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Science 307 (5717): 1965-1969

Copyright © 2005 by the American Association for the Advancement of Science

Noise Propagation in Gene Networks

Juan M. Pedraza, and Alexander van Oudenaarden*

Abstract: Accurately predicting noise propagation in gene networks is crucial for understanding signal fidelity in natural networks and designing noise-tolerant gene circuits. To quantify how noise propagates through gene networks, we measured expression correlations between genes in single cells. We found that noise in a gene was determined by its intrinsic fluctuations, transmitted noise from upstream genes, and global noise affecting all genes. A model was developed that explains the complex behavior exhibited by the correlations and reveals the dominant noise sources. The model successfully predicts the correlations as the network is systematically perturbed. This approach provides a step toward understanding and manipulating noise propagation in more complex gene networks.

Department of Physics, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

* To whom correspondence should be addressed: E-mail: avano{at}

Adaptation by stochastic switching of a monostable genetic circuit in Escherichia coli.
S. Tsuru, N. Yasuda, Y. Murakami, J. Ushioda, A. Kashiwagi, S. Suzuki, K. Mori, B.-W. Ying, and T. Yomo (2014)
Mol Syst Biol 7, 493
   Abstract »    Full Text »    PDF »
Temporal switching and cell-to-cell variability in Ca2+ release activity in mammalian cells.
N. Nakamura, T. Yamazawa, Y. Okubo, and M. Iino (2014)
Mol Syst Biol 5, 247
   Abstract »    Full Text »    PDF »
How selection affects phenotypic fluctuation.
Y. Ito, H. Toyota, K. Kaneko, and T. Yomo (2014)
Mol Syst Biol 5, 264
   Abstract »    Full Text »    PDF »
Protein sequestration generates a flexible ultrasensitive response in a genetic network.
N. E. Buchler and F. R. Cross (2014)
Mol Syst Biol 5, 272
   Abstract »    Full Text »    PDF »
Positive selection for elevated gene expression noise in yeast.
Z. Zhang, W. Qian, and J. Zhang (2014)
Mol Syst Biol 5, 299
   Abstract »    Full Text »    PDF »
Short-term memory in gene induction reveals the regulatory principle behind stochastic IL-4 expression.
L. Mariani, E. G. Schulz, M. H. Lexberg, C. Helmstetter, A. Radbruch, M. Lohning, and T. Hofer (2014)
Mol Syst Biol 6, 359
   Abstract »    Full Text »    PDF »
Colored extrinsic fluctuations and stochastic gene expression.
V. Shahrezaei, J. F. Ollivier, and P. S. Swain (2014)
Mol Syst Biol 4, 196
   Abstract »    Full Text »    PDF »
Noise in transcription negative feedback loops: simulation and experimental analysis.
Y. Dublanche, K. Michalodimitrakis, N. Kummerer, M. Foglierini, and L. Serrano (2014)
Mol Syst Biol 2, 41
   Abstract »    Full Text »    PDF »
Dynamics of single-cell gene expression.
D. Longo and J. Hasty (2014)
Mol Syst Biol 2, 64
   Abstract »    Full Text »    PDF »
Cell-free synthetic biology: a bottom-up approach to discovery by design.
M. L. Simpson (2014)
Mol Syst Biol 2, 69
   Full Text »    PDF »
Noise in timing and precision of gene activities in a genetic cascade.
A. Amir, O. Kobiler, A. Rokney, A. B. Oppenheim, and J. Stavans (2014)
Mol Syst Biol 3, 71
   Abstract »    Full Text »    PDF »
Single cell resolution in regulation of gene expression.
O. G. Bahcall (2014)
Mol Syst Biol 1, 2005.0015
   Full Text »    PDF »
Monitoring dynamics of single-cell gene expression over multiple cell cycles.
S. Cookson, N. Ostroff, W. L. Pang, D. Volfson, and J. Hasty (2014)
Mol Syst Biol 1, 2005.0024
   Abstract »    Full Text »    PDF »
A noisy 'Start' to the cell cycle.
