Systems biology articles within Nature Communications

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  • Article
    | Open Access

    Elucidating the gastroesophageal junction’s development is key to comprehending its disease susceptibility. Here, the authors mapped its development, uncovering cellular diversity and interaction dynamics using advanced spatiotemporal single-cell analysis.

    • Naveen Kumar
    • , Pon Ganish Prakash
    •  & Cindrilla Chumduri

  • Perspective
    | Open Access

    Engineering biology is a dynamic field that uses gene editing, synthesis, assembly, and engineering to design new or modified biological systems. Here the authors discuss the policy considerations and interventions needed to support a role for engineering biology in climate change mitigation.

    • Jonathan Symons
    • , Thomas A. Dixon
    •  & Isak S. Pretorius

  • Article
    | Open Access

    The unification of decision-making, communication, and memory would enable the programming of intelligent biotic systems. Here, the authors achieve this goal by engineering E. coli chassis cells with an array of inducible recombinases that mediate diverse genetic programs.

    • Brian D. Huang
    • , Dowan Kim
    •  & Corey J. Wilson

  • Article
    | Open Access

    The development of the human cerebellum is not well understood. Here, the authors analyse a large sample of neuroimaging scans from children and adolescents to develop growth models of the cerebellum which mirror age-related developmental trajectories of behaviour and function.

    • Carolin Gaiser
    • , Rick van der Vliet
    •  & Ryan L. Muetzel

  • Article
    | Open Access

    Production of proteins at scale and affordable cost has been a major need of the biotech sector for the last several decades. Here the authors present a design algorithm called UNILIB for boosting gene expression in eukaryotic cells developed using an oligo-library and machine learning approach, validated in both yeast and mammalian cells using unseen sequences.

    • Inbal Vaknin
    • , Or Willinger
    •  & Roee Amit

  • Article
    | Open Access

    Bispecific antibody architecture is often important for function but rarely optimized. Here, authors present a modular approach to assemble bispecifics in varied formats using a SpyTag/SpyCatcher approach called SpyMask, and build anti-HER2 bispecifics whose activities depend on binder orientation and bispecific geometry.

    • Claudia L. Driscoll
    • , Anthony H. Keeble
    •  & Mark R. Howarth

  • Article
    | Open Access

    Targeting the files containing content-of-interest is a challenge in DNA data storage. Here, the authors develop a CRISPR-powered search engine to quantitatively identify the keyword in files stored in DNA.

    • Jiongyu Zhang
    • , Chengyu Hou
    •  & Changchun Liu

  • Article
    | Open Access

    While tricarboxylic acid cycle (TCA cycle) is required for heterotrophic microbes, it reduces carbon yield of industrial products due to the release of excess CO2. Here, the authors construct an E. coli strain without a functional TCA cycle and demonstrate its feasibility as a chassis strain for production of four separate compounds.

    • Hang Zhou
    • , Yiwen Zhang
    •  & Baixue Lin

  • Article
    | Open Access

    Machine learning applied to large compendia of transcriptomic data has enabled the decomposition of bacterial transcriptomes to identify independently modulated sets of genes. Here the authors present iModulon-based engineering for precise identification of genes for cross-species function transfer to streamline synthetic biology for strain development and biomanufacturing.

    • Donghui Choe
    • , Connor A. Olson
    •  & Bernhard O. Palsson

  • Article
    | Open Access

    This work leverages a new diet database and six long term monitoring efforts of 361 taxa to build comparable pre- and post-heatwave ecosystem models. The study provides empirical demonstration of changes in ecosystem-wide patterns of energy flux and biomass in response to marine heatwaves.

    • Dylan G. E. Gomes
    • , James J. Ruzicka
    •  & Joshua D. Stewart

  • Article
    | Open Access

    Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

    • Shixuan Liu
    • , Camille Ezran
    •  & James E. Ferrell Jr.

  • Article
    | Open Access

    Mass spectrometry-based proteomics faces the challenge of processing vast data amounts. Here, the authors introduce AlphaPept, an open-source, Python-based framework that offers high speed analysis and easy integration for large-scale proteome analysis.

    • Maximilian T. Strauss
    • , Isabell Bludau
    •  & Matthias Mann

  • Article
    | Open Access

    Gene expression is inherently dynamic, due to complex regulation and stochastic biochemical events. Here the authors train a deep neural network to predict and dynamically control gene expression in thousands of individual bacteria in real-time which they then apply to control antibiotic resistance and study single-cell survival dynamics.

