Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Regulatory small RNA (sRNA) interact with mRNAs to regulate their stability, transcription, and translation via diverse mechanisms. Here, McKellar et al. apply RNase IIICLASH of multi-drug resistant Staphylococcus aureus under different culture conditions to link the network of RNA-RNA interactions to environmental conditions and find that the production of small membrane-permeabilizing toxins is strongly regulated by sRNAs.

    • Stuart W. McKellar
    • , Ivayla Ivanova
    •  & Sander Granneman

  • Article
    | Open Access

    Mechanistic models of how single cells respond to different perturbations can help integrate disparate big data sets or predict response to varied drug combinations. Here the authors develop a scalable, open-source pipeline for constructing and simulating large-scale, single-cell mechanistic models, an important building block for clinically-predictive mechanistic models and interpretable big data integration.

    • Cemal Erdem
    • , Arnab Mutsuddy
    •  & Marc R. Birtwistle

  • Article
    | Open Access

    Stable-isotope tracing allows quantifying metabolic activity by measuring isotopically labeled metabolites, but its metabolome coverage has been limited. Here, the authors develop a global isotope tracing approach with metabolome-wide coverage and use it to characterize metabolic activities in aging Drosophila.

    • Ruohong Wang
    • , Yandong Yin
    •  & Zheng-Jiang Zhu

  • Comment
    | Open Access

    Diagonal integration of multimodal single-cell data emerges as a trending topic. However, empowering diagonal methods for novel biological discoveries requires bridging huge gaps. Here, we comment on potential risks and future directions of diagonal integration for multimodal single-cell data.

    • Yang Xu
    •  & Rachel Patton McCord

  • Article
    | Open Access

    Small-scale bioreactors are increasingly used in quantitative biology. Here, the authors report ReacSight, a software solution to connect reactor arrays with sensitive measurement devices using low-cost pipetting robots and provide applications leveraging optogenetic control in yeast.

    • François Bertaux
    • , Sebastián Sosa-Carrillo
    •  & Gregory Batt

  • Article
    | Open Access

    A lack of understanding in the development and emergence of antimicrobial resistance presents as a problem for accurate infection diagnosis and treatment. Here, authors utilize Streptococcus pneumoniae and build a genome-wide atlas to understand the genes and interactions that contribute to altered drug susceptibility.

    • Dmitry Leshchiner
    • , Federico Rosconi
    •  & Tim van Opijnen

  • Article
    | Open Access

    Animals must reach the correct size during development, despite stochastic differences in their growth rate. Here, Stojanovski et al. show that a coupling of growth and development by an oscillatory timer buffers fluctuations in the growth of the nematode C. elegans to ensure its correct size.

    • Klement Stojanovski
    • , Helge Großhans
    •  & Benjamin D. Towbin

  • Article
    | Open Access

    Anti-cancer cytotoxic T cell responses largely vary among individuals. Here authors show, by stochastic modeling on high throughput T cell behavior and matched tumor spheroid fate data generated by a microfluidics system, that tumor killing is dependent on T cell cooperativity, which might contribute to the heterogeneity of T cell responses.

    • Gustave Ronteix
    • , Shreyansh Jain
    •  & Charles N. Baroud

  • 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

    Rubusoside and rebaudiosides are considered the next generation of sugar substitutes. In this article, the authors report the engineering of Saccharomyces cerevisiae, remodelling the complex metabolic networks by a modular engineering approach, obtaining rubusoside and rebaudiosides at titers of around 1.4 g/L and 100 mg/L, respectively.

    • Yameng Xu
    • , Xinglong Wang
    •  & Long Liu

  • 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

    Due to the complexity of the protein secretory pathway, strategy suitable for the production of a certain recombination protein cannot be generalized. Here, the authors construct a proteome-constrained genome-scale protein secretory model for yeast and show its application in the production of different misfolded or recombinant proteins.

