Navigating the Complex Web of Chemistry Using ChemSpider

Imagine a time when ….
The internet is searchable by chemical structure and substructure (e.g.Wikipedia, Google Scholar)
Chemistry articles are indexed and searchable by a free online service
The web is linked together through the “language of chemistry”
Publicly funded research data can be shared and discussed in the Open, maybe as ONS?

It’s Coming…Linked Data Cloud

For Synthesis…TotallySynthetic.com

Org Prep Daily (Blog)

Molbank (Open Access Journal)

Synthetic Pages (Website)

For Chemical Compounds
Vendor sites – Aldrich, Alfa Aesar, TCI and 100s of others
Government databases – PubChem, DSSTox, FDA databases, ChemIDPlus,…
Biological Databases – Protein Database, Stitch, KEGG, ChEBI,…
Analytical databases – Red Hen Spectra, NMRShiftDB,…

What is ChemSpider?
ChemSpider is:
Building a Structure Centric Community for Chemists
22.2 million compounds, >200 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

Linked across the internet

Kyoto Encyclopedia of Genes and Genomes

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

Links to Patents based on structure

Clickthrough to Patent (SureChem)

Pubmed Articles Linked

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

ChemSpider is a structure-centric hub
ChemSpider aggregates and links out across the internet
Data aggregate based on “structures and links”
What defines a chemical compound?

What is a compound?

Question Everything online: www.dhmo.org

PubChem

Caution! Question Everything!

Vancomycin
Who will curate?
PubChem is not resourced to clean these errors
How would you clean such a large dataset?

Vancomycin on ChemSpider 1 compound – 3 days

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 .”

What About Digitonin?

Comments on the Blog
Kirill Degtyarenko says:
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.

The FDA’s DailyMed

Structures on DailyMed

Lack of Stereochemisty

Incorrect Structures

Collaborative Knowledge Management

Drugbank

Taxol on PubChem

FDA’s DailyMed

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???

InChIKeys for Taxol
DrugBank: RCINICONZNJXQF-CLDWUXIMDD
ChEBI: RCINICONZNJXQF-GXKQXQCDDN
Wikipedia: RCINICONZNJXQF-MZXODVADBJ
ChEBI and Wikipedia are the SAME structure
Drugbank is a DIFFERENT structure – ONE stereocenter

Does one stereocenter matter?

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

Building a Structure Centric Community for Chemists

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

ChemSpider Searches

ChemSpider Complex Searches

ChemSpider Searches

InChIKey Searches Work

The InChI “Resolver”

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
101 years of content
$260 million revenue (2006)
>50 million substances
>60 million sequences

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

Chemistry – A Deposition Platform
CAS indexes published literature, patents and chemical vendors
CAS indexes ChemSpider – >303,000 records
“ Lost Chemistry” – syntheses in theses, lab notebooks? Compounds in private collections?
ChemSpider accepts public depositions, linking to websites, hosting of details etc. Accepts structures, text, spectra, images.

Structure Searching Articles…
Searching articles based on chemical structure and substructure is very expensive.. but is changing
The web IS ready - when will publishers deliver?
Structures can be shown
Spectra can be interactive
Graphics don’t need to be static
Publishers can enhance their articles

Semantic Mark-up for Chemistry
Semantic mark-up for chemistry is here
RSC project prospect (structure linking, IUPAC Gold Book ontology and other ontologies
Nature publishing group compound linking
ChemSpider Journal of Chemistry

Nature Chemistry Compound Pages

Project Prospect

ChemSpider and Publishing
The curation efforts on ChemSpider led to a set of validated dictionaries
Integrate best-in-class entity extraction with validated name dictionaries
Additional dictionaries gave reactions, groups, families, hardware and software vendors etc

Name Recognition
Azo aldehyde 2 was synthesized according to a reported method [17]. To a stirred solution of azo aldehyde 2 (1.08 g, 3.76 mmol ) in dry CH2Cl2 (30.00 mL) were successively added.
(3,4-diaminophenyl)phenyl methanone 1 (0.40 g, 1.88 mmol) and an excess of anhydrous MgSO4 (2.00 g, 16.67 mmol) .

ChemMantis and CJOC

Name-Structure Pairs

Converting Detected Names…
Names are searched against a validated dictionary (this expands as ChemSpider is curated)
If not found then they are passed through a Name to Structure algorithm
If they cannot convert then ChemSpider is searched for non-validated names

Manual Curation is Necessary

Deposit Structures

Custom Dictionaries
Entity Extraction built around modified algorithms from SureChem
Optimized for “publications”
Dictionaries for chemical entities, groups, reactions, elements, families, species…
Dictionaries can be expanded

Species – linked to Wikipedia

Semantic Linking of Structures
What would you want to link off a structure?
Chemical suppliers
Other publications
Analytical Data
Related Reactions
Wikipedia
Patents
“ Everything”

RSC Supplementary Info

ChemSpider Synthesis
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

Online Journals and Live Data

ChemSpider Everywhere
Linked from Wikipedia
Linked from Open Notebook Science sites using EMBED
Linked from Blogs using Structure/Spectra EMBED
Integrated into structure drawing packages such as ACD/ChemSketch, Symyx Draw, Open Source applets
Integrated to software offerings from Thermo, Waters, Agilent, Bruker

ChemSpider Everywhere : Embed

ChemSpider Everywhere: Spectral Game

ChemSpider Everywhere : ChemMobi

Not in a basement now...

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

You are invited..
Deposit your data with us
Structures
Spectra
Synthesis procedures
ChemSpider Synthesis is under development
What is Digitonin?

Acknowledgments
Valery Tkachenko and Sergey Golotvin
RSC infrastructure team
The ChemSpider advisory group
The Wikipedia Chemistry team
JC Bradley, Andy Lang – Spectral Game

Thank you [email_address] Twitter: ChemSpiderman www.chemspider.com/blog

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Navigating the Complex Web of Chemistry Using ChemSpider

by Antony Williams, ChemConnector on Oct 09, 2009

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Navigating the Complex Web of Chemistry Using ChemSpider — Presentation Transcript