Journal article
Reconstructing Dynamic Promoter Activity Profiles from Reporter Gene Data
Technical University of Denmark1
Department of Electrical Engineering, Technical University of Denmark2
Biomedical Engineering, Department of Electrical Engineering, Technical University of Denmark3
Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark4
iLoop, Translational Management, Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark5
Department of Biotechnology and Biomedicine, Technical University of Denmark6
Regulatory Genomics, Section for Synthetic Biology, Department of Biotechnology and Biomedicine, Technical University of Denmark7
Accurate characterization of promoter activity is important when designing expression systems for systems biology and metabolic engineering applications. Promoters that respond to changes in the environment enable the dynamic control of gene expression without the necessity of inducer compounds, for example.
However, the dynamic nature of these processes poses challenges for estimating promoter activity. Most experimental approaches utilize reporter gene expression to estimate promoter activity. Typically the reporter gene encodes a fluorescent protein that is used to infer a constant promoter activity despite the fact that the observed output may be dynamic and is a number of steps away from the transcription process.
In fact, some promoters that are often thought of as constitutive can show changes in activity when growth conditions change. For these reasons, we have developed a system of ordinary differential equations for estimating dynamic promoter activity for promoters that change their activity in response to the environment that is robust to noise and changes in growth rate.
Our approach, inference of dynamic promoter activity (PromAct), improves on existing methods by more accurately inferring known promoter activity profiles. This method is also capable of estimating the correct scale of promoter activity and can be applied to quantitative data sets to estimate quantitative rates.
Language: | English |
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Publisher: | American Chemical Society |
Year: | 2018 |
Pages: | 832-841 |
ISSN: | 21615063 |
Types: | Journal article |
DOI: | 10.1021/acssynbio.7b00223 |
ORCIDs: | Sams, Thomas , Workman, Christopher T and Maury, Jérôme |
Dynamic model Fluorescent proteins Growth profiling Ordinary differential equations Promoter activity
Biomass Cells, Cultured Computer Simulation Escherichia coli Escherichia coli Proteins Factor For Inversion Stimulation Protein Fis protein, E coli Fluorescence Genes, Reporter Green Fluorescent Proteins Models, Genetic Promoter Regions, Genetic RNA Xylose dynamic model fluorescent proteins growth profiling growthprofiling ordinary differential equations ordinarydifferential equations promoter activity