Regulatory networks

  • Article
    | Open Access

    Boolean networks allow a simplified representation of interactions. Here, the authors systematically analyze regulation in dozens of biological Boolean networks, finding mathematical regularities that suggest biological systems could be controlled through a relatively small number of components.

    • Enrico Borriello
    •  & Bryan C. Daniels
  • Article
    | Open Access

    Single-cell methods record molecule expressions of cells in a given tissue, but understanding interactions between cells remains challenging. Here the authors show by applying systems biology and machine learning approaches that they can infer and analyze cell-cell communication networks in an easily interpretable way.

    • Suoqin Jin
    • , Christian F. Guerrero-Juarez
    •  & Qing Nie
  • Article
    | Open Access

    Some cholesterol-lowering drugs can increase the risk of type 2 diabetes, but the mechanism behind this is not fully understood. Here the authors show that there is a single genetic regulatory module that influences both cholesterol levels and glucose levels, providing a link between cholesterol levels and diabetes.

    • Ariella T. Cohain
    • , William T. Barrington
    •  & Eric E. Schadt
  • Article
    | Open Access

    Robustness is a prominent feature of most biological systems, but most of the current efforts have been focused on studying homogeneous molecular networks. Here the authors propose a comprehensive framework for understanding how the interactions between genes, proteins, and metabolites contribute to the determinants of robustness.

    • Xueming Liu
    • , Enrico Maiorino
    •  & Amitabh Sharma
  • Article
    | Open Access

    Global interaction of chromatin-associated RNAs and DNA can be identified in situ. Here the authors report the genome-wide increase of interchromosomal RNA-DNA interactions and demonstrate the importance of such RNA-DNA contacts exemplified by LINC00607 RNA and SERPINE1 gene’s super enhancer in dysfunctional endothelial cell models.

    • Riccardo Calandrelli
    • , Lixia Xu
    •  & Sheng Zhong
  • Article
    | Open Access

    Single cell expression data allows for inferring cell-cell communication between cells expressing ligands and those expressing their cognate receptors. Here the authors present an updated and curated database of ligand-receptor pairs and a Python-based toolkit to construct and analyse communication networks from single cell and bulk expression data.

    • Rui Hou
    • , Elena Denisenko
    •  & Alistair R. R. Forrest
  • Article
    | Open Access

    Boolean Networks are a well-established model of biological networks, but usual interpretations can preclude the prediction of behaviours observed in quantitative systems. The authors introduce Most Permissive Boolean Networks, which are shown not to miss any behaviour achievable by the corresponding quantitative model.

    • Loïc Paulevé
    • , Juraj Kolčák
    •  & Stefan Haar
  • Article
    | Open Access

    Cellular signalling networks provide information to the cell, but the trade-off between accuracy of information transfer and energetic cost of doing so has not been assessed. Here, the authors investigate a MAPK signalling cascade in budding yeast and find that information is maximised per unit energetic cost.

    • Alexander Anders
    • , Bhaswar Ghosh
    •  & Victor Sourjik
  • Article
    | Open Access

    Mechanistic insight into the regulation of transcriptional modules remains scarce. Here, the authors identify statistically independent gene sets by applying independent component analysis to a high-quality E. coli RNA-seq data compendium and find that most gene sets represent the effects of specific transcriptional regulators.

    • Anand V. Sastry
    • , Ye Gao
    •  & Bernhard O. Palsson
  • Article
    | Open Access

    Parkinson’s disease (PD) is characterized by neurodegeneration associated with loss of dopaminergic (DA) neurons and deposition of Lewy bodies. Here, Wang et al. use co-expression network analysis to pinpoint disease pathways and propose reduced expression of STMN2 as a cause of presynaptic function loss in PD.

    • Qian Wang
    • , Yuanxi Zhang
    •  & Bin Zhang
  • Article
    | Open Access

    Our understanding of the mechanisms of drug interactions remains limited. Here the authors introduce a framework to study how complex cellular perturbations induced by different drugs affect each other in morphological feature space.

    • Michael Caldera
    • , Felix Müller
    •  & Jörg Menche
  • Article
    | Open Access

    An understanding of the ancestral state of the neural crest (NC) gene regulatory network (GRN) gives insight into vertebrate evolution. Here, the authors use transcriptomic and chromatin accessibility analyses of the lamprey NC, as well as cross-species enhancer assays, to identify GRN elements conserved throughout vertebrates.

