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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.

25215847

Projects: A2.5: Integration of insulin and Wnt signalling in hepatocytes, A3.2: Cross-talk of signaling pathways and endocytic machinery in hepato..., B2.1: Hepatic stellate cells as source and target for hepatocellular gro...

Phys Rev E Stat Nonlin Soft Matter Phys
Phys Rev E Stat Nonlin Soft Matter Phys 90(2): 023303
11th Aug 2014

Christian Tönsing, Jens Timmer, Clemens Kreutz

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[Jens Timmer] [Clemens Kreutz]

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  • Created: 30th Jan 2015 at 15:58

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