Systems biology. Accurate information transmission through dynamic biochemical signaling networks

Science. 2014 Dec 12;346(6215):1370-3. doi: 10.1126/science.1254933.


Stochasticity inherent to biochemical reactions (intrinsic noise) and variability in cellular states (extrinsic noise) degrade information transmitted through signaling networks. We analyzed the ability of temporal signal modulation--that is, dynamics--to reduce noise-induced information loss. In the extracellular signal-regulated kinase (ERK), calcium (Ca(2+)), and nuclear factor kappa-B (NF-κB) pathways, response dynamics resulted in significantly greater information transmission capacities compared to nondynamic responses. Theoretical analysis demonstrated that signaling dynamics has a key role in overcoming extrinsic noise. Experimental measurements of information transmission in the ERK network under varying signal-to-noise levels confirmed our predictions and showed that signaling dynamics mitigate, and can potentially eliminate, extrinsic noise-induced information loss. By curbing the information-degrading effects of cell-to-cell variability, dynamic responses substantially increase the accuracy of biochemical signaling networks.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Calcium Signaling*
  • Cell Line
  • Computer Simulation
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • Humans
  • MAP Kinase Signaling System*
  • NF-kappa B / metabolism*
  • Signal Transduction*
  • Signal-To-Noise Ratio
  • Single-Cell Analysis
  • Systems Biology


  • NF-kappa B
  • Extracellular Signal-Regulated MAP Kinases