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Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data

We introduce a manually constructed and curated regulatory network model that describes the current state of knowledge of transcriptional regulation of Bacillus subtilis. The model corresponds to an updated and enlarged version of the regulatory model of central metabolism originally proposed in 200...

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Autores principales: Faria, José P., Overbeek, Ross, Taylor, Ronald C., Conrad, Neal, Vonstein, Veronika, Goelzer, Anne, Fromion, Vincent, Rocha, Miguel, Rocha, Isabel, Henry, Christopher S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796004/
https://www.ncbi.nlm.nih.gov/pubmed/27047450
http://dx.doi.org/10.3389/fmicb.2016.00275
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author Faria, José P.
Overbeek, Ross
Taylor, Ronald C.
Conrad, Neal
Vonstein, Veronika
Goelzer, Anne
Fromion, Vincent
Rocha, Miguel
Rocha, Isabel
Henry, Christopher S.
author_facet Faria, José P.
Overbeek, Ross
Taylor, Ronald C.
Conrad, Neal
Vonstein, Veronika
Goelzer, Anne
Fromion, Vincent
Rocha, Miguel
Rocha, Isabel
Henry, Christopher S.
author_sort Faria, José P.
collection PubMed
description We introduce a manually constructed and curated regulatory network model that describes the current state of knowledge of transcriptional regulation of Bacillus subtilis. The model corresponds to an updated and enlarged version of the regulatory model of central metabolism originally proposed in 2008. We extended the original network to the whole genome by integration of information from DBTBS, a compendium of regulatory data that includes promoters, transcription factors (TFs), binding sites, motifs, and regulated operons. Additionally, we consolidated our network with all the information on regulation included in the SporeWeb and Subtiwiki community-curated resources on B. subtilis. Finally, we reconciled our network with data from RegPrecise, which recently released their own less comprehensive reconstruction of the regulatory network for B. subtilis. Our model describes 275 regulators and their target genes, representing 30 different mechanisms of regulation such as TFs, RNA switches, Riboswitches, and small regulatory RNAs. Overall, regulatory information is included in the model for ∼2500 of the ∼4200 genes in B. subtilis 168. In an effort to further expand our knowledge of B. subtilis regulation, we reconciled our model with expression data. For this process, we reconstructed the Atomic Regulons (ARs) for B. subtilis, which are the sets of genes that share the same “ON” and “OFF” gene expression profiles across multiple samples of experimental data. We show how ARs for B. subtilis are able to capture many sets of genes corresponding to regulated operons in our manually curated network. Additionally, we demonstrate how ARs can be used to help expand or validate the knowledge of the regulatory networks by looking at highly correlated genes in the ARs for which regulatory information is lacking. During this process, we were also able to infer novel stimuli for hypothetical genes by exploring the genome expression metadata relating to experimental conditions, gaining insights into novel biology.
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spelling pubmed-47960042016-04-04 Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data Faria, José P. Overbeek, Ross Taylor, Ronald C. Conrad, Neal Vonstein, Veronika Goelzer, Anne Fromion, Vincent Rocha, Miguel Rocha, Isabel Henry, Christopher S. Front Microbiol Microbiology We introduce a manually constructed and curated regulatory network model that describes the current state of knowledge of transcriptional regulation of Bacillus subtilis. The model corresponds to an updated and enlarged version of the regulatory model of central metabolism originally proposed in 2008. We extended the original network to the whole genome by integration of information from DBTBS, a compendium of regulatory data that includes promoters, transcription factors (TFs), binding sites, motifs, and regulated operons. Additionally, we consolidated our network with all the information on regulation included in the SporeWeb and Subtiwiki community-curated resources on B. subtilis. Finally, we reconciled our network with data from RegPrecise, which recently released their own less comprehensive reconstruction of the regulatory network for B. subtilis. Our model describes 275 regulators and their target genes, representing 30 different mechanisms of regulation such as TFs, RNA switches, Riboswitches, and small regulatory RNAs. Overall, regulatory information is included in the model for ∼2500 of the ∼4200 genes in B. subtilis 168. In an effort to further expand our knowledge of B. subtilis regulation, we reconciled our model with expression data. For this process, we reconstructed the Atomic Regulons (ARs) for B. subtilis, which are the sets of genes that share the same “ON” and “OFF” gene expression profiles across multiple samples of experimental data. We show how ARs for B. subtilis are able to capture many sets of genes corresponding to regulated operons in our manually curated network. Additionally, we demonstrate how ARs can be used to help expand or validate the knowledge of the regulatory networks by looking at highly correlated genes in the ARs for which regulatory information is lacking. During this process, we were also able to infer novel stimuli for hypothetical genes by exploring the genome expression metadata relating to experimental conditions, gaining insights into novel biology. Frontiers Media S.A. 2016-03-18 /pmc/articles/PMC4796004/ /pubmed/27047450 http://dx.doi.org/10.3389/fmicb.2016.00275 Text en Copyright © 2016 Faria, Overbeek, Taylor, Conrad, Vonstein, Goelzer, Fromion, Rocha, Rocha and Henry. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Faria, José P.
Overbeek, Ross
Taylor, Ronald C.
Conrad, Neal
Vonstein, Veronika
Goelzer, Anne
Fromion, Vincent
Rocha, Miguel
Rocha, Isabel
Henry, Christopher S.
Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data
title Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data
title_full Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data
title_fullStr Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data
title_full_unstemmed Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data
title_short Reconstruction of the Regulatory Network for Bacillus subtilis and Reconciliation with Gene Expression Data
title_sort reconstruction of the regulatory network for bacillus subtilis and reconciliation with gene expression data
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4796004/
https://www.ncbi.nlm.nih.gov/pubmed/27047450
http://dx.doi.org/10.3389/fmicb.2016.00275
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