Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Unwanted interactions between cellular components can complicate rational engineering of biological systems. Here the authors design insulated minimal promoters and operators that enable biophysical modeling of bacterial transcription without free parameters for precise circuit design.

    • Yeqing Zong
    • , Haoqian M. Zhang
    •  & Chunbo Lou

  • Article
    | Open Access

    Coupling of growth and product synthesis is an important principle in metabolic engineering, but its range of applicability is unclear. Here, the authors use a dedicated computational framework to study the feasibility of coupling the production of metabolites to growth in the genome-scale metabolic models of five production organisms, and show that coupling can be achieved for most metabolites.

    • Axel von Kamp
    •  & Steffen Klamt

  • Article
    | Open Access

    2,4-Dihydroxybutyric acid has potential to be a precursor to a range of industrially important products, however a natural metabolic pathway for its synthesis does not exist. Here the authors rationally design a synthetic pathway inE. coliby engineering enzymes from malate metabolism.

    • Thomas Walther
    • , Christopher M. Topham
    •  & Jean Marie François

  • Article
    | Open Access

    Circular dorsal ruffles (CDRs) are important for the vesicular uptake of extracellular matter, but the basis of their wave dynamics is not understood. Here, the authors propose and experimentally test a bistable reaction-diffusion system, which they show accounts for the typical CDR expansion and shrinkage and for aberrant formation of pinned waves and spirals.

    • Erik Bernitt
    • , Hans-Günther Döbereiner
    •  & Arik Yochelis

  • Article
    | Open Access

    In single-cell RNA sequencing data of heterogeneous cell populations, cell cycle stage of individual cells would often be informative. Here, the authors introduce a computational model to reconstruct a pseudo-time series from single cell transcriptome data, identify the cell cycle stages, identify candidate cell cycle-regulated genes and recover the methylome changes during the cell cycle.

    • Zehua Liu
    • , Huazhe Lou
    •  & Ting Chen

  • Article
    | Open Access

    The BioID approaches takes advantage of the promiscuous biotinylation enzyme (BirA*) to identify proteins that closely interact. Here the authors improve the resolution of BioID using a protein fragment complementation approach that allows the assignment of protein-protein interactions to specific complexes within a common interactome.

    • Isabel Myriam Schopp
    • , Cinthia Claudia Amaya Ramirez
    •  & Julien Béthune

  • Article
    | Open Access

    The R2TP/Prefoldin-like cochaperone complex is involved in the assembly of a number of protein complexes. Here the authors provide evidence that RUVBL1/RUVBL2, subunits of that cochaperone complex, directly interact with ZNHIT2 to regulate assembly of U5 small ribonucleoprotein.

    • Philippe Cloutier
    • , Christian Poitras
    •  & Benoit Coulombe

  • Article
    | Open Access

    Growth-coupled designs for chemical production are limited by native metabolic networks’ optimality for growth. Here, the authors introduce pathway orthogonality as a measure of the independence of biomass and chemical production pathways, identify metabolic valves that allow substrate utilization to be switched between the two, and demonstrate advantages of orthogonal designs.

    • Aditya Vikram Pandit
    • , Shyam Srinivasan
    •  & Radhakrishnan Mahadevan

  • Article
    | Open Access

    The leakiness of commonly used genetic components can make the construction of complex synthetic circuits difficult. Here the authors construct NOR gate architecture, using dCas9 fused to the chromatin remodeller Mxi1, that can be wired together into complex circuits.

    • Miles W. Gander
    • , Justin D. Vrana
    •  & Eric Klavins

  • Article
    | Open Access

    The type III secretion system is a needle-like molecular machine under tight regulatory control. Here the authors construct a synthetic type III secretion system gene cluster by deconstructing and rebuilding the wild-typeSalmonellapathogenicity island 1.

    • Miryoung Song
    • , David J. Sukovich
    •  & Christopher A. Voigt

  • Article
    | Open Access

    We can often observe only a small fraction of a system, which leads to biases in the inference of its global properties. Here, the authors develop a framework that enables overcoming subsampling effects, apply it to recordings from developing neural networks, and find that neural networks become critical as they mature.

    • A. Levina
    •  & V. Priesemann

  • Article
    | Open Access

    Genome-scale engineering is a powerful technique for understanding biology and designing microorganisms but has been limited to bacterial species. Here the authors present an automated platform for genome-scale engineering inSaccharomyces cerevisiaeusing CRISPR-Cas and RNAi.

    • Tong Si
    • , Ran Chao
    •  & Huimin Zhao

  • Article
    | Open Access

    Filamentous fungi are a valuable source of natural therapeutic products such as antibiotics. Here the authors engineer monocellularS. cerevisiaeto perform complex secondary metabolism typical of multicellular fungi in order to demonstrate biosynthesis and secretion of bioactive penicillin.

