Simplifications and approximations in a single-gene circuit modeling

Autores
Barton, Alejandro; Sesin, Pablo Ezequiel; Diambra, Luis Anibal
Año de publicación
2024
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The absence of detailed knowledge about regulatory interactions makes the use of phenomenological assumptions mandatory in cell biology modeling. Furthermore, the challenges associated with the analysis of these models compel the implementation of mathematical approximations. However, the constraints these methods introduce to biological interpretation are sometimes neglected. Consequently, understanding these restrictions is a very important task for systems biology modeling. In this article, we examine the impact of such simplifications, taking the case of a single-gene autoinhibitory circuit; however, our conclusions are not limited solely to this instance. We demonstrate that models grounded in the same biological assumptions but described at varying levels of detail can lead to different outcomes, that is, different and contradictory phenotypes or behaviors. Indeed, incorporating specific molecular processes like translation and elongation into the model can introduce instabilities and oscillations not seen when these processes are assumed to be instantaneous. Furthermore, incorporating a detailed description of promoter dynamics, usually described by a phenomenological regulatory function, can lead to instability, depending on the cooperative binding mechanism that is acting. Consequently, although the use of a regulating function facilitates model analysis, it may mask relevant aspects of the system’s behavior. In particular, we observe that the two cooperative binding mechanisms, both compatible with the same sigmoidal function, can lead to different phenotypes, such as transcriptional oscillations with different oscillation frequencies.
Fil: Barton, Alejandro. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Sesin, Pablo Ezequiel. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Materia
GENE CIRCUITS
SYSTEMS BIOLOGY
OSCILLATORY BEHAVIOR
MATHEMATICAL MODELING
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/239063
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Simplifications and approximations in a single-gene circuit modelingBarton, AlejandroSesin, Pablo EzequielDiambra, Luis AnibalGENE CIRCUITSSYSTEMS BIOLOGYOSCILLATORY BEHAVIORMATHEMATICAL MODELINGhttps://purl.org/becyt/ford/1.7https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1The absence of detailed knowledge about regulatory interactions makes the use of phenomenological assumptions mandatory in cell biology modeling. Furthermore, the challenges associated with the analysis of these models compel the implementation of mathematical approximations. However, the constraints these methods introduce to biological interpretation are sometimes neglected. Consequently, understanding these restrictions is a very important task for systems biology modeling. In this article, we examine the impact of such simplifications, taking the case of a single-gene autoinhibitory circuit; however, our conclusions are not limited solely to this instance. We demonstrate that models grounded in the same biological assumptions but described at varying levels of detail can lead to different outcomes, that is, different and contradictory phenotypes or behaviors. Indeed, incorporating specific molecular processes like translation and elongation into the model can introduce instabilities and oscillations not seen when these processes are assumed to be instantaneous. Furthermore, incorporating a detailed description of promoter dynamics, usually described by a phenomenological regulatory function, can lead to instability, depending on the cooperative binding mechanism that is acting. Consequently, although the use of a regulating function facilitates model analysis, it may mask relevant aspects of the system’s behavior. In particular, we observe that the two cooperative binding mechanisms, both compatible with the same sigmoidal function, can lead to different phenotypes, such as transcriptional oscillations with different oscillation frequencies.Fil: Barton, Alejandro. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Sesin, Pablo Ezequiel. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaNature2024-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/239063Barton, Alejandro; Sesin, Pablo Ezequiel; Diambra, Luis Anibal; Simplifications and approximations in a single-gene circuit modeling; Nature; Scientific Reports; 14; 1; 5-2024; 1-112045-2322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-024-63265-8info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-024-63265-8info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:47:28Zoai:ri.conicet.gov.ar:11336/239063instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-11-12 09:47:29.162CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Simplifications and approximations in a single-gene circuit modeling
title Simplifications and approximations in a single-gene circuit modeling
spellingShingle Simplifications and approximations in a single-gene circuit modeling
Barton, Alejandro
GENE CIRCUITS
SYSTEMS BIOLOGY
OSCILLATORY BEHAVIOR
MATHEMATICAL MODELING
title_short Simplifications and approximations in a single-gene circuit modeling
title_full Simplifications and approximations in a single-gene circuit modeling
