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Using a single fluorescent reporter gene to infer half-life of extrinsic noise and other parameters of gene expression
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Komorowski, Michal, Finkenstädt, Bärbel and Rand, D. A. (David A.) (2010) Using a single fluorescent reporter gene to infer half-life of extrinsic noise and other parameters of gene expression. Biophysical Journal, Vol.98 (No.12). pp. 2759-2769. doi:10.1016/j.bpj.2010.03.032 ISSN 0006-3495.
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Official URL: http://dx.doi.org/10.1016/j.bpj.2010.03.032
Abstract
Fluorescent and luminescent proteins are often used as reporters of transcriptional activity. Given the prevalence of noise in biochemical systems, the time-series data arising from these is of significant interest in efforts to calibrate stochastic models of gene expression and obtain information about sources of nongenetic variability. We present a statistical inference framework that can be used to estimate kinetic parameters of gene expression, as well as the strength and half-life of extrinsic noise from single fluorescent-reporter-gene time-series data. The method takes into account stochastic variability in a fluorescent signal resulting from intrinsic noise of gene expression, kinetics of fluorescent protein maturation, and extrinsic noise, which is assumed to arise at transcriptional level. We use the linear noise approximation and derive an explicit formula for the likelihood of observed fluorescent data. The method is embedded in a Bayesian paradigm, so that certain parameters can be informed from other experiments allowing portability of results across different studies. Inference is performed using Markov chain Monte Carlo. Fluorescent reporters are primary tools to observe dynamics of gene expression and the correct interpretation of fluorescent data is crucial to investigating these fundamental processes of cellular life. As both magnitude and frequency of the noise may have a dramatic effect on the cell fitness, the quantification of stochastic fluctuation is essential to the understanding of how genes are regulated. Our method provides a framework that addresses this important question.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QH Natural history > QH301 Biology | ||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Mathematics Faculty of Science, Engineering and Medicine > Science > Statistics Faculty of Science, Engineering and Medicine > Research Centres > Warwick Systems Biology Centre |
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| Journal or Publication Title: | Biophysical Journal | ||||
| Publisher: | Cell Press | ||||
| ISSN: | 0006-3495 | ||||
| Official Date: | 16 June 2010 | ||||
| Dates: |
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| Volume: | Vol.98 | ||||
| Number: | No.12 | ||||
| Number of Pages: | 11 | ||||
| Page Range: | pp. 2759-2769 | ||||
| DOI: | 10.1016/j.bpj.2010.03.032 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | Engineering and Physical Sciences Research Council (EPSRC), European Union Biomedical Simulations and Imaging Laboratory Network | ||||
| Grant number: | EP-0544587-1, GR-S29256-01, 005137 |
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