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Whitney Symposium Lecture June 2008
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Whitney Symposium Lecture June 2008

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A Presentation Given at the General Electric Whitney Symposium on Networks

A Presentation Given at the General Electric Whitney Symposium on Networks

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Whitney Symposium Lecture June 2008 Whitney Symposium Lecture June 2008 Presentation Transcript

  • Crowd-Sourcing to Build a Structure Centric Community for Chemists Antony Williams Whitney Symposium 2008 - Networks
  • Social Networking for Chemists
  • Network Drug Discovery Tools www.curehunter.com
  • Beware the Networks!
  • Collaborative Authoring in Academia
    • Group level collaboration via Wikis
  • Collaborative Authoring for Drug Discovery
    • Pfizerpedia
  • Collaborative Knowledge Management for Chemists – Wikipedia, Built by a Network
  • and biologists…WikiProteins
  • WikiProteins What Is Tegafur?
  • Commonly Lacking…
    • Approaches generally lack “structural intelligence”
      • Structures have properties (Mw, MF, exp. & pred. properties)
      • Collections of structures need to be searchable by structure
      • Most data collections are “self-contained” and rarely connecting to other resources via “structure”
  • A Search Engine 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 viagra?
      • What are the stereocenters of cholesterol?
      • Where can I find publications about Taxol?
      • 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
  • ChemSpider Data Content
    • Over 20 million unique chemical structures :
      • Online Databases –PubChem, Drugbank, HMDB, Wikipedia
      • Chemical Vendors – over 40 different vendors and growing
      • Personal Depositions – individual contributions
      • Journal Publishers
      • Content database vendors
      • Analytical data collections
      • Patents (9 MILLION Structures to search patents )
      • Web scraping
      • Content is linked back to the original data sources
  • A Structure Centric Community for Chemists
    • A FREE ACCESS platform for deposition, management, curation, annotation and extension of information associated with chemical structures
    • Semantically connect to other sites providing access to knowledge, data and information of determined quality
    • Search by alphanumeric text, chemical structure and substructure and combination searches
    • Predict properties for submitted structures
  • Tell me about Aspirin
  • Tell me about Aspirin
  • Links out to KEGG Kyoto Encyclopedia of Genes and Genomes
  • Tell me about Aspirin
  • Tell me About Aspirin
  • Tell me about Aspirin
  • Tell me about Aspirin
  • Abstract Compounds?
    • Is there any information about “Quesnoin”?
    • Type in the name (and there may be many) or other identifier
    • Paste a chemical structure
    • Draw the structure
  • Example Search
  • Example Search
  • Example Search 2
    • What compounds have a mass of 300+/-0.001?
    • or search a combination of intrinsic/predicted properties
  • Example Search 2
  • Complex Search
  • Search Open Access Journals – ChemSpider
  • Search PubMed – ChemSpider
  • The Quality of Data Online…
    • Aggregating data opens up quality issues
    • Structure-identifier associations are “dirty”
    • Structures are COMMONLY incorrect – stereochem issues
    • Manual curation of small databases is enough work – what about millions of structures?
    • Structures are far from perfect. What is a “correct structure”?
      • Full stereochemistry?
      • Historical timeline of structure?
      • Who is the authority?
  • Who holds THE Quality Authority?
    • Chemical Abstracts Service is the structural authority today. 1400 (?) employees, world standard in chemistry information
    • 101 years of knowledge, process and expertise. MANUAL curation is key. Robotic curation is enabling
    • How can an online, free access system peacefully co-exist with the authority?
  • Quality is a Major Issue- Search Butanol
  • Crowd-sourcing Database Compilation
  • Wikipedia – Crowdsourcing Chemistry
  • Wikipedia Chemistry Curation project
    • Only ca. 5000 organic structures, 7000 total structures
    • MONTHS of work so far 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 for stereo molecules.
  • Thymol Blue on ChemSpider
    • Data online includes:
      • UV-vis spectrum
      • Measured experimental properties
      • Link to Wikipedia article
      • Links to chromatography details
      • Multiple identifiers/trade names etc.
      • Links to vendors/suppliers/other databases
      • Safety information
  • Differences between ChemSpider/Wikipedia No Analytical Data Active editors – about 50 (?) Active depositors/curators – 30 No Prediction of properties ???? 5000 people/day; 1100 registered Detailed compound monographs Compound monographs linked Text Complex queries – Properties, Text, structure/substructure, OA publishers, Data Sources, … ~5000 organics, 2000 others >20 million unique structures Wikipedia ChemSpider
  • Differences between Wikipedia/ChemSpider Growing reputation as focused on quality Worldwide reputation as quality source Chemistry is the focus of ‘Spider Chemistry is a subset of the ‘Pedia Mixed “licensing” GFL licensing for everything Growing team of WP:Chem advocates, curators and admins 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