    • Feiran Li
    • , Yu Chen
    •  & Jens Nielsen

  • Article
    | Open Access

    Current DNA-based data storage platforms encode information only in the nucleotide sequence. Here, the authors report a 2DDNA platform that can store data in both sequence context and backbone structure, and has improved image inpainting and enhancement via automatic discoloration detection and deep learning.

    • Chao Pan
    • , S. Kasra Tabatabaei
    •  & Olgica Milenkovic

  • Article
    | Open Access

    In theory, driven biological oscillators can display complex dynamic behaviors, but these are experimentally difficult to observe. Here the authors, using microfluidics, show that a synthetic cell-free gene oscillator displays period doubling and even quadrupling.

    • Lukas Aufinger
    • , Johann Brenner
    •  & Friedrich C. Simmel

  • Article
    | Open Access

    Quorum-sensing bacteria produce and secrete autoinducers that trigger a behavioral change in the population when reaching a certain threshold. Here, Bettenworth et al. show that autoinducer synthase gene expression in Sinorhizobium meliloti occurs in asynchronous stochastic pulses, and that physiological cues modulate pulse frequency and, consequently, response behavior dynamics. Frequency-modulated pulsing in autoinducer synthase gene expression thus represents a time-based mechanism for information integration and collective decision-making.

    • Vera Bettenworth
    • , Simon van Vliet
    •  & Anke Becker

  • Article
    | Open Access

    A major challenge in coronavirus vaccination and treatment is to counteract rapid viral evolution and mutations. Here the authors show that CRISPR-Cas13d can be used as a broad-spectrum antiviral to inhibit human coronaviruses, including new SARS-CoV-2 variants, combined with small molecule drugs for an enhanced antiviral effect in human primary cells.

    • Leiping Zeng
    • , Yanxia Liu
    •  & Lei S. Qi

  • Article
    | Open Access

    Global diversity trends in the fossil record vary regionally through time and space, affecting our ability to interpret macroevolutionary history. Here, the authors propose a method to eliminate spatial sampling bias, estimate origination and extinction rates, and generate diversity estimates, applying this method to the Late Permian to Early Jurassic marine fossil record.

    • Joseph T. Flannery-Sutherland
    • , Daniele Silvestro
    •  & Michael J. Benton

  • 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

    Multisystem inflammatory syndrome may occur in children following COVID-19 infection. Here, the authors analyze gene signatures to show that MIS-C shares the same host immune response as the pre-pandemic inflammatory syndrome of Kawasaki disease but is further along in the spectrum in disease severity

    • Pradipta Ghosh
    • , Gajanan D. Katkar
    •  & Debashis Sahoo

  • Article
    | Open Access

    In E. coli, FtsA and FtsZ control the place and time of cell division. Here, the authors use in vitro experiments to show how FtsA can follow FtsZ treadmilling and that downstream proteins form dynamic copolymers with FtsA to initiate division.

    • Philipp Radler
    • , Natalia Baranova
    •  & Martin Loose

  • Article
    | Open Access

    Light-oxygen-voltage (LOV) photoreceptors perceive blue light to elicit spatio-temporally defined cellular responses, and their signalling process has been extensively characterized. Here the authors report that the light signal is still transduced in the absence of a conserved Gln residue, thought to be key.

    • Julia Dietler
    • , Renate Gelfert
    •  & Andreas Möglich

  • Article
    | Open Access

    Single Nucleotide Polymorphisms (SNPs) affect cellular regulatory networks, and SNP co-occurrences contribute to disease pathogenesis in ulcerative colitis (UC). Here the authors introduce iSNP, a precision medicine pipeline that combines genomics and network biology approaches to uncover patient specific pathways affected in complex diseases.

