title: Parameter estimation in biochemical systems models with alternating regression.
abstract: BACKGROUND
  The estimation of parameter values continues to be the bottleneck of the computational analysis of biological systems. It is therefore necessary to develop improved methods that are effective, fast, and scalable.
  
  
  RESULTS
  We show here that alternating regression (AR), applied to S-system models and combined with methods for decoupling systems of differential equations, provides a fast new tool for identifying parameter values from time series data. The key feature of AR is that it dissects the nonlinear inverse problem of estimating parameter values into iterative steps of linear regression. We show with several artificial examples that the method works well in many cases. In cases of no convergence, it is feasible to dedicate some computational effort to identifying suitable start values and search settings, because the method is fast in comparison to conventional methods that the search for suitable initial values is easily recouped. Because parameter estimation and the identification of system structure are closely related in S-system modeling, the AR method is beneficial for the latter as well. Specifically, we show with an example from the literature that AR is three to five orders of magnitudes faster than direct structure identifications in systems of nonlinear differential equations.
  
  
  CONCLUSIONS
  Alternating regression provides a strategy for the estimation of parameter values and the identification of structure and regulation in S-systems that is genuinely different from all existing methods. Alternating regression is usually very fast, but its convergence patterns are complex and will require further investigation. In cases where convergence is an issue, the enormous speed of the method renders it feasible to select several initial guesses and search settings as an effective countermeasure.
authors.affiliation: The Wallace H. Coulter Department of Biomedical Engineering at Georgia Institute of Technology and Emory University, 313 Ferst Drive, Atlanta, GA 30332, USA. gtg392p@mail.gatech.edu
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Chou
authors.forename: Harald
authors.initials: H
authors.lastname: Martens
authors.forename: Eberhard O
authors.initials: EO
authors.lastname: Voit
mesh_terms: D019295:Computational Biology; D016014:Linear Models; D008954:Models, Biological; D008962:Models, Theoretical