Included within the submission:
"Pairing experimentation and computational modelling to understand the role of tissue
inducer cells in the development of lymphoid organs"
Kieran Alden, Jon Timmis, Paul S Andrews, Henrique Veiga-Fernandes, Mark C Coles
| Skip to: | Domain Model | Platform Model | Assumptions | Simulation |
| A. Domain Model |
The domain model captures an abstraction of the biological domain. The state diagrams, created using a modified version of Unified Modelling language, provide a description of the states in which the identified agents (cell type) may exist within (the boxes), and the biological event that must take place for that agent to transition into the next state (the arrow). This does not contain any simulation-specific detail.
An Activity Diagram also forms part of this model, representing the low-level interactions between the cells (LTin, LTi, LTo Cell) which lead to the formation of PP. Cellular behaviours are described in boxes, decisions points indicated by diamonds and lines. Arrows indicate potential changes to cellular behaviour. Once loaded, click on the diagram to enlarge View Domain Model State Diagrams View Activity Diagram |
| B. Platform Model |
The Platform model details how the states and interactions captured in the domain model are coded into the simulation. The expected behaviour, which emerges from interactions between components in the system, is specifically not present in the platform model. Behaviour emerges from the simulation and are not coded into the simulation. In the platform model, how each cell behaves and how interactions are encoded is detailed. As this includes a variety of factors from the domain model a number of assumptions are made and documented.
Once loaded, click on the diagram to enlarge View Platform Model State Diagrams Intestine Environment Representation Adhesion Factors in the Platform Model Chemokines in the Platform Model Table of additional considerations included in the Platform Model Table of Parameters Identified in Domain and Platform Model |
| C. Assumptions Made |
Although in theory including all current understanding of a system is possible, such a model would be very difficult to construct and is unlikely to significantly improve the model. Therefore, the domain model is an abstraction of the biological system, with suitable assumptions made where
necessary and clearly documented for later scrutiny.
Further parameters are identified in forming the Platform Model and described, and as in the domain model the numerical values of some parameters are unknown. These parameters may capture the behaviour of component parts such as adhesion molecules, cytokines, and chemokines. Despite the importance of these factors, the number of molecules expressed by the different cell types, the level of chemokine expression required to induce cellular chemotaxis and the diffusion distribution of chemokines and cytokines in the localised environment all are currently unknown. Thus further assumptions are made based on known biology and documented. View Assumptions Tables for this Model |
| D. The Simulator |
The simulation can be run either with the default parameter values (set during calibration, leading to cell behaviour that is statistically similar to that seen ex vivo), or these can be set prior to the simulation run. |
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The following applet loads the entire MASON toolkit so it may take a second. Please note:
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