Introduction to ECELL Modeling

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Introduction to E-CELL Modeling

• Bin Hu
• Institute for Advanced Biosciences
• Keio University

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Contents

• Why modeling
• Life cycle of model development
• About E-CELL project
• Basic concepts in modeling using E-CELL
• Limitations of current modeling software

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Why we want to do modeling?
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Simple Answer

• Biological interactions cannot be analytically
  solved
• Complexity
• Limitations from experiment
• high expense
• moral limitations
• technologies
• qualitative

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Alan Turing's (1952) The Chemical Basis of
Morphogenesis It contains the first applications
of computer modeling in biology.
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The Life Cycle of a Model

• Extract data and relationships from literature
  and lab
• Build a dummy model
• Analyze the dummy model, model validation
• Debug the dummy model
• The no-longer dummy model
• Model predictions

repeated
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Dont be too happy if your model just works.
And dont be disappointed if your model does not
work.
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About E-CELL

• Started in 1990s (Tomita et al, 1997, 1999)
• Object-orientated
• Aimed at large-scale (whole cell level)
  simulation
• Support Multi-timescale, multi-algorithm
  simulation (Takahashi et al, 2004)
• Support script mode
• SBML compatible
• open source project

http//www.e-cell.org
For E-CELL 4, spatial information support
(Arjunan et al)
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History of E-Cell

• 1995 Complete genome of M. genitalium
  by TIGR
• 1996 The self sustaining cell was made
• 1999 E-Cell Simulation Environment
  Version 1(E-Cell1)
• 2002 E-Cell2 was released
• Latest stable version E-Cell 3
• In design E-Cell 4

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EML
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Reductionist Approach
Inside a space

• A list of variables
• Parameters
• A set of rules that changes these variables
  (Process)

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http//www.virtuallaboratory.net/Biofundamentals/l
ectureNotes/AllGraphics/animalCellCompartments.jpg
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In cytoplasm
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How to Define a Model

• Declare compartment and size
• For each compartment
• A list of variables with initial values
• Parameters
• A set of rules that changes these variables
  (Process)

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?
EML
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Model Editor
Stepper FixedODE1Stepper( DE1 ) no
property System System( / ) StepperID DE1
Variable Variable( SIZE )
Value 1e-18 Variable Variable( S
) Value 1000000 Variable
Variable( P ) Value
0 Variable Variable( E ) Value
1000 Process MichaelisUniUniFluxProcess( E
)
VariableReferenceList S0 .S -1
P0 .P 1

C0 .E 0 KmS 1 KcF
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em file
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Tracer Window
Product (P)
Substrate (S)
x axe time y axe quantity
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Hybrid/Intermediate Methods
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Model Scripting

• Scripting is a necessary function for power
  users.
• Benefit of scripting-support
• Easy model debug
• Model project automation

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Other Tools

• Parameter estimation method
• script mode
• Session manager
• Cluster support, parallel computation
• Mailing list

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Limitations

• Spacial simulation (in progress)
• Still no comprehensive analysis tools available
• A model debug tool
• Where to get the parameters?