  • Crowd-sourcing Curation
    • How to curate data for millions of structures?
    • Robot processes can clean up depositions
      • Search for Chloride and check molecular formula for Cl
      • Check for stereochemistry and remove names with stereo
    • Provide a simple-to-use platform to curate, annotate and tag data
    • Provide curator administration to prevent vandalism (Veropedia)
  • Multi-level Curation and Approval
  • Post Comments
    • Anyone can “Post Comments” associated with a structure. To curate data we require login to track
  • 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)
  • But, when registered and logged in…
    • Ability to curate and add to the database
      • Add structures
      • “ Clean” structures
      • Add data (spectra, CIFs, images)
      • Add links to other pages (URLs)
      • Add publication details
  • Adding to the Database - Structure
  • Adding New Text Data Add Publication Add Identifier Add URL
  • Adding Supplementary Info to a Structure
  • Can ChemSpider Enable Discovery?
    • Yes, chemists can search by text, structure, substructure or properties to look at relationships and probe drug discovery
  • ChemSpider – Research in Progress
    • Supporting Open Notebook Science as a repository – JC Bradley at Drexel University
    • For the purpose of online virtual screening
    • Applying descriptors of various types to filter a database of 20 million compounds
    • In progress:
      • Utilizing SimBioSys’ LASSO Descriptor
      • Collaboration based on NISS’ ChemModLab
  • LASSO Ligand Activity by Surface Similarity Order
  • LASSO Descriptors on ChemSpider SEMANTIC WEB in action
  • LASSO Searching Method 1
    • Ask the question “What are the top 1000 molecules with similar LASSO descriptors to the actives for the Estrogen Receptor”
  • It WORKS - Enrichment Plot
    • 60% of the actives were recovered in the top 1% of the database.
    • “ Environmental binders” are weak binders
    • The top ranked compounds may well be active ER binders
    • Likely candidates for experimental investigation
  • Tipping Point
    • Tipping point - the point at which a slow gradual change becomes irreversible and then proceeds with gathering pace
  • ChemSpider Forums/Blogs
    • Forum.chemspider.com
    • www.chemspider.com/blog
  • ChemSpider TouchGraph
  • What would we most like to do?
    • Enable “Collaborative Science”. What would that look like?
    • Access to chemical supplies when people need them
    • Awareness of available literature, patents, databases of curated content – whether Open Access or not. Transaction fees (or not) are between user and provider
    • Host Open Notebook Science exchanges
  • “ ChemSpider Inside”
    • Instrument vendors integrated ChemSpider to their metabolism ID project – ChemSpider linked to all Mass Spec Intruments doing Metabolite ID?
    • Wikipedia roundtrip linking to ChemSpider
    • Google indexing ChemSpider at “fixed rate”
    • Integration to desktop drawing packages
    • Members of Microsoft BioIT Alliance
    • Discussions on Taverna’s Workflow Sourceforge group
    • Hosting Open Access articles shortly…
  • Where to from here? Short term
    • Integrated text and structure/substructure searching of the Open Access literature is in development
    • Web-based scraping of structure-based information – examples in place
    • Enhanced web services layer to integrate searches
    • Deposit updated Patent Database (9 million structures)
    • Reaction handling and deposition
  • Where to from here? Mid-term
    • Spidering for Chemistry – extract data from articles, webpages and data sources AND stay within copyright
    • WiChempedia project – wiki-layers on top of ChemSpider, alongside Wikipedia curation project.
    • Deeper integration to text-based searching and conversion of chemical names to structures for online structure searching:
      • Improved integration with NCBI Entrez system
      • Deliver “dedicated websites” for specific publishers
  • Where to from here? Mid-Term
    • An extensible datamodel “on the fly” allows us to easily expand to integrate abstract data to structures
    • Data mine and curate “parameters” – physicochemical and physiological parameters to enable QSAR analysis, data modeling and provision of models online (UNC-Chapel Hill, NISS)
  • Our Challenges
    • There are “no employees”
    • ChemSpider is non-funded
    • System is hyper-dependent on ISP, power and limited compute power
    • We are upsetting a lot of people – evangelists, cheminformatics system vendors, publishers, data content providers
  • Acknowledgments
    • The ChemSpider team of volunteer developers
    • ChemSpider Advisory Group
    • Our curators, depositors and users
    • Suppliers of commercial software – Microsoft, ACD/Labs, OpenEye, ChemAxon, SimBioSys
    • SureChem – Structure Based Online Patent Searching
  • Further reading
    • www.chemspider.com/blog
    • Internet-based tools for communication and collaboration in chemistry, Drug Discovery Today, Volume 13, Numbers 11/12, June 2008 502-506, doi:10.1016/j.drudis.2008.03.015
    • A perspective of publicly accessible/open-access chemistry databases, Drug Discovery Today, Volume 13, Numbers 11/12, June 2008, 495-501, doi:10.1016/j.drudis.2008.03.017