CyberUnits Bricks: An Implementation Study of a Class Library for Simulating Nonlinear Biological Feedback Loops
Abstract Feedback loops and other types of information processing structures play a pivotal role in maintaining the internal milieu of living organisms. Although methods of biomedical cybernetics and systems biology help to translate between the structure and function of processing structures, computer simulations are necessary for studying nonlinear systems and the full range of dynamic responses of feedback control systems. Currently, available approaches for modelling and simulation comprise basically domain-specific environments, toolkits for computer algebra systems and custom software written in universal programming languages for a specific purpose, respectively. All of these approaches are faced with certain weaknesses. We therefore developed a cross-platform class library that provides versatile building bricks for writing computer simulations in a universal programming language (CyberUnits Bricks). It supports the definition of models, the simulative analysis of linear and nonlinear systems in the time and frequency domain and the plotting of block diagrams. We compared several programming languages that are commonly used in biomedical research (S in the R implementation and Python) or that are optimized for speed (Swift, C++ and Object Pascal). In benchmarking experiments with two prototypical feedback loops, we found the implementations in Object Pascal to deliver the fastest results. CyberUnits Bricks is available as open-source software that has been optimised for Embarcadero Delphi and the Lazarus IDE for Free Pascal.
- Referencias
- Cómo citar
- Del mismo autor
- Métricas
Alon, U. (2007). Network motifs: theory and experimental approaches. Nature Reviews Genetics, 8, )450-61. 10.1038/nrg2102
Alon, U. (2020). An Introduction to Systems Biology. CRC Press.
Berberich, J., Dietrich, J. W., Hoermann, R., & Mueller, M. A. (2018). Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T-3-Shunt and Sensitivity Analysis. Front Endocrinol (Lausanne), 9. 10.3389/fendo.2018.00091
Cruz-Loya, M., Chu, B. B., Jonklaas, J., Schneider, D. F., & DiStefano, J., 3rd (2022). Optimized Replacement T4 and T4+T3 Dosing in Male and Female Hypothyroid Patients With Different BMIs Using a Personalized Mechanistic Model of Thyroid Hormone Regulation Dynamics. Frontiers in endocrinology, 13, 888429. 10.3389/fendo.2022.888429
Curcio, L., D'Orsi, L., Cibella, F., Wagnert-Avraham, L., Nachman, D., & De Gaetano, A. (2020). A Simple Cardiovascu-lar Model for the Study of Hemorrhagic Shock. Computational and mathematical methods in medicine, 2020, 7936895. 10.1155/2020/7936895
Dietrich, J. W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Entwicklung und klinische Anwendung eines nichtlinearen Modells (Vol. 2). Logos-Verlag.
Dietrich, J. W. (2017). SimThyr. Report No. RRID:SCR_014351, (Zenodo, 2017).
Dietrich, J. W., & Boehm, B. O. (2006). Equilibrium behaviour of feedback-coupled physiological saturation kinetics. In Trappl R. (ed.), Cybernetics and Systems 2006 (Vol. 1, pp. 269-274). Austrian Society for Cybernetic Studies.
Dietrich, J. W. & Boehm, B. O. (2015). Die MiMe-NoCoDI-Plattform: Ein Ansatz für die Modellierung biologischer Regelkreise. German Med. Sci. DocAbstr. 284. 10.3205/15gmds058
Dietrich, J. W. & Boehm, B. O. (2021). SimulaBeta. Report No. RRID: SCR_021900, (Zenodo, 2021).
Dietrich, J. W., Dasgupta, R., Anoop, S., Jebasingh, F., Kurian, M. E., Inbakumari, M., Boehm, B. O., & Thomas, N. (2022). SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and be-ta cell function. Scientific reports, 12(1), 17659. 10.1038/s41598-022-22531-3
Dietrich, J. W., Landgrafe-Mende, G., Wiora, E., Chatzitomaris, A., Klein, H. H., Midgley, J. E., & Hoermann, R. (2016). Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Frontiers in endocrinology, 7, 57. 10.3389/fendo.2016.00057
Dietrich, J. W., Mitzdorf, U., Weitkunat, R., & Pickardt, C. R. (1997). The pituitary-thyroid feedback control: stability and oscillations in a new nonlinear model. Journal of Endocrinological Investigation, 20 (Suppl. to no. 5), 100.
