Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Microbiomes designed with predictable functions could enable broad applications in health, agriculture and bioprocessing. Here the authors use a model-guided approach to design diverse synthetic human gut communities for production of the health-relevant metabolite butyrate.

    • Ryan L. Clark
    • , Bryce M. Connors
    •  & Ophelia S. Venturelli

  • Article
    | Open Access

    Evolution selects for the fittest but must operate within the realm of the physically possible. Here, the authors present a theoretical framework that allows them to explore how ten abiotic constraints can shape the operation, regulation, and adaptation of metabolism in E. coli.

    • Amir Akbari
    • , James T. Yurkovich
    •  & Bernhard O. Palsson

  • Article
    | Open Access

    How dynamic transcription factors temporally interact to regulate stress survival in yeast is currently unclear. Here the authors integrate single-cell imaging, RNA-seq, and modeling to identify a new cell fate control mechanism mediated by temporal redundancy modulation during yeast stress response.

    • Yan Wu
    • , Jiaqi Wu
    •  & Yihan Lin

  • Article
    | Open Access

    Rewriting genomes allows for complete annotation of gene regulatory elements. Here the authors compare endogenous and rewritten segments of a genome and find extensive transcriptional changes, based on which they formulate design principles that aid in the programming of biological systems.

    • Mariëlle J. F. M. van Kooten
    • , Clio A. Scheidegger
    •  & Beat Christen

  • Article
    | Open Access

    Combining scRNA-seq with spatial information to enable the reconstruction of spatially-resolved cell atlases is challenging for rare cell types. Here the authors present ClumpSeq, an approach for sequencing small clumps of tissue attached cells, and apply it to establish spatial atlases for all secretory cell types in the small intestine.

    • Rita Manco
    • , Inna Averbukh
    •  & Shalev Itzkovitz

  • Article
    | Open Access

    The functional consequences of variation in human regulatory DNA depend on the local chromatin environment and the cell/tissue context. Here the authors use highly diverged hybrid mice to study genetic effects on DNA accessibility in vivo across multiple cell and tissue types.

    • Jessica M. Halow
    • , Rachel Byron
    •  & Matthew T. Maurano

  • Article
    | Open Access

    The ability to design functional sequences is central to protein engineering and biotherapeutics. Here the authors introduce a deep generative alignment-free model for sequence design applied to highly variable regions and design and test a diverse nanobody library with improved properties for selection experiments.

    • Jung-Eun Shin
    • , Adam J. Riesselman
    •  & Debora S. Marks

  • Article
    | Open Access

    Data-rich networks can be difficult to interpret beyond a certain size. Here, the authors introduce a platform that uses virtual reality to allow the visual exploration of large networks, while interfacing with data repositories and other analytical methods to improve the interpretation of big data.

    • Sebastian Pirch
    • , Felix Müller
    •  & Jörg Menche

  • Article
    | Open Access

    Encoding data in DNA is a promising approach to high density data storage. Here the authors present a prototype sequencing-free method that uses the spatial orientation of DNA strands with super-resolution microscopy readout.

    • George D. Dickinson
    • , Golam Md Mortuza
    •  & William L. Hughes

  • Article
    | Open Access

    Mucosal-associated invariant T (MAIT) cells are key in immunity and diseases, but how their effector polarization is controlled is still unclear. Here, the authors show that an IL-1β/IL-23/mTORC2 axis is essential for the induction of IL-17-producing MAIT17, while an IL-2/IL-15/mTORC1 axis is important for the homeostasis of IFN-γ-producing MAIT1.

    • Huishan Tao
    • , Yun Pan
    •  & Xiao-Ping Zhong

  • Article
    | Open Access

    Engineered microbial communities can divide labour between their members and interface with natural microbiomes. Here the authors demonstrate how a single toxin producing engineered strain can tune the composition of a two-strain community.

    • Alex J. H. Fedorec
    • , Behzad D. Karkaria
    •  & Chris P. Barnes

  • Article
    | Open Access

    Crohn’s disease results from transmural inflammation in the gut, but analyses of local immune populations are still lacking. Here, the authors show, by combining multiple single-cell approaches, that intraepithelial and lamina propria T cells are heterogenous, show unique phenotypes, and exhibit altered subsets upon inflammation.

