Regulatory networks articles within Nature Communications

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  • Article
    | Open Access

    Bacterial two-component systems consist of a sensor histidine kinase (HK) that perceives a signal, and a cognate response regulator (RR) that modulates target gene expression. Here, the authors combine experiments and mathematical modelling to show that phosphorylated HKs can be sequestered by non-cognate RRs, which prevents responses to weak signals.

    • Gaurav D. Sankhe
    • , Rubesh Raja
    •  & Deepak Kumar Saini

  • Article
    | Open Access

    Deciduous trees exhibit autumn senescence driven by environmental seasonality. Here, the authors show that senescence timing in aspen tree genotypes depends on environmental changes but also on the ability of each genotype to sustain stress tolerance mediated by the phytohormone salicylic acid.

    • Jenna Lihavainen
    • , Jan Šimura
    •  & Stefan Jansson

  • Article
    | Open Access

    Genotype networks are sets of genotypes connected by small mutational changes that share the same phenotype. Here the authors combine construction of over 20 synthetic gene regulatory networks with mathematical modeling to exemplify how gene regulatory networks provide robustness in face of mutations while enabling transitions to innovative phenotypes.

    • Javier Santos-Moreno
    • , Eve Tasiudi
    •  & Yolanda Schaerli

  • Article
    | Open Access

    Modification of transcribed mRNAs enables regulation of transcription but its extent in cancer cells is incompletely understood. Here, the authors analyse transcript assembly in over 1000 cancer cell lines and find unannotated transcripts are common, and are associated with drug sensitivity.

    • Wei Hu
    • , Yangjun Wu
    •  & Shengli Li

  • Article
    | Open Access

    Protein abundance is controlled at the transcriptional, translational and posttranslational levels. Here, Öztürk et al. determine proteome changes resulting from individual knockout of 3308 nonessential genes in the yeast S. pombe, infer gene functionality, and show that protein upregulation under stable transcript expression utilizes optimal codons.

    • Merve Öztürk
    • , Anja Freiwald
    •  & Falk Butter

  • Article
    | Open Access

    HOXA9 plays an important role in acute myeloid leukaemia (AML), but its relevance for other blood malignancies is unclear. Here, the authors show that HOXA9 has a binary switch function that can clinically stratify AML patients, and model how the interactions with JAK2, TET2 and NOTCH impact myeloproliferative neoplasms.

    • Laure Talarmain
    • , Matthew A. Clarke
    •  & Benjamin A. Hall

  • Article
    | Open Access

    Many diseases are caused by disruptions to the network of biochemical reactions that allow cells to respond to external signals. Here Nilsson et al develop a method to simulate cellular signaling using artificial neural networks to predict cellular responses and activities of signaling molecules.

    • Avlant Nilsson
    • , Joshua M. Peters
    •  & Douglas A. Lauffenburger

  • Article
    | Open Access

    Cell adhesion proteins have been described at sites away from the cell surface, including in the nucleus. Here, the authors report the scale of nuclear localisation of adhesion proteins, establishing a nucleo-adhesome and showing that nuclear adhesion proteins can cooperate to control transcription.

    • Adam Byron
    • , Billie G. C. Griffith
    •  & Margaret C. Frame

  • Article
    | Open Access

    Multiplex analyses of samples allow understanding complex processes in cancer initiation, progression and therapy response. Here, the authors present a fluorescence imaging-based visual barcode for livecell clonal-multiplexing which allows identifying signalling pathways clusters in response to different chemotherapy compounds.

    • Tom Kaufman
    • , Erez Nitzan
    •  & Ravid Straussman

  • Article
    | Open Access

    The molecular factors that drive invasiveness and metastasis in lung adenocarcinoma (LUAD) are not completely understood. Here, the authors use an integrative network approach to identify a gene signature of invasiveness in LUAD, and reveal Aurora kinases as master regulators of invasion.

    • Seungyeul Yoo
    • , Abhilasha Sinha
    •  & Charles A. Powell

  • Article
    | Open Access

    Transcription factors (TFs) interact with several other proteins in the process of transcriptional regulation. Here the authors identify 6703 and 1536 protein–protein interactions for 109 different human TFs through BioID and AP-MS analyses, respectively.

    • Helka Göös
    • , Matias Kinnunen
    •  & Markku Varjosalo

  • Article
    | Open Access

    Despite the clear causal relationship between genotype and phenotype in rare diseases, identifying the pathobiological mechanisms at various levels of biological organization remains a practical and conceptual challenge. Here, the authors introduce a network approach for evaluating the impact of rare gene defects across biological scales.

    • Pisanu Buphamalai
    • , Tomislav Kokotovic
    •  & Jörg Menche

  • Article
    | Open Access

    Anthropogenic change, such as urban heat islands, present challenges to biodiversity that can be overcome through phenotypic plasticity. Unlike their ancestral counterparts, urban lizards have fewer maladaptive gene expression responses to higher temperatures in a common garden experiment, suggesting the evolution of adaptive plasticity.

    • Shane C. Campbell-Staton
    • , Jonathan P. Velotta
    •  & Kristin M. Winchell

  • Article
    | Open Access

    Developing interpretable models is a major challenge in single cell deep learning. Here we show that the VEGA variational autoencoder model, whose decoder wiring mirrors gene modules, can provide direct interpretability to the latent space further enabling the inference of biological module activity.

    • Lucas Seninge
    • , Ioannis Anastopoulos
    •  & Joshua Stuart

  • Article
    | Open Access

    Practical implementation of genetic circuits is difficult due to low predictability and time-intensive troubleshooting. Here the authors present Cyberloop, which interfaces a computer with single cells to enable cell-in-the-loop testing and optimization of circuit designs before they are built.

    • Sant Kumar
    • , Marc Rullan
    •  & Mustafa Khammash

  • 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
    • , Juri 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

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