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
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
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
Simple Circulation DEMO
Disciplines
Modeling
Simulation
– computation
Visualization
Guyton's 1972 diagram corrected
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
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.
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
Modelica implementation: Guyton 1972 → HumMod 2011
Chalanges throughout disciplines
Simulation
– Automatize conversion from model to simulator
• MATLAB/Simulink → ActionScript, .NET
• Modelica → C, FMI, .NET
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
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
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
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
client
Moving computation to NGI-CZ/EGI
visualization
server
simulation
Web service
simulation controlData processing
REST, HTTP,JSON
Database
simulation simulation
...
Identification Algorithm
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 …
Summary
Challenges: understandability, sustainability
Modeling – acausal modeling in Modelica
Simulation – generated by tools
Visualization – web based
Research – promote results …
Education – virtual pacient ...