modelling and simulation of complex human physiology systems · modelling and simulation of complex...
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Modelling and simulation of complex human physiology systems
Tomáš Kulhánek
Institute of Pathological Physiology, First Faculty of Medicine, Charles Univerzity in Prague, Czech
Republic
CESNET z.s.p.o. (NGI-CZ)
EGI Champion
EGI CF13, Manchester, 10 April 2013
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Physiology
● Physiology is a branch of biology which studies all functions of the living body, including mechanical, physical and biochemical.
● Integrative physiology (excercise science) study how human body responds to external and internal stimuli
● Computational physiology developes and uses computational framework to support study of physiological systems
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What we do● Institute of Pathological Physiology
– Interdisciplinary team (~10 people)- physicians, mathematicians, computer scientists, biomedical engineers, painters/graphical designers, …
– mathematical modeling of human physiology, Software system for simulation application, Graphical design, Educational portal www.physiome.cz/atlas
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Simple Circulation DEMO
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Disciplines
Modeling
Simulation
– computation
Visualization
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Guyton's 1972 diagram corrected
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HumMod
Guyton, A. C., Coleman, T. G., & Grander, H. J. (1972). Circulation: Overall regulation. Ann. Rev. Physiol., 41, str. 13-41.
Robert Hester, Alison Brown, Leland Husband, Radu Iliescu, William Andrew Pruett, Richard L Summers, and Thomas Coleman. Hummod: A modeling environment for the simulation of integrative human physiology. Frontiers in Physiology, 2(12), 2011.
www.hummod.org
Kofránek, Jiří, Mateják, Marek, Privitzer, Pavol, Tribula, Martin: HumMod-Golem Edition – Large Scale Model of Physiological Systems for Web Based Medical Simulator. In Proceedings of Medicine 2.0 Conference, Stanford, 2011, Stanford University, 2011 (Lary Chu, ed.). Internet Proceedings
www.physiome.cz/hummod
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Tools
Simulink - Block diagram environment for multidomain simulation and Model-Based Design.
Modelica - is an open standard, object-oriented, declarative, multi-domain modeling language for component-oriented modeling of complex systems.
CellML is an open standard based on the XML markup language.to store and exchange computer-based mathematical models.
JSim is a Java-based simulation system for building quantitative numeric models and analyzing them with
respect to experimental reference data.
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Challenges throughout disciplines Modeling
– Sustainability
• MATLAB/Simulink – Causal block oriented modeling, model update and reuse is difficult – update all causalities
• Modelica – acausal object oriented modeling, model update is simple, causalities solved by tools
– Understandable and utilizable for domain experts
• SAPHIR Exemplar project based on Guyton 1972 inspired model instead of newer HumMod → VPH
• IUPS PHYSIOME – uses CellML language, set of models mainly based on Guyton 1972
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Modelica implementation: Guyton 1972 → HumMod 2011
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Chalanges throughout disciplines
Simulation
– Automatize conversion from model to simulator
• MATLAB/Simulink → ActionScript, .NET
• Modelica → C, FMI, .NET
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Chalanges throughout disciplines
Visualization
– Survive technology/platform death
• Native application (MS DOS, MS Windows, … )
• Web based simulators (Adobe Flash, MS Silverlight, HTML5)
– Understandable for student and resercher
• Education
• Research
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Chalanges throughout use cases
Education …
– Simulation takes ~ seconds
Research
– Hypothesis testing
– Identification of model parameter
• Compute model parameters that can't be measured
– Validation and verification of model
• Mathematical simulation corresponds to clinical and experimental data
– 1 000~1 000 000 instances of simulation, some of them can be parallelized
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Computation system - BOINC
Model evaluation – Binaries on MS Windows platform
Computation service – SOAP web service
BOINC – desktop grid - volunteer computing grid
DC-API – SZTAKI desktop grid API based upon BOINC
Computation nodes – BOINC clients
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client
identification and model parameter estimation
visualization
server
simulation
Web service
simulation controlData processing
REST, HTTP,JSON
Database
simulation simulation
...
Simulation tasks on dedicated cluster
Identification Algorithm
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client
Moving computation to NGI-CZ/EGI
visualization
server
simulation
Web service
simulation controlData processing
REST, HTTP,JSON
Database
simulation simulation
...
Identification Algorithm
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Curent and future research
EducationVirtual Patient ...
– LifeScienceBoost identification of parameters among partners in pathological physiology ...
Identification of dynamics of hematopoietic stem cells engrafted in submyeloablatively irradiated mice …
Validation and verification of acidbase balance model against real patients data
Analysis of human voice, psychoacoustic tests … (cooperation with Academy of Performing arts)
– Computer Science
Agent based simulation ...
Domain specific language for sustainable simulation application – MetaProgrammingSystem (http://www.jetbrains.com/mps/), Language oriented programming …
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Summary
Challenges: understandability, sustainability
Modeling – acausal modeling in Modelica
Simulation – generated by tools
Visualization – web based
Research – promote results …
Education – virtual pacient ...