J. A. Ubersax and J. E. Ferrell Jr (2014)
Mol Syst Biol 2, 2006.0014
   Full Text »    PDF »
Noise resistance in the spindle assembly checkpoint.
A. Doncic, E. Ben-Jacob, and N. Barkai (2014)
Mol Syst Biol 2, 2006.0027
   Abstract »    Full Text »    PDF »
Barriers to transmission of transcriptional noise in a c-fos c-jun pathway.
K. Shah and S. Tyagi (2014)
Mol Syst Biol 9, 687
   Abstract »    Full Text »    PDF »
Synthetic mammalian transgene negative autoregulation.
V. Shimoga, J. T. White, Y. Li, E. Sontag, and L. Bleris (2014)
Mol Syst Biol 9, 670
   Abstract »    Full Text »    PDF »
Heteroresistance at the Single-Cell Level: Adapting to Antibiotic Stress through a Population-Based Strategy and Growth-Controlled Interphenotypic Coordination.
X. Wang, Y. Kang, C. Luo, T. Zhao, L. Liu, X. Jiang, R. Fu, S. An, J. Chen, N. Jiang, et al. (2014)
mBio 5, e00942-13
   Abstract »    Full Text »    PDF »
Engineering of regulated stochastic cell fate determination.
M. Wu, R.-Q. Su, X. Li, T. Ellis, Y.-C. Lai, and X. Wang (2013)
PNAS 110, 10610-10615
   Abstract »    Full Text »    PDF »
Monitoring the Single-Cell Stress Response of the Diatom Thalassiosira pseudonana by Quantitative Real-Time Reverse Transcription-PCR.
X. Shi, W. Gao, S.-h. Chao, W. Zhang, and D. R. Meldrum (2013)
Appl. Envir. Microbiol. 79, 1850-1858
   Abstract »    Full Text »    PDF »
Minimal Effect of Gene Clustering on Expression in Escherichia coli.
L. W. Liang, R. Hussein, D. H. S. Block, and H. N. Lim (2013)
Genetics 193, 453-465
   Abstract »    Full Text »    PDF »
Optimality and robustness in quorum sensing (QS)-mediated regulation of a costly public good enzyme.
A. Pai, Y. Tanouchi, and L. You (2012)
PNAS 109, 19810-19815
   Abstract »    Full Text »    PDF »
Regulatory consequences of gene translocation in bacteria.
D. H. S. Block, R. Hussein, L. W. Liang, and H. N. Lim (2012)
Nucleic Acids Res. 40, 8979-8992
   Abstract »    Full Text »    PDF »
Direct comparison of small RNA and transcription factor signaling.
R. Hussein and H. N. Lim (2012)
Nucleic Acids Res. 40, 7269-7279
   Abstract »    Full Text »    PDF »
Stochastic steady state gain in a gene expression process with mRNA degradation control.
H. Kuwahara and R. Schwartz (2012)
J R Soc Interface 9, 1589-1598
   Abstract »    Full Text »    PDF »
Dynamical Systems Approach to Endothelial Heterogeneity.
E. R. Regan and W. C. Aird (2012)
Circ. Res. 111, 110-130
   Abstract »    Full Text »    PDF »
Identifying sources of variation and the flow of information in biochemical networks.
C. G. Bowsher and P. S. Swain (2012)
PNAS 109, E1320-E1328
   Abstract »    Full Text »    PDF »
Using Gene Expression Noise to Understand Gene Regulation.
B. Munsky, G. Neuert, and A. van Oudenaarden (2012)
Science 336, 183-187
   Abstract »    Full Text »    PDF »
Quantifying the Bicoid Morphogen Gradient in Living Fly Embryos.
A. H. Morrison, M. Scheeler, J. Dubuis, and T. Gregor (2012)
Cold Spring Harb Protoc 2012, pdb.top068536
   Abstract »    Full Text »    PDF »
Locked Nucleic Acid and Flow Cytometry-Fluorescence In Situ Hybridization for the Detection of Bacterial Small Noncoding RNAs.
K. L. Robertson and G. J. Vora (2012)
Appl. Envir. Microbiol. 78, 14-20
   Abstract »    Full Text »    PDF »
Tunable synthetic phenotypic diversification on Waddington's landscape through autonomous signaling.
