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Knowledge Engineering from
   Experimental Design
         ‘KEfED’
           Gully APC Burns

       Information Sciences Institute
      University of Southern California
The Cycle of Scientific
   Investigation (‘CoSI’)




Knowledge Engineering from
       Experimental Design
What is an elemental piece
  of biomedical scientific knowledge?
A typical seminar slide
What is an elemental piece
  of biomedical scientific knowledge?
For example...
The challenge of defining the
    biomedical semantic web
•  Currently consists of a very large number of statements like ‘mice
   like cheese’
   –  semantics at this level are complicated!
•  For example:
   –  “Novel neurotrophic factor CDNF protects midbrain dopamine neurons
      in vivo” [Lindholm et al 2007]
   –  “Hippocampo-hypothalamic connections: origin in subicular cortex,
      not ammon's horn.” [Swanson & Cowan 1975]
   –  “Intravenous 2-deoxy-D-glucose injection rapidly elevates levels of the
      phosphorylated forms of p44/42 mitogen-activated protein kinases
      (extracellularly regulated kinases 1/2) in rat hypothalamic
      parvicellular paraventricular neurons.” [Khan & Watts 2004]
•  Statements vary in their levels of reliability, specificity.
•  Existing semantic web approaches involve representations of
   argumentation / claim networks
•  Can we invent a new way to introduce formalism?
Knowledge Engineering from
        Experimental Design (‘KEfED’)
•  There is an implicit reasoning model employed
   by scientists to represent their observations
   based on the way they design experiments
  –    Standardized experimental templates
  –    Parameters [‘Independent Variables’]
  –    Measurements [‘Dependent Variables’]
  –    Calculations [‘Derived Variables’]
Basic KEfED Elements

  Logical Element       Icon
        Activity
  Experimental Object
      Parameter
     Measurement
        Branch
         Fork
Dependencies between variables are inherent in
         the experimental protocol
The KEfED Model is intuitive




 http://bmkeg.isi.edu/movies/abbreviatedBasicKefedEditor.mov
KEfED handles complex
      experimental designs
                      Khan et al. (2007), J.
                      Neurosci. 27:7344-60
                      [expt 2]




More
Below…
KEfED handles complex
       designs
Khan et al. (2007), J. Neurosci. 27:7344-60
[expt 2]
Example : Neural Connectivity -
                Observations
Tract Tracing Experiments
Neuroanatomical experiments to study neural connectivity.

                                                             labeling-density
                       ‘anterograde’



tracer-chemical

 injection-site

                                                            labeling-location

                      ‘retrograde’


  labeling-type
Example : Neural Connectivity -
              Interpretations
Tract Tracing Experiments > Neuroanatomical Elements
Interpretative entities that correspond to facts that may be aggregated into a model

                                               connection-
                   ‘Neural Connection’         strength

                                                                     connection-
        connection-                                                  termination
             origin



                                                                     terminal-field
                         Neuronal Population



cell-bodies.location

  cell-bodies
                                                         terminal-field.location
1st look at ‘BioScholar system’:
Neural Connectivity Reasoning Tool
1st look at ‘BioScholar system’:
Neural Connectivity Reasoning Tool
Peeking Under the Hood

‘PHAL Injection into SUBv generates labeling in MM’
=> ‘SUBv contains neurons that project to MM’
(expressed in First-Order-Logic within Powerloom Reasoner)



  Computation
  based on the
  context of each
  measurement
  based on
  parameters
Crux
•  KEfED as the basis for the design of a
   data repository
•  Collaboration with MSU + Science
   Commons
   –  Funded by MJFF + Kinetics Foundation to
     manage data from grantees
•  KEfED-editor can as a component in an
   external web-application
[http://yogo.msu.montana.edu/applications/crux.html]
Using Semantic Web Standards




[https://wiki.birncommunity.org:8443/display/NEWBIRNCC/KEfED+OWL+Model]
OBI
      •    Use a simplified ‘projection’
           with no semantic
           entailments.
      •    Seek a simple model with
           semantics embedded
           ‘within’ variables
             … work in progress here …
      •    Seek semantic-web-based
           links to:
             –  OBI
             –  SWAN / SIOC
            –  ISA-Tab tools
      •    Domain-specific Reasoning
           Models (from ‘CoSI’)
            –  Want to generate
               hypotheses /
               predictions that can be
               expressed as KEfED
               models?
            –  $6,000,000 question!
Future Directions
Acknowledgements

Funding                                  Computer Scientist Team
    –  Information Sciences Institute,       –  Tom Russ (ISI)
       seed funding                          –  Cartic Ramakrishnan (ISI)
    –  NIGMS (R01GM083871)                   –  Marcelo Tallis (ISI)
    –  NIMH (R01MH079068)                    –  Eduard Hovy (ISI)
    –  NSF (#0849977)
    –  Michael J Fox + Kinetics          Other Team members
       Foundations
                                             –  Alan Ruttenberg (ScienceCommons)
    –  BIRN @ ISI
                                             –  Michael Rogan (NYU)
                                             –  Gwen Jacobs (MSU)
Neuroscience Team Members                    –  Pol Llovet (MSU)
    –  Rick Thompson (USC)
    –  Jessica Turner (MRN)              Computer Scientist Contributors
                                             –  Hans Chalupsky (ISI)
Neuroscience Contributors                    –  Jerry Hobbs (ISI)
    –  Alan Watts (USC)                      –  Yolanda Gil (ISI)
    –  Larry Swanson (USC)                   –  Carl Kesselman (ISI)
    –  Arshad Khan (USC)                     –  Jose Luis Ambite (ISI)

