Systems biology articles within Nature

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  • Article
    | Open Access

    Combining single-cell RNA-sequencing with high-resolution multiplexed error-robust fluorescence in situ hybridization reveals in detail the cellular interactions and specialization of cardiac cell types that form and remodel the human heart.

    • Elie N. Farah
    • , Robert K. Hu
    •  & Neil C. Chi

  • Article
    | Open Access

    Introduction of a long synthetic DNA into yeast genomic loci results in high default transcriptional activity in yeast but low activity in mouse, suggesting distinct default levels of genomic activity in these organisms.

    • Brendan R. Camellato
    • , Ran Brosh
    •  & Jef D. Boeke

  • Article |

    Studies of vocal production in baleen whales show that their larynx has evolved unique structures that enable their low-frequency vocalizations but limit their active communication range.

    • Coen P. H. Elemans
    • , Weili Jiang
    •  & W. Tecumseh Fitch

  • Article
    | Open Access

    Analysis of the effects of more than 26,000 KRAS mutations on abundance and interactions with six other proteins is used to construct an energy landscape of KRAS and identify allosteric drug target sites.

    • Chenchun Weng
    • , Andre J. Faure
    •  & Ben Lehner

  • Article
    | Open Access

    Deep learning models were used to design synthetic cell-type-specific enhancers that work in fruit fly brains and human cell lines, an approach that also provides insights into these gene regulatory elements.

    • Ibrahim I. Taskiran
    • , Katina I. Spanier
    •  & Stein Aerts

  • Article
    | Open Access

    An extensive global transcriptomics analysis of in vivo responses to 86 cytokines across more than 17 immune cell types reveals enormous complexity of cellular responses to cytokines, providing the basis of the Immune Dictionary and its companion software Immune Response Enrichment Analysis.

    • Ang Cui
    • , Teddy Huang
    •  & Nir Hacohen

  • Article
    | Open Access

    A protein interaction network constructed with data from high-throughput affinity enrichment coupled to mass spectrometry provides a highly saturated yeast interactome with 31,004 interactions, including low-abundance complexes, membrane protein complexes and non-taggable protein complexes.

    • André C. Michaelis
    • , Andreas-David Brunner
    •  & Matthias Mann

  • Article |

    Anti-cancer treatment often results in a subset of the clonal cell population developing resistance to therapy, with resistant cells displaying a diversity of fate types resulting from the intrinsic variability among the clonal population before treatment.

    • Yogesh Goyal
    • , Gianna T. Busch
    •  & Arjun Raj

  • Article
    | Open Access

    We uncover the mechanism underlying the restriction point phenomenon, suggest a role for cyclin-dependent kinase 4 and 6 activity in S and G2 phases, and explain the behaviour of cells following loss of mitogen signalling.

    • James A. Cornwell
    • , Adrijana Crncec
    •  & Steven D. Cappell

  • Article |

    A context-aware, attention-based deep learning model pretrained on single-cell transcriptomes enables predictions in settings with limited data in network biology and could accelerate discovery of key network regulators and candidate therapeutic targets.

    • Christina V. Theodoris
    • , Ling Xiao
    •  & Patrick T. Ellinor

  • Article |

    Combining genome-wide CRISPR screens with massively parallel analyses of human and random DNA sequences reveal a unified mechanism for the surveillance and evolution of translation products from annotated noncoding DNA.

    • Jordan S. Kesner
    • , Ziheng Chen
    •  & Xuebing Wu

  • Article |

    A high throughput recruitment assay testing the transcriptional activity of more than 100,000 protein fragments tiling across most human chromatin regulators and transcription factors maps the locations and strengths of activation, repression and bifunctional domains, and identifies the sequences necessary for these functions.

    • Nicole DelRosso
    • , Josh Tycko
    •  & Lacramioara Bintu

  • Article |

    Analysis of Triton, a high-resolution dataset documenting the macroperforate planktonic foraminifera fossil record, reveals a global climate-linked equatorward shift of ecological and morphological community equitability over the past 8 million years.

    • Adam Woodhouse
    • , Anshuman Swain
    •  & Christopher M. Lowery

  • News & Views |

    A computational tool called CellOracle can predict how networks of genes interact to program cell identity during embryonic development. The tool should help to hone efforts to understand how development is regulated.

    • Jeffrey A. Farrell

  • Article |

    The zebrafish segmentation clock drives sequential segmentation of somites by periodically lowering double-phosphorylated Erk and therefore projecting its oscillation on the double-phosphorylated Erk gradient.

    • M. Fethullah Simsek
    • , Angad Singh Chandel
    •  & Ertuğrul M. Özbudak

  • Article
    | Open Access

    Synthetic cell adhesion molecules yield customized cell–cell interactions with adhesion properties that are similar to native interactions, and offer abilities for cell and tissue engineering and for systematically studying multicellular organization.

    • Adam J. Stevens
    • , Andrew R. Harris
    •  & Wendell A. Lim

  • Article |

    Single-cell RNA sequencing and single-molecule RNA transcript imaging have been used to characterize spatially and temporally resolved mouse liver and parasite expression programmes during infection with the rodent malaria parasite Plasmodium berghei ANKA.