R. Sekine, M. Yamamura, S. Ayukawa, K. Ishimatsu, S. Akama, M. Takinoue, M. Hagiya, and D. Kiga (2011)
PNAS 108, 17969-17973
   Abstract »    Full Text »    PDF »
Information Transduction Capacity of Noisy Biochemical Signaling Networks.
R. Cheong, A. Rhee, C. J. Wang, I. Nemenman, and A. Levchenko (2011)
Science 334, 354-358
   Abstract »    Full Text »    PDF »
Neuronal homeostasis: time for a change?.
T. O'Leary and D. J. A. Wyllie (2011)
J. Physiol. 589, 4811-4826
   Abstract »    Full Text »    PDF »
Flow Cytometry, Amped Up.
C. Benoist and N. Hacohen (2011)
Science 332, 677-678
   Abstract »    Full Text »    PDF »
Gene regulatory networks and the role of robustness and stochasticity in the control of gene expression.
L. T. MacNeil and A. J. M. Walhout (2011)
Genome Res. 21, 645-657
   Abstract »    Full Text »    PDF »
Impact of gene expression noise on organismal fitness and the efficacy of natural selection.
Z. Wang and J. Zhang (2011)
PNAS 108, E67-E76
   Abstract »    Full Text »    PDF »
Gene expression variations are predictive for stochastic noise.
D. Dong, X. Shao, N. Deng, and Z. Zhang (2011)
Nucleic Acids Res. 39, 403-413
   Abstract »    Full Text »    PDF »
Bimodal gene expression in noncooperative regulatory systems.
A. Ochab-Marcinek and M. Tabaka (2010)
PNAS 107, 22096-22101
   Abstract »    Full Text »    PDF »
A General Mechanism for Network-Dosage Compensation in Gene Circuits.
M. Acar, B. F. Pando, F. H. Arnold, M. B. Elowitz, and A. van Oudenaarden (2010)
Science 329, 1656-1660
   Abstract »    Full Text »    PDF »
Quantifying E. coli Proteome and Transcriptome with Single-Molecule Sensitivity in Single Cells.
Y. Taniguchi, P. J. Choi, G.-W. Li, H. Chen, M. Babu, J. Hearn, A. Emili, and X. S. Xie (2010)
Science 329, 533-538
   Abstract »    Full Text »    PDF »
Exploiting the determinants of stochastic gene expression in Saccharomyces cerevisiae for genome-wide prediction of expression noise.
J. Li, R. Min, F. J. Vizeacoumar, K. Jin, X. Xin, and Z. Zhang (2010)
PNAS 107, 10472-10477
   Abstract »    Full Text »    PDF »
Computational limits to binary genes.
N. R. Zabet and D. F. Chu (2010)
J R Soc Interface 7, 945-954
   Abstract »    Full Text »    PDF »
Tuning and controlling gene expression noise in synthetic gene networks.
K. F. Murphy, R. M. Adams, X. Wang, G. Balazsi, and J. J. Collins (2010)
Nucleic Acids Res. 38, 2712-2726
   Abstract »    Full Text »    PDF »
Site-specific chromosomal integration of large synthetic constructs.
T. E. Kuhlman and E. C. Cox (2010)
Nucleic Acids Res. 38, e92
   Abstract »    Full Text »    PDF »
Modeling stochasticity and robustness in gene regulatory networks.
A. Garg, K. Mohanram, A. Di Cara, G. De Micheli, and I. Xenarios (2009)
Bioinformatics 25, i101-i109
   Abstract »    Full Text »    PDF »
Population heterogeneity in Methylobacterium extorquens AM1.
T. J. Strovas and M. E. Lidstrom (2009)
Microbiology 155, 2040-2048
   Abstract »    Full Text »    PDF »
Synthetic Gene Networks That Count.
A. E. Friedland, T. K. Lu, X. Wang, D. Shi, G. Church, and J. J. Collins (2009)
Science 324, 1199-1202
   Abstract »    Full Text »    PDF »
A stochastic spectral analysis of transcriptional regulatory cascades.
