An effective model of endogenous clocks and external stimuli determining circadian rhythms

Abstract Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. T...

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Autores principales:	Tim Breitenbach, Charlotte Helfrich-Förster, Thomas Dandekar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2659b1069a20416d86b430653097a3df
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spelling	oai:doaj.org-article:2659b1069a20416d86b430653097a3df2021-12-02T15:08:10ZAn effective model of endogenous clocks and external stimuli determining circadian rhythms10.1038/s41598-021-95391-y2045-2322https://doaj.org/article/2659b1069a20416d86b430653097a3df2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95391-yhttps://doaj.org/toc/2045-2322Abstract Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/ .Tim BreitenbachCharlotte Helfrich-FörsterThomas DandekarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tim Breitenbach Charlotte Helfrich-Förster Thomas Dandekar An effective model of endogenous clocks and external stimuli determining circadian rhythms
description	Abstract Circadian endogenous clocks of eukaryotic organisms are an established and rapidly developing research field. To investigate and simulate in an effective model the effect of external stimuli on such clocks and their components we developed a software framework for download and simulation. The application is useful to understand the different involved effects in a mathematical simple and effective model. This concerns the effects of Zeitgebers, feedback loops and further modifying components. We start from a known mathematical oscillator model, which is based on experimental molecular findings. This is extended with an effective framework that includes the impact of external stimuli on the circadian oscillations including high dose pharmacological treatment. In particular, the external stimuli framework defines a systematic procedure by input-output-interfaces to couple different oscillators. The framework is validated by providing phase response curves and ranges of entrainment. Furthermore, Aschoffs rule is computationally investigated. It is shown how the external stimuli framework can be used to study biological effects like points of singularity or oscillators integrating different signals at once. The mathematical framework and formalism is generic and allows to study in general the effect of external stimuli on oscillators and other biological processes. For an easy replication of each numerical experiment presented in this work and an easy implementation of the framework the corresponding Mathematica files are fully made available. They can be downloaded at the following link: https://www.biozentrum.uni-wuerzburg.de/bioinfo/computing/circadian/ .
format	article
author	Tim Breitenbach Charlotte Helfrich-Förster Thomas Dandekar
author_facet	Tim Breitenbach Charlotte Helfrich-Förster Thomas Dandekar
author_sort	Tim Breitenbach
title	An effective model of endogenous clocks and external stimuli determining circadian rhythms
title_short	An effective model of endogenous clocks and external stimuli determining circadian rhythms
title_full	An effective model of endogenous clocks and external stimuli determining circadian rhythms
title_fullStr	An effective model of endogenous clocks and external stimuli determining circadian rhythms
title_full_unstemmed	An effective model of endogenous clocks and external stimuli determining circadian rhythms
title_sort	effective model of endogenous clocks and external stimuli determining circadian rhythms
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/2659b1069a20416d86b430653097a3df
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An effective model of endogenous clocks and external stimuli determining circadian rhythms

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