A priori global identifiability is a structural property of biological and physiological models. It is considered a prerequisite for well-posed estimation, since it concerns the possibility of recovering uniquely the unknown model parameters from measured input-output data, under ideal conditions (noise-free observations and error-free model structure). Of course, determining if the parameters can be uniquely recovered from observed data is essential before investing resources, time and effort in performing actual biomedical experiments. Many interesting biological models are nonlinear but identifiability analysis for nonlinear system turns out to be a difficult mathematical problem. Different methods have been proposed in the literature to test identifiability of nonlinear models but, to the best of our knowledge, so far no software tools have been proposed for automatically checking identifiability of nonlinear models. In this paper, we describe a software tool implementing a differential algebra algorithm to perform parameter identifiability analysis for (linear and) nonlinear dynamic models described by polynomial or rational equations. Our goal is to provide the biological investigator a completely automatized software, requiring minimum prior knowledge of mathematical modelling and no in-depth understanding of the mathematical tools. The DAISY (Differential Algebra for Identifiability of SYstems) software will potentially be useful in biological modelling studies, especially in physiology and clinical medicine, where research experiments are particularly expensive and/or difficult to perform. Practical examples of use of the software tool DAISY are presented. DAISY is available at the web site http://www.dei.unipd.it/~pia/.

A prerequisite for well-posedness of parameter estimation of biological and physiological systems is a priori global identifiability, a property which concerns uniqueness of the solution for the unknown model parameters. Assessing a priori global identifiability is particularly difficult for nonlinear dynamic models. Various approaches have been proposed in the literature but no solution exists in the general case. In this paper, we present a new algorithm for testing global identifiability of nonlinear dynamic models, based on differential algebra. The characteristic set associated to the dynamic equations is calculated in an efficient way and computer algebra techniques are used to solve the resulting set of nonlinear algebraic equations. The algorithm is capable of handling many features arising in biological system models, including zero initial conditions and time-varying parameters. Examples of usage of the algorithm for analyzing a priori global identifiability of nonlinear models of biological and physiological systems are presented.

No abstract

andreas.raue@fdm.uni-freiburg.de.