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Bioinformatics. 2012 Sep 15;28(18):i535-i541. doi: 10.1093/bioinformatics/bts377.

Trajectory-oriented Bayesian experiment design versus Fisher A-optimal design: an in depth comparison study.

Author information

  • 1Institute for Systems Theory and Automatic Control, University of Stuttgart, Pfaffenwaldring 9, Stuttgart 70550, Germany. patrick.weber@ist.uni-stuttgart.de

Abstract

MOTIVATION:

Experiment design strategies for biomedical models with the purpose of parameter estimation or model discrimination are in the focus of intense research. Experimental limitations such as sparse and noisy data result in unidentifiable parameters and render-related design tasks challenging problems. Often, the temporal resolution of data is a limiting factor and the amount of possible experimental interventions is finite. To address this issue, we propose a Bayesian experiment design algorithm to minimize the prediction uncertainty for a given set of experiments and compare it to traditional A-optimal design.

RESULTS:

In an in depth numerical study involving an ordinary differential equation model of the trans-Golgi network with 12 partly non-identifiable parameters, we minimized the prediction uncertainty efficiently for predefined scenarios. The introduced method results in twice the prediction precision as the same amount of A-optimal designed experiments while introducing a useful stopping criterion. The simulation intensity of the algorithm's major design step is thereby reasonably affordable. Besides smaller variances in the predicted trajectories compared with Fisher design, we could also achieve smaller parameter posterior distribution entropies, rendering this method superior to A-optimal Fisher design also in the parameter space.

AVAILABILITY:

Necessary software/toolbox information are available in the supplementary material. The project script including example data can be downloaded from http://www.ist.uni-stuttgart.de/%7eweber/BayesFisher2012.

CONTACT:

patrick.weber@ist.uni-stuttgart.de

SUPPLEMENTARY INFORMATION:

Supplementary data are available at Bioinformatics online.

PMID:
22962478
PMCID:
PMC3436804
DOI:
10.1093/bioinformatics/bts377
[PubMed - indexed for MEDLINE]
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