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Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome

View ORCID ProfileKevin Rychel, View ORCID ProfileAnand V. Sastry, View ORCID ProfileBernhard O. Palsson
doi: https://doi.org/10.1101/2020.04.26.062638
Kevin Rychel
aDepartment of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA
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Anand V. Sastry
aDepartment of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA
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Bernhard O. Palsson
aDepartment of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA
bDepartment of Pediatrics, University of California San Diego, La Jolla, CA, 92093, USA
cNovo Nordisk Foundation Center for Biosustainability, 2800, Kongens Lyngby, Denmark
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  • For correspondence: palsson@ucsd.edu
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Abstract

The transcriptional regulatory network (TRN) of Bacillus subtilis coordinates cellular functions of fundamental interest, including metabolism, biofilm formation, and sporulation. Here, we use unsupervised machine learning to modularize the transcriptome and quantitatively describe regulatory activity under diverse conditions, creating an unbiased summary of gene expression. We obtain 83 independently modulated gene sets that explain most of the variance in expression, and demonstrate that 76% of them represent the effects of known regulators. The TRN structure and its condition-dependent activity uncover novel or recently discovered roles for at least 5 regulons, such as a relationship between histidine utilization and quorum sensing. The TRN also facilitates quantification of population-level sporulation states, revealing a putative anaerobic metabolism role for SigG. As this TRN covers the majority of the transcriptome and concisely characterizes the global expression state, it could inform research on nearly every aspect of transcriptional regulation in B. subtilis.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted April 28, 2020.
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Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome
Kevin Rychel, Anand V. Sastry, Bernhard O. Palsson
bioRxiv 2020.04.26.062638; doi: https://doi.org/10.1101/2020.04.26.062638
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Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome
Kevin Rychel, Anand V. Sastry, Bernhard O. Palsson
bioRxiv 2020.04.26.062638; doi: https://doi.org/10.1101/2020.04.26.062638

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