Estratégias numéricas e de otimização para inferência da dinâmica de redes bioquímicas

Abstract

Estimating parameters of dynamic models of biological systems using time series is becoming very important because a huge amount of experimental data is being measured by modern molecular biology. A resolution-based approach on inverse problems can be used in solving this type of problem. The choice of the mathematical model is an important task, since many models can be used, with varying levels of accuracy in their representations. The Biochemical Systems Theory (BST) makes use of ordinary differential equations and power series expansions to represent biochemical processes. The S-system is one of the models used by BST that allows the transformation of the original system of differential equations in a decoupled system of algebric equations, favouring the solution of the inverse problem. This transformation can compromise the quality of the response if the value of the derivatives at points of time series are not obtained accurately. To estimate the derivatives we intend to explore the complex-step method, which has advantages over the finite difference method, best known and used . So the search for the variables that define the equations of the system can be performed. The Alternating Regression method is one of the fastest for this type of problem, but the initial choice of parameters has influence on its performance, which may not even be found. We intend to evaluate the Cross-entropy method, which has the advantage of performing global searches and for this reason the choice of the initial search parameters does not cause as much influence on the results. Also, will be assessed a hybrid method that makes use of the main advantages of Alternating Regression and Cross-entropy to solve the problem. Systematic numerical experiments will be conducted for both the step of estimating derivatives as for the optimization step to estimate the variables of the equations of the system.