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Bayesian model selection for the Drosophila gap gene network

BACKGROUND: The gap gene system controls the early cascade of the segmentation pathway in Drosophila melanogaster as well as other insects. Owing to its tractability and key role in embryo patterning, this system has been the focus for both computational modelers and experimentalists. The gap gene e...

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Autores principales: Zubair, Asif, Rosen, I. Gary, Nuzhdin, Sergey V., Marjoram, Paul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567646/
https://www.ncbi.nlm.nih.gov/pubmed/31195954
http://dx.doi.org/10.1186/s12859-019-2888-0
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author Zubair, Asif
Rosen, I. Gary
Nuzhdin, Sergey V.
Marjoram, Paul
author_facet Zubair, Asif
Rosen, I. Gary
Nuzhdin, Sergey V.
Marjoram, Paul
author_sort Zubair, Asif
collection PubMed
description BACKGROUND: The gap gene system controls the early cascade of the segmentation pathway in Drosophila melanogaster as well as other insects. Owing to its tractability and key role in embryo patterning, this system has been the focus for both computational modelers and experimentalists. The gap gene expression dynamics can be considered strictly as a one-dimensional process and modeled as a system of reaction-diffusion equations. While substantial progress has been made in modeling this phenomenon, there still remains a deficit of approaches to evaluate competing hypotheses. Most of the model development has happened in isolation and there has been little attempt to compare candidate models. RESULTS: The Bayesian framework offers a means of doing formal model evaluation. Here, we demonstrate how this framework can be used to compare different models of gene expression. We focus on the Papatsenko-Levine formalism, which exploits a fractional occupancy based approach to incorporate activation of the gap genes by the maternal genes and cross-regulation by the gap genes themselves. The Bayesian approach provides insight about relationship between system parameters. In the regulatory pathway of segmentation, the parameters for number of binding sites and binding affinity have a negative correlation. The model selection analysis supports a stronger binding affinity for Bicoid compared to other regulatory edges, as shown by a larger posterior mean. The procedure doesn’t show support for activation of Kruppel by Bicoid. CONCLUSIONS: We provide an efficient solver for the general representation of the Papatsenko-Levine model. We also demonstrate the utility of Bayes factor for evaluating candidate models for spatial pattering models. In addition, by using the parallel tempering sampler, the convergence of Markov chains can be remarkably improved and robust estimates of Bayes factors obtained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2888-0) contains supplementary material, which is available to authorized users.
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spelling pubmed-65676462019-06-27 Bayesian model selection for the Drosophila gap gene network Zubair, Asif Rosen, I. Gary Nuzhdin, Sergey V. Marjoram, Paul BMC Bioinformatics Research Article BACKGROUND: The gap gene system controls the early cascade of the segmentation pathway in Drosophila melanogaster as well as other insects. Owing to its tractability and key role in embryo patterning, this system has been the focus for both computational modelers and experimentalists. The gap gene expression dynamics can be considered strictly as a one-dimensional process and modeled as a system of reaction-diffusion equations. While substantial progress has been made in modeling this phenomenon, there still remains a deficit of approaches to evaluate competing hypotheses. Most of the model development has happened in isolation and there has been little attempt to compare candidate models. RESULTS: The Bayesian framework offers a means of doing formal model evaluation. Here, we demonstrate how this framework can be used to compare different models of gene expression. We focus on the Papatsenko-Levine formalism, which exploits a fractional occupancy based approach to incorporate activation of the gap genes by the maternal genes and cross-regulation by the gap genes themselves. The Bayesian approach provides insight about relationship between system parameters. In the regulatory pathway of segmentation, the parameters for number of binding sites and binding affinity have a negative correlation. The model selection analysis supports a stronger binding affinity for Bicoid compared to other regulatory edges, as shown by a larger posterior mean. The procedure doesn’t show support for activation of Kruppel by Bicoid. CONCLUSIONS: We provide an efficient solver for the general representation of the Papatsenko-Levine model. We also demonstrate the utility of Bayes factor for evaluating candidate models for spatial pattering models. In addition, by using the parallel tempering sampler, the convergence of Markov chains can be remarkably improved and robust estimates of Bayes factors obtained. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12859-019-2888-0) contains supplementary material, which is available to authorized users. BioMed Central 2019-06-13 /pmc/articles/PMC6567646/ /pubmed/31195954 http://dx.doi.org/10.1186/s12859-019-2888-0 Text en © The Author(s) 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License(http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Zubair, Asif
Rosen, I. Gary
Nuzhdin, Sergey V.
Marjoram, Paul
Bayesian model selection for the Drosophila gap gene network
title Bayesian model selection for the Drosophila gap gene network
title_full Bayesian model selection for the Drosophila gap gene network
title_fullStr Bayesian model selection for the Drosophila gap gene network
title_full_unstemmed Bayesian model selection for the Drosophila gap gene network
title_short Bayesian model selection for the Drosophila gap gene network
title_sort bayesian model selection for the drosophila gap gene network
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567646/
https://www.ncbi.nlm.nih.gov/pubmed/31195954
http://dx.doi.org/10.1186/s12859-019-2888-0
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