Aug 12, 2009 - Treg Network Model. Mark Read, Jon. Timmis, Paul S. Andrews, Vipin. Kumar. Context, Motivation, and EAE. Applying UML to. Modelling EAE.
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing?
Using UML to model EAE and its Regulatory Network Mark Read1 , Jon Timmis1,2 , Paul S. Andrews1 , Vipin Kumar3
Tying it all Together Modelling Feedback In Summary
1. Department of Computer Science, University of York, UK, YO10 5DD {markread | jtimmis | psa}@cs.york.ac.uk 2. Department of Electronics, University of York, UK, YO10 5DD 3. Laboratory of Autoimmunity, Torrey Pines Institute of Molecule Studies, San Diego, USA.
Wednesday 12th August 2009
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Outline
Context, Motivation, and EAE Applying UML to Modelling EAE.
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Context, Motivation, and EAE
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Applying UML to Modelling EAE.
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What’s Missing?
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In Summary
Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Outline
Context, Motivation, and EAE Applying UML to Modelling EAE.
1
Context, Motivation, and EAE
2
Applying UML to Modelling EAE.
3
What’s Missing?
4
In Summary
Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Motivation for modelling and simulating EAE
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback
Pool together data and animate the temporal dimension. Investigate hypotheses. Suggest experiments. Better understand the system.
In Summary
We see modelling as a necessary pre-requisit to creation of a simulation: Demonstrate our understanding. Serves as a specification for simulation. By more principled. Validation?
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Unified Modelling Language
Unified Modelling Language (UML) [3] is a collection of diagrammatic modelling tools. Designed to aid the specification and construction of software systems. Diagrams can represent: static and dynamics aspects of system. single- to multi- element scope.
It has been suggested that UML can be used to model immunological systems, eg [1, 2]. We investigate the applicability of UML to modelling immunology through a case study.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
EAE Overview Experimental Autoimmune Encephalomyelitis (EAE) Autoimmune disease in mice, model for MS in humans. Immune system attacks central nervous system. ’Network’ of immune cell interactions, including Treg cells, can prevent debilitating EAE. Emulate network’s operation in humans - requires study. The network is complex, hence the desire for models and simulations.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
EAE & Regulatory Network.
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Figure: Static relationships between elements of the system - diagram incomplete (!). 6 / 23
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Outline
Context, Motivation, and EAE Applying UML to Modelling EAE.
1
Context, Motivation, and EAE
2
Applying UML to Modelling EAE.
3
What’s Missing?
4
In Summary
Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Activity Diagrams - Capture Scenarios
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Proven very useful. Shows the necessary order of events for high level behaviours to occur. My system has two emergent behaviours - instigation of each is represented by an activity diagram. Do not capture massive parallelism.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Activity Diagrams - EAE instigation
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Class Diagram - Specifying Everything
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Figure: Static relationships between elements of the system.
This does not really help anyone. Too many small interacting elements. 9 / 23
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Class Diagram - EAE instigation
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Figure: Class diagram derived from activity diagram. 10 / 23
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Class diagrams
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing?
Class diagram of scenario (depicted as activity diagram). Adds focus.
Tying it all Together Modelling Feedback In Summary
Can depict additional details. Thought provoking - what can happen at the same time?
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
State machine diagrams
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback
Incredibly useful. Use in later stages of modelling. Do not convey system wide dynamics well (though most can be inferred). Excellent at generating questions.
In Summary
Do you really understand what you think you understand? Some dynamics not depicted too well (decay, variable secretion). ODE? Guards such as ‘sufficient time in state’ appear a lot!
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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CD4 Th1 state machine diagram
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
A different kind of state chart
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Figure: ‘state chart’ of INF-g (a molecule) 14 / 23
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Outline
Context, Motivation, and EAE Applying UML to Modelling EAE.
1
Context, Motivation, and EAE
2
Applying UML to Modelling EAE.
3
What’s Missing?
4
In Summary
Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing?
“Expected Behaviours” diagram!
Ties together the other diagrams. Detail the observed phenomenon in the biological domain. Describe the ‘expected behaviours’...
Tying it all Together Modelling Feedback In Summary
...which we hypothesise to be responsible for them. Detail at (an abstract level) the real physical players that we believe to be responsible for the expected behaviours. What we are doing here is forming hypotheses about the system, and defining what we intend to model.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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“Expected Behaviours” diagram!
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Modelling Feedback
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
How and where to show feedback?
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Figure: Class diagram with feedback.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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How and where to show feedback?
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Outline
Context, Motivation, and EAE Applying UML to Modelling EAE.
1
Context, Motivation, and EAE
2
Applying UML to Modelling EAE.
3
What’s Missing?
4
In Summary
Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
In Summary
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Activity diagrams are good at depicting scenarios. Class diagrams have been of limited value. State machine diagrams are very good at depicting single entity dynamics. But some aspects might be better represented with ODEs.
An overview of the entire system is useful. Feedback is important, but UML does not cope well.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
Future Directions
For my PhD: These models form a basis for a simulation I am near completing. Many interesting questions raised in creating the simulation. The models presented here are but a first iteration (of what could be many). For UML and immunology: Meta-language/domain specific language that can better communicate immunological concepts. Validation of models and simulations.
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Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Thanks for listening!
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams What’s Missing? Tying it all Together Modelling Feedback In Summary
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Any Questions?
Treg Network Model Mark Read, Jon Timmis, Paul S. Andrews, Vipin Kumar
Bibliography I
Context, Motivation, and EAE Applying UML to Modelling EAE. Activity Diagrams Class Diagrams State Machine Diagrams
Hugues Bersini. Immune system modeling: The OO way. In ICARIS, pages 150–163, 2006.
What’s Missing? Tying it all Together Modelling Feedback In Summary
David Harel. Statecharts: A visual formalism for complex systems. Science of Computer Programming, 8(3):231–274, June 1987. Object Management Group. Maintainer of the unified modelling language standards. http://www.uml.org.
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