title_fullStr Simplifications and approximations in a single-gene circuit modeling
title_full_unstemmed Simplifications and approximations in a single-gene circuit modeling
title_sort Simplifications and approximations in a single-gene circuit modeling
dc.creator.none.fl_str_mv Barton, Alejandro
Sesin, Pablo Ezequiel
Diambra, Luis Anibal
author Barton, Alejandro
author_facet Barton, Alejandro
Sesin, Pablo Ezequiel
Diambra, Luis Anibal
author_role author
author2 Sesin, Pablo Ezequiel
Diambra, Luis Anibal
author2_role author
author
dc.subject.none.fl_str_mv GENE CIRCUITS
SYSTEMS BIOLOGY
OSCILLATORY BEHAVIOR
MATHEMATICAL MODELING
topic GENE CIRCUITS
SYSTEMS BIOLOGY
OSCILLATORY BEHAVIOR
MATHEMATICAL MODELING
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.7
https://purl.org/becyt/ford/1
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The absence of detailed knowledge about regulatory interactions makes the use of phenomenological assumptions mandatory in cell biology modeling. Furthermore, the challenges associated with the analysis of these models compel the implementation of mathematical approximations. However, the constraints these methods introduce to biological interpretation are sometimes neglected. Consequently, understanding these restrictions is a very important task for systems biology modeling. In this article, we examine the impact of such simplifications, taking the case of a single-gene autoinhibitory circuit; however, our conclusions are not limited solely to this instance. We demonstrate that models grounded in the same biological assumptions but described at varying levels of detail can lead to different outcomes, that is, different and contradictory phenotypes or behaviors. Indeed, incorporating specific molecular processes like translation and elongation into the model can introduce instabilities and oscillations not seen when these processes are assumed to be instantaneous. Furthermore, incorporating a detailed description of promoter dynamics, usually described by a phenomenological regulatory function, can lead to instability, depending on the cooperative binding mechanism that is acting. Consequently, although the use of a regulating function facilitates model analysis, it may mask relevant aspects of the system’s behavior. In particular, we observe that the two cooperative binding mechanisms, both compatible with the same sigmoidal function, can lead to different phenotypes, such as transcriptional oscillations with different oscillation frequencies.
Fil: Barton, Alejandro. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
Fil: Sesin, Pablo Ezequiel. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Diambra, Luis Anibal. Universidad Nacional de La Plata. Centro Regional de Estudios Genómicos; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina
description The absence of detailed knowledge about regulatory interactions makes the use of phenomenological assumptions mandatory in cell biology modeling. Furthermore, the challenges associated with the analysis of these models compel the implementation of mathematical approximations. However, the constraints these methods introduce to biological interpretation are sometimes neglected. Consequently, understanding these restrictions is a very important task for systems biology modeling. In this article, we examine the impact of such simplifications, taking the case of a single-gene autoinhibitory circuit; however, our conclusions are not limited solely to this instance. We demonstrate that models grounded in the same biological assumptions but described at varying levels of detail can lead to different outcomes, that is, different and contradictory phenotypes or behaviors. Indeed, incorporating specific molecular processes like translation and elongation into the model can introduce instabilities and oscillations not seen when these processes are assumed to be instantaneous. Furthermore, incorporating a detailed description of promoter dynamics, usually described by a phenomenological regulatory function, can lead to instability, depending on the cooperative binding mechanism that is acting. Consequently, although the use of a regulating function facilitates model analysis, it may mask relevant aspects of the system’s behavior. In particular, we observe that the two cooperative binding mechanisms, both compatible with the same sigmoidal function, can lead to different phenotypes, such as transcriptional oscillations with different oscillation frequencies.
publishDate 2024
dc.date.none.fl_str_mv 2024-05
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/239063
Barton, Alejandro; Sesin, Pablo Ezequiel; Diambra, Luis Anibal; Simplifications and approximations in a single-gene circuit modeling; Nature; Scientific Reports; 14; 1; 5-2024; 1-11
2045-2322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/239063
identifier_str_mv Barton, Alejandro; Sesin, Pablo Ezequiel; Diambra, Luis Anibal; Simplifications and approximations in a single-gene circuit modeling; Nature; Scientific Reports; 14; 1; 5-2024; 1-11
2045-2322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41598-024-63265-8
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41598-024-63265-8
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Nature
publisher.none.fl_str_mv Nature
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.24909

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