    • Natalia Jaeger
    • , Ramya Gamini
    •  & Marco Colonna

  • Article
    | Open Access

    Inducible gene expression systems should minimise leaky output and offer a large achievable range of expression. Here, the authors regulate transcription and translation together to suppress noise and create digital-like responses, while maintaining a large expression range in vivo and in vitro.

    • F. Veronica Greco
    • , Amir Pandi
    •  & Thomas E. Gorochowski

  • Article
    | Open Access

    Network motif models focus on small sub-networks in biological systems to quantitatively describe overall behavior but they often overlook time delays. Here, the authors systematically examine the most common network motifs via delay differential equations (DDE), often leading to more concise descriptions.

    • David S. Glass
    • , Xiaofan Jin
    •  & Ingmar H. Riedel-Kruse

  • Article
    | Open Access

    The top down cheminformatics method is usually used for the reconstitution of heterologous pathway to produce plant natural products. Here, the authors report a bottom up computational workflow for the identification of potential products and the enzymes required to make them in a noscapine pathway in yeast.

    • Jasmin Hafner
    • , James Payne
    •  & Christina Smolke

  • Article
    | Open Access

    CRISPRi allows for the simultaneous control of many genes, however the sgRNAs compete for binding to dCas9. Here the authors design a dCas9 concentration regulator to allow independent regulation of multiple genes.

    • Hsin-Ho Huang
    • , Massimo Bellato
    •  & Domitilla Del Vecchio

  • Article
    | Open Access

    Transcription factor over-expression-based cellular conversion methods often endure low conversion efficiency. Here the authors show how to increase conversion efficiency by combining a computational method for prioritizing more efficient TF combinations with a transposon-based genomic integration system for delivery.

    • Sascha Jung
    • , Evan Appleton
    •  & Antonio del Sol

  • Article
    | Open Access

    Short read RNA sequencing and DNA sequence contain useful information for profiling polyadenylation sites, but each also possesses inherent limitations when examined independently. Aptardi combines these data and significantly improves annotation of polyadenylation sites in the expressed transcriptome.

    • Ryan Lusk
    • , Evan Stene
    •  & Laura M. Saba

  • Article
    | Open Access

    The SRC Homology 3 (SH3) domains mediate protein–protein interactions (PPIs). Here, the authors assess the SH3-mediated PPIs in yeast, and show that the identity of the protein itself and the position of the SH3 both affect the interaction specificity and thus the PPI-dependent cellular functions.

    • Ugo Dionne
    • , Émilie Bourgault
    •  & Christian R. Landry

  • Comment
    | Open Access

    Synthetic metagenomics could potentially unravel the complexities of microbial ecosystems by revealing the simplicity of microbial communities captured in a single cell. Conceptionally, a yeast cell carrying a representative synthetic metagenome could uncover the complexity of multi-species interactions, illustrated here with wine ferments.

    • Ignacio Belda
    • , Thomas C. Williams
    •  & Isak S. Pretorius

  • Article
    | Open Access

    The authors generated a Synthetic Morphogenic Membrane System by encapsulating a dynamic microtubule aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized liposomes. This reconstitution of artificial proto-cells reveals how non-equilibrium phenomena affect cellular information processing in morphogenesis.

    • Konstantin Gavriljuk
    • , Bruno Scocozza
    •  & Philippe I. H. Bastiaens

  • Article
    | Open Access

    Both ecological opportunity and phenotypic modularity have been suggested to facilitate adaptive radiations. Feiner et al. show that Anolis lizards evolved a new modularity structure in their island adaptive radiation, but that this modularity did not produce the same extreme diversification when Anolis returned to the mainland.

    • Nathalie Feiner
    • , Illiam S. C. Jackson
    •  & Tobias Uller

  • Article
    | Open Access

    Epigenetic mechanisms associated with the differentiation state of cancer cells and their heterogeneity influence tumor responses to oncogene-targeted therapies. In this study, the authors perform an epigenetic compound screen and single-cell analysis in BRAF-mutant melanoma cells to identify compounds that block three distinct drug-tolerant epigenetic states associated with either one of the lysine-specific histone demethylases Kdm1a or Kdm4b, or BET proteins.

