title: Noise-processing by signaling networks.
abstract: Signaling networks mediate environmental information to the cell nucleus. To perform this task effectively they must be able to integrate multiple stimuli and distinguish persistent signals from transient environmental fluctuations. However, the ways in which signaling networks process environmental noise are not well understood. Here we outline a mathematical framework that relates a network's structure to its capacity to process noise, and use this framework to dissect the noise-processing ability of signaling networks. We find that complex networks that are dense in directed paths are poor noise processors, while those that are sparse and strongly directional process noise well. These results suggest that while cross-talk between signaling pathways may increase the ability of signaling networks to integrate multiple stimuli, too much cross-talk may compromise the ability of the network to distinguish signal from noise. To illustrate these general results we consider the structure of the signalling network that maintains pluripotency in mouse embryonic stem cells, and find an incoherent feedforward loop structure involving Stat3, Tfcp2l1, Esrrb, Klf2 and Klf4 is particularly important for noise-processing. Taken together these results suggest that noise-processing is an important function of signaling networks and they may be structured in part to optimize this task.
authors.affiliation: Mathematical Sciences, University of Southampton, SO17 1BJ, Southampton, UK.
authors.forename: Styliani
authors.initials: S
authors.lastname: Kontogeorgaki
authors.affiliation: Mathematical Sciences, University of Southampton, SO17 1BJ, Southampton, UK.|Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.
authors.forename: Rubén J
authors.identifier: http://orcid.org/0000-0001-6479-3028
authors.initials: RJ
authors.lastname: Sánchez-García
authors.affiliation: Biological Sciences, University of Southampton, SO17 1BJ, Southampton, UK.|Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK.
authors.forename: Rob M
authors.initials: RM
authors.lastname: Ewing
authors.affiliation: School of Mathematics, University of Edinburgh, EH9 3FD, Edinburgh, UK.
authors.forename: Konstantinos C
authors.initials: KC
authors.lastname: Zygalakis
authors.affiliation: Mathematical Sciences, University of Southampton, SO17 1BJ, Southampton, UK. bdm@soton.ac.uk.|Centre for Human Development, Stem Cells and Regeneration, Faculty of Medicine, University of Southampton, SO17 1BJ, Southampton, UK. bdm@soton.ac.uk.|Institute for Life Sciences, University of Southampton, SO17 1BJ, Southampton, UK. bdm@soton.ac.uk.
authors.forename: Ben D
authors.identifier: http://orcid.org/0000-0002-5396-9750
authors.initials: BD
authors.lastname: MacArthur