A modular approach for modeling the cell cycle based on functional response curves.

Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to...

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Autores principales:	Jolan De Boeck, Jan Rombouts, Lendert Gelens
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/723023fb54cf44e1afbc655c1fe92912
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spelling	oai:doaj.org-article:723023fb54cf44e1afbc655c1fe929122021-12-02T19:58:06ZA modular approach for modeling the cell cycle based on functional response curves.1553-734X1553-735810.1371/journal.pcbi.1009008https://doaj.org/article/723023fb54cf44e1afbc655c1fe929122021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.pcbi.1009008https://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to accomplish this is by replacing the detailed reaction mechanisms of certain modules in the model by a mathematical expression that qualitatively describes the dynamical behavior of these modules. Such an approach has been widely adopted for ultrasensitive responses, for which underlying reaction mechanisms are often replaced by a single Hill function. Also time delays are usually accounted for by using an explicit delay in delay differential equations. In contrast, however, S-shaped response curves, which by definition have multiple output values for certain input values and are often encountered in bistable systems, are not easily modeled in such an explicit way. Here, we extend the classical Hill function into a mathematical expression that can be used to describe both ultrasensitive and S-shaped responses. We show how three ubiquitous modules (ultrasensitive responses, S-shaped responses and time delays) can be combined in different configurations and explore the dynamics of these systems. As an example, we apply our strategy to set up a model of the cell cycle consisting of multiple bistable switches, which can incorporate events such as DNA damage and coupling to the circadian clock in a phenomenological way.Jolan De BoeckJan RomboutsLendert GelensPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 17, Iss 8, p e1009008 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Jolan De Boeck Jan Rombouts Lendert Gelens A modular approach for modeling the cell cycle based on functional response curves.
description	Modeling biochemical reactions by means of differential equations often results in systems with a large number of variables and parameters. As this might complicate the interpretation and generalization of the obtained results, it is often desirable to reduce the complexity of the model. One way to accomplish this is by replacing the detailed reaction mechanisms of certain modules in the model by a mathematical expression that qualitatively describes the dynamical behavior of these modules. Such an approach has been widely adopted for ultrasensitive responses, for which underlying reaction mechanisms are often replaced by a single Hill function. Also time delays are usually accounted for by using an explicit delay in delay differential equations. In contrast, however, S-shaped response curves, which by definition have multiple output values for certain input values and are often encountered in bistable systems, are not easily modeled in such an explicit way. Here, we extend the classical Hill function into a mathematical expression that can be used to describe both ultrasensitive and S-shaped responses. We show how three ubiquitous modules (ultrasensitive responses, S-shaped responses and time delays) can be combined in different configurations and explore the dynamics of these systems. As an example, we apply our strategy to set up a model of the cell cycle consisting of multiple bistable switches, which can incorporate events such as DNA damage and coupling to the circadian clock in a phenomenological way.
format	article
author	Jolan De Boeck Jan Rombouts Lendert Gelens
author_facet	Jolan De Boeck Jan Rombouts Lendert Gelens
author_sort	Jolan De Boeck
title	A modular approach for modeling the cell cycle based on functional response curves.
title_short	A modular approach for modeling the cell cycle based on functional response curves.
title_full	A modular approach for modeling the cell cycle based on functional response curves.
title_fullStr	A modular approach for modeling the cell cycle based on functional response curves.
title_full_unstemmed	A modular approach for modeling the cell cycle based on functional response curves.
title_sort	modular approach for modeling the cell cycle based on functional response curves.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/723023fb54cf44e1afbc655c1fe92912
work_keys_str_mv	AT jolandeboeck amodularapproachformodelingthecellcyclebasedonfunctionalresponsecurves AT janrombouts amodularapproachformodelingthecellcyclebasedonfunctionalresponsecurves AT lendertgelens amodularapproachformodelingthecellcyclebasedonfunctionalresponsecurves AT jolandeboeck modularapproachformodelingthecellcyclebasedonfunctionalresponsecurves AT janrombouts modularapproachformodelingthecellcyclebasedonfunctionalresponsecurves AT lendertgelens modularapproachformodelingthecellcyclebasedonfunctionalresponsecurves
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A modular approach for modeling the cell cycle based on functional response curves.

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