Online Public Compound Databases

Online Public Compound Databases Antony Williams

Introductions….
Hi….I’m Antony Williams, ChemSpiderman
NMR Spectroscopist by training
Worked in gov’t lab, academia, Fortune 500, start-up, founded ChemSpider, now work for the Royal Society of Chemistry
I am the host of ChemSpider…
25 million compounds
Linked to 400 data sources
You’ll hear more….

What’s your interest in Public Compound DBs ?
What public compound databases do you use?
What are you looking to find?
What proprietary databases do you presently use?
What do you trust?
Why are for-fee databases not enough?
What issues do you have with free chemistry databases/resources online?
What would the ideal solution provide????

Content is King and Quality Costs
Chemistry “content” is big money
Patent searching
Structures and properties
Drug databases
Literature databases
Chemical Abstracts Service (CAS), the “Gold Standard” in Chemistry related information
103 years of content
$260 million revenue (2006)
>50 million substances
>60 million sequences

What’s the Status of Chemistry online?
Encyclopedic articles (Wikipedia)
Chemical vendor databases (eMolecules)
Metabolic pathway databases (WikiPathways)
Virtual Screening databases (ZINC DB)
Property databases (Beilstein)
Screening assay results (PubChem)
Patents with chemical structures (SureChem)
ADME/Tox data (OEChem)
Scientific publications (Many publishers)
Compound aggregators (ChemSpider)
Blogs/Wikis and Open Notebook Science (Many)

Synthesis Blogs…TotallySynthetic.com

Org Prep Daily

Molbank (Open Access Journal)

Synthetic Pages (Website)

Lots of “Public Compound” Databases
PubChem
Drugbank
ChEBI/ChEMBL
KEGG
LipidMAPs
ChemIDPlus
eMolecules
ZINC
ChemSpider
Lots of chemical vendors
What’s missing??? What do you use online?

Where Would You look? What Do You Trust?

Linked Data on the Web Taken from: Rafael Sidis’ Blog

What is a compound?

Connections Can Lead Anywhere

Where Would You look? What Do You Trust?

PubChem

PubChem
PubChem is “a repository of screening data”
BUT, publishers, vendors, lots of chemical data holders..almost 30 million compounds
Properties, 3D optimized structures, links to various databases, chemical names, registry numbers, synonyms, trade names
PubChem is a repository – non-curated, no way to annotate or clean data. Data are free, not “open”

LIVE DEMO of PubChem
Name a chemical compound – search and review
Next slides:
Methane…
Diamond
Vancomycin
Taxol
Cholesterol

Chemistry on The Internet Is Messy

It’s Methane…

What’s Methane?

What ELSE is Methane???

The Challenges of Internet Data
Text-based searches commonly will get you to “representative data”
Accurate chemical structures are hard to find!
Wikipedia IS a good source of accurate chemistry data..not perfect but good.
See Tacrolimus
Tell the story of Domoic Acid – Next Slide

The EXPERTS must get it right?!

Wikipedia, C&E News, PubChem
C&E News (from ACS)

Feedback from Steve Ritter
“ As for where we source our structures, our primary source is the researcher and peer-reviewed papers , because many compounds are novel.
..we always double check them against one or more primary sources, typically Merck Index and SciFinder.
Although CAS and C&EN are both part of the ACS Publications Division, we at C&EN still have to pay for our SciFinder access, strangely enough.”

Feedback from Steve Ritter
“ As a rule, we at C&EN don’t use Wikipedia as a primary source for structures or chemical information, and I recommend that policy to anyone .”
“ It would be nice to have an authoritative web-based source of standard, well-drawn structures for chemists to go to so they can freely cut and paste structures into their papers, PowerPoint presentations, and anything else they might need. Maybe Wikipedia will be that source one day .”

The Challenges of Internet Data
Text-based searches commonly will get you to “representative data”
Accurate chemical structures are hard to find!
Wikipedia IS a good source of accurate chemistry data..not perfect but good.
See Tacrolimus
Tell the story of Domoic Acid
Unfortunately, question everything 

Question Everything online: www.dhmo.org

The FDA’s DailyMed

Structures on DailyMed

Lack of Stereochemistry

Does Stereochemistry Matter?

Does one stereocenter matter?
Distaval, Talimol, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, and Softenon

Does one stereocenter matter?
Distaval, Talimol, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, Softenon, Thalidomide

Incorrect Structures

Collaborative Knowledge Management

Taxol on PubChem

Drugbank

Digitonin? More Crowdsourcing…

Comments on the Blog
September 15th, 2009 at 1:57 pm It looks like both ChEBI and Wikipedia structures are wrong as far as aglycon is concerned. According to http://www3.interscience.wiley.com/journal/20330/abstract
“… for the first time to confirm beyond all doubt the structure suggested by Tschesche and Wulff for digitonin by means of modern NMR techniques, and to assign all proton and carbon resonances.” Structure 1 shows methyl group at C-20 going UP, i.e. 20β (while by default spirostan is 20α).

