RT Journal Article SR Electronic T1 Machine learning uncovers independently regulated modules in the Bacillus subtilis transcriptome JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.04.26.062638 DO 10.1101/2020.04.26.062638 A1 Kevin Rychel A1 Anand V. Sastry A1 Bernhard O. Palsson YR 2020 UL http://biorxiv.org/content/early/2020/04/28/2020.04.26.062638.abstract AB 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 StatementThe authors have declared no competing interest.