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The propagation of perturbations in rewired bacterial gene networks

Author

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  • Rebecca Baumstark

    (EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
    Universitat Pompeu Fabra (UPF))

  • Sonja Hänzelmann

    (Research Program on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM)
    Universitat Pompeu Fabra)

  • Saburo Tsuru

    (Graduate School of Information Science and Technology, Osaka University)

  • Yolanda Schaerli

    (EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
    Universitat Pompeu Fabra (UPF))

  • Mirko Francesconi

    (EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
    Universitat Pompeu Fabra (UPF))

  • Francesco M. Mancuso

    (EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
    Genomics Cancer Group, Vall d 'Hebron Institute of Oncology (VHIO))

  • Robert Castelo

    (Research Program on Biomedical Informatics (GRIB), Hospital del Mar Medical Research Institute (IMIM)
    Universitat Pompeu Fabra)

  • Mark Isalan

    (EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG)
    Universitat Pompeu Fabra (UPF)
    Imperial College London)

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.

Suggested Citation

  • Rebecca Baumstark & Sonja Hänzelmann & Saburo Tsuru & Yolanda Schaerli & Mirko Francesconi & Francesco M. Mancuso & Robert Castelo & Mark Isalan, 2015. "The propagation of perturbations in rewired bacterial gene networks," Nature Communications, Nature, vol. 6(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms10105
    DOI: 10.1038/ncomms10105
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    Cited by:

    1. Yichao Han & Wanji Li & Alden Filko & Jingyao Li & Fuzhong Zhang, 2023. "Genome-wide promoter responses to CRISPR perturbations of regulators reveal regulatory networks in Escherichia coli," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. Alexander Rivkind & Hallel Schreier & Naama Brenner & Omri Barak, 2020. "Scale free topology as an effective feedback system," PLOS Computational Biology, Public Library of Science, vol. 16(5), pages 1-24, May.

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