Reducing complexity: An iterative strategy for parameter determination in biological networks

Abstract The dynamics of biological networks are fundamental to a variety of processes in many areas of biology and medicine. Understanding of such networks on a systemic level is facilitated by mathematical models describing these networks. However, since mathematical models of signalling networks commonly aim to describe several highly connected biological quantities and many model parameters cannot be measured directly, quantitative dynamic models often present challenges with respect to model calibration. Here, we propose an iterative fitting routine to decompose the problem of fitting a system of coupled ordinary differential equations describing a signalling network into smaller subproblems. Parameters for each differential equation are estimated separately using a Differential Evolution algorithm while all other dynamic quantities in the model are treated as input to the system. The performance of this algorithm is evaluated on artificial networks with known structure and known model parameters and compared to a conventional optimisation procedure for the same problem. Our analysis indicates that the procedure results in a significantly higher quality of fit and more efficient reconstruction of the true parameters than the conventional algorithm.