    • Dorit Hockman
    • , Vanessa Chong-Morrison
    •  & Tatjana Sauka-Spengler
  • Article
    | Open Access

    Cell fate commitment is understood in terms of bistable regulatory circuits with hysteresis, but inherent stochasticity in gene expression is incompatible with hysteresis. Here, the authors quantify how, under slow dynamics, the dependency of the non-stationary solutions on the initial state of the cells can lead to transient hysteresis.

    • M. Pájaro
    • , I. Otero-Muras
    •  & A. A. Alonso
  • Article
    | Open Access

    Interactions between metabolites and transcription factors are known to control gene expression but analyzing these events at genome-scale is challenging. Here, the authors integrate dynamic metabolome and transcriptome data from E.coli to predict regulatory metabolite-transcription factor interactions.

    • Martin Lempp
    • , Niklas Farke
    •  & Hannes Link
  • Article
    | Open Access

    Queen pheromones are used by eusocial insects to regulate all aspects of colony life. Here, Holman et al. compare the effects of queen pheromone on gene expression and splicing in four eusocial insect species, giving insight into the mechanism and evolution of division of reproductive labour.

    • Luke Holman
    • , Heikki Helanterä
    •  & Alexander S. Mikheyev
  • Article
    | Open Access

    Temporal control of transcriptional networks enables organisms to adapt to changing environment. Here, the authors use a scaled-up cell-based assay to identify direct targets of nitrogen-early responsive transcription factors and validate a network path mediating dynamic nitrogen signaling in Arabidopsis.

    • Matthew D. Brooks
    • , Jacopo Cirrone
    •  & Gloria M. Coruzzi
  • Article
    | Open Access

    A steep gradient of Cdc42 is at the front of migrating cells, whereas the active Rac1 gradient is graded. Here the authors show that Cdc42 gradients follow the distribution of GEFs and govern direction of migration, while Rac1 gradients require the activity of the GAP β2-chimaerin and control cell speed.

    • S. de Beco
    • , K. Vaidžiulytė
    •  & M. Coppey
  • Article
    | Open Access

    DNA damage induces checkpoints to ensure that damage is not transferred to the next generation, but the molecular pathways responsible for checkpoint recovery are not clear. Here the authors show that the nutrient sensor mTORC1 is a determinant for G2/M checkpoint recovery through regulation of cyclin B1 and PLK1 expression.

    • Hui-Ju Hsieh
    • , Wei Zhang
    •  & Guang Peng
  • Article
    | Open Access

    The intractability of most stochastic models of gene regulatory networks (GRNs) limits their utility. Here, the authors present a linear-mapping approximation mapping models onto simpler ones, giving approximate but accurate analytic or semi- analytic solutions for a wide range of model GRNs.

    • Zhixing Cao
    •  & Ramon Grima
  • Article
    | Open Access

    During atherosclerosis, endothelial cells release purines in response to oxidized phospholipids. Here, Hitzel et al. show that oxidized phospholipids activate an MTHFD2-regulated gene network in endothelial cells which reprograms amino acid metabolism towards production of purines and thus compensates for their loss.

    • Juliane Hitzel
    • , Eunjee Lee
    •  & Ralf P. Brandes
  • Article
    | Open Access

    The precise timing of neurodevelopmental splicing switches and the underlying regulatory mechanisms remain poorly understood. This study identifies two major waves of developmental switches under the control of distinct combinations of RNA-binding proteins in central and peripheral nervous systems.

    • Sebastien M. Weyn-Vanhentenryck
    • , Huijuan Feng
    •  & Chaolin Zhang
  • Article
    | Open Access

    Single cell analysis provides insight into cell states and transitions, but to interpret the data, improved algorithms are needed. Here, the authors present CellRouter as a method to analyse single-cell trajectories from RNA-sequencing data, and provide insight into erythroid, myeloid and lymphoid differentiation.

    • Edroaldo Lummertz da Rocha
    • , R. Grant Rowe
    •  & George Q. Daley
  • Article
    | Open Access

    Innate immunity combines intra- and intercellular signalling to develop responses that limit pathogen spread. Here the authors analyse feedback and feedforward loops connecting IRF3, NF-κB and STAT pathways, and suggest they allow coordinating cell fate decisions in cellular populations in response to the virus-mimicking agent poly(I:C).

