Cause and cure of sloppiness in ordinary differential equation models


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.


DOI: 10.1103/PhysRevE.90.023303

Projects: SBEpo - Systems Biology of Erythropoietin

Publication type: Not specified

Journal: Phys. Rev. E

Citation: Phys. Rev. E 90(2)

Date Published: 1st Aug 2014

Registered Mode: Not specified

Authors: Christian Tönsing, Jens Timmer, Clemens Kreutz

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Tönsing, C., Timmer, J., & Kreutz, C. (2014). Cause and cure of sloppiness in ordinary differential equation models. In Physical Review E (Vol. 90, Issue 2). American Physical Society (APS).

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Created: 23rd Nov 2016 at 15:09

Last updated: 23rd Nov 2016 at 15:13

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