title: The propagation of perturbations in rewired bacterial gene networks.
abstract: What happens to gene expression when you add new links to a gene regulatory network? To answer this question, we profile 85 network rewirings in E. coli. Here we report that concerted patterns of differential expression propagate from reconnected hub genes. The rewirings link promoter regions to different transcription factor and σ-factor genes, resulting in perturbations that span four orders of magnitude, changing up to ∼ 70% of the transcriptome. Importantly, factor connectivity and promoter activity both associate with perturbation size. Perturbations from related rewirings have more similar transcription profiles and a statistical analysis reveals ∼ 20 underlying states of the system, associating particular gene groups with rewiring constructs. We examine two large clusters (ribosomal and flagellar genes) in detail. These represent alternative global outcomes from different rewirings because of antagonism between these major cell states. This data set of systematically related perturbations enables reverse engineering and discovery of underlying network interactions.
authors.affiliation: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Baumstark
authors.affiliation: Research Program on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), Dr Aiguader 88, 08003 Barcelona, Spain.|Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Sonja
authors.initials: S
authors.lastname: Hänzelmann
authors.affiliation: Department of Bioinformatic Engineering, Graduate School of Information Science and Technology, Osaka University, 1-5 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Saburo
authors.initials: S
authors.lastname: Tsuru
authors.affiliation: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Schaerli
authors.affiliation: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Mirko
authors.initials: M
authors.lastname: Francesconi
authors.affiliation: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.|Genomics Cancer Group, Vall d 'Hebron Institute of Oncology (VHIO), Carrer Natzaret 15-17, 08035 Barcelona, Spain.
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Mancuso
authors.affiliation: Research Program on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM), Dr Aiguader 88, 08003 Barcelona, Spain.|Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Dr Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Robert
authors.initials: R
authors.lastname: Castelo
authors.affiliation: EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), Dr Aiguader 88, 08003 Barcelona, Spain.|Universitat Pompeu Fabra (UPF), Dr Aiguader 88, 08003 Barcelona, Spain.|Department of Life Sciences, Imperial College London, London SW7 2AZ, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Isalan
mesh_terms: D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics* / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D011401:Promoter Regions, Genetic
chemical_list: D029968:Escherichia coli Proteins