    • Jean-Baptiste Lugagne
    • , Caroline M. Blassick
    •  & Mary J. Dunlop

  • Article
    | Open Access

    Cardiac macrophage contributes to the onset of cardiac fibrosis, but the underneath mechanisms remain unclear. Here the authors show that mouse cardiac macrophages from circulating monocytes may trans-differentiate into myofibroblast under hypertensive conditions for fibrosis development, with an AKLBH5/IL11 molecular axis modulating this macrophage-to-myofibroblast transition.

    • Tao Zhuang
    • , Mei-Hua Chen
    •  & Cheng-Chao Ruan

  • Article
    | Open Access

    The soil microbiome communicates with plant roots using a chemical language. Here, using p-coumaroyl-homoserine lactone as the synthetic communication signal, the authors demonstrate programmable microbe-to-plant communication from the sender in the soil bacteria to a receiver in the plant.

    • Alice Boo
    • , Tyler Toth
    •  & Christopher A. Voigt

  • Article
    | Open Access

    Conventional blue denim dyeing has both environmental and health-related consequences. Here, Bidart et al. use enzyme engineering to develop a viable method for the bulk production of indican and demonstrate dying processes which could significantly reduce the negative consequences of this billion-dollar industry.

    • Gonzalo Nahuel Bidart
    • , David Teze
    •  & Ditte Hededam Welner

  • Article
    | Open Access

    Recent protein design methods rely on large neural networks, yet it is unclear which dependencies are critical for determining function. Here, authors show that learning the per residue mutation preferences, without considering interactions, enables design of functional and diverse protein variants.

    • David Ding
    • , Ada Y. Shaw
    •  & Debora S. Marks

  • Article
    | Open Access

    Interfacing living systems with electronics for biosensing and biocomputing applications is challenging. Here, Gao et al. present hybrid transistors with electroactive bacteria capable of extracellular electron transfer, enabling transduction of biological computations to electrical readouts.

    • Yang Gao
    • , Yuchen Zhou
    •  & Benjamin K. Keitz

  • Article
    | Open Access

    Kinetic modeling of in vitro enzymatic reaction networks (ERNs) is severely hampered by the lack of training data. Here, authors introduce a methodology that combines an active learning-like approach and flow chemistry to create optimized datasets for an intricate ERN.

    • Bob van Sluijs
    • , Tao Zhou
    •  & Wilhelm T. S. Huck

  • Review Article
    | Open Access

    Engineering the form and function of root systems and their associated microbiota could provide a means to mitigate adverse climate-driven effects. Here, the authors review the recent developments in plant and rhizobacterial synthetic biology and highlight engineering targets for applications in root systems and rhizosphere.

    • Carin J. Ragland
    • , Kevin Y. Shih
    •  & José R. Dinneny

  • Article
    | Open Access

    Surgery poses significant risks for patients, with attempts to mitigate these risks using multimodal perioperative care pathways. Here, the authors show that preoperative hypercaloric carbohydrate drinks not only alleviate surgical stress but also demonstrates the replicability of this protection using FGF21 treatment alone.

    • Thomas Agius
    • , Raffaella Emsley
    •  & Alban Longchamp

  • Article
    | Open Access

    Age-associated myometrial dysfunction can cause complications during pregnancy and labor. Here, the authors report that aging myometrium is characterized by diminished contractile capillary cells, altered gene expression, and disrupted cellular communication leading to impaired angiogenesis, increased fibrosis and inflammation.

    • Paula Punzon-Jimenez
    • , Alba Machado-Lopez
    •  & Aymara Mas

  • Article
    | Open Access

    Achieving genetic circuits on single DNA molecules could have varied applications. Here, authors observed proteins emerging from single DNA molecules through coupled transcription-translation complexes, and show that nascent proteins lingered on DNA, regulating cascaded reactions on the same DNA and allowing the design of a pulsatile genetic circuit.

    • Ferdinand Greiss
    • , Nicolas Lardon
    •  & Roy Bar-Ziv

  • Article
    | Open Access

    Batch effects hinder multi-sample single-cell data analyses. Here, authors present STACAS, a scalable single-cell RNA-seq data integration tool that uses prior cell type knowledge to preserve biological variability, demonstrating robustness to noisy input cell type labels.