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Kefed introduction 12-06-10-0043

  • 1. Knowledge Engineering from Experimental Design ‘KEfED’ Gully APC Burns Information Sciences Institute University of Southern California
  • 2. The Cycle of Scientific Investigation (‘CoSI’) Knowledge Engineering from Experimental Design
  • 3. What is an elemental piece of biomedical scientific knowledge? A typical seminar slide
  • 4. What is an elemental piece of biomedical scientific knowledge? For example...
  • 5. The challenge of defining the biomedical semantic web •  Currently consists of a very large number of statements like ‘mice like cheese’ –  semantics at this level are complicated! •  For example: –  “Novel neurotrophic factor CDNF protects midbrain dopamine neurons in vivo” [Lindholm et al 2007] –  “Hippocampo-hypothalamic connections: origin in subicular cortex, not ammon's horn.” [Swanson & Cowan 1975] –  “Intravenous 2-deoxy-D-glucose injection rapidly elevates levels of the phosphorylated forms of p44/42 mitogen-activated protein kinases (extracellularly regulated kinases 1/2) in rat hypothalamic parvicellular paraventricular neurons.” [Khan & Watts 2004] •  Statements vary in their levels of reliability, specificity. •  Existing semantic web approaches involve representations of argumentation / claim networks •  Can we invent a new way to introduce formalism?
  • 6. Knowledge Engineering from Experimental Design (‘KEfED’) •  There is an implicit reasoning model employed by scientists to represent their observations based on the way they design experiments –  Standardized experimental templates –  Parameters [‘Independent Variables’] –  Measurements [‘Dependent Variables’] –  Calculations [‘Derived Variables’]
  • 7. Basic KEfED Elements Logical Element Icon Activity Experimental Object Parameter Measurement Branch Fork
  • 8. Dependencies between variables are inherent in the experimental protocol
  • 9. The KEfED Model is intuitive http://bmkeg.isi.edu/movies/abbreviatedBasicKefedEditor.mov
  • 10. KEfED handles complex experimental designs Khan et al. (2007), J. Neurosci. 27:7344-60 [expt 2] More Below…
  • 11. KEfED handles complex designs Khan et al. (2007), J. Neurosci. 27:7344-60 [expt 2]
  • 12. Example : Neural Connectivity - Observations Tract Tracing Experiments Neuroanatomical experiments to study neural connectivity. labeling-density ‘anterograde’ tracer-chemical injection-site labeling-location ‘retrograde’ labeling-type
  • 13. Example : Neural Connectivity - Interpretations Tract Tracing Experiments > Neuroanatomical Elements Interpretative entities that correspond to facts that may be aggregated into a model connection- ‘Neural Connection’ strength connection- connection- termination origin terminal-field Neuronal Population cell-bodies.location cell-bodies terminal-field.location
  • 14. 1st look at ‘BioScholar system’: Neural Connectivity Reasoning Tool
  • 15. 1st look at ‘BioScholar system’: Neural Connectivity Reasoning Tool
  • 16. Peeking Under the Hood ‘PHAL Injection into SUBv generates labeling in MM’ => ‘SUBv contains neurons that project to MM’ (expressed in First-Order-Logic within Powerloom Reasoner) Computation based on the context of each measurement based on parameters
  • 17. Crux •  KEfED as the basis for the design of a data repository •  Collaboration with MSU + Science Commons –  Funded by MJFF + Kinetics Foundation to manage data from grantees •  KEfED-editor can as a component in an external web-application [http://yogo.msu.montana.edu/applications/crux.html]
  • 18. Using Semantic Web Standards [https://wiki.birncommunity.org:8443/display/NEWBIRNCC/KEfED+OWL+Model]
  • 19. OBI •  Use a simplified ‘projection’ with no semantic entailments. •  Seek a simple model with semantics embedded ‘within’ variables … work in progress here … •  Seek semantic-web-based links to: –  OBI –  SWAN / SIOC –  ISA-Tab tools •  Domain-specific Reasoning Models (from ‘CoSI’) –  Want to generate hypotheses / predictions that can be expressed as KEfED models? –  $6,000,000 question!
  • 21. Acknowledgements Funding Computer Scientist Team –  Information Sciences Institute, –  Tom Russ (ISI) seed funding –  Cartic Ramakrishnan (ISI) –  NIGMS (R01GM083871) –  Marcelo Tallis (ISI) –  NIMH (R01MH079068) –  Eduard Hovy (ISI) –  NSF (#0849977) –  Michael J Fox + Kinetics Other Team members Foundations –  Alan Ruttenberg (ScienceCommons) –  BIRN @ ISI –  Michael Rogan (NYU) –  Gwen Jacobs (MSU) Neuroscience Team Members –  Pol Llovet (MSU) –  Rick Thompson (USC) –  Jessica Turner (MRN) Computer Scientist Contributors –  Hans Chalupsky (ISI) Neuroscience Contributors –  Jerry Hobbs (ISI) –  Alan Watts (USC) –  Yolanda Gil (ISI) –  Larry Swanson (USC) –  Carl Kesselman (ISI) –  Arshad Khan (USC) –  Jose Luis Ambite (ISI)