BioSPICE and Problem-Solving Environments for Systems Biology Clifford A. Shaffer Department of Computer Science Virginia Tech

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BioSPICE and Problem-Solving Environments for
Systems BiologyClifford A. ShafferDepartment
of Computer ScienceVirginia Tech
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Systems Biology

• Focus on regulatory mechanisms for biochemical
  networks
• Start with a wiring diagram
• Some example problems
• Cell Cycle
• Circadian Rhythms

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Budding
Sister chromatid separation
Cln2
SBF
Mass
Cdh1

Cln3
and
Bck2
SCF
Cdc20
MBF
Clb5
DNA synthesis
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Simulation of the budding yeast cell cycle
mass
Sic1
Cln2
Clb2
Cdh1
Cdc20
Time (min)
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Usage Scenario
Data Notebook
Wiring Diagram
Differential Equations
Parameter Values
Simulation
Analysis
Comparator
Data Notebook
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The Cell (Modeler) Cycle

• Outer Loop
• Define Reaction Equations
• Inner Loop
• Adjust parameters, initial conditions

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Fundamental Activities

• Collect information
• Search literature (databases), Lab notebooks
• Define/modify models
• A user interface problem
• Run simulations
• Equation solvers (ODEs, PDEs, deterministic,
  stochastic)
• Compare simulation results to experimental data
• Analysis

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Our Mission Build Software to Help the Modelers

• Now Typical cycle time for changing the model is
  one month
• Collect data on paper lab notebooks
• Convert to differential equations by hand
• Calibrate the model by trial and error
• Inadequate analysis tools
• Goal Change the model once per day.
• Bottleneck should shift to the experimentalists

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Tools

• Specifications for defining models (markup
  languages)
• Electronic Lab Notebooks and access to
  literature, experiments, etc.
• User interface for specifying models, parameters,
  initial conditions
• Automated parameter estimation (calibration)
• Analysis tools for comparing simulation results
  and experimental results
• Database support for simulations (data mining)

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BioSPICE

• DARPA project
• Approximately 15 groups
• Many (not all) of the systems biology modelers
  and software developers
• An explicit integration team
• Goal Define mechanisms for interoperability of
  software tools, build an expandable problem
  solving environment for systems biology
• Result software tools contributed by the
  community to the community