On fitting of mathematical models of cell signaling pathways using adjoint systems.

This paper concerns the problem of fitting of mathematical models of cell signaling pathways. Such models frequently take the form of a set of nonlinear ordinary differential equations. While the model is continuous-time, the performance index, used in the fitting procedure, involves measurements taken only at discrete-time moments. Adjoint sensitivity analysis is a tool that can be used for finding a gradient of a performance index in the space of the model's parameters. The paper uses a structural formulation of sensitivity analysis, especially dedicated for hybrid, continuous/discrete-time systems. A numerical example of fitting of the mathematical model of the NF-kB regulatory module is presented.