A. M. Walczak, A. Mugler, and C. H. Wiggins (2009)
PNAS 106, 6529-6534
   Abstract »    Full Text »    PDF »
High Content Cell Screening in a Microfluidic Device.
R. Cheong, C. J. Wang, and A. Levchenko (2009)
Mol. Cell. Proteomics 8, 433-442
   Abstract »    Full Text »    PDF »
Signatures of combinatorial regulation in intrinsic biological noise.
A. Warmflash and A. R. Dinner (2008)
PNAS 105, 17262-17267
   Abstract »    Full Text »    PDF »
Small-scale copy number variation and large-scale changes in gene expression.
Y. Mileyko, R. I. Joh, and J. S. Weitz (2008)
PNAS 105, 16659-16664
   Abstract »    Full Text »    PDF »
A genetic timer through noise-induced stabilization of an unstable state.
M. Turcotte, J. Garcia-Ojalvo, and G. M. Suel (2008)
PNAS 105, 15732-15737
   Abstract »    Full Text »    PDF »
Synthetic biology: discovering new worlds and new words: The new and not so new aspects of this emerging research field.
V. de Lorenzo and A. Danchin (2008)
EMBO Rep. 9, 822-827
   Full Text »    PDF »
Information flow and optimization in transcriptional regulation.
G. Tkacik, C. G. Callan Jr., and W. Bialek (2008)
PNAS 105, 12265-12270
   Abstract »    Full Text »    PDF »
Boolean network models of cellular regulation: prospects and limitations.
S. Bornholdt (2008)
J R Soc Interface 5, S85-S94
   Abstract »    Full Text »    PDF »
Relationship between cellular response and behavioral variability in bacterial chemotaxis.
T. Emonet and P. Cluzel (2008)
PNAS 105, 3304-3309
   Abstract »    Full Text »    PDF »
Effects of Molecular Memory and Bursting on Fluctuations in Gene Expression.
J. M. Pedraza and J. Paulsson (2008)
Science 319, 339-343
   Abstract »    Full Text »    PDF »
Steady-state expression of self-regulated genes.
T. Fournier, J.P. Gabriel, C. Mazza, J. Pasquier, J.L. Galbete, and N. Mermod (2007)
Bioinformatics 23, 3185-3192
   Abstract »    Full Text »    PDF »
Phenotypic variability of growing cellular populations.
T. Lu, T. Shen, M. R. Bennett, P. G. Wolynes, and J. Hasty (2007)
PNAS 104, 18982-18987
   Abstract »    Full Text »    PDF »
Cell-to-Cell Heterogeneity in Growth Rate and Gene Expression in Methylobacterium extorquens AM1.
T. J. Strovas, L. M. Sauter, X. Guo, and M. E. Lidstrom (2007)
J. Bacteriol. 189, 7127-7133
   Abstract »    Full Text »    PDF »
Biology by design: reduction and synthesis of cellular components and behaviour.
P. Marguet, F. Balagadde, C. Tan, and L. You (2007)
J R Soc Interface 4, 607-623
   Abstract »    Full Text »    PDF »
Chromosome-specific and noisy IFNB1 transcription in individual virus-infected human primary dendritic cells.
J. Hu, S. C. Sealfon, F. Hayot, C. Jayaprakash, M. Kumar, A. C. Pendleton, A. Ganee, A. Fernandez-Sesma, T. M. Moran, and J. G. Wetmur (2007)
Nucleic Acids Res.
   Abstract »    Full Text »    PDF »
Computational methods for diffusion-influenced biochemical reactions.
M. Dobrzynski, J. V. Rodriguez, J. A. Kaandorp, and J. G. Blom (2007)
Bioinformatics 23, 1969-1977
   Abstract »    Full Text »    PDF »
Combinatorial promoter design for engineering noisy gene expression.
K. F. Murphy, G. Balazsi, and J. J. Collins (2007)
PNAS 104, 12726-12731
   Abstract »    Full Text »    PDF »
Stochastic fluctuations in metabolic pathways.
