Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 334 (6054): 354-358

Copyright © 2011 by the American Association for the Advancement of Science

Information Transduction Capacity of Noisy Biochemical Signaling Networks

Raymond Cheong,1 Alex Rhee,1 Chiaochun Joanne Wang,1 Ilya Nemenman,2 Andre Levchenko1,*

Abstract: Molecular noise restricts the ability of an individual cell to resolve input signals of different strengths and gather information about the external environment. Transmitting information through complex signaling networks with redundancies can overcome this limitation. We developed an integrative theoretical and experimental framework, based on the formalism of information theory, to quantitatively predict and measure the amount of information transduced by molecular and cellular networks. Analyzing tumor necrosis factor (TNF) signaling revealed that individual TNF signaling pathways transduce information sufficient for accurate binary decisions, and an upstream bottleneck limits the information gained via multiple integrated pathways. Negative feedback to this bottleneck could both alleviate and enhance its limiting effect, despite decreasing noise. Bottlenecks likewise constrain information attained by networks signaling through multiple genes or cells.

1 Department of Biomedical Engineering, Johns Hopkins University, 3400 North Charles Street, Baltimore, MD 21218, USA.
2 Departments of Physics and Biology, Emory University, 400 Dowman Drive, Atlanta, GA 30322, USA.

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

Cracking the NF-{kappa}B Code.
K. E. Tkach, J. E. Oyler, and G. Altan-Bonnet (2014)
Science Signaling 7, pe5
   Abstract »    Full Text »    PDF »
Information transfer by leaky, heterogeneous, protein kinase signaling systems.
M. Voliotis, R. M. Perrett, C. McWilliams, C. A. McArdle, and C. G. Bowsher (2014)
PNAS 111, E326-E333
   Abstract »    Full Text »    PDF »
Switching of the Relative Dominance Between Feedback Mechanisms in Lipopolysaccharide-Induced NF-{kappa}B Signaling.
M.-H. Sung, N. Li, Q. Lao, R. A. Gottschalk, G. L. Hager, and I. D. C. Fraser (2014)
Science Signaling 7, ra6
   Abstract »    Full Text »    PDF »
T cells translate individual, quantal activation into collective, analog cytokine responses via time-integrated feedbacks.
K. E. Tkach, D. Barik, G. Voisinne, N. Malandro, M. M. Hathorn, J. W. Cotari, R. Vogel, T. Merghoub, J. Wolchok, O. Krichevsky, et al. (2014)
eLife Sci 3, e01944
   Abstract »    Full Text »    PDF »
Structure and dynamics of core/periphery networks.
P. Csermely, A. London, L.-Y. Wu, and B. Uzzi (2013)
jcomplexnetw 1, 93-123
   Abstract »    Full Text »    PDF »
Adaptive molecular networks controlling chemotactic migration: dynamic inputs and selection of the network architecture.
H. Chang and A. Levchenko (2013)
Phil Trans R Soc B 368, 20130117
   Abstract »    Full Text »    PDF »
Robustness and Compensation of Information Transmission of Signaling Pathways.
S. Uda, T. H. Saito, T. Kudo, T. Kokaji, T. Tsuchiya, H. Kubota, Y. Komori, Y.-i. Ozaki, and S. Kuroda (2013)
Science 341, 558-561
   Abstract »    Full Text »    PDF »
Models of signalling networks - what cell biologists can gain from them and give to them.
K. A. Janes and D. A. Lauffenburger (2013)
J. Cell Sci. 126, 1913-1921
   Abstract »    Full Text »    PDF »
Spatial partitioning improves the reliability of biochemical signaling.
A. Mugler, F. Tostevin, and P. R. ten Wolde (2013)
PNAS 110, 5927-5932
   Abstract »    Full Text »    PDF »
How Information Theory Handles Cell Signaling and Uncertainty.
M. D. Brennan, R. Cheong, and A. Levchenko (2012)
Science 338, 334-335
   Abstract »    Full Text »    PDF »
TWEAK and cIAP1 Regulate Myoblast Fusion Through the Noncanonical NF-{kappa}B Signaling Pathway.
E. K. Enwere, J. Holbrook, R. Lejmi-Mrad, J. Vineham, K. Timusk, B. Sivaraj, M. Isaac, D. Uehling, R. Al-awar, E. LaCasse, et al. (2012)
Science Signaling 5, ra75
   Abstract »    Full Text »    PDF »
Developmental Pattern Formation: Insights from Physics and Biology.
A. Kicheva, M. Cohen, and J. Briscoe (2012)
Science 338, 210-212
   Abstract »    Full Text »    PDF »
The magnitude and colour of noise in genetic negative feedback systems.
M. Voliotis and C. G. Bowsher (2012)
Nucleic Acids Res. 40, 7084-7095
   Abstract »    Full Text »    PDF »
Dynamics of TGF-{beta} signaling reveal adaptive and pulsatile behaviors reflected in the nuclear localization of transcription factor Smad4.
A. Warmflash, Q. Zhang, B. Sorre, A. Vonica, E. D. Siggia, and A. H. Brivanlou (2012)
PNAS 109, E1947-E1956
   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 »
Every Bit Counts.
P. J. Thomas (2011)
Science 334, 321-322
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 4 October 2011.
A. Levchenko and A. M. VanHook (2011)
Science Signaling 4, pc20
   Abstract »    Full Text »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882