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Multi-Objective Optimization of Experiments Using Curvature and Fisher Information Matrix

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Submitted:

14 September 2017

Posted:

15 September 2017

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Abstract
The bottleneck in creating dynamic models of biological networks and processes often lies in estimating unknown kinetic model parameters from experimental data. In this regard, experimental conditions have a strong influence on parameter identifiability and should therefore be optimized to give the maximum information for parameter estimation. Existing model-based design of experiment (MBDOE) methods commonly rely on the Fisher Information Matrix (FIM) for defining a metric of data informativeness. When the model behavior is highly nonlinear, FIM-based criteria may lead to suboptimal designs since the FIM only accounts for the linear variation of the model outputs with respect to the parameters. In this work, we developed a multi-objective optimization (MOO) MBDOE, where model nonlinearity was taken into consideration through the use of curvature. The proposed MOO MBDOE involved maximizing data informativeness using a FIM-based metric and at the same time minimizing the model curvature. We demonstrated the advantages of the MOO MBDOE over existing FIM-based and other curvature-based MBDOEs in an application to the kinetic modeling of fed-batch fermentation of Baker's yeast.
Keywords: 
design of experiments; multi-objective optimization; Fisher information matrix; curvature; biological processes; mathematical modeling
Subject: 
Computer Science and Mathematics  -   Applied Mathematics
Copyright: This open access article is published under a Creative Commons CC BY 4.0 license, which permit the free download, distribution, and reuse, provided that the author and preprint are cited in any reuse.

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