E. Levine and T. Hwa (2007)
PNAS 104, 9224-9229
   Abstract »    Full Text »    PDF »
Deterministic characterization of stochastic genetic circuits.
M. Scott, T. Hwa, and B. Ingalls (2007)
PNAS 104, 7402-7407
   Abstract »    Full Text »    PDF »
A synthetic time-delay circuit in mammalian cells and mice.
W. Weber, J. Stelling, M. Rimann, B. Keller, M. Daoud-El Baba, C. C. Weber, D. Aubel, and M. Fussenegger (2007)
PNAS 104, 2643-2648
   Abstract »    Full Text »    PDF »
Designing biological systems.
D. A. Drubin, J. C. Way, and P. A. Silver (2007)
Genes & Dev. 21, 242-254
   Abstract »    Full Text »    PDF »
From Fluctuations to Phenotypes: The Physiology of Noise.
M. S. Samoilov, G. Price, and A. P. Arkin (2006)
Sci. STKE 2006, re17
   Abstract »    Full Text »    PDF »
Dynamic partitioning for hybrid simulation of the bistable HIV-1 transactivation network.
M. Griffith, T. Courtney, J. Peccoud, and W. H. Sanders (2006)
Bioinformatics 22, 2782-2789
   Abstract »    Full Text »    PDF »
Synthetic biology--putting engineering into biology.
M. Heinemann and S. Panke (2006)
Bioinformatics 22, 2790-2799
   Abstract »    Full Text »    PDF »
Spatial stochastic modelling of the phosphoenolpyruvate-dependent phosphotransferase (PTS) pathway in Escherichia coli.
J. V. Rodriguez, J. A. Kaandorp, M. Dobrzynski, and J. G. Blom (2006)
Bioinformatics 22, 1895-1901
   Abstract »    Full Text »    PDF »
Stochastic models for regulatory networks of the genetic toggle switch.
T. Tian and K. Burrage (2006)
PNAS 103, 8372-8377
   Abstract »    Full Text »    PDF »
Predicting stochastic gene expression dynamics in single cells.
J. T. Mettetal, D. Muzzey, J. M. Pedraza, E. M. Ozbudak, and A. van Oudenaarden (2006)
PNAS 103, 7304-7309
   Abstract »    Full Text »    PDF »
The Upstream-activating Sequences of the {sigma}54 Promoter Pu of Pseudomonas putida Filter Transcription Readthrough from Upstream Genes.
F. Velazquez, S. Fernandez, and V. de Lorenzo (2006)
J. Biol. Chem. 281, 11940-11948
   Abstract »    Full Text »    PDF »
Rules for biological regulation based on error minimization..
G. Shinar, E. Dekel, T. Tlusty, and U. Alon (2006)
PNAS 103, 3999-4004
   Abstract »    Full Text »    PDF »
Absolute rate theories of epigenetic stability.
A. M. Walczak, J. N. Onuchic, and P. G. Wolynes (2005)
PNAS 102, 18926-18931
   Abstract »    Full Text »    PDF »
Topology of biological networks and reliability of information processing.
K. Klemm and S. Bornholdt (2005)
PNAS 102, 18414-18419
   Abstract »    Full Text »    PDF »
Delay-induced stochastic oscillations in gene regulation.
D. Bratsun, D. Volfson, L. S. Tsimring, and J. Hasty (2005)
PNAS 102, 14593-14598
   Abstract »    Full Text »    PDF »
Noise in Gene Expression: Origins, Consequences, and Control.
J. M. Raser and E. K. O'Shea (2005)
Science 309, 2010-2013
   Abstract »    Full Text »    PDF »
Real-time RNA profiling within a single bacterium.
T. T. Le, S. Harlepp, C. C. Guet, K. Dittmar, T. Emonet, T. Pan, and P. Cluzel (2005)
PNAS 102, 9160-9164
   Abstract »    Full Text »    PDF »
MOLECULAR BIOLOGY: Signal Processing in Single Cells.
F. J. Isaacs, W. J. Blake, and J. J. Collins (2005)
Science 307, 1886-1888
   Abstract »    Full Text »    PDF »

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