Reconstruction of the regulatory network for Bacillus subtilis and reconciliation with gene expression data

Faria, Jose P.; Overbeek, Ross; Taylor, Ronald C.; Conrad, Neal; Vonstein, Veronika; Goelzer, Anne; Fromion, Vincent; Rocha, Miguel; Rocha, Isabel; Henry, Christopher S.

doi:10.3389/fmicb.2016.00275

Reconstruction of the regulatory network for Bacillus subtilis and reconciliation with gene expression data

Journal Article · Fri Mar 18 00:00:00 EDT 2016 · Frontiers in Microbiology

DOI:https://doi.org/10.3389/fmicb.2016.00275· OSTI ID:1337227

Faria, Jose P. ^[1]; Overbeek, Ross ^[2]; Taylor, Ronald C. ^[3]; Conrad, Neal ^[4]; Vonstein, Veronika ^[2]; Goelzer, Anne ^[5]; Fromion, Vincent ^[5]; Rocha, Miguel ^[6]; Rocha, Isabel ^[6]; Henry, Christopher S. ^[7]

Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States); Univ. of Minho, Braga (Portugal)
Fellowship for Interpretation of Genomes, Burr Ridge, IL (United States)
Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Argonne National Lab. (ANL), Argonne, IL (United States)
Paris-Saclay Univ., Jouy-en-Josas (France)
Univ. of Minho, Braga (Portugal)
Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)

Here, we introduce a manually constructed and curated regulatory network model that describes the current state of knowledge of transcriptional regulation of B. 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 approximately 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 atomic regulons for B. subtilis are able to capture many sets of genes corresponding to regulated operons in our manually curated network. Additionally, we demonstrate how atomic regulons 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.

View Accepted Manuscript (DOE)

Research Organization:: Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

Sponsoring Organization:: USDOE

Grant/Contract Number:: AC05-76RL01830

OSTI ID:: 1337227

Alternate ID(s):: OSTI ID: 1393150

Report Number(s):: PNNL-SA--115053; KP1601010

Journal Information:: Frontiers in Microbiology, Journal Name: Frontiers in Microbiology Vol. 7; ISSN 1664-302X

Publisher:: Frontiers Research FoundationCopyright Statement

Country of Publication:: United States

Language:: English

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stimuli

Reconstruction of the regulatory network for Bacillus subtilis and reconciliation with gene expression data

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