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Distributed parameter identification for a label-structured cell population dynamics model using CFSE histogram time-series data. (English) Zbl 1231.92027

Summary: We address the problem of robust identification of unknown parameters of a cell population dynamics model from experimental data on the kinetics of cells labelled with a fluorescence marker defining the division age of the cell. The model is formulated by a first order hyperbolic PDE for the distribution of cells with respect to the structure variable \(x\) (or \(z\)) being the intensity level (or the \(\log _{10}\)-transformed intensity level) of the marker. The parameters of the model are the rate functions of cell division, death, label decay and the label dilution factor. We develop a computational approach to the identification of the model parameters with a particular focus on the cell birth rate \(\alpha (z)\) as a function of the marker intensity, assuming the other model parameters are scalars to be estimated. To solve the inverse problem numerically, we parameterize \(\alpha (z)\) and apply a maximum likelihood approach. The parametrization is based on cubic Hermite splines defined on a coarse mesh with either equally spaced a priori fixed nodes or nodes to be determined in the parameter estimation procedure. Ill-posedness of the inverse problem is indicated by multiple minima. To treat the ill-posed problem, we apply Tikhonov regularization with the regularization parameter determined by the discrepancy principle. We show that the solution of the regularized parameter estimation problem is consistent with the data set with an accuracy within the noise level in the measurements.

MSC:

92C35 Physiological flow
35R30 Inverse problems for PDEs
93B30 System identification
92-08 Computational methods for problems pertaining to biology
62P10 Applications of statistics to biology and medical sciences; meta analysis
Full Text: DOI

References:

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