  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.
