Practical identifiability of mathematical models of biomedical processes

Authors

  • S. I. Kabanikhin Institute of Computational Mathematics and Mathematical Geophysics of SB RAS
  • Z. M. Bektemessov al-Farabi Kazakh National University
  • O. I. Krivorotko Institute of Computational Mathematics and Mathematical Geophysics of SB RAS
  • D. A. Voronov Institute of Computational Mathematics and Mathematical Geophysics of SB RAS

DOI:

https://doi.org/10.26577/jmmcs-2017-3-479
        256 2144

Keywords:

practical identifiability, dynamic systems, сonfidence interval method, inverse problem

Abstract

The paper is devoted to a numerical study of the uniqueness and stability of problems of
determining the parameters of dynamical systems arising in pharmacokinetics, immunology,
epidemiology, sociology, etc. by incomplete measurements of certain states of the system at fixed
time. Significance of parameters difficult to measure is very high in many areas, as their definition
will allow physicians and doctors to make an effective treatment plan and to select the optimal set
of medicines. Due to the fact that the problems under consideration are ill-posed, it is necessary to
investigate the degree of ill-posedness before its numerical solution. One of the most effective ways
is to study the practical identifiability of systems of nonlinear ordinary differential equations that
will allow us to establish a set of identifiable parameters for further numerical solution of inverse
problems. The paper presents three methods for investigating practical identifiability: the Monte
Carlo method, the matrix correlation method, and the confidence intervals method. It is presented
two mathematical models of the pharmacokinetics of the C-peptide and unidentifiable parameters
were determined using the PottersWheel and AMIGO software packages. The similarity of results
is shown, and also the advantages of each of the packages are demonstrated. This investigation
will allow us to construct a regularized unique solution of the inverse problem.

References

[1] Audoly S., "On the Identifiability of Linear Compartmental System: a Revisited Transfer Function Approach Based on
Topological Properties."Mathematical Biosciences 10(1983): 308.
[2] Bellman R., "On Structural Identifiability."Mathematical Biosciences 30(1970): 437.
[3] Bellu G. and Saccomani M.P., "DAISY: A New Software Tool to Test Global Identifiability of Biological and Physiological
Systems."Comput.methods programs biomed 88(2007): 94.
[4] Brown R., "Compartmental System Analysis: State of the Art."IEEE Transactions on Biomedical Engineering 14(1980):
58.
[5] Brown R., "Identifiability: role in design of pharmacokinetic experiments."IEEE Transactions on Biomedical Engineering
14(1982): 67.
[6] Carson E. and Cobelli C., Modelling Methodology for Physiology and Medicine. (New-York: Academic Press, 2001), 421.
[7] Carson E. and Cobelli C., Introduction to Modelling in Physiology and Medicine. (New-York: Academic Press, 2008), 324.
[8] Cobelli C. and Lepschy G., "Identifiability of Compartmental Systems and Related Structural Properties."Mathematical
Biosciences 132(1976): 156.
[9] Cobeli C. and DiStefano J., "Parameter and Structural Identifiability Concepts and Ambiguities: a Critical Review and
Analysis"Amer. J. Physiology-Regulatory, Integrative and Comparative Physiology 239(1980): 380.
[10] DiStefano J., "Tracer Experiment Design for Unique Identification of Nonlinear Physiological Systems"Amer. J. Physiology
6(1976): 397.
[11] Gabasov R. and Kirillova F.M. Qualitative Theory of Optimal Processes. (Moscow: Science, 1970), 508.
[12] Glover K. and Willems J., "Parametrization of Linear Dynamical Systems: Canonical Forms and Identifiability."IEEE
Trans. on Automatic Control 19(1974): 943.
[13] Grewal M. and Glover K., "Identifiability of Linear and Nonlinear Dynamical Systems."IEEE Trans. on Automatic Control
21(1976): 837.
[14] Kabanikhin S.I., Voronov D.A., Grodz A.A. and Krivorotko O.I., "Identifiability of Mathematical Models of Medical
Biology."Vavilovsky Journal of Genetics and Breeding 19(2015): 870, accessed December 18, 2016, doi:10.18699/VJ15.097
[15] Karelin V.V., "Algorithm for the Estimation of the Vector of Parameters of Linear Dynamical Systems with Discrete-
Measurable Functions."Questions of mechanics and control processes 359(1982).
[16] Levakov A.A., "Identification of Nonlinear Systems."Differential Equations 19(1983): 1078.
[17] Meshkat N., "Identifiable Reparametrizations of Linear Compartment Models."J. Symbolic Computation 63(2014): 116.
[18] Meshkat N. and Anderson J.D. "Alternative to Ritt’s Pseudodivision for Finding the Input-Output Equations of Multi-
Output Models."Mathematical Biosciences 239(2012): 218.
[19] Meshkat N., Kuo C.E. and DiStefano J., "Finding and Using Identifiable Parameter Combinations in Nonlinear Dynamic
Systems Biology Models and COMBOS: A Novel Web Implementation."Plos One. 9(2014).
[20] Meshkat N., Eisenberg M. and DiStefano J., "An Algorithm for Finding Globally Identifiable Parameter Combinations of
Nonlinear ODE Models using Groebner Bases."Mathematical Biosciences 222(2009): 72.
[21] Mori J.D., "Optimal Nonuniform Sampling Interval and Test Input Design for Identification of Physiological Systems
from Very Limited Data."IEEE Trans Aut Control 24(1979): 990.
[22] Reid J.G., "Structural Identifiability in Linear Time Invariant Systems."IEEE Trans. on Automatic Control AC-22(1977):
281.
[23] Saccomani M., "An Effective Automatic Procedure for Testing Parameter Identifiability of HIV/AIDS Models."Bulletin
of Mathematical Biology 73(2011): 1968.
[24] Saccomani M. and Cobelli C., "Qualitative Experiment Design in Physiological System Identification."IEEE Control
System 12(1992): 37.
[25] Shcherbak V.F., "Conditions for the Identifiability of Dynamic Systems."Mathematical Physics 34(1983): 180.
[26] Tunali T.T., "New Results for Identifiability of Nonlinear Systems."IEEE Transactions on Automatic Control 15(1987):
192.
[27] Vajda S., "Identifiability of First Order Reaction Systems."Reaction Kinetics, Mechanisms and Catalysis 11(1979): 95.

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How to Cite

Kabanikhin, S. I., Bektemessov, Z. M., Krivorotko, O. I., & Voronov, D. A. (2017). Practical identifiability of mathematical models of biomedical processes. Journal of Mathematics, Mechanics and Computer Science, 95(3), 105–118. https://doi.org/10.26577/jmmcs-2017-3-479