    • Ali R. Awan
    • , Benjamin A. Blount
    •  & Tom Ellis

  • Article
    | Open Access

    The coevolution of viruses and host cells can be mapped with interactomics. Here the authors identify coupling of human and viral promoters, and show that HIV-reactivation from dormancy is coincident with migration of HIV-infected cells owing to coupling of human CXCR4 and HIV LTR promoters.

    • Kathrin Bohn-Wippert
    • , Erin N. Tevonian
    •  & Roy D. Dar

  • Article
    | Open Access

    Synthetic circuits in host cells compete with endogenous processes for limited resources. Here the authors use MazF to funnel cellular resources to a synthetic circuit to increase product production and demonstrate how resource allocation can be manipulated.

    • Ophelia S. Venturelli
    • , Mika Tei
    •  & Adam P Arkin

  • 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

    While we have abundant data for transcription factor (TF) binding sites and TF expression at the mRNA level, our knowledge of TFs at the protein level and their DNA-binding activities is sparser. Here, the authors address this by using the catTFRE approach to profile active TFs in 24 adult and 8 fetal mouse tissues, and presenting the TF networks in major mouse organs.

    • Quan Zhou
    • , Mingwei Liu
    •  & Jun Qin

  • Article
    | Open Access

    Protein RNA interactions are dynamic and regulated in response to environmental changes. Here the authors describe ‘kinetic CRAC’, an approach that allows time resolved analyses of protein RNA interactions with minute time point resolution and apply it to gain insight into the function of the RNA-binding protein Nab3.

    • Rob van Nues
    • , Gabriele Schweikert
    •  & Sander Granneman

  • Article
    | Open Access

    Large-scale metabolic models of organisms from microbes to mammals can provide great insight into cellular function, but their analysis remains challenging. Here, the authors provide an approximate analytic method to estimate the feasible solution space for the flux vectors of metabolic networks, enabling more accurate analysis under a wide range of conditions of interest.

    • Alfredo Braunstein
    • , Anna Paola Muntoni
    •  & Andrea Pagnani

  • Article
    | Open Access

    While rare cell subpopulations frequently make the difference between health and disease, their detection remains a challenge. Here, the authors devise CellCnn, a representation learning approach to detecting such rare cell populations from high-dimensional single cell data, and, among other examples, demonstrate its capacity for detecting rare leukaemic blasts in minimal residual disease.

    • Eirini Arvaniti
    •  & Manfred Claassen

  • Article
    | Open Access

    While yeasts lack dedicated photoreceptors, they nonetheless possess metabolic rhythms responsive to light. Here the authors find that light signalling in budding yeast involves the production of H2O2, which in turn regulates protein kinase A through a peroxiredoxin-thioredoxin redox relay.

    • Kristofer Bodvard
    • , Ken Peeters
    •  & Mikael Molin

  • Article
    | Open Access

    Targeting virulence rather than bacterial growth is less likely to select for antibiotic resistance, but many possible targets function in both processes. Here, the authors reconstruct a genome-scale metabolic network ofP. aeruginosastrain PA14 and update that of strain PAO1, which, together with mutant screens, enable them to identify genes uniquely critical for virulence factor production.

    • Jennifer A. Bartell
    • , Anna S. Blazier
    •  & Jason A. Papin

  • Article
    | Open Access

    Understanding of dysregulation in cancers requires knowledge, beyond cancer genomes, of the interactions of cancer-associated proteins. Here, the authors use high-throughput, time-resolved FRET to map protein–protein interactions to establish a lung cancer protein network, and demonstrate its utility in revealing new oncogenic pathways and connectivity of tumour suppressors with druggable targets.

    • Zenggang Li
    • , Andrei A. Ivanov
    •  & Haian Fu

  • Article
    | Open Access

    Long noncoding-RNAs have been linked to hepatocellular carcinoma (HCC) and some can be used as prognostic markers. Here the authors, by analysing RNA-seq in 60 clinical samples from 20 patients, provide a resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.

    • Yang Yang
    • , Lei Chen
    •  & Zhi John Lu

  • 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

    Organisms improve their fitness by adjusting their gene expression to the environment, for example bacteria scale the expression of metabolic enzymes near linearly to their growth rate. Here, the authors show that such linear scaling often maximizes growth rate, but that linear scaling is suboptimal under some conditions.

    • Benjamin D. Towbin
    • , Yael Korem
    •  & Uri Alon

  • Article
    | Open Access

    Kinetic models of microbial metabolism have great potential to aid metabolic engineering efforts, but the challenge of parameterization has so far limited them to core metabolism. Here, the authors introduce a genome-scale metabolic model of E. colimetabolism that satisfies fluxomic data for a wild-type and 25 mutant strains in various growth conditions.

