Parameters estimation approach for the MEA/hiPSC-CM assays

Julien Bouyssier 1 Mostafa Bendahmane 1 Yves Coudière 1 Jean-Frédéric Gerbeau 2 Julien Pedron 1 Philippe Zitoun 3 Nejib Zemzemi 1
1 CARMEN - Modélisation et calculs pour l'électrophysiologie cardiaque
IMB - Institut de Mathématiques de Bordeaux, Inria Bordeaux - Sud-Ouest, IHU-LIRYC
2 REO - Numerical simulation of biological flows
LJLL - Laboratoire Jacques-Louis Lions, UPMC - Université Pierre et Marie Curie - Paris 6, Inria de Paris
Abstract : We propose a mathematical approach for the analysis of drugs effects on the electrical activity of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) based on multi-electrode array (MEA) experiments. Our goal is to produce an in silico tool able to simulate drugs action in MEA/hiPSC-CM assays and to fit the drug model parameters to the experimental data. The electrical activity of the stem cells at the ion-channel level is modelled using the Paci et.al. (2013) transmembrane potential model. We use the bidomain model in order to describe the propagation of the electrical wave in the stem cells preparation. The field potential (FP) measured by the MEA is modeled by the extra-cellular potential of the bidomain equations. First, we propose a strategy allowing us to generate a FP in good agreement with the experimental data. Second, we introduce a drug/ion channels interaction based on a pore block model. We conduct different simulations for five drugs. Results show that the model reflects properly the main effects of these drugs on the FP. In order to estimate the parameters of the drug model, we define a cost function minimizing the distance between the simulated and the experimental FPs. We use an optimization procedure based on a gradient descent method where the cost function gradient is computed using an adjoint approach. Results, based on simulated observations, show that this procedure is able to estimate either the drug doze or its IC50 value.
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Poster
Journées scientifiques du LIRYC, Sep 2016, pessac, France
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Julien Bouyssier, Mostafa Bendahmane, Yves Coudière, Jean-Frédéric Gerbeau, Julien Pedron, et al.. Parameters estimation approach for the MEA/hiPSC-CM assays. Journées scientifiques du LIRYC, Sep 2016, pessac, France. 〈hal-01409683〉

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