Introduction of Conceptual Entities in E-Cell

2007 Moriyoshi Koizumi <mozo@sfc.keio.ac.jp>

The Problem That Matters

• E-Cell doesn't provide comprehensive support for meta-information in models.
  • It burdens users when it comes to large-scale modeling.
• Added semantics:
  • Concepts
    • Units
    • Entity relationships
  • Annotation
    • Descriptions about the functions of an entities.
• The Workaround
  • Users handle semantics by the means of EMPY.
  • Examples
    • Unit conversion

      @{
      VOLUME = 1e-18
      N_A = 6.02e+23
      }
      ...
      Variable Variable( M )
      {
        Value  @(3.6132E-01 * N_A * VOLUME);
      }
      

    • Annotation

      @{MAIN_STEPPER='NR1'}
      @{MAIN_PROCESS='GillespieProcess'}
      @{UNFOLDING_PROCESS='GillespieProcess'}
      ...
      Process @(MAIN_PROCESS)( S32Trans )
      {
        ...
      }
      

Solutions

• Facades
• Prototypes
• Attributes

Facades

• A Facade is a convenience System that separates its content from the outer entities.
• Delegates and exposes any properties of the contents as its properties (“terminals”.)
• A facade may act as if it was a Variable.
• User-defined rules are incorporated as assignment processes.
• Rule implementation with Facades

  Process ExpressionAssignmentProcess(C)
  {
    Expression R0.Value * N_A * getSuperSystem().getSuperSystem().Size;
    VariableReferenceList 
      [ R0 Variable:.:MolarConc 0 ]
    VariableReferenceList
      [ R1 Variable:.:Quantity 1 ]
  }
  

Prototypes

• A prototype is an immutable entity that acts just as a template.
• On the creation of a new entity associated with a prototype, all of its properties and contents are copied from the prototype.
• Allows users to reuse functional components of the models.
• It is also possible to store initial condition to a prototype of the whole model.
• Example

  Process ExpressionAssignmentProcess(C)
      : ProtoC
  {
    VariableReferenceList 
      [ R0 Variable:.:S0 0 ]
    VariableReferenceList
      [ R1 Variable:.:P0 1 ]
  }
  

Attributes

• A set of information that annotates.
• Any entities and properties can be annotated with arbitrary number of attributes.
• Examples of attributes
  • Unit

    Variable Variable(S0)
    {
        @@Unit(MolarConc)
        Value 0.01
    }
    

  • Text description of an entity

    @@Description("relocated from nucleus to cytoplasm")
    Variable Variable(R0)
    {
        Name  "PER mRNA"
    }
    

  • Relationships of entities (reactant / product / modifier etc.)

    Process MassActionFluxProcess(P0)
    {
      @@Relationship(Reactant)
      VariableReferenceList 
        [ R0 Variable:.:S0 -1 ]
      @@Relationship(Product)
      VariableReferenceList
        [ P0 Variable:.:P0 1 ]
      @@Relationship(Modifier)
      VariableReferenceList
        [ M0 Variable:.:M0 0 ]
    }
    

Applications

• Ontology-based model representation
  • Modeling support tools
    • More intuitive modeling based on the domain rules.
  • Visualization (E-Cell 3D, etc.)
    • Sophisticated representation of pathway dynamics.