    • Maciej Czerkies
    • , Zbigniew Korwek
    •  & Tomasz Lipniacki
  • Article
    | Open Access

    How pathogens maintain phenotypic robustness during infection is poorly understood. Here the authors couple the virulence regulatory network (VRN) of the pathogen R. solanacearum to a model of its metabolic network, and find that the VRN activates functionally redundant primary metabolism genes to promote phenotypic robustness during infection.

    • Rémi Peyraud
    • , Ludovic Cottret
    •  & Stéphane Genin
  • Article
    | Open Access

    How gene regulatory pathways control cell fate decisions in single cells is not fully understood. Here the authors present an integrated dual-input microfluidic chip and a linked analysis software, enabling tracking of gene regulatory responses of single bacterial cells to changing conditions.

    • Matthias Kaiser
    • , Florian Jug
    •  & Erik van Nimwegen
  • Article
    | Open Access

    Somatic copy number alterations (SCNA) can confound gene co-expression analysis in cancers. Here the authors develop a method to remove the effects of SCNA in co-expression analysis, improving the analysis of network rewiring in cancer, and provide a database with adjusted data from TCGA.

    • Ling Cai
    • , Qiwei Li
    •  & Guanghua Xiao
  • Article
    | Open Access

    Cybergenetics aims to monitor and regulate cellular processes in real-time using computer monitoring and feedback of biological readouts. Here the authors use a feedback loop and periodic forcing to maintain cells with a bistable synthetic circuit near its unstable state.

    • Jean-Baptiste Lugagne
    • , Sebastián Sosa Carrillo
    •  & Pascal Hersen
  • Article
    | Open Access

    Peptide CSP regulates natural competence in pneumococci and has been proposed as a quorum-sensing signal or a probe for sensing environmental cues. Here, the authors show that CSP levels can indeed act as an indicator of cell density and also incorporate information on environmental factors or cell history.

    • Stefany Moreno-Gámez
    • , Robin A. Sorg
    •  & Jan-Willem Veening
  • Article
    | Open Access

    Gene networks evolve by transcription factor (TF) duplication and divergence of their binding site specificities, but little is known about the global constraints at play. Here, the authors study the coevolution of TFs and binding sites using a biophysical-evolutionary approach, and show that the emerging complex fitness landscapes strongly influence regulatory evolution with a role for crosstalk.

    • Tamar Friedlander
    • , Roshan Prizak
    •  & Gašper Tkačik
  • Article
    | Open Access

    Recent works suggest that cellular networks may respond to novel challenges on the time-scale of cellular lifetimes through large-scale perturbation of gene expression and convergence to a new state. Here, the authors demonstrate the theoretical feasibility of exploratory adaptation in cellular networks by showing that convergence to new states depends on known features of these networks.

    • Hallel I. Schreier
    • , Yoav Soen
    •  & Naama Brenner
  • Article
    | Open Access

    The bacteriophage lambda and its hostEscherichia coli provide a model system to study cell-fate decisions. Here, Trinh et al. develop a four-colour fluorescence system at the single-cell/single-virus/single-viral-DNA level and find phages cooperate during lysogenization and compete during lysis.

    • Jimmy T. Trinh
    • , Tamás Székely
    •  & Lanying Zeng
  • Article
    | Open Access

    Cells must function despite the noisiness of their processes by tolerating or reducing such variability. Here, the authors combine experiment and modelling to show that a network motif that mediates network-dosage compensation also reduces noise in network output, suggesting that noise is tuneable.

    • Weilin Peng
    • , Ruijie Song
    •  & Murat Acar
  • Article
    | Open Access

    Limited specificity of transcription factor-DNA interactions leads to crosstalk in gene regulation. Here the authors consider global crosstalk in regulatory networks of growing size and complexity, and show that it imposes constraints on gene regulation and on the evolution of regulatory networks.

    • Tamar Friedlander
    • , Roshan Prizak
    •  & Gašper Tkačik
  • Article
    | Open Access

    Proteins are sometimes implicated in separate and seemingly unrelated processes, so called moonlighting functions. Here the authors use bioinformatics tools to identify extreme multifunctional proteins and define a signature of extreme multifunctionality.

    • Charles E. Chapple
    • , Benoit Robisson
    •  & Christine Brun
  • Article
    | Open Access

    Autism genes converge in midfetal cortical co-expression networks, and chromatin regulators such as CHD8 are increasingly associated with autism spectrum disorder (ASD). Here the authors map CHD8 targets in developing brain, and find that CHD8 directly regulates other ASD risk genes during human neurodevelopment.

    • Justin Cotney
    • , Rebecca A. Muhle
    •  & James P. Noonan