Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Single cell growth rate variability has been difficult to understand. Here, the authors apply a generalization of flux balance analysis to single cells based on maximum entropy modeling, and find that growth rate fluctuations of E. coli reflect metabolic flux variability and growth sub-optimality, in turn highlighting information costs for growth optimization.

    • Daniele De Martino
    • , Anna MC Andersson
    •  & Gašper Tkačik

  • Article
    | Open Access

    Finding one’s way to a food source along a complex gradient is central to survival for many animals. Here, the authors report that in C. elegans, the distinct response dynamics of two sensory neurons to odor gradients can support a navigation model more efficient than the biased-random walk.

    • Eyal Itskovits
    • , Rotem Ruach
    •  & Alon Zaslaver

  • Article
    | Open Access

    Time series single cell expression data has large variance between time points and is challenging for analysis. Here, the authors develop a new dimension reduction and data visualization tool for large scale temporal scRNA-seq data which identifies trajectories and subpopulations.

    • Wuming Gong
    • , Il-Youp Kwak
    •  & Daniel J. Garry

  • Article
    | Open Access

    Repurposing approved drugs could accelerate treatment options for various diseases. Here, the authors use network proximity of disease gene products and drug targets in the human protein interactome to identify drug-disease associations for cardiovascular disease, and validate these using longitudinal healthcare data.

    • Feixiong Cheng
    • , Rishi J. Desai
    •  & Joseph Loscalzo

  • Article
    | Open Access

    Mitochondrial populations in cells may consist of heteroplasmic mixtures of mtDNA types, and their evolution through development, aging and generations is central to genetic diseases. Here the authors dissect these population dynamics using a large mouse-based data set to characterise the dynamics of heteroplasmy mean and variance throughout life and across generations.

    • Joerg P. Burgstaller
    • , Thomas Kolbe
    •  & Iain G. Johnston

  • Article
    | Open Access

    Control of transgene expression should ideally be easy and with minimal side effects. Here the authors present a synthetic biology-based approach in which the caffeine in coffee regulates a genetic circuit controlling glucagon-like peptide 1 expression in diabetic mice.

    • Daniel Bojar
    • , Leo Scheller
    •  & Martin Fussenegger

  • Article
    | Open Access

    Generating artificial cells able to carry out metabolic activities out-of-equilibrium is a current challenge in synthetic biology. Here the authors use a microfluidic platform for integration and analysis of minimal metabolic reactions in artificial microcompartments formed of water-in-oil droplets.

    • Thomas Beneyton
    • , Dorothee Krafft
    •  & Jean-Christophe Baret

  • Article
    | Open Access

    Diatoms account for 40% of marine primary production and their sensitivity to ocean acidification could have ecosystem-wide consequences. Here, the authors developed and applied a stress test, demonstrating that resilience of diatoms increases significantly in ocean acidification conditions.

    • Jacob J. Valenzuela
    • , Adrián López García de Lomana
    •  & Nitin S. Baliga

  • Article
    | Open Access

    Nodes with high centrality in protein–protein interaction (PPI) networks are known to be essential in some organisms. Here, the authors in contrast find that in the interactome of A. thaliana central nodes are enriched in conditional and immune phenotypes and are preferred targets of pathogens.

    • Hadia Ahmed
    • , T. C. Howton
    •  & M. Shahid Mukhtar

  • 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

    How bacteria migrate collectively despite individual phenotypic variation is not understood. Here, the authors show that cells spontaneously sort themselves within moving bands such that variations in individual tumble bias, a determinant of gradient climbing speed, are compensated by the local gradient steepness experienced by individuals.

    • X. Fu
    • , S. Kato
    •  & T. Emonet

  • Article
    | Open Access

    The Sc2.0 project has built the Synthetic Chromosome Rearrangement and Modification by LoxP-mediated Evolution (SCRaMbLE) system into their synthetic chromosomes. Here the authors use SCRaMbLE to rapidly develop, diversify and screen strains for diverse production and growth characteristics.

    • B. A. Blount
    • , G-O. F. Gowers
    •  & T. Ellis

  • Article
    | Open Access

    The use of synthetic chromosomes and the recombinase-based SCRaMbLE system could enable rapid strain evolution through massive chromosome rearrangements. Here the authors present ReSCuES, which uses auxotrophic markers to rapidly identify yeast with rearrangements for strain engineering.

