 The Fidelity of Dynamic Signaling by Noisy Biomolecular NetworksClive Bowsher, Margaritis Voliotis and Peter S Swain PLOS Computational Biology, 2013, vol. 9, issue 3, 1-9 Abstract: Cells live in changing, dynamic environments. To understand cellular decision-making, we must therefore understand how fluctuating inputs are processed by noisy biomolecular networks. Here we present a general methodology for analyzing the fidelity with which different statistics of a fluctuating input are represented, or encoded, in the output of a signaling system over time. We identify two orthogonal sources of error that corrupt perfect representation of the signal: dynamical error, which occurs when the network responds on average to other features of the input trajectory as well as to the signal of interest, and mechanistic error, which occurs because biochemical reactions comprising the signaling mechanism are stochastic. Trade-offs between these two errors can determine the system's fidelity. By developing mathematical approaches to derive dynamics conditional on input trajectories we can show, for example, that increased biochemical noise (mechanistic error) can improve fidelity and that both negative and positive feedback degrade fidelity, for standard models of genetic autoregulation. For a group of cells, the fidelity of the collective output exceeds that of an individual cell and negative feedback then typically becomes beneficial. We can also predict the dynamic signal for which a given system has highest fidelity and, conversely, how to modify the network design to maximize fidelity for a given dynamic signal. Our approach is general, has applications to both systems and synthetic biology, and will help underpin studies of cellular behavior in natural, dynamic environments. Author Summary: Cells do not live in constant conditions, but in environments that change over time. To adapt to their surroundings, cells must therefore sense fluctuating concentrations and ‘interpret’ the state of their environment to see whether, for example, a change in the pattern of gene expression is needed. This task is achieved via the noisy computations of biomolecular networks. But what levels of signaling fidelity can be achieved and how are dynamic signals encoded in the network's outputs? Here we present a general technique for analyzing such questions. We identify two sources of signaling error: dynamic error, which occurs when the network responds to features of the input other than the signal of interest; and mechanistic error, which arises because of the inevitable stochasticity of biochemical reactions. We show analytically that increased biochemical noise can sometimes improve fidelity and that, for genetic autoregulation, feedback can be deleterious. Our approach also allows us to predict the dynamic signal for which a given signaling network has highest fidelity and to design networks to maximize fidelity for a given signal. We thus propose a new way to analyze the flow of information in signaling networks, particularly for the dynamic environments expected in nature. Date: 2013 Downloads: (external link) Related works: Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text Persistent link: https://EconPapers.repec.org/RePEc:plo:pcbi00:1002965 DOI: 10.1371/journal.pcbi.1002965 Access Statistics for this article More articles in PLOS Computational Biology from Public Library of Science |
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