LAPSE:2018.0268
Published Article
LAPSE:2018.0268
Multi-Objective Optimization of Experiments Using Curvature and Fisher Information Matrix
Erica Manesso, Srinath Sridharan, Rudiyanto Gunawan
July 31, 2018
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, as the FIM only accounts for the linear variation in the model outputs with respect to the parameters. In this work, we developed a multi-objective optimization (MOO) MBDOE, for which the 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
biological processes, curvature, design of experiments, Fisher information matrix, mathematical modeling, multi-objective optimization
Suggested Citation
Manesso E, Sridharan S, Gunawan R. Multi-Objective Optimization of Experiments Using Curvature and Fisher Information Matrix. (2018). LAPSE:2018.0268
Author Affiliations
Manesso E: Institute for Chemical and Bioengineering, ETH Zurich, 8093 Zurich, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland
Sridharan S: Saw Swee Hock School of Public Health, National University of Singapore, Singapore 117549, Singapore
Gunawan R: Institute for Chemical and Bioengineering, ETH Zurich, 8093 Zurich, Switzerland; Swiss Institute of Bioinformatics, 1015 Lausanne, Switzerland [ORCID]
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Journal Name
Processes
Volume
5
Issue
4
Article Number
E63
Year
2017
Publication Date
2017-11-01
Published Version
ISSN
2227-9717
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PII: pr5040063, Publication Type: Journal Article
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LAPSE:2018.0268
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doi:10.3390/pr5040063
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Jul 31, 2018
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