Playing with biological networks

1
Playing with biological networks

• Specific Aim 2a
• Develop tools and technologies that will permit
  definition and extraction of reusable model
  components from within quantitative cell
  biological models.

2
The Problem

• VCell current capabilities
• BioModel-level reusability
• Molecule/reaction-level reusability
• New requirements for
• Modeling large networks
• Modeling experiments

3
The Solution

• Create reusable building blocks of arbitrary
  size and complexity
• Overall strategy
• Analyze use-cases
• Create design specification
• Create implementation specification
• Prototype
• Review specifications and prioritize
• First pass at full development (v. 1.0)
• Testing

4
Use Case 1

• Complexes

5
Modeling Complexes
6
Modeling Complexes
7
Use Case 2

• Networks

8
Modeling Networks
9
Modeling Networks
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VCell Modules

• PhysiologyModules
• ApplicationModules
• Virtual instruments
• Virtual protocols

11
Requirements for Module Reuse

• Proper concept/context separation
• Physiology vs. Application, hypothesis vs.
  experiment
• Proper identification
• Controlled vocabularies ontologies, database
  bindings, namespaces
• Proper documentation of modeling assumptions
• Constraint mappings
• Proper encapsulation
• Required, optional, or prohibited interactions
  topologies

12
PhysiologyModule Design

• Module definition
• Species and interactions that are considered part
  of the module
• Is a subset of a graph (nodes and edges)
• Module description
• Properties of all module components
• Is the actual encapsulation of a reusable model
• The concept of connectors
• A standard way of interfacing
• Can be extended to a formal API

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PhysiologyModules Connectors

• Structural connectors
• Enumeration of structures with related topology
  information
• Species connectors
• Enumeration of exposable species nodes
• Interaction connectors
• Enumeration of exposable interaction nodes
• Enumeration of required external species nodes
  with related linkage information

14
Related Developments

• Experiment abstractions (protocols, instruments)
• Rule-based model-building automation
• Large multi-state complex representations
• Modeling ontologies
• Language extensions (VCML, SBML)
• Initialization and the steady-state problem