Building a Foundation for the Semantic Web by Hosting a Crowdsourced Databasing Platform for Chemistry

What’s the Status of Chemistry online? Encyclopedic articles (Wikipedia) Chemical vendor databases Metabolic pathway databases Virtual Screening databases Property databases Screening assay results Patents with chemical structures (IBM & SureChem) ADME/Tox data Scientific publications Compound aggregators Blogs/Wikis and Open Notebook Science

Encyclopedic articles (Wikipedia)

Chemical vendor databases

Metabolic pathway databases

Virtual Screening databases

Property databases

Screening assay results

Patents with chemical structures (IBM & SureChem)

ADME/Tox data

Scientific publications

Compound aggregators

Blogs/Wikis and Open Notebook Science

For Synthesis…TotallySynthetic.com

Org Prep Daily (Blog)

Molbank (Open Access Journal)

Synthetic Pages (Website)

Encyclopedic Articles (Wikipedia)

Lots of “Public Compound” Databases PubChem Drugbank ChEBI/ChEMBL KEGG LipidMAPs ChemIDPlus eMolecules ZINC Lots of chemical vendors ChemSpider

PubChem

Drugbank

ChEBI/ChEMBL

KEGG

LipidMAPs

ChemIDPlus

eMolecules

ZINC

Lots of chemical vendors

ChemSpider

Where Would You look? What Do You Trust?

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

Compounds and Identifiers

Connecting Chemistry on the Web Connections are made actively by purposeful linking via semantic web links (i.e. RDF and triple stores) by integrating via identifiers (InChI, CAS #, names and web service look ups)

Connections are made

actively by purposeful linking

via semantic web links (i.e. RDF and triple stores)

by integrating via identifiers (InChI, CAS #, names and web service look ups)

Connections Can Lead Anywhere

The FUTURE of Chemistry on the Web 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 Publicly funded research data can be shared and discussed in the Open, maybe as ONS? There is structure based access to property data (ADME/Tox), spectra, clean name-structure dictionaries

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

Publicly funded research data can be shared and discussed in the Open, maybe as ONS?

There is structure based access to property data (ADME/Tox), spectra, clean name-structure dictionaries

What is ChemSpider? ChemSpider is: Building a Structure Centric Community for Chemists >20 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

>20 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

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 Searches

ChemSpider Searches

ChemSpider Complex Searches

Question Everything online: www.dhmo.org

Searching Dihydrogen Monoxide…

Politicians, Chemistry and DHMO  March 2004 , Aliso Viejo, California considered banning foam containers at city-sponsored events because dihydrogen monoxide is part of their production. 2007 Jacqui Dean , New Zealand National Party MP write a letter to Associate Minister of Health Jim Anderton asking "Does the Expert Advisory Committee on Drugs have a view on the banning of this drug?"

March 2004 , Aliso Viejo, California considered banning foam containers at city-sponsored events because dihydrogen monoxide is part of their production.

2007 Jacqui Dean , New Zealand National Party MP write a letter to Associate Minister of Health Jim Anderton asking "Does the Expert Advisory Committee on Drugs have a view on the banning of this drug?"

Caution! Question Everything!

PubChem

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 – discussions over 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 has a “ down ” Methyl group so all spirostane-related structures would be wrong

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 has a “ down ” Methyl group so all spirostane-related structures would be wrong

The FDA’s DailyMed

Structures on DailyMed

Lack of Stereochemisty

Incorrect Structures

Wow!

Collaborative Knowledge Management

Drugbank

Taxol on PubChem

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

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

ChemSpider Searches

ChemSpider Searches

InChIKey Searches Work

The InChI “Resolver”

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

Who says what Taxol is?

What is the “timeline” for a molecule?

How do we clean up the Public data?

Crowdsourcing

Depositions From Crowds CAS indexes published literature, patents and chemical vendors ( indexes ChemSpider too ) “ Lost Chemistry” syntheses in theses lab notebooks compounds in private collections ChemSpider accepts public depositions: structures, text, spectra, images.

CAS indexes published literature, patents and chemical vendors ( indexes ChemSpider too )

“ Lost Chemistry”

syntheses in theses

lab notebooks

compounds in private collections

ChemSpider accepts public depositions: structures, text, spectra, images.

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

“ Lathosterol”

“ Lathosterol”

“ Lathosterol”

“ Lathosterol” Removed

“ Lathosterol” on PubChem

“ Lathosterol” on PubChem

“ Lathosterol” on PubChem

Validate Names for PubMed “Caldarchaeol”

Publishers are experimenting … invited researchers to prototype tools dealing with the ever-increasing amount of online life sciences information The winners built: Reflect: Automated Annotation of Scientific Terms : http://reflect.ws

… invited researchers to prototype tools dealing with the ever-increasing amount of online life sciences information

The winners built:

Reflect: Automated Annotation of Scientific Terms : http://reflect.ws

Reflect

Entity-Extraction, Mark-up, Annotate

Success Depends on Dictionaries

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

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

Curation led to a set of validated dictionaries

Integrated best-in-class entity extraction with validated name dictionaries

Additional dictionaries gave reactions, groups, families, hardware and software vendors etc

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

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’s Project Prospect

In Development 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

RSC Supplementary Info

RSC Supplementary Info

Online Journals and Live Data

ChemSpider Everywhere : Embed

ChemSpider Everywhere: Spectral Game

ChemSpider Everywhere Crowdsourced Curation of Spectra Building a Structure Centric Community for Chemists

ChemSpider Everywhere ChemMobi Building a Structure Centric Community for Chemists

ChemSpider Everywhere Linked from Wikipedia Linked from Open Notebook Science sites 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

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

It’s a long road ahead…

More representative…

Where is ChemSpider Lacking? ChemSpider is limited to “defined chemicals”. No support for: Polymers Minerals Markush structures ChemSpider is very dependent on InChIs Stereochemistry around non-carbon centers Organometallics are not correctly represented There are millions of errors on ChemSpider

ChemSpider is limited to “defined chemicals”. No support for:

Polymers

Minerals

Markush structures

ChemSpider is very dependent on InChIs

Stereochemistry around non-carbon centers

Organometallics are not correctly represented

There are millions of errors on ChemSpider

What’s next? Keep cleaning and depositing data Deprecate/redeposit at PubChem Layer on RDF for the semantic web Integrate software: Symyx Jdraw, NMRShiftDB Integrate RSC content – a massive archive! Integrate RSC publishing workflows and databases

Keep cleaning and depositing data

Deprecate/redeposit at PubChem

Layer on RDF for the semantic web

Integrate software: Symyx Jdraw, NMRShiftDB

Integrate RSC content – a massive archive!

Integrate RSC publishing workflows and databases

You are invited.. Curate ChemSpider data and link to us Deposit your data with us Structures Spectra Synthesis procedures ChemSpider Synthesis is under development Help assert what is Digitonin?

Curate ChemSpider data and link to us

Deposit your data with us

Structures

Spectra

Synthesis procedures

ChemSpider Synthesis is under development

Help assert what is Digitonin?

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

Not in a basement now...

And the Downside

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