    • Zhouqing Luo
    • , Lihui Wang
    •  & Junbiao Dai

  • Article
    | Open Access

    SCRaMbLE has been used to rearrange synthetic chromosomes that have been introduced into host yeast. Here the authors produce semi-synthetic heterozygous diploid strains for rapid selection of phenotypes and map the rearrangements underlying selected phenotypes such as thermoresistance and caffeine resistance.

    • Michael J. Shen
    • , Yi Wu
    •  & Jef D. Boeke

  • Review Article
    | Open Access

    CRISPR has rapidly become an indispensable tool for biological research. Here Mazhar Adli reviews the current toolbox for editing and manipulating the genome and looks toward future developments in this fast moving field.

    • Mazhar Adli

  • Article
    | Open Access

    Synthetic biology principles are often used to design circuits that tune gene expression in response to changes in intracellular environments. Here the authors design a modular platform for intracellular protein sensing devices with transcriptional output.

    • Velia Siciliano
    • , Breanna DiAndreth
    •  & Ron Weiss

  • Article
    | Open Access

    Bacterial populations communicate with AI-2 signaling molecules, helping to coordinate biofilm development and other group behaviors. Here the authors design a genetic circuit for mammalian cells that allows them to sense bacterial populations and interfere with quorum communication.

    • Ferdinand Sedlmayer
    • , Dennis Hell
    •  & Martin Fussenegger

  • Article
    | Open Access

    Robust perfect adaptation (RPA), the ability of a system to return to its pre-stimulus state in the presence of a new signal, enables organisms to respond to further changes in stimuli. Here, the authors identify the modular structure of the full set of network topologies that can confer RPA on complex networks.

    • Robyn P. Araujo
    •  & Lance A. Liotta

  • Article
    | Open Access

    Cell protrusion dynamics are heterogeneous at the subcellular level, but current analyses operate at the cellular or ensemble level. Here the authors develop a computational framework to quantify subcellular protrusion phenotypes and reveal the underlying actin regulator dynamics at the leading edge.

    • Chuangqi Wang
    • , Hee June Choi
    •  & Kwonmoo Lee

  • Article
    | Open Access

    The bacterial transcription-repair coupling factor Mfd displaces stalled RNA polymerase (RNAP) by promoting transcription termination at sites of DNA lesions. Here the authors find—using single molecule imaging in live Escherichia coli—that RNAP stalls frequently during transcription, and needs to be rescued by Mfd during normal growth.

    • Han N. Ho
    • , Antoine M. van Oijen
    •  & Harshad Ghodke

  • Article
    | Open Access

    Bacterial promoters initiate gene transcription and have distinct sequence features. Here, the authors show that random sequences that contain no information are just on the verge of functioning as promoters in Escherichia coli.

    • Avihu H. Yona
    • , Eric J. Alm
    •  & Jeff Gore

  • Article
    | Open Access

    VIPER has been successfully used to assess the regulatory activities of proteins from gene expression data, but its dependence on tissue-specific molecular profiles limits its applicability. MetaVIPER, introduced here, enables inference of the protein activities in orphan tissues and single cells.

    • Hongxu Ding
    • , Eugene F. Douglass Jr.
    •  & Andrea Califano

  • Article
    | Open Access

    The translation of heterologous proteins places a burden on host cell resources, affecting growth and productivity. Here the authors develop a cell-free assay to measure resource consumption and predict in vivo burden.

    • Olivier Borkowski
    • , Carlos Bricio
    •  & Tom Ellis

  • Article
    | Open Access

    Sign epistasis clearly constrains evolution, but its causes are difficult to decipher. Here, the authors study epistasis in a signalling cascade, and arrive at a general criterion and understanding of sign epistasis as arising from the inherent hierarchy between signalling cascade components.

    • Philippe Nghe
    • , Manjunatha Kogenaru
    •  & Sander J. Tans

  • Article
    | Open Access

    Two-component systems are a major family of signal transduction pathways and a rich source of sensors for biotechnology. Here, the authors develop a general method for rationally tuning two-component system input detection thresholds via specific point mutations in sensor histidine kinase proteins.

    • Brian P. Landry
    • , Rohan Palanki
    •  & Jeffrey J. Tabor

  • Article
    | Open Access

    Biochemical processes require both high sensitivity and low fluctuation which is incompatible with the fluctuation dissipation theorem. Here Fei et al. model biochemical oscillators to show how free energy dissipation leads to both a suppression of phase fluctuation and an enhancement of phase sensitivity.