Dietrich, J. W., Tesche A., Pickard C. R. and Mitzdorf U. (2004). Thyrotropic feedback control: Evidence for an addition-al ultrashort feedback loop from fractal analysis. Cybernetics and Systems, 35(4), 315-331. 10.1080/01969720490443354
DiStefano, J. (1990). Schaum’s Outline of Feedback and Control System. McGraw-Hill.
Franklin, G. F., Powell, J. D., Emami-Naeini, A. (2002). Feedback Control of Dynamic Systems. Prentice Hall.
Free Pascal Team. (1991-2021). Free Pascal: A 32-, 64- and 16-bit professional Pascal compiler. Report No. RRID: SCR_014360, (Fair-fax, VA, 1993-2021).
Glad, T., Ljung, L. (2000). Control Theory. Taylor & Francis.
Han, S. X., Eisenberg, M., Larsen, P. R., & DiStefano, J., 3rd (2016). THYROSIM App for Education and Research Pre-dicts Potential Health Risks of Over-the-Counter Thyroid Supplements. Thyroid: official journal of the American Thyroid Association, 26(4), 489-498. 10.1089/thy.2015.0373
Head, R. J., Lumbers, E. R., Jarrott, B., Tretter, F., Smith, G., Pringle, K. G., Islam, S., & Martin, J. H. (2022). Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and re-sponse to treatment. Pharmacology research & perspectives, 10(1), e00922. 10.1002/prp2.922
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2013). Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? European Journal of Endocrinology, 168(2), 271-280. 10.1530/EJE-12-0819
Hoermann, R., Midgley, J. E., Larisch, R., & Dietrich, J. W. (2015). Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. Front Endocrinol (Lausanne), 6, 177. 10.3389/fendo.2015.00177
Hoermann, R., Pekker, M. J., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2022). Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change. Frontiers in endocrinology, 13, 825107. 10.3389/fendo.2022.825107
Holzmann, G. (2006). The Power of 10: Rules for Developing Safety-Critical Code. IEEE Computer. 39(6), 95-9. 10.1109%2FMC.2006.212
Kamburelis, M. (2023). Why use Pascal? https://castle-engine.io/why_pascal
Kolar-Anić, L., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A., & Dietrich, J. W. (2023). Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback. Computers in biology and medicine, 160, 106980. 10.1016/j.compbiomed.2023.106980
Lazarus Team. (1993-2023). Lazarus: The professional Free Pascal RAD IDE. Report No. RRID: SCR_014362, (Fairfax, VA, 1993-2023).
McEwen B. S. (1998). Stress, adaptation, and disease. Allostasis and allostatic load. Annals of the New York Academy of Sciences, 840, 33-44. 10.1111/j.1749-6632.1998.tb09546.x
McEwen, B. S., & Stellar, E. (1993). Stress and the individual. Mechanisms leading to disease. Archives of internal medicine, 153(18), 2093-2101. 10.1001/archinte.1993.00410180039004
Midgley, J. E. M., Hoermann, R., Larisch, R., & Dietrich, J. W. (2013). Physiological states and functional relation be-tween thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. J Clin Pathol, 66(4), 335-342. 10.1136/jclinpath-2012-201213
Neuber, H. (1989). Simulation von Regelkreisen auf Personal Computern in Pascal und Fortran 77. IWT.
Pereira, R., Couto, M., Ribeiro, F., Rua, R., Cunha, J., Fernandes, J. P., & Saraiva, J. (2021). Ranking programming lan-guages by energy efficiency. Science of Computer Programming, 205, 102609. 10.1016/j.scico.2021.102609
Pompa, M., Panunzi, S., Borri, A., & De Gaetano, A. (2021). A comparison among three maximal mathematical models of the glucose-insulin system. PloS one, 16(9), e0257789. 10.1371/journal.pone.0257789
R Core Team. (2023). R: A Language and Environment for Statistical Computing. Report No. RRID:SCR_001905, (R Foundation for Statistical Computing, Vienna, Austria, 2018).
