communications

A Plea to Gov’t DBs…

Please improve gov’t DB communications

Please buddy up and get closer together

A Plea to Gov’t DBs…

Please improve gov’t DB communications

Please buddy up and get closer together

Get into deep conversations

Acknowledgments

Our development team – headed by THAT man..

Many in this room: InChI, PubChem, DssTOX, FDA, ChEBI/ChEMBL, SureChem, many more

Curators – special gratitude to Barrie Walker!

Software providers – OpenEye, ChemDoodle, ACD/Labs, GGA Software, Open Source (Jmol, JSpecView, OpenBabel)

Thank you

Email: williamsa@rsc.org Twitter: ChemConnectorPersonal Blog: www.chemconnector.comSLIDES: www.slideshare.net/AntonyWilliams