Crowdsourcing, Collaborations and Text-Mining in a World of Open Chemistry Antony Williams Nature Publishing Group Presentation, New York, May 2009

The Changing Scope of My Roles and Information Access Postdoctoral position, NRC, Canada (1988-1990) NMR Facility Director, University of Ottawa (1990-1991) NMR Technology Leader, Eastman-Kodak (1991-1997). VP and Chief Science officer for ACD/Labs, a commercial scientific software company (1997-2007). Consultant to cheminformatics/scientific software companies, publishers, academia “ ChemSpiderman” – host of a rich resource of Free Access web-based information for chemists.

Postdoctoral position, NRC, Canada (1988-1990)

NMR Facility Director, University of Ottawa (1990-1991)

NMR Technology Leader, Eastman-Kodak (1991-1997).

VP and Chief Science officer for ACD/Labs, a commercial scientific software company (1997-2007).

Consultant to cheminformatics/scientific software companies, publishers, academia

“ ChemSpiderman” – host of a rich resource of Free Access web-based information for chemists.

Access to Information For me… PhD : Libraries primary source of information PostDoc/Academia: Libraries and librarians Eastman Kodak: Software tools and databases Kodak and ACD/Labs: Replaced by the internet Today: The Internet enhanced by a network of collaborators…

For me…

PhD : Libraries primary source of information

PostDoc/Academia: Libraries and librarians

Eastman Kodak: Software tools and databases

Kodak and ACD/Labs: Replaced by the internet

Today: The Internet enhanced by a network of collaborators…

Content is King Chemistry “content” is big money – Chemistry publishing and content is worth $100s of millions/year Patent searching Structures and properties Drug databases Literature databases Chemical Abstracts Service (CAS), a division of the ACS is “Gold Standard” in Chemistry related information 101 years of content, $260 million revenue (2006), >40 million substances and 60 million sequences

Chemistry “content” is big money – Chemistry publishing and content is worth $100s of millions/year

Patent searching

Structures and properties

Drug databases

Literature databases

Chemical Abstracts Service (CAS), a division of the ACS is “Gold Standard” in Chemistry related information

101 years of content, $260 million revenue (2006), >40 million substances and 60 million sequences

The Language of Chemistry My language….

My language….

And its dialects….

As a chemist… I look for information about chemicals/chemistry What is a particular structure ? What alternative names/identifiers? Reaction synthesis? Physical properties? Analytical data? Purchase? Tell me more? Similar stuff – what other compounds are “like” mine?

I look for information about chemicals/chemistry

What is a particular structure ?

What alternative names/identifiers?

Reaction synthesis?

Physical properties?

Analytical data?

Purchase?

Tell me more?

Similar stuff – what other compounds are “like” mine?

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? Cheminformatics has as much of a public face as bioinformatics

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?

Cheminformatics has as much of a public face as bioinformatics

Linked Data Cloud

Chemistry on the Internet Much of the information online is User Beware! The Quality of information is “diverse” Technologies can “link and connect” information but validation and curation is key to providing quality The LinkedData web is of less value when the data linked are “wrong”

Much of the information online is User Beware!

The Quality of information is “diverse”

Technologies can “link and connect” information but validation and curation is key to providing quality

The LinkedData web is of less value when the data linked are “wrong”

“ Good Stuff” TotallySynthetic.com

PubChem

What is “wrong”?

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? ChemSpider can answer all of these questions

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?

ChemSpider can answer all of these questions

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

Search Cholesterol

Link outs

Links out to KEGG Kyoto Encyclopedia of Genes and Genomes

Complex Data and Information

Other Searches What compounds have a mass of 300+/-0.001? or search a combination of intrinsic/predicted properties

What compounds have a mass of 300+/-0.001?

or search a combination of intrinsic/predicted properties

Other Searches

Complex Search

The Quality of Online Chemistry…

The Quality of

Online Chemistry…

Quality is a Major Issue- Search Butanol OLD EXAMPLE..now fixed

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

C&E News (from ACS)

Does one stereocenter matter? Thalidomide

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 ChemSpider: 1 compound – 3 days

Question Everything www.dhmo.org

DailyMed “ DailyMed provides high quality information about marketed drugs. This information includes FDA approved labels (package inserts).”

“ DailyMed provides high quality information about marketed drugs.

This information includes FDA approved labels (package inserts).”

The FDA’s DailyMed

Structures on DailyMed Poor Representations

Structures on DailyMed Lack of Stereochemisty

Incorrect Structures Scanning (?) Issues

Incorrect Structures

Does it Matter? Does it matter to the consumer that the structures are wrong? No…what matters is what is in the bottle is the right medication! To make DailyMed structure searchable it DOES matter To data mine DailyMed it matters To mark up DailyMed it matters

Does it matter to the consumer that the structures are wrong? No…what matters is what is in the bottle is the right medication!

To make DailyMed structure searchable it DOES matter

To data mine DailyMed it matters

To mark up DailyMed it matters

Wikis for Science Who in the room hasn’t used Wikipedia? Is it trustworthy? What are the advantages and disadvantages of the Wiki environment? How suitable is it for Chemistry?