    • Mehwish Khaliq
    • , Mohan Manikkam
    •  & Mohammad Fallahi-Sichani

  • Article
    | Open Access

    Industrial sugarcane ethanol fermentations are accomplished by a microbial community dominated by S. cerevisiae and co-occurring bacteria. Here, the authors investigate how microbial community composition contributes to community function and reveal the role of acetaldehyde in improving yeast growth rate and ethanol production.

    • Felipe Senne de Oliveira Lino
    • , Djordje Bajic
    •  & Morten Otto Alexander Sommer

  • Article
    | Open Access

    The cost and complexity of whole genome sequencing limits its use in identifying and validating sequences used for genetic engineering and synthetic biology. Here the authors present Prymetime, an integrated workflow to sequence engineered strains and identify engineering in metagenomes.

    • Joseph H. Collins
    • , Kevin W. Keating
    •  & Eric M. Young

  • Article
    | Open Access

    A quantitative assessment of promoter function can improve the precision of cellular engineering. Here the authors develop a method to simultaneously count plasmid DNA, RNA transcripts and protein expression in single living bacteria.

    • Bin Shao
    • , Jayan Rammohan
    •  & Christopher A. Voigt

  • Review Article
    | Open Access

    DNA has the potential to store vast amounts of data but it is subject to physical decay. In this Perspective, the authors propose that the stability of DNA should be a key consideration in how it is used for data storage.

    • Karishma Matange
    • , James M. Tuck
    •  & Albert J. Keung

  • Article
    | Open Access

    The cell source and dynamics of Notch ligands during the regulation of muscle stem cells is unclear. Here, the authors show that the Notch ligand Dll1 has to oscillate in order to control the balance between self-renewal and differentiation of muscle stem cells, with Hes1 acting as transcriptional pacemaker for the oscillatory network.

    • Yao Zhang
    • , Ines Lahmann
    •  & Carmen Birchmeier

  • Article
    | Open Access

    Understanding how cells discriminate between stimuli is an ongoing challenge. Here, the authors propose a mathematical framework for inferring the mutual information encoded in temporal signaling dynamics and use it to study how information is transmitted over time in response to different stimuli in NFκB, MAPK and p53 signaling pathways.

    • Ying Tang
    • , Adewunmi Adelaja
    •  & Alexander Hoffmann

  • Article
    | Open Access

    Transmission by pre-symptomatic and asymptomatic viral carriers makes intervention and containment of the COVID-19 extremely challenging. Here, the authors construct an epidemiological model that focuses on transmission around the symptom onset, exploring specific transmission control measures.

    • Liang Tian
    • , Xuefei Li
    •  & Lei-Han Tang

  • Article
    | Open Access

    Kinases drive fundamental changes in cell state, but predicting kinase activity based on substrate-level changes can be challenging. Here the authors introduce a computational framework that utilizes similarities between substrates to robustly infer kinase activity.

    • Serhan Yılmaz
    • , Marzieh Ayati
    •  & Mehmet Koyutürk

  • Article
    | Open Access

    Honey bee workers take on different tasks for the colony as they age. Here, the authors develop a method to extract a descriptor of the individuals’ social networks and show that interaction patterns predict task allocation and distinguish different developmental trajectories.

    • Benjamin Wild
    • , David M. Dormagen
    •  & Tim Landgraf

  • Article
    | Open Access

    The thymus supports T cell immunity by providing the environment for thymocyte differentiation. Here the authors profile human thymic stroma at the single cell level, identifying ionocytes as a new medullary population and defining tissue specific antigen expression in multiple stromal cell types.

    • Jhoanne L. Bautista
    • , Nathan T. Cramer
    •  & Audrey V. Parent

  • 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

    Establishing protein gradients for asymmetric cell division is fundamental across all kingdoms of life. Here the authors construct asymmetric cell division in E. coli by localizing the expression of RNA polymerase using an orthogonal unipolar scaffold, and restricting diffusion of its products.

    • Da-Wei Lin
    • , Yang Liu
    •  & Hsiao-Chun Huang

  • Article
    | Open Access

    p53 mediates the response to irradiation, however, tissues with similar levels of p53 have different radiation sensitivities. Here, the authors show that the in vivo p53 dynamics varies in these tissues after radiation, and the use of Mdm2 inhibitor to sustain p53 activity enhances radiosensitivity.

    • Jacob Stewart-Ornstein
    • , Yoshiko Iwamoto
    •  & Galit Lahav

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