Röhler, R. (1973). Biologische Kybernetik - Regelungsvorgänge in Organismen. Vieweg+Teubner Verlag. 10.1007/978-3-322-94729-1
Schulkin, J., & Sterling, P. (2019). Allostasis: A Brain-Centered, Predictive Mode of Physiological Regulation. Trends in neurosciences, 42(10), 740-752. 10.1016/j.tins.2019.07.010
Tretter F. (2018). From mind to molecules and back to mind-Metatheoretical limits and options for systems neuropsychiatry. Chaos, 28(10), 106325. 10.1063/1.5040174
Tretter, F., Wolkenhauer, O., Meyer-Hermann, M., Dietrich, J. W., Green, S., Marcum, J., & Weckwerth, W. (2021). The Quest for System-Theoretical Medicine in the COVID-19 Era. Frontiers in medicine, 8, 640974. 10.3389/fmed.2021.640974
Tretter, F., Peters, E. M. J., Sturmberg, J., Bennett, J., Voit, E., Dietrich, J. W., Smith, G., Weckwerth, W., Grossman, Z., Wolkenhauer, O., & Marcum, J. A. (2023). Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology. Journal of evaluation in clinical practice, 29(3), 415-429. 10.1111/jep.13772
Varjú, D. (1977). Systemtheorie für Biologen und Mediziner. Springer-Verlag,
Wolff, T. M., Veil, C., Dietrich, J. W., & Muller, M. A. (2022). Mathematical modeling and simulation of thyroid homeo-stasis: Implications for the Allan-Herndon-Dudley syndrome. Front Endocrinol (Lausanne), 13, 882788. 10.3389/fendo.2022.882788
Alon, U. (2020). An Introduction to Systems Biology. CRC Press.
Berberich, J., Dietrich, J. W., Hoermann, R., & Mueller, M. A. (2018). Mathematical Modeling of the Pituitary-Thyroid Feedback Loop: Role of a TSH-T-3-Shunt and Sensitivity Analysis. Front Endocrinol (Lausanne), 9. 10.3389/fendo.2018.00091
Cruz-Loya, M., Chu, B. B., Jonklaas, J., Schneider, D. F., & DiStefano, J., 3rd (2022). Optimized Replacement T4 and T4+T3 Dosing in Male and Female Hypothyroid Patients With Different BMIs Using a Personalized Mechanistic Model of Thyroid Hormone Regulation Dynamics. Frontiers in endocrinology, 13, 888429. 10.3389/fendo.2022.888429
Curcio, L., D'Orsi, L., Cibella, F., Wagnert-Avraham, L., Nachman, D., & De Gaetano, A. (2020). A Simple Cardiovascu-lar Model for the Study of Hemorrhagic Shock. Computational and mathematical methods in medicine, 2020, 7936895. 10.1155/2020/7936895
Dietrich, J. W. (2002). Der Hypophysen-Schilddrüsen-Regelkreis. Entwicklung und klinische Anwendung eines nichtlinearen Modells (Vol. 2). Logos-Verlag.
Dietrich, J. W. (2017). SimThyr. Report No. RRID:SCR_014351, (Zenodo, 2017).
Dietrich, J. W., & Boehm, B. O. (2006). Equilibrium behaviour of feedback-coupled physiological saturation kinetics. In Trappl R. (ed.), Cybernetics and Systems 2006 (Vol. 1, pp. 269-274). Austrian Society for Cybernetic Studies.
Dietrich, J. W. & Boehm, B. O. (2015). Die MiMe-NoCoDI-Plattform: Ein Ansatz für die Modellierung biologischer Regelkreise. German Med. Sci. DocAbstr. 284. 10.3205/15gmds058
Dietrich, J. W. & Boehm, B. O. (2021). SimulaBeta. Report No. RRID: SCR_021900, (Zenodo, 2021).
