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Modern mathematical methods in modeling and dynamics of regulatory systems of gene-environment networks

Defterli, Özlem
Inferring and anticipation of genetic networks based on experimental data and environmental measurements is a challenging research problem of mathematical modeling. In this thesis, we discuss gene-environment network models whose dynamics are represented by a class of time-continuous systems of ordinary differential equations containing unknown parameters to be optimized. Accordingly, time-discrete version of that model class is studied and improved by using different numerical methods. In this aspect, 3rd-order Heun’s method and 4th-order classical Runge-Kutta method are newly introduced, iteration formulas are derived and corresponding matrix algebras are newly obtained. We use nonlinear mixed-integer programming for the parameter estimation and present the solution of a constrained and regularized given mixed-integer problem. By using this solution and applying the 3rd-order Heun’s and 4th-order classical Runge-Kutta methods in the timediscretized model, we generate corresponding time-series of gene-expressions by this thesis. Two illustrative numerical examples are studied newly with an artificial data set and a realworld data set which expresses a real phenomenon. All the obtained approximate results are compared to see the goodness of the new schemes. Different step-size analysis and sensitivity tests are also investigated to obtain more accurate and stable predictions of time-series results for a better service in the real-world application areas. The presented time-continuous and time-discrete dynamical models are identified based on given data, and studied by means of an analytical theory and stability theories of rarefication, regularization and robustification.