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Interface Focus. 2013 Aug 6;3(4):20130008. doi: 10.1098/rsfs.2013.0008.

Convergence in parameters and predictions using computational experimental design.

Author information

  • 1Department of Biological Engineering , Massachusetts Institute of Technology , Cambridge, MA 02139 , USA ; Computer Science and Artificial Intelligence Laboratory , Massachusetts Institute of Technology , Cambridge, MA 02139 , USA.
  • 2Department of Electrical Engineering and Computer Science , Massachusetts Institute of Technology , Cambridge, MA 02139 , USA.
  • 3Department of Biological Engineering , Massachusetts Institute of Technology , Cambridge, MA 02139 , USA ; Computer Science and Artificial Intelligence Laboratory , Massachusetts Institute of Technology , Cambridge, MA 02139 , USA ; Department of Electrical Engineering and Computer Science , Massachusetts Institute of Technology , Cambridge, MA 02139 , USA.

Abstract

Typically, biological models fitted to experimental data suffer from significant parameter uncertainty, which can lead to inaccurate or uncertain predictions. One school of thought holds that accurate estimation of the true parameters of a biological system is inherently problematic. Recent work, however, suggests that optimal experimental design techniques can select sets of experiments whose members probe complementary aspects of a biochemical network that together can account for its full behaviour. Here, we implemented an experimental design approach for selecting sets of experiments that constrain parameter uncertainty. We demonstrated with a model of the epidermal growth factor-nerve growth factor pathway that, after synthetically performing a handful of optimal experiments, the uncertainty in all 48 parameters converged below 10 per cent. Furthermore, the fitted parameters converged to their true values with a small error consistent with the residual uncertainty. When untested experimental conditions were simulated with the fitted models, the predicted species concentrations converged to their true values with errors that were consistent with the residual uncertainty. This paper suggests that accurate parameter estimation is achievable with complementary experiments specifically designed for the task, and that the resulting parametrized models are capable of accurate predictions.

KEYWORDS:

Fisher information; optimal experimental design; ordinary differential equation modelling; parameter uncertainty; systems biology

PMID:
24511374
PMCID:
PMC3915829
DOI:
10.1098/rsfs.2013.0008
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