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Boolean factor graph model for biological systems: the yeast cell-cycle network

BACKGROUND: The desire to understand genomic functions and the behavior of complex gene regulatory networks has recently been a major research focus in systems biology. As a result, a plethora of computational and modeling tools have been proposed to identify and infer interactions among biological...

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Autores principales: Kotiang, Stephen, Eslami, Ali
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447535/
https://www.ncbi.nlm.nih.gov/pubmed/34535069
http://dx.doi.org/10.1186/s12859-021-04361-8
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author Kotiang, Stephen
Eslami, Ali
author_facet Kotiang, Stephen
Eslami, Ali
author_sort Kotiang, Stephen
collection PubMed
description BACKGROUND: The desire to understand genomic functions and the behavior of complex gene regulatory networks has recently been a major research focus in systems biology. As a result, a plethora of computational and modeling tools have been proposed to identify and infer interactions among biological entities. Here, we consider the general question of the effect of perturbation on the global dynamical network behavior as well as error propagation in biological networks to incite research pertaining to intervention strategies. RESULTS: This paper introduces a computational framework that combines the formulation of Boolean networks and factor graphs to explore the global dynamical features of biological systems. A message-passing algorithm is proposed for this formalism to evolve network states as messages in the graph. In addition, the mathematical formulation allows us to describe the dynamics and behavior of error propagation in gene regulatory networks by conducting a density evolution (DE) analysis. The model is applied to assess the network state progression and the impact of gene deletion in the budding yeast cell cycle. Simulation results show that our model predictions match published experimental data. Also, our findings reveal that the sample yeast cell-cycle network is not only robust but also consistent with real high-throughput expression data. Finally, our DE analysis serves as a tool to find the optimal values of network parameters for resilience against perturbations, especially in the inference of genetic graphs. CONCLUSION: Our computational framework provides a useful graphical model and analytical tools to study biological networks. It can be a powerful tool to predict the consequences of gene deletions before conducting wet bench experiments because it proves to be a quick route to predicting biologically relevant dynamic properties without tunable kinetic parameters. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04361-8.
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spelling pubmed-84475352021-09-17 Boolean factor graph model for biological systems: the yeast cell-cycle network Kotiang, Stephen Eslami, Ali BMC Bioinformatics Research BACKGROUND: The desire to understand genomic functions and the behavior of complex gene regulatory networks has recently been a major research focus in systems biology. As a result, a plethora of computational and modeling tools have been proposed to identify and infer interactions among biological entities. Here, we consider the general question of the effect of perturbation on the global dynamical network behavior as well as error propagation in biological networks to incite research pertaining to intervention strategies. RESULTS: This paper introduces a computational framework that combines the formulation of Boolean networks and factor graphs to explore the global dynamical features of biological systems. A message-passing algorithm is proposed for this formalism to evolve network states as messages in the graph. In addition, the mathematical formulation allows us to describe the dynamics and behavior of error propagation in gene regulatory networks by conducting a density evolution (DE) analysis. The model is applied to assess the network state progression and the impact of gene deletion in the budding yeast cell cycle. Simulation results show that our model predictions match published experimental data. Also, our findings reveal that the sample yeast cell-cycle network is not only robust but also consistent with real high-throughput expression data. Finally, our DE analysis serves as a tool to find the optimal values of network parameters for resilience against perturbations, especially in the inference of genetic graphs. CONCLUSION: Our computational framework provides a useful graphical model and analytical tools to study biological networks. It can be a powerful tool to predict the consequences of gene deletions before conducting wet bench experiments because it proves to be a quick route to predicting biologically relevant dynamic properties without tunable kinetic parameters. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12859-021-04361-8. BioMed Central 2021-09-17 /pmc/articles/PMC8447535/ /pubmed/34535069 http://dx.doi.org/10.1186/s12859-021-04361-8 Text en © The Author(s) 2021 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Kotiang, Stephen
Eslami, Ali
Boolean factor graph model for biological systems: the yeast cell-cycle network
title Boolean factor graph model for biological systems: the yeast cell-cycle network
title_full Boolean factor graph model for biological systems: the yeast cell-cycle network
title_fullStr Boolean factor graph model for biological systems: the yeast cell-cycle network
title_full_unstemmed Boolean factor graph model for biological systems: the yeast cell-cycle network
title_short Boolean factor graph model for biological systems: the yeast cell-cycle network
title_sort boolean factor graph model for biological systems: the yeast cell-cycle network
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8447535/
https://www.ncbi.nlm.nih.gov/pubmed/34535069
http://dx.doi.org/10.1186/s12859-021-04361-8
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