Frequency domain analysis of noise in simple gene circuits

Chris D. Cox, James M. McCollum, Derek W. Austin, Michael S. Allen, Roy David Dar, Michael L. Simpson

Research output: Contribution to journalArticle

Abstract

Recent advances in single cell methods have spurred progress in quantifying and analyzing stochastic fluctuations, or noise, in genetic networks. Many of these studies have focused on identifying the sources of noise and quantifying its magnitude, and at the same time, paying less attention to the frequency content of the noise. We have developed a frequency domain approach to extract the information contained in the frequency content of the noise. In this article we review our work in this area and extend it to explicitly consider sources of extrinsic and intrinsic noise. First we review applications of the frequency domain approach to several simple circuits, including a constitutively expressed gene, a gene regulated by transitions in its operator state, and a negatively autoregulated gene. We then review our recent experimental study, in which time-lapse microscopy was used to measure noise in the expression of green fluorescent protein in individual cells. The results demonstrate how changes in rate constants within the gene circuit are reflected in the spectral content of the noise in a manner consistent with the predictions derived through frequency domain analysis. The experimental results confirm our earlier theoretical prediction that negative autoregulation not only reduces the magnitude of the noise but shifts its content out to higher frequency. Finally, we develop a frequency domain model of gene expression that explicitly accounts for extrinsic noise at the transcriptional and translational levels. We apply the model to interpret a shift in the autocorrelation function of green fluorescent protein induced by perturbations of the translational process as a shift in the frequency spectrum of extrinsic noise and a decrease in its weighting relative to intrinsic noise.

Original languageEnglish (US)
Article number026102
JournalChaos
Volume16
Issue number2
DOIs
StatePublished - Jan 1 2006
Externally publishedYes

Fingerprint

frequency domain analysis
Frequency Domain Analysis
Frequency domain analysis
genes
Genes
Gene
Frequency Domain
Networks (circuits)
Proteins
Protein
Genetic Network
Domain Model
Prediction
Frequency Spectrum
Cell
Autocorrelation Function
Rate Constant
Autocorrelation
Gene expression
Microscopy

ASJC Scopus subject areas

  • Statistical and Nonlinear Physics
  • Mathematical Physics
  • Physics and Astronomy(all)
  • Applied Mathematics

Cite this

Cox, C. D., McCollum, J. M., Austin, D. W., Allen, M. S., Dar, R. D., & Simpson, M. L. (2006). Frequency domain analysis of noise in simple gene circuits. Chaos, 16(2), [026102]. https://doi.org/10.1063/1.2204354

Frequency domain analysis of noise in simple gene circuits. / Cox, Chris D.; McCollum, James M.; Austin, Derek W.; Allen, Michael S.; Dar, Roy David; Simpson, Michael L.

In: Chaos, Vol. 16, No. 2, 026102, 01.01.2006.

Research output: Contribution to journalArticle

Cox, CD, McCollum, JM, Austin, DW, Allen, MS, Dar, RD & Simpson, ML 2006, 'Frequency domain analysis of noise in simple gene circuits', Chaos, vol. 16, no. 2, 026102. https://doi.org/10.1063/1.2204354
Cox CD, McCollum JM, Austin DW, Allen MS, Dar RD, Simpson ML. Frequency domain analysis of noise in simple gene circuits. Chaos. 2006 Jan 1;16(2). 026102. https://doi.org/10.1063/1.2204354
Cox, Chris D. ; McCollum, James M. ; Austin, Derek W. ; Allen, Michael S. ; Dar, Roy David ; Simpson, Michael L. / Frequency domain analysis of noise in simple gene circuits. In: Chaos. 2006 ; Vol. 16, No. 2.
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