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ACS Synth Biol. 2018 Mar 16;7(3):832-841. doi: 10.1021/acssynbio.7b00223. Epub 2018 Feb 19.

Reconstructing Dynamic Promoter Activity Profiles from Reporter Gene Data.

Author information

1
Department of Biotechnology and Biomedicine , Technical University of Denmark , 2800 Lyngby , Denmark.
2
Department of Electrical Engineering , Technical University of Denmark , 2800 Lyngby , Denmark.
3
Novo Nordisk Foundation Center for Biosustainability , Technical University of Denmark , 2800 Lyngby , Denmark.

Abstract

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.

KEYWORDS:

dynamic model; fluorescent proteins; growth profiling; ordinary differential equations; promoter activity

PMID:
29457721
DOI:
10.1021/acssynbio.7b00223
[Indexed for MEDLINE]
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