Who in the room hasn’t used Wikipedia?

Is it trustworthy?

What are the advantages and disadvantages of the Wiki environment?

How suitable is it for Chemistry?

Collaborative Knowledge Management for Chemists

Wikipedia Chemistry Curation project Only ca. 6000 organic structures, 8000 total structures Over 18 months of work for a team of 6 people Many errors removed in the process. Curation process is a daily event for users/depositors Slow and torturous process http://en.wikipedia.org/wiki/Talk:Tacrolimus#IUPAC_Name_and_structure

Only ca. 6000 organic structures, 8000 total structures

Over 18 months of work for a team of 6 people

Many errors removed in the process. Curation process is a daily event for users/depositors

Slow and torturous process

http://en.wikipedia.org/wiki/Talk:Tacrolimus#IUPAC_Name_and_structure

Wikipedia Curation Looking for self-consistency across a Wikipedia Page Primary key is the article TITLE The chemical shown needs to match the title Cyclic self-consistency – and decisions must get made

Looking for self-consistency across a Wikipedia Page

Primary key is the article TITLE

The chemical shown needs to match the title

Cyclic self-consistency – and decisions must get made

Wikipedia Links to Drugbank

Taxol on PubChem

Taxol on Daily Med

Differences between ChemSpider/Wikipedia No, but links. Analytical Data Active editors > 50 (?) Active depositors/curators – 30 No Prediction of properties ???? 6000 people/day; 3800 registered Detailed compound monographs Compound monographs linked Text Complex queries – Properties, Text, structure/substructure, OA publishers, Data Sources, … ~6000 organics, 2000 others >21 million unique structures Wikipedia ChemSpider

Differences between Wikipedia/ChemSpider Growing reputation as focused on quality Worldwide reputation as quality source – good and bad Chemistry is the focus of ‘Spider Chemistry is a subset of the ‘Pedia Mixed “licensing” GFL licensing for everything Growing team of advocates, curators and users Strong team of WP:Chem advocates, curators and admins “ Out of a basement” on three servers and 5 volunteers Established infrastructure and Wikipedia Foundation Team Primarily Microsoft .NET technologies with OS components Supported by tried and tested Media-Wiki platform. ChemSpider Wikipedia

The InChI Identifier

Multiple Layers Source: Unofficial InChI FAQ page

Source: Unofficial InChI FAQ page

InChIs Structure but NOT substructure

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

The InChI Resolver

Coming Soon…Linked Articles

How bad can it get??? And who is right????

Curating ChemSpider Anyone can “Post Comments” associated with a structure. To curate data we require login to track

Anyone can “Post Comments” associated with a structure. To curate data we require login to track

Multi-level Curation and Approval

Crowd-sourcing Chemistry Crowd-sourced curation: identify and tag errors, edit names, synonyms, identify records for deprecation ALSO Crowd-sourced deposition: anyone can deposit data (structures, text, images, analytical data)

Crowd-sourced curation: identify and tag errors, edit names, synonyms, identify records for deprecation

ALSO

Crowd-sourced deposition: anyone can deposit data (structures, text, images, analytical data)

Structure-Centric We want to search “information” by structure, substructure, similarity of structure Specific focus on Open Chemistry at present Standard approaches would be: Identify chemical names “entity extraction” Convert chemical names to structures and index ChemSpider has a validated dictionary of structure-name pairs Use name extraction, name-conversion and dictionary look-up. THEN curate.

We want to search “information” by structure, substructure, similarity of structure

Specific focus on Open Chemistry at present

Standard approaches would be:

Identify chemical names “entity extraction”

Convert chemical names to structures and index

ChemSpider has a validated dictionary of structure-name pairs

Use name extraction, name-conversion and dictionary look-up. THEN curate.

“Entity Extraction” Rule-based recognition of systematic names: Use a lexeme of name fragments Rules for identifying bounds of a name Look-up dictionary: Drug Names Trivial Names Numbers : Registry IDs, EINECS/ELINCS Massive look-up dictionary of validated identifiers on ChemSpider

Rule-based recognition of systematic names:

Use a lexeme of name fragments

Rules for identifying bounds of a name

Look-up dictionary:

Drug Names

Trivial Names

Numbers : Registry IDs, EINECS/ELINCS

Massive look-up dictionary of validated identifiers on ChemSpider

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) at 0 oC were successively added (3,4-diaminophenyl)phenyl methanone 1 (0.40 g, 1.88 mmol) and a excces of anhydrous MgSO4 (2.00 g,16.67 mmol) . The resulting mixture was stirred for 6 hours at room temperature [18]. The mixture was filtered and washed with dichloromethane . Then the solvent was evaporated under reduced pressure to give azo Schiff base 3 as a red solid which was recrystalized from ethanol 95% (1.28 g, 91 %)

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) at 0 oC were successively added (3,4-diaminophenyl)phenyl methanone 1 (0.40 g, 1.88 mmol) and a excces of anhydrous MgSO4 (2.00 g,16.67 mmol) .

