title: Cause and cure of sloppiness in ordinary differential equation models.
abstract: Data-based mathematical modeling of biochemical reaction networks, e.g., by nonlinear ordinary differential equation (ODE) models, has been successfully applied. In this context, parameter estimation and uncertainty analysis is a major task in order to assess the quality of the description of the system by the model. Recently, a broadened eigenvalue spectrum of the Hessian matrix of the objective function covering orders of magnitudes was observed and has been termed as sloppiness. In this work, we investigate the origin of sloppiness from structures in the sensitivity matrix arising from the properties of the model topology and the experimental design. Furthermore, we present strategies using optimal experimental design methods in order to circumvent the sloppiness issue and present nonsloppy designs for a benchmark model.
authors.affiliation: Institute of Physics, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Tönsing
authors.affiliation: Institute of Physics, University of Freiburg, 79104 Freiburg, Germany and BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Timmer
authors.affiliation: Institute of Physics, University of Freiburg, 79104 Freiburg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Kreutz
mesh_terms: D008962:Models, Theoretical; D017711:Nonlinear Dynamics; D049490:Systems Biology / Q000379:methods; D035501:Uncertainty