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Stochastic Delay Accelerates Signaling in Gene Networks
The creation of protein from DNA is a dynamic process consisting of numerous reactions, such as transcription, translation and protein folding. Each of these reactions is further comprised of hundreds or thousands of sub-steps that must be completed before a protein is fully mature. Consequently, th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213172/ https://www.ncbi.nlm.nih.gov/pubmed/22102802 http://dx.doi.org/10.1371/journal.pcbi.1002264 |
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author | Josić, Krešimir López, José Manuel Ott, William Shiau, LieJune Bennett, Matthew R. |
author_facet | Josić, Krešimir López, José Manuel Ott, William Shiau, LieJune Bennett, Matthew R. |
author_sort | Josić, Krešimir |
collection | PubMed |
description | The creation of protein from DNA is a dynamic process consisting of numerous reactions, such as transcription, translation and protein folding. Each of these reactions is further comprised of hundreds or thousands of sub-steps that must be completed before a protein is fully mature. Consequently, the time it takes to create a single protein depends on the number of steps in the reaction chain and the nature of each step. One way to account for these reactions in models of gene regulatory networks is to incorporate dynamical delay. However, the stochastic nature of the reactions necessary to produce protein leads to a waiting time that is randomly distributed. Here, we use queueing theory to examine the effects of such distributed delay on the propagation of information through transcriptionally regulated genetic networks. In an analytically tractable model we find that increasing the randomness in protein production delay can increase signaling speed in transcriptional networks. The effect is confirmed in stochastic simulations, and we demonstrate its impact in several common transcriptional motifs. In particular, we show that in feedforward loops signaling time and magnitude are significantly affected by distributed delay. In addition, delay has previously been shown to cause stable oscillations in circuits with negative feedback. We show that the period and the amplitude of the oscillations monotonically decrease as the variability of the delay time increases. |
format | Online Article Text |
id | pubmed-3213172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32131722011-11-18 Stochastic Delay Accelerates Signaling in Gene Networks Josić, Krešimir López, José Manuel Ott, William Shiau, LieJune Bennett, Matthew R. PLoS Comput Biol Research Article The creation of protein from DNA is a dynamic process consisting of numerous reactions, such as transcription, translation and protein folding. Each of these reactions is further comprised of hundreds or thousands of sub-steps that must be completed before a protein is fully mature. Consequently, the time it takes to create a single protein depends on the number of steps in the reaction chain and the nature of each step. One way to account for these reactions in models of gene regulatory networks is to incorporate dynamical delay. However, the stochastic nature of the reactions necessary to produce protein leads to a waiting time that is randomly distributed. Here, we use queueing theory to examine the effects of such distributed delay on the propagation of information through transcriptionally regulated genetic networks. In an analytically tractable model we find that increasing the randomness in protein production delay can increase signaling speed in transcriptional networks. The effect is confirmed in stochastic simulations, and we demonstrate its impact in several common transcriptional motifs. In particular, we show that in feedforward loops signaling time and magnitude are significantly affected by distributed delay. In addition, delay has previously been shown to cause stable oscillations in circuits with negative feedback. We show that the period and the amplitude of the oscillations monotonically decrease as the variability of the delay time increases. Public Library of Science 2011-11-10 /pmc/articles/PMC3213172/ /pubmed/22102802 http://dx.doi.org/10.1371/journal.pcbi.1002264 Text en Josic et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Josić, Krešimir López, José Manuel Ott, William Shiau, LieJune Bennett, Matthew R. Stochastic Delay Accelerates Signaling in Gene Networks |
title | Stochastic Delay Accelerates Signaling in Gene Networks |
title_full | Stochastic Delay Accelerates Signaling in Gene Networks |
title_fullStr | Stochastic Delay Accelerates Signaling in Gene Networks |
title_full_unstemmed | Stochastic Delay Accelerates Signaling in Gene Networks |
title_short | Stochastic Delay Accelerates Signaling in Gene Networks |
title_sort | stochastic delay accelerates signaling in gene networks |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3213172/ https://www.ncbi.nlm.nih.gov/pubmed/22102802 http://dx.doi.org/10.1371/journal.pcbi.1002264 |
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