Identifying Sources of Variation and the Flow of Information in Biochemical
Identifying sources of variation and the flow PNAS PLUS of information in biochemical networks Clive G. Bowshera,1 and Peter S. Swainb,1 aSchool of Mathematics, University of Bristol, Bristol BS8 1TW, United Kingdom; and bSynthSys—Synthetic and Systems Biology, University of Edinburgh, Edinburgh EH9 3JD, United Kingdom Edited by Ken A. Dill, Stony Brook University, Stony Brook, NY, and approved March 6, 2012 (received for review November 24, 2011) To understand how cells control and exploit biochemical fluctua- Each Y could be, for example, the number of molecules of another tions, we must identify the sources of stochasticity, quantify their biochemical species, a property of the intra- or extracellular envir- effects, and distinguish informative variation from confounding onment, a characteristic of cell morphology (8), a reaction rate “noise.” We present an analysis that allows fluctuations of bio- that depends on the concentration of a cellular component such chemical networks to be decomposed into multiple components, as ATP, or even the number of times a particular type of reaction Y gives conditions for the design of experimental reporters to mea- has occurred. We emphasize that the variables are the stochastic sure all components, and provides a technique to predict the mag- variables whose effects are of interest: They are not all possible sources of stochasticity. nitude of these components from models. Further, we identify a Y Y Y particular component of variation that can be used to quantify the We wish to determine how fluctuations in 1, 2, and 3 af- fect fluctuations in Z, the output of the network.
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