    • Massimo Andreatta
    • , Léonard Hérault
    •  & Santiago J. Carmona

  • Article
    | Open Access

    In contrast to their clinical success as inhibitors and targeting agents, antibodies have generally been ineffective as receptor agonists. Here, Romei et al. leverage a natural homotypic interface to tune antibody geometry, enabling optimization of agonist activity for multiple therapeutic targets.

    • Matthew G. Romei
    • , Brandon Leonard
    •  & Greg A. Lazar

  • Article
    | Open Access

    Xanthohumol is a prenylated flavonoid produced by hops and is an important flavor substance in beer. Here, the authors engineer brewing yeast for the de novo biosynthesis of xanthohumol from glucose by balancing the three parallel biosynthetic pathways.

    • Shan Yang
    • , Ruibing Chen
    •  & Yongjin J. Zhou

  • Article
    | Open Access

    Current cell annotation methods using high-plex spatial proteomics data are resource intensive and demand iterative expert input. Here, the authors present MAPS (Machine learning for Analysis of Proteomics in Spatial biology), an approach that facilitates rapid and precise cell type identification with human-level accuracy from spatial proteomics data.

    • Muhammad Shaban
    • , Yunhao Bai
    •  & Faisal Mahmood

  • Article
    | Open Access

    Automated and non-invasive mammalian cell analysis is currently lagging behind due to a lack of methods suitable for a variety of cell lines and applications. Here the authors develop a high throughput non-invasive method for tracking suspension and adhesion mammalian cell growth based on plate reader measures to characterize engineered cell lines.

    • Alice Grob
    • , Chiara Enrico Bena
    •  & Francesca Ceroni

  • Article
    | Open Access

    Cheese fermentation and flavour formation are the result of complex biochemical reactions driven by the activity of multiple microorganisms. Here, the authors identify microbial interactions as a mechanism underlying flavour formation in Cheddar cheese.

    • Chrats Melkonian
    • , Francisco Zorrilla
    •  & Ahmad A. Zeidan

  • Review Article
    | Open Access

    As synthetic biology permeates society, the signal processing circuits in engineered living systems must be customized to meet practical demands. In this review, the authors outline design strategies for the DNA, RNA, and protein-level circuits and the hybrid “multi-level” circuits.

    • Yuanli Gao
    • , Lei Wang
    •  & Baojun Wang

  • Article
    | Open Access

    Co-fractionation mass spectrometry (CF-MS) is a powerful technique for mapping protein interactions under physiological conditions. Here, the authors uniformly re-process 411 CF-MS experiments and carry out meta-analyses of protein abundance, protein-protein interactions, and phosphorylation sites in the resulting resource.

    • Michael A. Skinnider
    • , Mopelola O. Akinlaja
    •  & Leonard J. Foster

  • Article
    | Open Access

    Little is known about how malaria parasites adapt the speed of their development to their mosquito vectors. Using an evolutionary modelling framework, this study predicts that the metabolic status of mosquitoes shapes the parasites’ life-history strategies and transmission dynamics.

    • Paola Carrillo-Bustamante
    • , Giulia Costa
    •  & Elena A. Levashina

  • Article
    | Open Access

    Reconstructing transcriptome-wide spatially-resolved gene expressions requires modelling nonlinear patterns and spatial structures in RNA profiling data. Here, authors introduce a graph-guided neural hierarchical tensor decomposition model that incorporates spatial and functional relations for the task.

    • Tianci Song
    • , Charles Broadbent
    •  & Rui Kuang

  • Article
    | Open Access

    Analysis of newly synthesized proteins upon perturbation can provide detailed insights into immediate proteome remodeling, which drives cellular responses. Here, the authors report an optimized semi-automated workflow for the quantitative analysis of the newly synthesized proteome.

    • Toman Borteçen
    • , Torsten Müller
    •  & Jeroen Krijgsveld

  • Article
    | Open Access

    Global epistasis can be used to reconstruct fitness landscapes and infer adaptive trajectories. Here, the authors investigate how environmental variation impacts patterns of global epistasis, finding that global epistasis in the malaria parasite P. falciparum can be modulated by drug concentration in the environment.

    • Juan Diaz-Colunga
    • , Alvaro Sanchez
    •  & C. Brandon Ogbunugafor

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