Multiplexing information flow through dynamic signalling systems
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We consider how a signalling system can act as an information hub by multiplexing information arising from multiple signals. We formally define multiplexing, mathematically characterise which systems can multiplex and how well they can do it. While the results of this paper are theoretical, to motivate the idea of multiplexing, we provide experimental evidence that tentatively suggests that the NF-κB transcription factor can multiplex information about changes in multiple signals. We believe that our theoretical results may resolve the apparent paradox of how a system like NF-κB that regulates cell fate and inflammatory signalling in response to diverse stimuli can appear to have the low information carrying capacity suggested by recent studies on scalar signals. In carrying out our study, we introduce new methods for the analysis of large, nonlinear stochastic dynamic models, and develop computational algorithms that facilitate the calculation of fundamental constructs of information theory such as Kullback–Leibler divergences and sensitivity matrices, and link these methods to a new theory about multiplexing information. We show that many current models such as those of the NF-κB system cannot multiplex effectively and provide models that overcome this limitation using post-transcriptional modifications.
Minas , G , Woodcock , D J , Ashall , L , Harper , C V , White , M R H & Rand , D A 2020 , ' Multiplexing information flow through dynamic signalling systems ' , PLoS Computational Biology , vol. 16 , no. 8 , e1008076 , pp. e1008076 . https://doi.org/10.1371/journal.pcbi.1008076
PLoS Computational Biology
Copyright: © 2020 Minas et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
DescriptionD.A.R. was partly funded by the European Union Seventh Framework Programme (FP7/2007- 2013) under Grant Agreement 305564. G.M and D.A.R. were partly funded by EPSRC EP/P019811/1 Mathematical Foundations of Information and Decisions in Dynamic Cell Signalling. G.M, D.J.W, C.V.H., M.R.H.W, and D.A.R. were partly funded by BBSRC SLOLA BB/K003097/1 Systems biology analysis of biological timers and inflammation. D.J.W., L.A., C.V.R., M.R.H.W., and D.A.R. were partly funded by BBSRC BB/F005938/1 Dynamics and function of the NF-kappaB signalling system. The microarray data used in this study are available at ArrayExpress database (https://www.ebi.ac.uk/arrayexpress) under accession number E-MTAB-5158.
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