The resulting mixture was stirred for 6 hours at room temperature [18]. The mixture was filtered and washed with dichloromethane . Then the solvent was evaporated under reduced pressure to give azo Schiff base 3 as a red solid which was recrystalized from ethanol 95% (1.28 g, 91 %)

How Many Chemical Names? “ She had the drive to derive success in any venture and was well versed in Karate . When the man in the tartan shirt approached her with a dagger in his hand she spat in his face, took the stance of a commando and took advantage of his shock to release the dagger from his grip and causing him to recoil . He went home and took an aspirin after the beating.”

“ She had the drive to derive success in any venture and was well versed in Karate . When the man in the tartan shirt approached her with a dagger in his hand she spat in his face, took the stance of a commando and took advantage of his shock to release the dagger from his grip and causing him to recoil . He went home and took an aspirin after the beating.”

ChemMantis Chem ical M arkup A nd N omenclature T ransformation I ntegrated S ystem

Chem ical M arkup A nd N omenclature T ransformation I ntegrated S ystem

Making Open Access Articles Searchable Proof of Concept Can we HOST Chemistry Open Access articles on ChemSpider and add-value Can we identify chemical names in Open Access articles in a user-friendly manner Can we convert names to structures in Open-Access articles and expand ChemSpider and provide structure searching of Open Access chemistry articles? Can we provide an environment for chemists to mark-up their own articles and crowd-source markup of an archive?

Can we HOST Chemistry Open Access articles on ChemSpider and add-value

Can we identify chemical names in Open Access articles in a user-friendly manner

Can we convert names to structures in Open-Access articles and expand ChemSpider and provide structure searching of Open Access chemistry articles?

Can we provide an environment for chemists to mark-up their own articles and crowd-source markup of an archive?

Document markup

Markup – 3 seconds!

On the fly conversion

Shorthand Formulae Supported

One Click to more Info…

A Platform for Markup Can we provide a platform for document markup for chemists? Workflow: Upload word docs, RTF files or point to HTML and load Apply entity extraction, convert names to structures, mark-up automatically and ask for user participation Deposit all structures on ChemSpider under embargo and wait for article DOI to release

Can we provide a platform for document markup for chemists?

Workflow:

Upload word docs, RTF files or point to HTML and load

Apply entity extraction, convert names to structures, mark-up automatically and ask for user participation

Deposit all structures on ChemSpider under embargo and wait for article DOI to release

Challenges Computer software can generate chemical names better than the majority of chemists The majority of chemical names are generated by humans, and Incorrect – convert to the wrong structure or are ambiguous One name, Multiple Structures

Computer software can generate chemical names better than the majority of chemists

The majority of chemical names are generated by humans, and Incorrect – convert to the wrong structure or are ambiguous

One name, Multiple Structures

Names and Structures Dichloroacetone Trichloromethylsilane

Dichloroacetone

Trichloromethylsilane

Ambiguity

Ambiguity in Abbreviations - DPA

Ambiguity in Abbreviations - THF

Import is Easy Make articles Public/Private (embargo date soon) Auto-markup and check by user

Make articles Public/Private (embargo date soon)

Auto-markup and check by user

IUPAC PAC Articles

Supports Word .DOC, HTML, RTF

Nature Publications

Entity Balloons Structures are the language of chemistry Show structures to chemists and search/link from there

Structures are the language of chemistry

Show structures to chemists and search/link from there

Integrations Out to Other Sources

Integrations Out to Other Sources

Reactions

Manual Curation is Always Necessary

Text- Indexing and ChemSpider? ChemSpider text-indexes almost 500,000 Open Access and Free Access articles Collection is growing and more publishers have already agreed. Including theses in the future.

ChemSpider text-indexes almost 500,000 Open Access and Free Access articles

Collection is growing and more publishers have already agreed. Including theses in the future.

Open Access Literature Search

Dictionaries are Easily Enhanced Copy-Paste into appropriate Entity Dictionary Impacts all future markups Expanding knowledgebases of information Linked out to rich sources of information

Copy-Paste into appropriate Entity Dictionary

Impacts all future markups

Expanding knowledgebases of information

Linked out to rich sources of information

Build Dictionaries Ontologies Next

Other Dictionaries - Species We are considering Bacteria Fungi Enzymes Viruses PDB codes….

We are considering

Bacteria

Fungi

Enzymes

Viruses

PDB codes….

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 Functionality (like YouTube)

ChemSpider Everywhere www.spectralgame.com

ChemSpider Everywhere Crowdsourced Curation of Spectra

ChemSpider Everywhere RSC Compounds

ChemSpider Everywhere Nature Chemistry Nature Chemistry articles are annotated to identify all of the chemical compounds mentioned throughout the text. Those compounds are linked out to other information resources including PubChem and ChemSpider .

Nature Chemistry articles are annotated to identify all of the chemical compounds mentioned throughout the text.

Those compounds are linked out to other information resources including PubChem and ChemSpider .

ChemSpider Everywhere ChemMobi

Structure RSS Feeds with InChIs

Conclusions www.chemspider.com www.chemspider.com/journal InChIs and Internet Chemistry http://inchis.chemspider.com

www.chemspider.com

www.chemspider.com/journal

InChIs and Internet Chemistry

http://inchis.chemspider.com