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Title

On-Line Optimal Input Design Increases the Efficiency and Accuracy of the Modelling of an Inducible Synthetic Promoter

AuthorsBandeira, Lucía ; Hou, Zhaozheng; Kothamachu, Varun B.; Balsa-Canto, Eva ; Swain, Peter S.; Menolascina, Filippo
KeywordsModel-based optimal experimental design
Synthetic biology
Model calibration
Optimal inputs
System identification
Issue Date1-Sep-2018
PublisherMultidisciplinary Digital Publishing Institute
CitationProcesses 6(9): 148 (2018)
AbstractSynthetic biology seeks to design biological parts and circuits that implement new functions in cells. Major accomplishments have been reported in this field, yet predicting a priori the in vivo behaviour of synthetic gene circuits is major a challenge. Mathematical models offer a means to address this bottleneck. However, in biology, modelling is perceived as an expensive, time-consuming task. Indeed, the quality of predictions depends on the accuracy of parameters, which are traditionally inferred from poorly informative data. How much can parameter accuracy be improved by using model-based optimal experimental design (MBOED)? To tackle this question, we considered an inducible promoter in the yeast S. cerevisiae. Using in vivo data, we re-fit a dynamic model for this component and then compared the performance of standard (e.g., step inputs) and optimally designed experiments for parameter inference. We found that MBOED improves the quality of model calibration by ∼60%. Results further improve up to 84% when considering on-line optimal experimental design (OED). Our in silico results suggest that MBOED provides a significant advantage in the identification of models of biological parts and should thus be integrated into their characterisation.
Publisher version (URL)https://doi.org/10.3390/pr6090148
URIhttp://hdl.handle.net/10261/169991
DOI10.3390/pr6090148
E-ISSN2227-9717
Appears in Collections:(IIM) Artículos
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