Open AccessAn experimentally supported model of the Bacillus subtilis global transcriptional regulatory network
Author(s) -
ArrietaOrtiz Mario L,
Hafemeister Christoph,
Bate Ashley Rose,
Chu Timothy,
Greenfield Alex,
Shuster Bentley,
Barry Samantha N,
Gallitto Matthew,
Liu Brian,
Kacmarczyk Thadeous,
Santoriello Francis,
Chen Jie,
Rodrigues Christopher DA,
Sato Tsutomu,
Rudner David Z,
Driks Adam,
Bonneau Richard,
Eichenberger Patrick
Publication year - 2015
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20156236
Subject(s) - biology , bacillus subtilis , gene regulatory network , computational biology , regulation of gene expression , genetics , gene , gene expression , bacteria
Organisms from all domains of life use gene regulation networks to control cell growth, identity, function, and responses to environmental challenges. Although accurate global regulatory models would provide critical evolutionary and functional insights, they remain incomplete, even for the best studied organisms. Efforts to build comprehensive networks are confounded by challenges including network scale, degree of connectivity, complexity of organism–environment interactions, and difficulty of estimating the activity of regulatory factors. Taking advantage of the large number of known regulatory interactions in Bacillus subtilis and two transcriptomics datasets (including one with 38 separate experiments collected specifically for this study), we use a new combination of network component analysis and model selection to simultaneously estimate transcription factor activities and learn a substantially expanded transcriptional regulatory network for this bacterium. In total, we predict 2,258 novel regulatory interactions and recall 74% of the previously known interactions. We obtained experimental support for 391 (out of 635 evaluated) novel regulatory edges (62% accuracy), thus significantly increasing our understanding of various cell processes, such as spore formation.