Dietrich, J. W., Dasgupta, R., Anoop, S., Jebasingh, F., Kurian, M. E., Inbakumari, M., Boehm, B. O., & Thomas, N. (2022). SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and be-ta cell function. Scientific reports, 12(1), 17659. 10.1038/s41598-022-22531-3
Dietrich, J. W., Landgrafe-Mende, G., Wiora, E., Chatzitomaris, A., Klein, H. H., Midgley, J. E., & Hoermann, R. (2016). Calculated Parameters of Thyroid Homeostasis: Emerging Tools for Differential Diagnosis and Clinical Research. Frontiers in endocrinology, 7, 57. 10.3389/fendo.2016.00057
Dietrich, J. W., Mitzdorf, U., Weitkunat, R., & Pickardt, C. R. (1997). The pituitary-thyroid feedback control: stability and oscillations in a new nonlinear model. Journal of Endocrinological Investigation, 20 (Suppl. to no. 5), 100.
Dietrich, J. W., Tesche A., Pickard C. R. and Mitzdorf U. (2004). Thyrotropic feedback control: Evidence for an addition-al ultrashort feedback loop from fractal analysis. Cybernetics and Systems, 35(4), 315-331. 10.1080/01969720490443354
DiStefano, J. (1990). Schaum’s Outline of Feedback and Control System. McGraw-Hill.
Franklin, G. F., Powell, J. D., Emami-Naeini, A. (2002). Feedback Control of Dynamic Systems. Prentice Hall.
Free Pascal Team. (1991-2021). Free Pascal: A 32-, 64- and 16-bit professional Pascal compiler. Report No. RRID: SCR_014360, (Fair-fax, VA, 1993-2021).
Glad, T., Ljung, L. (2000). Control Theory. Taylor & Francis.
Han, S. X., Eisenberg, M., Larsen, P. R., & DiStefano, J., 3rd (2016). THYROSIM App for Education and Research Pre-dicts Potential Health Risks of Over-the-Counter Thyroid Supplements. Thyroid: official journal of the American Thyroid Association, 26(4), 489-498. 10.1089/thy.2015.0373
Head, R. J., Lumbers, E. R., Jarrott, B., Tretter, F., Smith, G., Pringle, K. G., Islam, S., & Martin, J. H. (2022). Systems analysis shows that thermodynamic physiological and pharmacological fundamentals drive COVID-19 and re-sponse to treatment. Pharmacology research & perspectives, 10(1), e00922. 10.1002/prp2.922
Hoermann, R., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2013). Is pituitary TSH an adequate measure of thyroid hormone-controlled homoeostasis during thyroxine treatment? European Journal of Endocrinology, 168(2), 271-280. 10.1530/EJE-12-0819
Hoermann, R., Midgley, J. E., Larisch, R., & Dietrich, J. W. (2015). Homeostatic Control of the Thyroid-Pituitary Axis: Perspectives for Diagnosis and Treatment. Front Endocrinol (Lausanne), 6, 177. 10.3389/fendo.2015.00177
Hoermann, R., Pekker, M. J., Midgley, J. E. M., Larisch, R., & Dietrich, J. W. (2022). Principles of Endocrine Regulation: Reconciling Tensions Between Robustness in Performance and Adaptation to Change. Frontiers in endocrinology, 13, 825107. 10.3389/fendo.2022.825107
Holzmann, G. (2006). The Power of 10: Rules for Developing Safety-Critical Code. IEEE Computer. 39(6), 95-9. 10.1109%2FMC.2006.212
Kamburelis, M. (2023). Why use Pascal? https://castle-engine.io/why_pascal
Kolar-Anić, L., Čupić, Ž., Maćešić, S., Ivanović-Šašić, A., & Dietrich, J. W. (2023). Modelling of the thyroid hormone synthesis as a part of nonlinear reaction mechanism with feedback. Computers in biology and medicine, 160, 106980. 10.1016/j.compbiomed.2023.106980
Lazarus Team. (1993-2023). Lazarus: The professional Free Pascal RAD IDE. Report No. RRID: SCR_014362, (Fairfax, VA, 1993-2023).
