1 / 27

Fusing and Composing Macromolecular Regulatory Network Models

Ranjit Randhawa* Clifford A. Shaffer* John J. Tyson + Departments of Computer Science* and Biology + Virginia Tech Blacksburg, VA 24061. Fusing and Composing Macromolecular Regulatory Network Models. Regulatory Network Modeling.

thomasmatos
Download Presentation

Fusing and Composing Macromolecular Regulatory Network Models

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Ranjit Randhawa* Clifford A. Shaffer* John J. Tyson+ Departments of Computer Science* and Biology+ Virginia Tech Blacksburg, VA 24061 Fusing and Composing Macromolecular Regulatory Network Models

  2. Regulatory Network Modeling • Wish to deduce physiological properties of a cell from wiring diagrams of control systems

  3. Frogegg Model

  4. Budding Yeast Model • Wiring diagrams are converted to reactions for simulation • Example: Chen and Tyson’s budding yeast model contains over 30 ODEs, some nonlinear. • About 140 rate constant parameters • Validate model by comparing simulation results against morphological outcomes from over 100 mutants defective in the regulatory network.

  5. Budding Yeast Wiring Diagram

  6. Budding Yeast Model

  7. Problem • These models are reaching the limits of human comprehension • Making the model suitable for stochastic simulation increases the number of reactions by a factor of 3-5. • Models of the Mammalian cell cycle will require 100-1000 (more for stochastic simulation).

  8. Solution • Some mechanism must be found to describe models as collections of small building blocks that are combined to form the full model.

  9. Systems Biology Markup Language • SBML is the current standard interchange language within the community of systems biology modelers. • We implement our proposals within the context of SBML language additions.

  10. Sample Models

  11. Fused and Composed Models

  12. Fusion • Given two or more existing models, we wish to create a new model that combines the information. • Remains standard SBML • We provide a tool to support users combining models. • Implemented in “wizard” style

  13. Fusion: Matching Tables • Fusion is done primarily by defining matching of SBML components • Compartments, reactions, species, etc. • A series of matching tables • Order is important to deal with dependencies

  14. Fusion Tool Setup Wizard

  15. Species Mapping Table

  16. Reaction Mapping Table

  17. Composition • Connects submodels together to form a hierarchy of models • Submodels are each valid SBML models • Add language features to SBML to support composition • Describe hierarchy • Describe interactions, links, replacements • No information hiding within models

  18. Composition and the Fusion Wizard • There are significant similarities between fusion and composition • Fusion defines a series of steps taken to merge models • Series of steps captured by the fusion tool can be viewed as an “audit trail” used in generating the mapping tables • Precisely this same information can be used to describe the set of instructions needed to connect/link the submodels for composition

  19. Composition Hierarchy <model id="Big"> <listOfCompartments> <compartment id="comp1" volume="1"/> </listOfCompartments> <listOfSubmodels> <model id="Little"> <listOfCompartments> <compartment id="comp2" volume="1"/> </listOfCompartments> </model> </listOfSubmodels> </model>

  20. Links <link> <from object="comp1"/> <to object="Submodel_Little" <subobject object="comp2"/> </to> </link>

  21. Is Composition the Right Model? • Composition allows us to take existing models and use them as components to build larger models • No information hiding • Submodels might fit together more or less well • Links let us replace things in one model with things in another • Good for legacy models(?) • We might do better to build models from components designed to work as components, with proper information hiding.

  22. Aggregation • In aggregation, models are built up from components • Each component could be, for example, a collection of reactions • This collection exposes certain variables for input/output via “ports” • Hopefully this is a natural concept for modelers • Not intended as a solution for reusing legacy models.

  23. Toggle Switch

  24. Iconified Toggle Switch

  25. Toggle Switch Component

  26. Flattening • Flattening generates a standard SBML file from our modified file, for the purpose of running simulations, etc. • An automated form of fusion. • The additional language features provide what the user would provide during fusion, so automation is possible.

  27. Summary • We recognize four distinct activities related to model decomposition [Status] • Fusion: Take existing models and merge them [Implemented] • Composition: Build up from existing models, no information hiding [Implemented] • Aggregation: Build up from building blocks, controlled interfaces [Designing stage] • Flattening: Merge the building blocks back into a “flat” (non-composed) model (for making simulation runs) [Implemented]

More Related