    • Amichay Afriat
    • , Vanessa Zuzarte-Luís
    •  & Shalev Itzkovitz

  • Article |

    The combination of synthetic biology and materials engineering enabled the development of biosensors that produce electrical readouts and real-time detection capabilities.

    • Joshua T. Atkinson
    • , Lin Su
    •  & Caroline M. Ajo-Franklin

  • Research Briefing |

    Molecular networks have been developed that can classify complex mixtures of DNA sequences that cannot be categorized by a single linear classifier. To do this, artificial ‘neurons’ powered by enzymes are wired together to form an architecture that mimics the structure of a neural network.

  • Article |

     Mimicking traditional digital neural networks with DNA-encoded ‘enzymatic’ neurons overcomes issues with other chemical approaches, and could allow notable increases in miniaturization and molecular implementation of these AI models, with potential applications including DNA data storage or cancer diagnosis.

    • S. Okumura
    • , G. Gines
    •  & A. J. Genot

  • News & Views |

    Evidence from turtles and computer models indicates that a pattern of neuronal activity known as rotational dynamics governs locomotion. The finding challenges long-standing models of locomotor control.

    • Martha W. Bagnall

  • Article
    | Open Access

    A multi-omic atlas of brain organoid development facilitates the inference of an underlying gene regulatory network using the newly developed Pando framework and shows—in conjunction with perturbation experiments—that GLI3 controls forebrain fate establishment through interaction with HES4/5 regulomes.

    • Jonas Simon Fleck
    • , Sophie Martina Johanna Jansen
    •  & Barbara Treutlein

  • Article |

    Different pairs of antibiotics show qualitatively different bacterial clearance interactions—some pairs show reciprocal suppression whereby the drug mixture efficacy is weaker than the individual drugs alone, and the clearance efficacy decreases as more drugs are added.

    • Viktória Lázár
    • , Olga Snitser
    •  & Roy Kishony

  • Article |

    An approach called cell state transition assessment and regulation uses diverse multiomics data to map cell states, model their transitions, and understand the signalling networks that control them.

    • Oleksii S. Rukhlenko
    • , Melinda Halasz
    •  & Boris N. Kholodenko

  • Article |

    A bacteriogenic strategy for constructing membrane-bounded, molecularly crowded, and compositionally, structurally and morphologically complex synthetic cells provides opportunities for the fabrication of new synthetic cell modules and augmented living/synthetic cell constructs.

    • Can Xu
    • , Nicolas Martin
    •  & Stephen Mann

  • Research Briefing |

    We genetically reprogrammed yeast to produce the alkaloids vindoline and catharanthine — the longest biosynthetic pathway to be transferred from a plant to a microorganism. In principle, similarly engineered yeast strains could produce more than 3,000 other monoterpene indole alkaloids and unnatural analogues.

  • Article
    | Open Access

    A synthetic cell-cell adhesion logic using swarming E. coli with 4 bits of information is introduced, enabling the programming of interfaces that combine to form universal tessellation patterns over a large scale.

    • Honesty Kim
    • , Dominic J. Skinner
    •  & Ingmar H. Riedel-Kruse

  • Article
    | Open Access

    Systematic measurements of the interactions between proteins found on the surfaces of human leukocytes provides a global view of the way that immune cells are dynamically connected by receptors.

    • Jarrod Shilts
    • , Yannik Severin
    •  & Gavin J. Wright

  • Article |

    A new high-throughput assay applied to 1,000 enhancers and 1,000 promoters in human cells reveals how different classes of enhancers and promoters control RNA expression.

    • Drew T. Bergman
    • , Thouis R. Jones
    •  & Jesse M. Engreitz

  • Article
    | Open Access

    Experiments in yeast show that introns have a role in inducing phenotypic heterogeneity and that intron-mediated regulation of ribosomal proteins confers a fitness advantage by enabling yeast populations to diversify under nutrient-scarce conditions.

    • Martin Lukačišin
    • , Adriana Espinosa-Cantú
    •  & Tobias Bollenbach

  • Article |

    A framework for studying and engineering gene regulatory DNA sequences, based on deep neural sequence-to-expression models trained on large-scale libraries of random DNA, provides insight into the evolution, evolvability and fitness landscapes of regulatory DNA.

    • Eeshit Dhaval Vaishnav
    • , Carl G. de Boer
    •  & Aviv Regev

  • Article
    | Open Access

    The SARS-CoV-2 Alpha variant suppresses innate immune responses more effectively than isolates of first-wave SARS-CoV-2, and this is a result of mutations outside of the spike coding region that lead to upregulation of viral innate immune antagonists.

    • Lucy G. Thorne
    • , Mehdi Bouhaddou
    •  & Nevan J. Krogan

  • Article
    | Open Access

    A new technique called immunoGAM, which combines genome architecture mapping (GAM) with immunoselection, enabled the discovery of specialized chromatin conformations linked to gene expression in specific cell populations from mouse brain tissues.

    • Warren Winick-Ng
    • , Alexander Kukalev
    •  & Ana Pombo

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