    • Ali Khodayari
    •  & Costas D. Maranas

  • Article
    | Open Access

    Genetic circuits usually employ the same set of transcription factors which can act via repression or activation of the target promoter. Here the authors present dual activator-repressor switches, designed via directed evolution, for orthogonal logic gates and multi-input circuit architectures.

    • Andreas K. Brödel
    • , Alfonso Jaramillo
    •  & Mark Isalan

  • Article
    | Open Access

    High-throughput time-series data is increasingly available, yet estimating time-derivatives from such data can remain a challenge. Here, the authors provide a non-parametric method for inferring the first and second time-derivatives from multiple replicates of time-series data and for estimating errors in this inference and in any summary statistics.

    • Peter S. Swain
    • , Keiran Stevenson
    •  & Teuta Pilizota

  • Article
    | Open Access

    Crohn’s disease is associated with altered intestinal microbiota. Here, the authors show that the microbe Atopobium parvulumis associated with Crohn’s disease patients, triggers colitis in a mouse model, and that scavenging microbe-induced hydrogen sulfide improved symptoms in mice.

    • Walid Mottawea
    • , Cheng-Kang Chiang
    •  & Alain Stintzi

  • Article
    | Open Access

    Why do populations of highly similar T cells have heterogeneous division destinies in response to antigenic stimulus? Here the authors develop a multiplex-dye assay and a mathematical framework to test clonal heterogeneity and show distinction in division destiny is a result of inter-clonal variability as lineage imprinting ensures clones share similar proliferation fates.

    • J. M. Marchingo
    • , G. Prevedello
    •  & K. R. Duffy

  • Article
    | Open Access

    Nonlinearity in synthetic molecular circuits is usually achieved by manipulation of network topology or of production kinetics. Here, the authors achieve bistability and other nonlinear behaviours by manipulating the individual degradation rate laws of circuit components using saturable pathways.

    • Kevin Montagne
    • , Guillaume Gines
    •  & Yannick Rondelez

  • Article
    | Open Access

    Dysfunction in insulin secretion is a main driver of type 2 diabetes development. Here the authors monitor phosphoproteome modulation in cells stimulated with glucose and treated with drugs affecting glucose-mediated insulin secretion to reveal phosphorylation sites implicated in insulin secretion control and gene expression regulation.

    • Francesca Sacco
    • , Sean J. Humphrey
    •  & Matthias Mann

  • Article
    | Open Access

    Translating omics data sets into biological insight is one of the great challenges of our time. Here, the authors make headway by synchronising pairs of omics data types via invariants across conditions and by integrating datasets into a genome-scale model of E. coli metabolism and gene expression.

    • Ali Ebrahim
    • , Elizabeth Brunk
    •  & Bernhard O. Palsson

  • Article
    | Open Access

    Absolute concentration robustness (ACR), independence of the steady-state concentration of a molecule from the environment, is difficult to predict. Here, the authors derive a network structure-based necessary condition for ACR, and suggest that metabolites satisfying the condition are prevalent.

    • Jeanne M. O. Eloundou-Mbebi
    • , Anika Küken
    •  & Zoran Nikoloski

  • Article
    | Open Access

    Directed evolution is a powerful technique for generating improved biological systems through repeated rounds of mutagenesis and selection. Here the authors engineer the yeast retrotransposon Ty1 to enable the creation of large mutant libraries in vivoand use this system to generate improved variants of single enzymes and multigene pathways.

    • Nathan Crook
    • , Joseph Abatemarco
    •  & Hal S. Alper

  • Article
    | Open Access

    Assembling multiple biological components into synthetic lipid vesicles is a limiting step in the manufacture of biomimetic cell-like structures. Here the authors use fusogenic proteoliposomes of opposite charge for fast assembly of a minimal electron transport chain consisting of F1F0 ATP-synthase and the proton pump bo3-oxidase.

    • Robert R. Ishmukhametov
    • , Aidan N. Russell
    •  & Richard M. Berry

  • 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

    Many drugs are small molecule inhibitors of cell signalling. Through single cell analysis and mathematical modelling here the authors show that cell-to-cell variability diversifies inhibition response into digital and analogue, and that the two translate into distinct long-term functional responses.

    • Robert M. Vogel
    • , Amir Erez
    •  & Grégoire Altan-Bonnet

  • Article
    | Open Access

    How genetic diversity generates complex phenotypes along a continuum remains a fundamental question of biology. Here—applying the emerging SWATH proteomics technology—the authors describe a proteome wide association study (PWAS) of Drosophila wing size and identify functional protein clusters associated with this trait.

    • Hirokazu Okada
    • , H. Alexander Ebhardt
    •  & Ernst Hafen

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