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A pilot KB of biological pathways important in Alzheimer’s Disease

A pilot KB of biological pathways important in Alzheimer’s Disease. Tim Clark twclark@partners.org MassGeneral Institute for Neurodegenerative Disease June Kinoshita junekino@alzforum.org Alzheimer Research Forum October 27, 2004.

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A pilot KB of biological pathways important in Alzheimer’s Disease

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  1. A pilot KB of biological pathways important in Alzheimer’s Disease Tim Clark twclark@partners.org MassGeneral Institute for Neurodegenerative Disease June Kinoshita junekino@alzforum.org Alzheimer Research Forum October 27, 2004

  2. A pilot KB of biological pathways important in Alzheimer’s Disease • Core goals • Collaborators • Technology • Target: core pathways • Curation and deployment • Computability & KB concept model • Truth maintenance approach • Community involvement • Summary

  3. Core goals • KB of biological signaling pathways in AD • Web-deployed via the AlzForum website • Curation by true domain experts • Computability & linkability of all statements • Keep database current with the science • Promote and incorporate active discussion

  4. Collaborators • Alzheimer Research Forum • www.alzforum.org • MassGeneral Institute for Neurodegenerative Disease • www.mghmind.org • Industrial partners • Alzheimer Disease researchers • at Harvard-affiliated hospitals & clinical centers

  5. Technology • Semantic Web (SW) technology is highly appropriate for this application • This application is also an excellent demonstration platform for SW technology

  6. Target: core pathways in AD • Zero in on pathways of central relevance • Proposed initial focus • genetics relevance (presenilin pathway) • therapeutics relevance (cholesterol pathway) • Expansion of focus • multiple-disease relevance (protein misfolding) • Others as proposed by advisors

  7. Curation by true domain experts • We want real, leading researchers to curate • Experts must not become fulltime curators • Implies limitation of scope for each curator • The toys in the cereal box (motivation) • Credit for ideas • Private whiteboard space in KB • Active collaboration space • Ability to disagree & challenge statements • Part of the KB design

  8. Web-deployed via AlzForum • AlzForum is a global platform on AD • 70,000+ sessions per month • 32,000 visitors view 150,000 pages per month • Referenced by 7,700+ web sites • 2,000+ registered members • 3,000+ subscribers to newsletter • The very top scientists in AD research serve each year on the AlzForum Editorial Board • There is an active participant community • Online scientific dialogues and discussions

  9. Computability: beyond the “dead” graphical model…

  10. …to a formal “computable” modelKB concept model -example-

  11. AlzForum public view of KB Drs. Sane, Doe & Roe see these statements (public KB): “Dr. Sane believes (100%) that A inactivates B” “Dr. Schmo believes (90%) that A inactivates B”

  12. Individual private view of KB Dr. Sane also sees these “private” statements in addition to the public view: “Dr. Sane believes (65%) that B complexes with D and E (private finding)” “Dr. Schmo believes (60%) that A activates B (personal communication)”

  13. Truth maintenance: Absolute or relative? • Truth maintenance is typically conceived to be about eliminating contradiction in the KB • Okay on “boutique” scientific KBs • Does not scale as a process due to limitations of expertise • Successful large KBs studiously avoid truth maintenance • Medline: correct bibliographic info = correct entry • Disregard truth or falsity of the science • “Let community process deal with it”, outside the KB • Our approach: consciously import contradiction into the KB • “Relativization” (reification) of all statements • Private “idea incubation” sections of KB (the Personal Whiteboard) • Explicit statement publication to wide or narrow audience

  14. Promote and incorporate active discussion as part of the KB • Scientists currently play an active role in AlzForum • We plan to leverage the investment that developed this community, into participation in the KB-building effort • We will support commentaries upon (and criticisms of) KB statements as part of the KB itself • We will feed back the KB contents and software via the AlzForum website to registered members

  15. Why we think it will work • Right time for this KB • Right technology for this KB • Right KB for this technology • Right technology and science community

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