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Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria
The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316585/ https://www.ncbi.nlm.nih.gov/pubmed/22479409 http://dx.doi.org/10.1371/journal.pone.0033532 |
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author | Ahmad, Jamil Niazi, Umar Mansoor, Sajid Siddique, Umair Bibby, Jaclyn |
author_facet | Ahmad, Jamil Niazi, Umar Mansoor, Sajid Siddique, Umair Bibby, Jaclyn |
author_sort | Ahmad, Jamil |
collection | PubMed |
description | The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL) – a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis. |
format | Online Article Text |
id | pubmed-3316585 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33165852012-04-04 Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria Ahmad, Jamil Niazi, Umar Mansoor, Sajid Siddique, Umair Bibby, Jaclyn PLoS One Research Article The discrete modeling formalism of René Thomas is a well known approach for the modeling and analysis of Biological Regulatory Networks (BRNs). This formalism uses a set of parameters which reflect the dynamics of the BRN under study. These parameters are initially unknown but may be deduced from the appropriately chosen observed dynamics of a BRN. The discrete model can be further enriched by using the model checking tool HyTech along with delay parameters. This paves the way to accurately analyse a BRN and to make predictions about critical trajectories which lead to a normal or diseased response. In this paper, we apply the formal discrete and hybrid (discrete and continuous) modeling approaches to characterize behavior of the BRN associated with MyD88-adapter-like (MAL) – a key protein involved with innate immune response to infections. In order to demonstrate the practical effectiveness of our current work, different trajectories and corresponding conditions that may lead to the development of cerebral malaria (CM) are identified. Our results suggest that the system converges towards hyperinflammation if Bruton's tyrosine kinase (BTK) remains constitutively active along with pre-existing high cytokine levels which may play an important role in CM pathogenesis. Public Library of Science 2012-03-30 /pmc/articles/PMC3316585/ /pubmed/22479409 http://dx.doi.org/10.1371/journal.pone.0033532 Text en Ahmad 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 Ahmad, Jamil Niazi, Umar Mansoor, Sajid Siddique, Umair Bibby, Jaclyn Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria |
title | Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria |
title_full | Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria |
title_fullStr | Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria |
title_full_unstemmed | Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria |
title_short | Formal Modeling and Analysis of the MAL-Associated Biological Regulatory Network: Insight into Cerebral Malaria |
title_sort | formal modeling and analysis of the mal-associated biological regulatory network: insight into cerebral malaria |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3316585/ https://www.ncbi.nlm.nih.gov/pubmed/22479409 http://dx.doi.org/10.1371/journal.pone.0033532 |
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