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?

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,…

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,…

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,…

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

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

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

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

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”

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?

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?

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?

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)

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.”

“ 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 .”

“ 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).

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 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

Wow!

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???

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

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

Distaval, Talimol, Nibrol, Sedimide, Quietoplex, Contergan, Neurosedyn, and Softenon

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

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…

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 Searches

ChemSpider Complex Searches

ChemSpider 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

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

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.

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

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

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

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) .

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

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

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”

What would you want to link off a structure?

Chemical suppliers

Other publications

Analytical Data

Related Reactions

Wikipedia

Patents

“ Everything”

RSC Supplementary Info

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

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

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

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?

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

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