    • Johanne Brooks-Warburton
    • , Dezso Modos
    •  & Tamas Korcsmaros

  • Article
    | Open Access

    The endosymbiotic theory posits that chloroplasts in eukaryotes arise from bacterial endosymbionts. Here, the authors engineer the yeast/cyanobacteria chimeras and show that the engineered cyanobacteria perform chloroplast-like functions to support the growth of yeast cells under photosynthetic conditions.

    • Jason E. Cournoyer
    • , Sarah D. Altman
    •  & Angad P. Mehta

  • Article
    | Open Access

    In microscopy, applications in which reactiveness is needed are multifarious. Here the authors report MicroMator, a Python software package for reactive experiments, which they use for applications requiring real-time tracking and light-targeting at the single-cell level.

    • Zachary R. Fox
    • , Steven Fletcher
    •  & Gregory Batt

  • Article
    | Open Access

    Identifying effective drug combinations to treat cancer is a challenging task, either experimentally or computationally. Here, the authors develop a bipartite network modelling approach to propose drug combination strategies in acute myeloid leukaemia using patient and cell line drug screening data.

    • Mohieddin Jafari
    • , Mehdi Mirzaie
    •  & Jing Tang

  • Article
    | Open Access

    Here, the authors simulate COVID-19 outbreaks on an empirical contact network derived from digital contact data collected on cruise ships. They model impacts of different control measures and find that combinations of measures, particularly vaccination and rapid antigen testing, are important for mitigating outbreaks.

    • Rachael Pung
    • , Josh A. Firth
    •  & Adam J. Kucharski

  • Article
    | Open Access

    T cell large granular lymphocytic leukemia (T-LGLL) is a lymphoproliferative disorder involving clonally expanded T cell clones and is not fully understood. Here the authors show that the rest of the immune repertoire is interconnected with the T-LGLL clonotype(s) and is more mature, cytotoxic and clonally restricted than in other cancers and autoimmune disorders.

    • Jani Huuhtanen
    • , Dipabarna Bhattacharya
    •  & Satu Mustjoki

  • Article
    | Open Access

    Alternative splicing (AS) is a highly-regulated post-transcriptional mechanism known to modulate isoform expression within genes and contribute to cell-type identity. Here, the authors present acorde, a pipeline that successfully leverages bulk long reads and single-cell data to confidently detect alternative isoform co-expression relationships.

    • Angeles Arzalluz-Luque
    • , Pedro Salguero
    •  & Ana Conesa

  • Article
    | Open Access

    Synthetic biology has enabled the design of strategies for bacteria-based cancer immunotherapy. Here the authors report the development of focused ultrasound-activatable therapeutic bacteria engineered to express anti-CTLA-4 and anti-PD-L1 nanobodies for cancer immunotherapy.

    • Mohamad H. Abedi
    • , Michael S. Yao
    •  & Mikhail G. Shapiro

  • 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

    “Mapping the dark matter of metabolism remains an open challenge that can be addressed globally and systematically by existing computational solutions. Here the authors present ATLASx, a repository of known and predicted enzymatic reaction, connecting millions of compounds to help synthetic biologists and metabolic engineers to design and explore metabolic pathways.”

    • Homa MohammadiPeyhani
    • , Jasmin Hafner
    •  & Vassily Hatzimanikatis

  • Article
    | Open Access

    Stability and tunability are two desirable properties of microbial consortia-based bioproduction. Here, the authors integrate a caffeate-responsive biosensor into two and three strains coculture system to achieve autonomous regulation of strain ratios for coniferol and silybin/isosiltbin production, respectively.

    • Xianglai Li
    • , Zhao Zhou
    •  & Qipeng Yuan

  • Article
    | Open Access

    Producing plant secondary metabolites by microbes is limited by the known enzymatic reactions. Here, the authors apply machine learning to predict missing link enzymes of benzylisoquinoline alkaloid (BIA) biosynthesis in Papaver somniferum, and validate the specialized activities through heterologous production.

    • Christopher J. Vavricka
    • , Shunsuke Takahashi
    •  & Tomohisa Hasunuma

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