ChemSpider -Connecting and Curating Online Chemistry Resources

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Antony WilliamsEBI, November 30th 2010

Chemistry on the Internet 100s of websites serving up chemistry data, SDF

files of structures and data Some primary resources : PubChem, ChEBI,

DrugBank, ChemIDPlus, Wikipedia

ChemSpider “links” chemistry on the internet Almost 25 million compounds, 400 data sources Allows community deposition, curation, annotation Integrating properties, publications, patents, media Text, structure, substructure (in testing) searching

www.chemspider.com

Search for a Chemical

Available Information…

Linked to vendors, safety data, toxicity, metabolism

We Have Delivered the Vision

“Build a Structure Centric Community toServe Chemists”

Integrate chemical structure data on the web Create a “structure-based hub” to information,

data and algorithmic predictions Let chemists contribute their own data Allow the community to curate/correct data

How Did We Build It?

We deal in Molfiles or SDF files – including coordinates

We do rudimentary filtering – valence checking, charge imbalance – prior to deposition

We have our own “business logic” to standardize We use InChI to “aggregate tautomers” to one

record Link out to external sites where possible using IDs

Inherited Errors

We have inherited errors from every database… all public compound databases, including ours, have errors

“Incorrect” structures – assertions, timelines etc “Incorrect” names associated with structures Properties Links Publications ENORMOUS CHALLENGE

What is the Structure of Vitamin K?

A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K

What is the Structure of Vitamin K1?

CAS’s Common Chemistry

Wikipedia

ChEBI – Manual Curation

PubChem

“2-methyl-3-(3,7,11,15-tetramethylhexadec-2-enyl)naphthalene-1,4-dione”

Variants of systematic names on PubChem

2-methyl-3-[(E,7R,11R)-3,7,11,15-tetramethyl 2-methyl-3-[(E,7S,11R)-3,7,11,15-tetramethyl 2-methyl-3-[(E,7R,11S)-3,7,11,15-tetramethyl 2-methyl-3-[(E,7S,11S)-3,7,11,15-tetramethyl 2-methyl-3-[(E,11S)-3,7,11,15-tetramethyl 2-methyl-3-[(E)-3,7,11,15-tetramethyl 2-methyl-3-(3,7,11,15-tetramethyl 2-methyl-3-[(E)-3,7,11,15-tetramethyl

Public Domain Chemistry Databases

Our databases are a mess…

Non-curated databases are proliferating errors We source and deposit data between databases Original sources of errors hard to determine Curation is time-consuming, challenging and

exacting

An examination of quality in databases – inter/intra lab comparison of processes for 150 drugs

Vytorin: Ezetimibe/Simvastatin

Symbicort: Budesonide + Formoterol

ChemIDPlus

Wikipedia

DrugBank: Search Symbicort…

Symbicort: Budesonide + Formoterol PubChem

8 structures called Budesonide. 1 “correct” 6 structures called Formoterol. 1 “correct” Search on “Symbicort” gives 1 structure.

Taxol: Paclitaxel 44 structures

Taxol: Paclitaxel Bioassay Data

Most Bioassay data associated with structure with one ambiguous stereocenter

Data on the Web – Good or Bad??

Taken from: Rafael Sidis’ Blog

Data on the Registry

How are data handled in Pharma?

Algorithms for “collapsing” data? Skeletons only? Processing structure-name pairs? Manual curation? Does it matter relative to the noise in the

measurements?

Do correct structure representations matter, and to who?????

EPA’s DailyMed

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

Why Curated Dictionaries Matter

Success Depends on Dictionaries

Online Curation

Online databases generally do NOT allow curation or annotation

If you find errors they stay there! ChemSpider allows immediate curation

Crowdsourcing Works

Over 100 people have deposited data (structures, spectra, etc) and participated in data curation

Different level curators check each others work Wikipedia is the modern primary example Some curators are “madmen”…

Crowdsourcing Works

Over 100 people have deposited data (structures, spectra, etc) and participated in data curation

Different level curators check each others work Wikipedia is the modern primary example Some curators are “madmen”… The Oxford English Dictionary

Collaborative Data Curation

How can we COLLECTIVELY clean online data?

ChemSpider has inherited junk from >400 data sources. Some of this has proliferated into PubChem. We should deprecate it.

We need to develop a way to share curation actions back to original data sources

A mindset of bigger is better is problematic. How many “real chemicals” are in the public databases?

ChemSpider

ChemSpider is free to use. Multiple web services are available. New data added daily. Curation and data validation ongoing everyday. Provided by the RSC.

www.chemspider.com

Thank you

Email: williamsa@rsc.org Twitter: ChemConnectorBlog: www.chemspider.com/blogPersonal Blog: www.chemconnector.comSLIDES: www.slideshare.net/AntonyWilliams

ChemSpider -Connecting and Curating Online Chemistry Resources

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