A pilot KB of biological pathways important in Alzheimers Disease

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A pilot KB of biological pathways important in
Alzheimers Disease

• Tim Clark twclark_at_partners.org
• MassGeneral Institute for Neurodegenerative
  Disease
• June Kinoshita junekino_at_alzforum.org
• Alzheimer Research Forum
• October 27, 2004

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A pilot KB of biological pathways important in
Alzheimers Disease

• Core goals
• Collaborators
• Technology
• Target core pathways
• Curation and deployment
• Computability KB concept model
• Truth maintenance approach
• Community involvement
• Summary

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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

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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

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Technology

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

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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

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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

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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

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Computability beyond the dead graphical model
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to a formal computable modelKB concept model
-example-
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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
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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)
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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

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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

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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