Whitney Symposium Lecturejune 2008 1220331644496491 9

Crowd-Sourcing to Build a Crowd-Sourcing to Build a Structure Centric Structure Centric

Community for Chemists Community for Chemists

Antony WilliamsAntony WilliamsWhitney Symposium 2008 - NetworksWhitney Symposium 2008 - Networks

Building a Structure Centric Community for Chemists

Social Networking for Social Networking for ChemistsChemists


Network Drug Discovery ToolsNetwork Drug Discovery Toolswww.curehunter.comwww.curehunter.com


Beware the Networks!Beware the Networks!


Collaborative Authoring in Collaborative Authoring in AcademiaAcademia

Group level collaboration via WikisGroup level collaboration via Wikis


Collaborative Authoring for Drug Collaborative Authoring for Drug DiscoveryDiscovery

PfizerpediaPfizerpedia


Collaborative Knowledge Collaborative Knowledge Management Management

for Chemists – Wikipedia, Built by for Chemists – Wikipedia, Built by a Networka Network


and biologists…WikiProteinsand biologists…WikiProteins


WikiProteinsWikiProteins

What Is

Tegafur?


Commonly Lacking…Commonly Lacking…

Approaches generally lack “structural Approaches generally lack “structural intelligence”intelligence” Structures have properties (Mw, MF, exp. & Structures have properties (Mw, MF, exp. &

pred. properties)pred. properties) Collections of structures need to be Collections of structures need to be

searchable by structuresearchable by structure Most data collections are “self-contained” and Most data collections are “self-contained” and

rarely connecting to other resources via rarely connecting to other resources via “structure”“structure”


A Search Engine for ChemistsA Search Engine for Chemists

Questions a chemist might ask…Questions a chemist might ask… What is the melting point of n-butanol? What is the melting point of n-butanol? What is the chemical structure of Xanax?What is the chemical structure of Xanax? Chemically, what is viagra?Chemically, what is viagra? What are the stereocenters of cholesterol?What are the stereocenters of cholesterol? Where can I find publications about Taxol?Where can I find publications about Taxol? What are the different trade names for What are the different trade names for

Ketoconazole?Ketoconazole? What is the NMR spectrum of Aspirin?What is the NMR spectrum of Aspirin? What are the safety handling issues for Thymol What are the safety handling issues for Thymol

Blue?Blue?

ChemSpider can answer all of these questionsChemSpider can answer all of these questions


ChemSpider Data ContentChemSpider Data Content

Over 20 million unique chemical structures :Over 20 million unique chemical structures : Online Databases –PubChem, Drugbank, HMDB, Online Databases –PubChem, Drugbank, HMDB,

WikipediaWikipedia Chemical Vendors – over 40 different vendors and Chemical Vendors – over 40 different vendors and

growinggrowing Personal Depositions – individual contributionsPersonal Depositions – individual contributions Journal Publishers Journal Publishers Content database vendorsContent database vendors Analytical data collectionsAnalytical data collections Patents (9 MILLION Structures to search patentsPatents (9 MILLION Structures to search patents)) Web scrapingWeb scraping

Content is linked back to the original data sourcesContent is linked back to the original data sources


A Structure Centric Community A Structure Centric Community for Chemistsfor Chemists

A FREE ACCESS platform for deposition, A FREE ACCESS platform for deposition, management, curation, annotation and management, curation, annotation and extension of information associated with extension of information associated with chemical structureschemical structures

Semantically connect to other sites Semantically connect to other sites providing access to knowledge, data and providing access to knowledge, data and information of determined qualityinformation of determined quality

Search by alphanumeric text, chemical Search by alphanumeric text, chemical structure and substructure and combination structure and substructure and combination searchessearches

Predict properties for submitted structuresPredict properties for submitted structures


Tell me about AspirinTell me about Aspirin




Links out to KEGGLinks out to KEGGKyoto Encyclopedia of Genes and Kyoto Encyclopedia of Genes and

Genomes Genomes




Tell me About AspirinTell me About Aspirin






Abstract Compounds?Abstract Compounds?

Is there any information about Is there any information about “Quesnoin”?“Quesnoin”?

