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Model selection in systems biology depends on experimental design.

Published version
Peer-reviewed

Type

Article

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Authors

Silk, Daniel 
Kirk, Paul DW 
Barnes, Chris P 
Toni, Tina 
Stumpf, Michael PH 

Abstract

Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis.

Description

Keywords

Computational Biology, Computer Simulation, Mathematical Concepts, Models, Biological, Monte Carlo Method, Signal Transduction, Systems Biology

Journal Title

PLoS Comput Biol

Conference Name

Journal ISSN

1553-734X
1553-7358

Volume Title

10

Publisher

Public Library of Science (PLoS)