#### Abstract

A central challenge in computational modeling of biological systems is the determination of the model parameters. In such cases, estimating these variables or parameters from other easily obtained measurements can be extremely useful. For example, time-series dynamic genomic data can be used to develop models representing dynamic genetic regulatory networks, which can be used to design intervention strategies to cure major diseases and to better understand the behavior of biological systems. Unfortunately, biological measurements are usually highly infected by errors that hide the important characteristics in the data. Therefore, these noisy measurements need to be filtered to enhance their usefulness in practice. This paper addresses the problem of state and parameter estimation of biological phenomena modeled by S-systems using Bayesian approaches, where the nonlinear observed system is assumed to progress according to a probabilistic state space model. The performances of various conventional and state-of-the-art state estimation techniques are compared. These techniques include the extended Kalman filter (EKF), unscented Kalman filter (UKF), particle filter (PF), and the developed variational Bayesian filter (VBF). Specifically, two comparative studies are performed. In the first comparative study, the state variables (the enzyme CadA, the model cadBA, the cadaverine Cadav and the lysine Lys for a model of the Cad System in Escherichia coli (CSEC)) are estimated from noisy measurements of these variables, and the various estimation techniques are compared by computing the estimation root mean square error (RMSE) with respect to the noise-free data. In the second comparative study, the state variables as well as the model parameters are simultaneously estimated. In this case, in addition to comparing the performances of the various state estimation techniques, the effect of the number of estimated model parameters on the accuracy and convergence of these techniques is also assessed. The results of both comparative studies show that the UKF provides a higher accuracy than the EKF due to the limited ability of EKF to accurately estimate the mean and covariance matrix of the estimated states through lineralization of the nonlinear process model. The results also show that the VBF provides a relative improvement over PF. This is because, unlike the PF which depends on the choice of sampling distribution used to estimate the posterior distribution, the VBF yields an optimum choice of the sampling distribution, which also utilizes the observed data. The results of the second comparative study show that, for all techniques, estimating more model parameters affects the estimation accuracy as well as the convergence of the estimated states and parameters. The VBF, however, still provides advantages over other methods with respect to estimation accuracy as well convergence.