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The propagation of perturbations in rewired bacterial gene networks.

Rebecca Baumstark, Sonja Hanzelmann, Saburo Tsuru, Yolanda Schaerli, Mirko Francesconi, Francesco M Mancuso, Robert Castelo, and Mark Isalan (2015)

Nat Commun, 6:10105.

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 fromreconnected hub genes. The rewirings link promoter regions to different transcription factor and sigma-factor genes, resulting in perturbations that span four orders of magnitude, changing up to approximately 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 approximately 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.

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