Type in the name (and there may be Type in the name (and there may be many) or other identifiermany) or other identifier

Paste a chemical structurePaste a chemical structure Draw the structureDraw the structure


Example SearchExample Search


Example Search Example Search


Example Search 2Example Search 2

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

or search a combination of intrinsic/predicted or search a combination of intrinsic/predicted propertiesproperties


Example Search 2Example Search 2


Complex SearchComplex Search


Search Open Access Journals – Search Open Access Journals – ChemSpiderChemSpider


Search PubMed – ChemSpiderSearch PubMed – ChemSpider


The Quality of Data Online…The Quality of Data Online…

Aggregating data opens up quality issuesAggregating data opens up quality issues Structure-identifier associations are “dirty”Structure-identifier associations are “dirty” Structures are COMMONLY incorrect – Structures are COMMONLY incorrect –

stereochem issuesstereochem issues Manual curation of small databases is enough Manual curation of small databases is enough

work – what about millions of structures?work – what about millions of structures? Structures are far from perfect. What is a Structures are far from perfect. What is a

“correct structure”?“correct structure”? Full stereochemistry? Full stereochemistry? Historical timeline of structure?Historical timeline of structure? Who is the authority?Who is the authority?


Who holds THE Quality Who holds THE Quality Authority?Authority?

Chemical Abstracts Service is the Chemical Abstracts Service is the structural authority today. 1400 (?) structural authority today. 1400 (?) employees, world standard in chemistry employees, world standard in chemistry informationinformation

101 years of knowledge, process and 101 years of knowledge, process and expertise. MANUAL curation is key. expertise. MANUAL curation is key. Robotic curation is enablingRobotic curation is enabling

How can an online, free access system How can an online, free access system peacefully co-exist with the authority? peacefully co-exist with the authority?


Quality is a Major Issue- Quality is a Major Issue- Search ButanolSearch Butanol


Crowd-sourcing Database Crowd-sourcing Database CompilationCompilation


Wikipedia – Crowdsourcing Wikipedia – Crowdsourcing ChemistryChemistry


Wikipedia Chemistry Curation Wikipedia Chemistry Curation projectproject

Only ca. 5000 organic structures, 7000 Only ca. 5000 organic structures, 7000 total structurestotal structures

MONTHS of work so far for a team of 6 MONTHS of work so far for a team of 6 peoplepeople

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

Slow and torturous process for stereo Slow and torturous process for stereo molecules.molecules.


Thymol Blue on ChemSpiderThymol Blue on ChemSpider

Data online includes:Data online includes: UV-vis spectrumUV-vis spectrum Measured experimental propertiesMeasured experimental properties Link to Wikipedia articleLink to Wikipedia article Links to chromatography detailsLinks to chromatography details Multiple identifiers/trade names etc.Multiple identifiers/trade names etc. Links to vendors/suppliers/other databasesLinks to vendors/suppliers/other databases Safety informationSafety information


Differences between Differences between ChemSpider/WikipediaChemSpider/Wikipedia

ChemSpiderChemSpider WikipediaWikipedia

>20 million unique >20 million unique structuresstructures

~5000 organics, 2000 ~5000 organics, 2000 othersothers

Complex queries – Complex queries – Properties, Text, Properties, Text, structure/substructure, structure/substructure, OA publishers, Data OA publishers, Data Sources, …Sources, …

TextText

Prediction of propertiesPrediction of properties NoNo

Analytical DataAnalytical Data NoNo

Active depositors/curators Active depositors/curators – 30 – 30

Active editors – about 50 Active editors – about 50 (?)(?)

5000 people/day; 1100 5000 people/day; 1100 registeredregistered

????????

Compound monographs Compound monographs linkedlinked

Detailed compound Detailed compound monographsmonographs


Differences between Differences between Wikipedia/ChemSpiderWikipedia/ChemSpider

WikipediaWikipedia ChemSpiderChemSpider

Supported by tried and Supported by tried and tested Media-Wiki tested Media-Wiki platform.platform.

PrimarilyPrimarily Microsoft .NET Microsoft .NET technologies with OS technologies with OS components components

Established infrastructure Established infrastructure and Wikipedia Foundation and Wikipedia Foundation TeamTeam

““Out of a basement” on Out of a basement” on three servers and 5 three servers and 5 volunteersvolunteers

Chemistry is a subset of Chemistry is a subset of the ‘Pediathe ‘Pedia

Chemistry is the focus of Chemistry is the focus of ‘Spider‘Spider

GFL licensing for GFL licensing for everythingeverything

Mixed “licensing”Mixed “licensing”

Strong team of WP:Chem Strong team of WP:Chem advocates, curators and advocates, curators and adminsadmins

Growing team of Growing team of WP:Chem advocates, WP:Chem advocates, curators and adminscurators and admins

Worldwide reputation as Worldwide reputation as quality sourcequality source

Growing reputation as Growing reputation as focused on qualityfocused on quality


Crowd-sourcing CurationCrowd-sourcing Curation

How to curate data for millions of How to curate data for millions of structures? structures?