McEwen B. S. (1998). Stress, adaptation, and disease. Allostasis and allostatic load. Annals of the New York Academy of Sciences, 840, 33-44. 10.1111/j.1749-6632.1998.tb09546.x
McEwen, B. S., & Stellar, E. (1993). Stress and the individual. Mechanisms leading to disease. Archives of internal medicine, 153(18), 2093-2101. 10.1001/archinte.1993.00410180039004
Midgley, J. E. M., Hoermann, R., Larisch, R., & Dietrich, J. W. (2013). Physiological states and functional relation be-tween thyrotropin and free thyroxine in thyroid health and disease: in vivo and in silico data suggest a hierarchical model. J Clin Pathol, 66(4), 335-342. 10.1136/jclinpath-2012-201213
Neuber, H. (1989). Simulation von Regelkreisen auf Personal Computern in Pascal und Fortran 77. IWT.
Pereira, R., Couto, M., Ribeiro, F., Rua, R., Cunha, J., Fernandes, J. P., & Saraiva, J. (2021). Ranking programming lan-guages by energy efficiency. Science of Computer Programming, 205, 102609. 10.1016/j.scico.2021.102609
Pompa, M., Panunzi, S., Borri, A., & De Gaetano, A. (2021). A comparison among three maximal mathematical models of the glucose-insulin system. PloS one, 16(9), e0257789. 10.1371/journal.pone.0257789
R Core Team. (2023). R: A Language and Environment for Statistical Computing. Report No. RRID:SCR_001905, (R Foundation for Statistical Computing, Vienna, Austria, 2018).
Röhler, R. (1973). Biologische Kybernetik - Regelungsvorgänge in Organismen. Vieweg+Teubner Verlag. 10.1007/978-3-322-94729-1
Schulkin, J., & Sterling, P. (2019). Allostasis: A Brain-Centered, Predictive Mode of Physiological Regulation. Trends in neurosciences, 42(10), 740-752. 10.1016/j.tins.2019.07.010
Tretter F. (2018). From mind to molecules and back to mind-Metatheoretical limits and options for systems neuropsychiatry. Chaos, 28(10), 106325. 10.1063/1.5040174
Tretter, F., Wolkenhauer, O., Meyer-Hermann, M., Dietrich, J. W., Green, S., Marcum, J., & Weckwerth, W. (2021). The Quest for System-Theoretical Medicine in the COVID-19 Era. Frontiers in medicine, 8, 640974. 10.3389/fmed.2021.640974
Tretter, F., Peters, E. M. J., Sturmberg, J., Bennett, J., Voit, E., Dietrich, J. W., Smith, G., Weckwerth, W., Grossman, Z., Wolkenhauer, O., & Marcum, J. A. (2023). Perspectives of (/memorandum for) systems thinking on COVID-19 pandemic and pathology. Journal of evaluation in clinical practice, 29(3), 415-429. 10.1111/jep.13772
Varjú, D. (1977). Systemtheorie für Biologen und Mediziner. Springer-Verlag,
Wolff, T. M., Veil, C., Dietrich, J. W., & Muller, M. A. (2022). Mathematical modeling and simulation of thyroid homeo-stasis: Implications for the Allan-Herndon-Dudley syndrome. Front Endocrinol (Lausanne), 13, 882788. 10.3389/fendo.2022.882788
Dietrich, J. W., Siegmar, N., Hojjati, J. R., Gardt, O., & Boehm, B. O. (2024). CyberUnits Bricks: An Implementation Study of a Class Library for Simulating Nonlinear Biological Feedback Loops. ADCAIJ: Advances in Distributed Computing and Artificial Intelligence Journal, 13(1), e31762. https://doi.org/10.14201/adcaij.31762
Downloads
Download data is not yet available.
+
−