title: An experimentally supported model of the Bacillus subtilis global transcriptional regulatory network.
abstract: 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.
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Mario L
authors.initials: ML
authors.lastname: Arrieta-Ortiz
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hafemeister
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Ashley Rose
authors.initials: AR
authors.lastname: Bate
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Chu
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: Greenfield
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Bentley
authors.initials: B
authors.lastname: Shuster
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Samantha N
authors.initials: SN
authors.lastname: Barry
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Gallitto
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Liu
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Thadeous
authors.initials: T
authors.lastname: Kacmarczyk
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Francis
authors.initials: F
authors.lastname: Santoriello
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: Christopher D A
authors.initials: CD
authors.lastname: Rodrigues
authors.affiliation: Department of Frontier Bioscience, Hosei University, Koganei, Tokyo, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA.
authors.forename: David Z
authors.initials: DZ
authors.lastname: Rudner
authors.affiliation: Department of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Driks
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA Courant Institute of Mathematical Science, Computer Science Department, New York, NY, USA Simons Foundation, Simons Center for Data Analysis, New York, NY, USA rbonneau@simonsfoundation.org pe19@nyu.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Bonneau
authors.affiliation: Center for Genomics and Systems Biology, Department of Biology, New York University, New York, NY, USA rbonneau@simonsfoundation.org pe19@nyu.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Eichenberger
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics*; D030541:Databases, Genetic; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D053263:Gene Regulatory Networks / Q000235:genetics*; D005798:Genes, Bacterial / Q000235:genetics; D008957:Models, Genetic; D013171:Spores, Bacterial / Q000235:genetics; D049490:Systems Biology; D059467:Transcriptome / Q000235:genetics*
keywords: Bacillus subtilis; network inference; sporulation; transcriptional networks