Robot processes can clean up depositionsRobot processes can clean up depositions Search for Chloride and check molecular formula Search for Chloride and check molecular formula

for Clfor Cl Check for stereochemistry and remove names Check for stereochemistry and remove names

with stereo with stereo Provide a simple-to-use platform to curate, Provide a simple-to-use platform to curate,

annotate and tag data annotate and tag data Provide curator administration to prevent Provide curator administration to prevent

vandalism (Veropedia)vandalism (Veropedia)


Multi-level Curation and Multi-level Curation and ApprovalApproval


Post CommentsPost Comments Anyone can “Post Comments” associated Anyone can “Post Comments” associated

with a structure. To curate data we with a structure. To curate data we require login to trackrequire login to track


Crowd-sourcing ChemistryCrowd-sourcing Chemistry

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

ALSOALSO

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


But, when registered and But, when registered and logged in…logged in…

Ability to curate and add to the databaseAbility to curate and add to the database Add structuresAdd structures ““Clean” structuresClean” structures Add data (spectra, CIFs, images) Add data (spectra, CIFs, images) Add links to other pages (URLs)Add links to other pages (URLs) Add publication detailsAdd publication details


Adding to the Database - Adding to the Database - StructureStructure


Adding New Text DataAdding New Text Data

Add Publication

Add Identifier

Add URL


Adding Supplementary Info to a Adding Supplementary Info to a StructureStructure


Can ChemSpider Enable Can ChemSpider Enable Discovery?Discovery?

Yes, chemists can search by text, structure, Yes, chemists can search by text, structure, substructure or properties to look at substructure or properties to look at relationships and probe drug discoveryrelationships and probe drug discovery


ChemSpider – Research in ChemSpider – Research in ProgressProgress

Supporting Open Notebook Science as a Supporting Open Notebook Science as a repository – JC Bradley at Drexel repository – JC Bradley at Drexel UniversityUniversity

For the purpose of online virtual screening For the purpose of online virtual screening Applying descriptors of various types to Applying descriptors of various types to

filter a database of 20 million compoundsfilter a database of 20 million compounds

In progress:In progress: Utilizing SimBioSys’ LASSO DescriptorUtilizing SimBioSys’ LASSO Descriptor Collaboration based on NISS’ ChemModLabCollaboration based on NISS’ ChemModLab


LASSO LASSO Ligand Activity by Surface Ligand Activity by Surface

Similarity Order Similarity Order


LASSO Descriptors on ChemSpiderLASSO Descriptors on ChemSpiderSEMANTIC WEB in actionSEMANTIC WEB in action


LASSO Searching Method 1LASSO Searching Method 1

Ask the question “What are the top 1000 Ask the question “What are the top 1000 molecules with similar LASSO descriptors molecules with similar LASSO descriptors to the actives for the Estrogen Receptor”to the actives for the Estrogen Receptor”


It WORKS - Enrichment PlotIt WORKS - Enrichment Plot

60% of the actives were recovered in the top 1% of 60% of the actives were recovered in the top 1% of the database.the database.

““Environmental binders” are weak binders Environmental binders” are weak binders The top ranked compounds may well be active ER The top ranked compounds may well be active ER

bindersbinders Likely candidates for experimental investigationLikely candidates for experimental investigation


Tipping PointTipping Point

Tipping pointTipping point - the - the pointpoint at which a slow at which a slow gradual change gradual change becomes irreversible becomes irreversible and then proceeds with and then proceeds with gathering pacegathering pace


ChemSpider Forums/BlogsChemSpider Forums/Blogs

Forum.chemspider.comForum.chemspider.com www.chemspider.com/blogwww.chemspider.com/blog


ChemSpider TouchGraphChemSpider TouchGraph


What would we most like to What would we most like to do?do?

Enable “Collaborative Science”. What Enable “Collaborative Science”. What would that look like?would that look like?

Access to chemical supplies when people Access to chemical supplies when people need themneed them

Awareness of available literature, patents, Awareness of available literature, patents, databases of curated content – whether databases of curated content – whether Open Access or not. Transaction fees (or Open Access or not. Transaction fees (or not) are between user and providernot) are between user and provider

Host Open Notebook Science exchangesHost Open Notebook Science exchanges


““ChemSpider Inside”ChemSpider Inside” Instrument vendors integrated ChemSpider to Instrument vendors integrated ChemSpider to

their metabolism ID project – ChemSpider linked their metabolism ID project – ChemSpider linked to all Mass Spec Intruments doing Metabolite to all Mass Spec Intruments doing Metabolite ID?ID?