    • Chenyi Fei
    • , Yuansheng Cao
    •  & Yuhai Tu

  • Article
    | Open Access

    Publicly available RNA-seq data is provided mostly in raw form, resulting in a barrier for integrative analyses. Here, Lachmann et al. develop a high-throughput processing infrastructure and search database (ARCHS4) that provides processed RNA-seq data for 187,946 publicly available mouse and human samples to support exploration and reuse.

    • Alexander Lachmann
    • , Denis Torre
    •  & Avi Ma’ayan

  • Article
    | Open Access

    Compartmentalization of proteins can potentially increase the productivity of engineered metabolic pathways. Here the authors use encapsulins to build non-endogenous organelles in Saccharomyces cerevisiae.

    • Yu Heng Lau
    • , Tobias W. Giessen
    •  & Pamela A. Silver

  • Article
    | Open Access

    Exosomes function as intercellular information transmitters and are candidates for delivery of therapeutic agents. Here the authors present EXOtic, a synthetic biology device for in-situ production of designer exosomes and demonstrate in vivo application in models of Parkinson's disease.

    • Ryosuke Kojima
    • , Daniel Bojar
    •  & Martin Fussenegger

  • Article
    | Open Access

    Efficient assimilation of nutrients is essential for the production of value-added products in microbial fermentation. Here the authors design a semi-synthetic xylose regulon to improve growth characteristics of Saccharomyces cerevisiae on this non-native sugar.

    • Venkatesh Endalur Gopinarayanan
    •  & Nikhil U. Nair

  • Article
    | Open Access

    The suprachiasmatic nucleus (SCN) has been thought of as the master circadian clock, but peripheral circadian clocks do exist. Here, the authors show that the choroid plexus displays oscillations more robust than the SCN and that can be described as a Poincaré oscillator with negative twist.

    • Jihwan Myung
    • , Christoph Schmal
    •  & Toru Takumi

  • 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

    G protein-coupled receptors (GPCRs) activate intracellular signalling pathways upon extracellular stimulation. Here authors record single cell responses of GPCR signalling which allows the direct estimation of its channel capacity for each cell along with the reproducibility of its response.

    • Amiran Keshelava
    • , Gonzalo P. Solis
    •  & Vladimir L. Katanaev

  • Article
    | Open Access

    The domestication of plants and animals causes genomic changes underlying various morphologic, physiologic and behavioral changes. Here, Naval-Sanchez et al. provide a ChIP-Seq validated comparative functional annotation of the sheep genome, and show widespread evolution of proximal regulatory elements.

    • Marina Naval-Sanchez
    • , Quan Nguyen
    •  & James Kijas

  • Article
    | Open Access

    Single cell RNA-sequencing analysis poses challenges in replication due to technical biases and analytic variability among bioinformatics pipelines. Here, Crow et al develop MetaNeighbor for measuring cell-type replication across datasets, and use it to identify marker genes for neuron subtypes with evidence of replication.

    • Megan Crow
    • , Anirban Paul
    •  & Jesse Gillis

  • Article
    | Open Access

    Biological self-organization uses hierarchical induction of gene expression but this has not been exploited by synthetic biology. Here the authors use an AND gate based on a split T7 RNA polymerase to organize programmed hierarchical patterning of gene expression across a bacterial population.

    • Christian R. Boehm
    • , Paul K. Grant
    •  & Jim Haseloff

  • Article
    | Open Access

    Current methods for prioritization of non-coding genetic risk variants are based on sequence and chromatin features. Here, Gao et al. develop ARVIN, which predicts causal regulatory variants using disease-relevant gene-regulatory networks, and validate this approach in reporter gene assays.

    • Long Gao
    • , Yasin Uzun
    •  & Kai Tan

  • Article
    | Open Access

    Competition between synthetic genetic circuits and host genes for shared resources can complicate circuit design and lead to failure. Here the authors demonstrate, mathematically and experimentally, the use of orthogonal ribosomes to decouple competing genes.

    • Alexander P. S. Darlington
    • , Juhyun Kim
    •  & Declan G. Bates

  • Article
    | Open Access

    Biomarkers of the tipping point before metastasis in hepatocellular carcinoma (HCC) could help stratify patient treatment. Here, the authors study dynamic network biomarkers to identify CALM3 as a potential suppressor of metastasis, the level of which can predict overall survival and relapse-free survival in postoperative HCC.

    • Biwei Yang
    • , Meiyi Li
    •  & Jinglin Xia

  • 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

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