Systems biology is a field that builds complex multi-scale models of systems that are evolved rather than engineered. No unifying theory exists for biology as it does for engineering domains. Thus, models appear in very diverse forms. Components can be genes, cells, organs or even whole ecosystems. These components can intuitively be represented as classes in an object-oriented language, making systems biology a perfect application for Modelica. However, we still only see very few models from this domain. In an attempt to change this, we show that Modelica can exactly reproduce the simulation results of a reference implementation of an established biological model of the human baroreflex. Our implementation highlights the strengths of Modelica like the event finding mechanism, which makes the model more precise.
We also show that biological systems pose interesting challenges like signals with non-uniform delays and the interaction of complex rhythms.
Anja Brunberg and Dirk Abel. Simulation verkoppelter physiologischer Regelkreise mit Hilfe der objektorientierten Modellbibliothek „HumanLib“. In Automatisierungstechnische Verfahren für die Medizin, 9. Workshop, Tagungsband, pages 29–30, Zürich, Switzerland,
2010. doi: 10.1524/auto.2011.0951.
Andrea Duggento, Nicola Toschi, and Maria Guerrisi. Modeling of human baroreflex: Considerations on the Seidel–Herzel model. Fluctuation and Noise Letters, 11(1): 1240017, 2012. doi: 10.1142/S0219477512400172.
Gernot Ernst. Heart rate variability. Springer-Verlag, London, England, 2014. ISBN 978-1-4471-4308-6. doi: 10.1007/978-1-4471-4309-3.
Robin Holliday. Epigenetics: A historical overview. Epigenetics, 1(2):76–80, 2006. doi: 10.4161/epi.1.2.2762.
Hermann-Georg Holzhütter, Dirk Drasdo, Tobias Preusser, Jörg Lippert, and Adriano M. Henney. The virtual liver: A multidisciplinary, multilevel challenge for systems biology. Wiley Interdisciplinary Reviews: Systems Biology and Medicine, 4(3):221–235, 2012. doi: 10.1002/wsbm.1158.
Peter Hunter, Peter Robbins, and Denis Noble. The IUPS human physiome project. Pflügers Archiv - European Journal of Physiology, 445(1):1–9, 2002. doi: 10.1007/s00424-002-0890-1.
Edda Klipp, Wolfram Liebermeister, ChristophWierling, Axel Kowald, Hans Lehrach, and Ralf Herwig. Systems biology: A textbook. Wiley-Blackwell, Hoboken, New Jersey, 2011.
Kiyoshi Kotani, Kiyoshi Takamasu, Yosef Ashkenazy, H. Stanley, and Yoshiharu Yamamoto. Model for cardiorespiratory synchronization in humans. Physical Review E, 65(5): 051923, 2002. doi: 10.1103/PhysRevE.65.051923.
Kiyoshi Kotani, Zbigniew Struzik, Kiyoshi Takamasu, H. Stanley, and Yoshiharu Yamamoto. Model for complex heart rate dynamics in health and diseases. Physical Review E, 72(4):041904, 2005. doi: 10.1103/PhysRevE.72.041904.
Andreas Kremling. Kompendium Systembiologie: Mathematische Modellierung und Modellanalyse. Vieweg+Teubner, Wiesbaden, Germany, 2012. ISBN 978-3-8348-1907-9.
Henry Markram. The blue brain project. Nature Reviews Neuroscience, 7(2):153–160, 2006. doi: 10.1038/nrn1848.
Marek Mateják, Tomáš Kulhánek, Jan Šilar, Pavol Privitzer, Filip Ježek, and Jirí Kofránek. Physiolibrary - Modelica library for physiology. In Proceedings of the 10th International Modelica Conference, pages 499–505, Lund, Sweden, 2014. doi: 10.3384/ecp14096499.
Mohsen Naghavi, Haidong Wang, Rafael Lozano, Adrian Davis, Xiaofeng Liang, Maigeng Zhou, and Stein Emil Vollset. Global, regional, and national age-sex specific allcause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. The Lancet, 385(9963):117–171, 2014. doi: 10.1016/S0140-6736(14)61682-2.
Emma Larsdotter Nilsson and Peter Fritzson. A metabolic specialization of a general purpose modelica library for biological and biochemical systems. In Proceedings of the 4th International Modelica Conference, pages 85–93, Hamburg, Germany, 2005.
Denis Noble. The rise of computational biology. Nature Reviews Molecular Cell Biology, 3(6):459–463, 2002. doi: 10.1038/nrm810.
Chris P. Ponting, Peter L. Oliver, andWolf Reik. Evolution and functions of long noncoding RNAs. Cell, 136(4):629–641, 2009. doi: 10.1016/j.cell.2009.02.006.
R. Ranzinger andWilliam S. York. Glyco-bioinformatics today (august 2011) – solutions and problems. In Proceedings of the 2nd Beilstein Symposium on Glyco-Bioinformatics, Potsdam, Germany, 2012.
Henrik Seidel. Nonlinear dynamics of physiological rhythms. PhD thesis, Technische Universität Berlin, Berlin, Germany, 1997.
Henrik Seidel and Hanspeter Herzel. Modelling heart rate variability due to respiration and baroreflex. In Erik Mosekilde and Ole G. Mouritsen, editors, Modelling the Dynamics of Biological Systems, number 65 in Springer Series in Synergetics, pages 205–229. Springer, Berlin Heidelberg, Germany,
1995. ISBN 978-3-642-79292-2.
Henrik Seidel and Hanspeter Herzel. Bifurcations in a nonlinear model of the baroreceptor-cardiac reflex. Physica D: Nonlinear Phenomena, 115(1-2):145–160, 1998. doi: 10.1016/S0167-2789(97)00229-7.
Eberhard O. Voit. A first course in systems biology. Garland Science, New York City, New York, 2013. ISBN 978-0-8153-4467-4.