Wikipedia roundtrip linking to ChemSpiderWikipedia roundtrip linking to ChemSpider Google indexing ChemSpider at “fixed rate”Google indexing ChemSpider at “fixed rate” Integration to desktop drawing packagesIntegration to desktop drawing packages Members of Microsoft BioIT AllianceMembers of Microsoft BioIT Alliance Discussions on Taverna’s Workflow Sourceforge Discussions on Taverna’s Workflow Sourceforge

groupgroup Hosting Open Access articles shortly…Hosting Open Access articles shortly…


Where to from here? Where to from here? Short Short termterm

Integrated text and structure/substructure Integrated text and structure/substructure searching of the Open Access literature is in searching of the Open Access literature is in developmentdevelopment

Web-based scraping of structure-based Web-based scraping of structure-based information – examples in placeinformation – examples in place

Enhanced web services layer to integrate Enhanced web services layer to integrate searchessearches

Deposit updated Patent Database (9 million Deposit updated Patent Database (9 million structures)structures)

Reaction handling and depositionReaction handling and deposition


Where to from here? Where to from here? Mid-termMid-term

Spidering for Chemistry – extract data from Spidering for Chemistry – extract data from articles, webpages and data sources AND stay articles, webpages and data sources AND stay within copyrightwithin copyright

WiChempedia project – wiki-layers on top of WiChempedia project – wiki-layers on top of ChemSpider, alongside Wikipedia curation ChemSpider, alongside Wikipedia curation project. project.

Deeper integration to text-based searching Deeper integration to text-based searching and conversion of chemical names to and conversion of chemical names to structures for online structure searching: structures for online structure searching: Improved integration with NCBI Entrez systemImproved integration with NCBI Entrez system Deliver “dedicated websites” for specific publishersDeliver “dedicated websites” for specific publishers


Where to from here? Where to from here? Mid-TermMid-Term

An extensible datamodel “on the fly” An extensible datamodel “on the fly” allows us to easily expand to integrate allows us to easily expand to integrate abstract data to structures abstract data to structures

Data mine and curate “parameters” – Data mine and curate “parameters” – physicochemical and physiological physicochemical and physiological parameters to enable QSAR analysis, parameters to enable QSAR analysis, data modeling and provision of models data modeling and provision of models online (UNC-Chapel Hill, NISS)online (UNC-Chapel Hill, NISS)


Our ChallengesOur Challenges

There are “no There are “no employees”employees”

ChemSpider is non-ChemSpider is non-fundedfunded

System is hyper-System is hyper-dependent on ISP, power dependent on ISP, power and limited compute and limited compute powerpower

We are upsetting a lot of We are upsetting a lot of people – evangelists, people – evangelists, cheminformatics system cheminformatics system vendors, publishers, data vendors, publishers, data content providerscontent providers


Acknowledgments Acknowledgments

The ChemSpider team of volunteer The ChemSpider team of volunteer developersdevelopers

ChemSpider Advisory GroupChemSpider Advisory Group Our curators, depositors and usersOur curators, depositors and users Suppliers of commercial software – Suppliers of commercial software –

Microsoft, ACD/Labs, OpenEye, Microsoft, ACD/Labs, OpenEye, ChemAxon, SimBioSysChemAxon, SimBioSys

SureChem – Structure Based Online SureChem – Structure Based Online Patent SearchingPatent Searching


Further readingFurther reading

www.chemspider.com/blogwww.chemspider.com/blog Internet-based tools for communication and Internet-based tools for communication and

collaboration in chemistry, Drug Discovery collaboration in chemistry, Drug Discovery Today, Volume 13, Numbers 11/12, June Today, Volume 13, Numbers 11/12, June 2008 502-506, 2008 502-506, doi:10.1016/j.drudis.2008.03.015doi:10.1016/j.drudis.2008.03.015

A perspective of publicly accessible/open-A perspective of publicly accessible/open-access chemistry databases, Drug Discovery access chemistry databases, Drug Discovery Today, Volume 13, Numbers 11/12, June Today, Volume 13, Numbers 11/12, June 2008, 495-501, 2008, 495-501, doi:10.1016/j.drudis.2008.03.017doi:10.1016/j.drudis.2008.03.017

Documents

Whitney Symposium Lecturejune 2008 1220331644496491 9