CAS as an authority

The Blogging Community Participate

Will it ever end?
The community says the structure of digitonin has “up” 20-Methyl.
If so, then multiple substances related to digitonin have OPPOSITE stereo at 20-Methyl
The spirostane skeleton is considered to have a “down” Methyl group so all spirostane-related structures would be wrong
The ACD/Dictionary has 24 structures with close skeleton and all have the “down” Methyl group.

Chemistry is REALLY Messy

Vancomycin
Who will curate?
How would you clean such a large dataset?
Assertions!!!

An Introduction to the InChI Identifier

Multiple Layers

InChIStrings Hash to InChIKeys

InChIs for Taxol

Back to Taxol
DrugBank: RCINICONZNJXQF-CLDWUXIMDD
ChEBI: RCINICONZNJXQF-GXKQXQCDDN
Wikipedia: RCINICONZNJXQF-MZXODVADBJ
Which one is correct???

Vancomycin – Search the Internet

Full Molecule Search: 4 Hits

Full Skeleton Search: 104 Hits

Vancomycin on ChemSpider 1 compound – 3 days

Assertion and Chemical Entities
Who says what Taxol is?
What is the “timeline” for a molecule?
How do we clean up the Public data?

InChIKeys for Taxol
DrugBank: RCINICONZNJXQF-CLDWUXIMDD
ChEBI: RCINICONZNJXQF-GXKQXQCDDN
Wikipedia: RCINICONZNJXQF-MZXODVADBJ
Structure validation is tough work!
Who is validating chemistry data online???

Bio-Break
Next Up – QUALITY CHOICES for online data
An introduction to ChemSpider
Crowdsourced Participation and Curation

Tony’s Quality Choices For Data
Chemical Abstracts Service and Reaxys – not free but definitely high quality!
Wikipedia Chemistry is good
ChEBI (look for “starred” compounds to indicate manual curation)
DSSTox – manually curated EPA database. Very high quality
ChemIDPlus – ongoing curation and good quality
The databases of David Wishart – manually curated. Good but not perfect – DrugBank, HMDB, FooDB and others

ChEBI: http://www.ebi.ac.uk/chebi/
Chemical Entities of Biological Interest from the European Bioinformatics Institute

DSSTox: http://www.epa.gov/comptox/dsstox/
Distributed Structure Searching for Toxicology from Ann Richards at the Environmental Protection Agency

ChemIDPlus – 350,000 Compounds http://chem.sis.nlm.nih.gov/chemidplus/

DrugBank: http://www.drugbank.ca/

And Our Own Work... ChemSpider
ChemSpider is:
Building a Structure Centric Community for Chemists
>25 million compounds, >400 data sources
A deposition and curation platform
A publishing platform for the community
Grows daily – more depositions, more links, more data sources

How Was ChemSpider Built?
ChemSpider was a “hobby project”
Housed in a basement and running off three servers – one bought, two built
Sensitive to weather and power stability
Went live at ACS Spring 2007 in Chicago

Search Cholesterol

Live DEMO
ChemSpider demo…

Link off a structure in ChemSpider
Chemical suppliers
Other publications
Analytical Data
Related Reactions
Wikipedia
Patents
“ Everything”

Answering Questions for Chemists
Questions a chemist might ask…
What is the melting point of n-butanol?
What is the chemical structure of Xanax?
Chemically, what is phenolphthalein?
What are the stereocenters of cholesterol?
Where can I find publications about xylene?
What are the different trade names for Ketoconazole?
What is the NMR spectrum of Aspirin?
What are the safety handling issues for Thymol Blue?

Complex Data and Information

Crowd-sourcing Chemistry Curation
Crowd-sourced curation: identify/tag errors, edit names, synonyms, identify records to deprecate

Multi-level Curation and Approval

ChemSpider SyntheticPages
ChemSpider Synthesis will be a home for all things “synthetic”
An online resource for synthetic procedures from blogs, other online resources, RSC supplementary info, other publishers etc.
Public peer-review and feedback for synthetic procedures

ChemSpider Everywhere : Embed

ChemSpider Everywhere: Spectral Game

ChemSpider Everywhere Crowdsourced Curation of Spectra

ChemSpider Everywhere ChemMobi

Where is ChemSpider Lacking?
More databases coming online monthly
Quality of data remains the primary issue
ChemSpider is limited to “defined chemicals”. No support for:
Polymers
Minerals
Markush structures

It’s a long road ahead…

Conclusions
The internet enables chemistry, at a reduced cost
Web 2.0 is here and improving quality
Question Quality!
Crowdsourcing to expand, curate and integrate
InChIs are enabling chemistry on the internet

Thank you [email_address] Twitter: ChemSpiderman www.chemspider.com/blog SLIDES: www.slideshare.net/AntonyWilliams

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Online Public Compound Databases

by Antony Williams, ChemConnector

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