Numerical algebraic geometry for model selection and its application to the life sciences

Researchers working with mathematical models are often confronted by the related problems of parameter estimation, model validation, and model selection. These are all optimization problems, well-known to be challenging due to non-linearity, non-convexity and multiple local optima. Furthermore, the challenges are compounded when only partial data is available. Here, we consider polynomial models (e.g., mass-action chemical reaction networks at steady state) and describe a framework for their analysis based on optimization using numerical algebraic geometry. Specifically, we use probability-one polynomial homotopy continuation methods to compute all critical points of the objective function, then filter to recover the global optima. Our approach exploits the geometric structures relating models and data, and we demonstrate its utility on examples from cell signaling, synthetic biology, and epidemiology.Comment: References added, additional clarification

Algebraic Systems Biology: A Case Study for the Wnt Pathway

Steady state analysis of dynamical systems for biological networks give rise to algebraic varieties in high-dimensional spaces whose study is of interest in their own right. We demonstrate this for the shuttle model of the Wnt signaling pathway. Here the variety is described by a polynomial system in 19 unknowns and 36 parameters. Current methods from computational algebraic geometry and combinatorics are applied to analyze this model.Comment: 24 pages, 2 figure

Coordinate-independent singular perturbation reduction for systems with three time scales

On the basis of recent work by Cardin and Teixeira on ordinary differential equations with more than two time scales, we devise a coordinate-independent reduction for systems with three time scales; thus no a priori separation of variables into fast, slow etc. is required. Moreover we consider arbitrary parameter dependent systems and extend earlier work on Tikhonov-Fenichel parameter values -- i.e. parameter values from which singularly perturbed systems emanate upon small perturbations -- to the three time-scale setting. We apply our results to two standard systems from biochemistry

Complexity of Model Testing for Dynamical Systems with Toric Steady States

In this paper we investigate the complexity of model selection and model testing for dynamical systems with toric steady states. Such systems frequently arise in the study of chemical reaction networks. We do this by formulating these tasks as a constrained optimization problem in Euclidean space. This optimization problem is known as a Euclidean distance problem; the complexity of solving this problem is measured by an invariant called the Euclidean distance (ED) degree. We determine closed-form expressions for the ED degree of the steady states of several families of chemical reaction networks with toric steady states and arbitrarily many reactions. To illustrate the utility of this work we show how the ED degree can be used as a tool for estimating the computational cost of solving the model testing and model selection problems