Automated piecewise power-law modeling of biological systems

Recent trends suggest that future biotechnology will increasingly rely on mathematical models of the biological systems under investigation. In particular, metabolic engineering will make wider use of metabolic pathway models in stoichiometric or fully kinetic format. A significant obstacle to the use of pathway models is the identification of suitable process descriptions and their parameters. We recently showed that, at least under favorable conditions, Dynamic Flux Estimation (DFE) permits the numerical characterization of fluxes from sets of metabolic time series data. However, DFE does not prescribe how to convert these numerical results into functional representations. In some cases, Michaelis-Menten rate laws or canonical formats are well suited, in which case the estimation of parameter values is easy. However, in other cases, appropriate functional forms are not evident, and exhaustive searches among all possible candidate models are not feasible. We show here how piecewise power-law functions of one or more variables offer an effective default solution for the almost unbiased representation of uni- and multivariate time series data. The results of an automated algorithm for their determination are piecewise power-law fits, whose accuracy is only limited by the available data. The individual power-law pieces may lead to discontinuities at break points or boundaries between sub-domains. In many practical applications, these boundary gaps do not cause problems. Potential smoothing techniques, based on differential inclusions and Filippov's theory, are discussed in Appendix A.