Distributed parameter identification for a label-structured cell population dynamics model using CFSE histogram time-series data.
In this work we address the problem of the 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.
Luzyanina
Tatyana
T
Institute of Mathematical Problems in Biology, RAS, Pushchino, Russia. luzyanina@impb.psn.ru
Roose
Dirk
D
Bocharov
Gennady
G
D000465:Algorithms; D016923:Cell Death; D002455:Cell Division; D049109:Cell Proliferation; D016001:Confidence Intervals; D005434:Flow Cytometry / Q000379:methods*; D005452:Fluoresceins / Q000032:analysis* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D016013:Likelihood Functions; D008954:Models, Biological; D013194:Staining and Labeling; D013388:Succinimides / Q000032:analysis* / Q000737:chemistry; D013601:T-Lymphocytes / Q000166:cytology
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D013388:Succinimides