Linear parameter estimation of rational biokinetic functions

Abstract

For rational biokinetic functions such as the Michaelis–Menten equation, in general, a nonlinear least-squares method is a good estimator. However, a major drawback of a nonlinear least-squares estimator is that it can end up in a local minimum. Rearranging and linearizing rational biokinetic functions for parameter estimation is common practice ( e.g. Lineweaver–Burk linearization). By rearranging, however, the error is distorted. In addition, the rearranged model frequently leads to a so-called ‘errors-in-variables’ estimation problem. Applying the ordinary least squares (OLS) method to the linearly reparameterized function ensures a global minimum, but its estimates become biased if the regression variables contain errors and thus bias compensation is needed. Therefore, in this paper, a bias compensated total least squares (CTLS) method, which as OLS is a direct method, is proposed to solve the estimation problem. The applicability of a general linear reparameterization procedure and the advances of CTLS over ordinary least squares and nonlinear least squares approaches are shown by two simulation examples. The examples contain Michaelis–Menten kinetics and enzyme kinetics with substrate inhibition. Furthermore, CTLS is demonstrated with real data of an activated sludge experiment. It is concluded that for rational biokinetic models CTLS is a powerful alternative to the existing least-squares methods.