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Formal verification confirms the role of p53 protein in cell fate decision mechanism

The bio-cell cycle is controlled by a complex biochemical network of signaling pathways. Modeling such challenging networks accurately is imperative for the understanding of their detailed dynamical behavior. In this paper, we construct, analyze, and verify a hybrid Petri net (HPN) model of a comple...

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Autores principales: Mahmoud, Eman Abdelaziz, Herajy, Mostafa, Ziedan, Ibrahim E., Shehata, Hazem I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925526/
https://www.ncbi.nlm.nih.gov/pubmed/36510032
http://dx.doi.org/10.1007/s12064-022-00381-x
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author Mahmoud, Eman Abdelaziz
Herajy, Mostafa
Ziedan, Ibrahim E.
Shehata, Hazem I.
author_facet Mahmoud, Eman Abdelaziz
Herajy, Mostafa
Ziedan, Ibrahim E.
Shehata, Hazem I.
author_sort Mahmoud, Eman Abdelaziz
collection PubMed
description The bio-cell cycle is controlled by a complex biochemical network of signaling pathways. Modeling such challenging networks accurately is imperative for the understanding of their detailed dynamical behavior. In this paper, we construct, analyze, and verify a hybrid Petri net (HPN) model of a complex biochemical network that captures the role of an important protein (namely p53) in deciding the fate of the cell. We model the behavior of the cell nucleus and cytoplasm as two stochastic and continuous Petri nets, respectively, combined together into a single HPN. We use simulative model checking to verify three different properties that capture the dynamical behavior of p53 protein with respect to the intensity of the ionizing radiation (IR) to which the cell is exposed. For each IR dose, 1000 simulation runs are carried out to verify each property. Our verification results showed that the fluctuations in p53, which relies on IR intensity, are compatible with the findings of the preceding simulation studies that have previously examined the role of p53 in cell fate decision.
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spelling pubmed-99255262023-02-15 Formal verification confirms the role of p53 protein in cell fate decision mechanism Mahmoud, Eman Abdelaziz Herajy, Mostafa Ziedan, Ibrahim E. Shehata, Hazem I. Theory Biosci Original Article The bio-cell cycle is controlled by a complex biochemical network of signaling pathways. Modeling such challenging networks accurately is imperative for the understanding of their detailed dynamical behavior. In this paper, we construct, analyze, and verify a hybrid Petri net (HPN) model of a complex biochemical network that captures the role of an important protein (namely p53) in deciding the fate of the cell. We model the behavior of the cell nucleus and cytoplasm as two stochastic and continuous Petri nets, respectively, combined together into a single HPN. We use simulative model checking to verify three different properties that capture the dynamical behavior of p53 protein with respect to the intensity of the ionizing radiation (IR) to which the cell is exposed. For each IR dose, 1000 simulation runs are carried out to verify each property. Our verification results showed that the fluctuations in p53, which relies on IR intensity, are compatible with the findings of the preceding simulation studies that have previously examined the role of p53 in cell fate decision. Springer Berlin Heidelberg 2022-12-12 2023 /pmc/articles/PMC9925526/ /pubmed/36510032 http://dx.doi.org/10.1007/s12064-022-00381-x Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Mahmoud, Eman Abdelaziz
Herajy, Mostafa
Ziedan, Ibrahim E.
Shehata, Hazem I.
Formal verification confirms the role of p53 protein in cell fate decision mechanism
title Formal verification confirms the role of p53 protein in cell fate decision mechanism
title_full Formal verification confirms the role of p53 protein in cell fate decision mechanism
title_fullStr Formal verification confirms the role of p53 protein in cell fate decision mechanism
title_full_unstemmed Formal verification confirms the role of p53 protein in cell fate decision mechanism
title_short Formal verification confirms the role of p53 protein in cell fate decision mechanism
title_sort formal verification confirms the role of p53 protein in cell fate decision mechanism
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9925526/
https://www.ncbi.nlm.nih.gov/pubmed/36510032
http://dx.doi.org/10.1007/s12064-022-00381-x
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