Systems biology

  • 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
  • Article
    | Open Access

    Mesoscale connectomic mapping of the cortico–basal ganglia–thalamic network reveals key architectural and information processing features.

    • Nicholas N. Foster
    • , Joshua Barry
    •  & Hong-Wei Dong
  • Article |

    An analysis of the interactions between 15 drugs and 25 gut bacterial strains shows that bioaccumulation of drugs within bacterial cells is another mechanism through which gut microorganisms can alter drug availability and efficacy.

    • Martina Klünemann
    • , Sergej Andrejev
    •  & Kiran R. Patil
  • Article |

    A proximity-dependent biotinylation technique defines the location of more than 4,000 proteins in a human cell, and almost 36,000 proximal interactions between proteins, including those at the interface of the mitochondria and ER.

    • Christopher D. Go
    • , James D. R. Knight
    •  & Anne-Claude Gingras
  • Article |

    The natural antisense transcript MAPT-AS1 interferes with translation of mRNA transcript into tau protein in the brain and may represent a general mechanism for controlling levels of intrinsically disordered proteins, with particular relevance for neurodegeneration.

    • Roberto Simone
    • , Faiza Javad
    •  & Rohan de Silva
  • Article |

    Two complete volumetric reconstructions of the Caenorhabditis elegans main neuropil (the nerve ring) reveal multi-scale spatial organization that supports both conserved and variable circuitry, and enables the derivation of a modular structure–function model of the neuropil.

    • Christopher A. Brittin
    • , Steven J. Cook
    •  & Netta Cohen
  • Article |

    Thermal proteome profiling combined with a reverse genetics approach provides insights into the abundance and thermal stability of the global proteome of Escherichia coli.

    • André Mateus
    • , Johannes Hevler
    •  & Mikhail M. Savitski
  • Article |

    Transcriptomics, proteomics, single-cell RNA sequencing, population-wide genetic association studies and structure–function analyses provide a picture of how the differential expression of G-protein-coupled receptor isoforms can diversify signalling in different tissues.

    • Maria Marti-Solano
    • , Stephanie E. Crilly
    •  & M. Madan Babu
  • Article |

    A robotic pipeline is used to survey a library of mutations in a Drosphila gene enhancer, showing that most mutations altered gene expression and had widespread pleiotropic effects that are likely to constrain regulatory evolution.

    • Timothy Fuqua
    • , Jeff Jordan
    •  & Justin Crocker
  • Article |

    An organoid-based screening platform maps the genetic interactions underlying intestinal development and regeneration, showing that retinoic acid metabolism maintains the balance between regeneration and homeostasis, and that an antagonist of the retinoid X receptor promotes regeneration in vivo.

    • Ilya Lukonin
    • , Denise Serra
    •  & Prisca Liberali
  • Perspective |

    The LifeTime initiative is an ambitious, multidisciplinary programme that aims to improve healthcare by tracking individual human cells during disease processes and responses to treatment in order to develop and implement cell-based interceptive medicine in Europe.

    • Nikolaus Rajewsky
    • , Geneviève Almouzni
    •  & Frauke Zipp
  • Article |

    A systems-level map of the Arabidopsis hormone signalling network, comprising more than 2,000 binary protein–protein interactions, reveals hundreds of interpathway contact points, many of which mediate crosstalk between different hormone pathways.

    • Melina Altmann
    • , Stefan Altmann
    •  & Pascal Falter-Braun
  • Article |

    Structural cells implement a broad range of immune-regulatory functions beyond their roles as barriers and connective tissues, and they utilize an epigenetically encoded potential for immune gene activation in their rapid response to viral infection.

    • Thomas Krausgruber
    • , Nikolaus Fortelny
    •  & Christoph Bock
  • Article |

    Single-molecule fluorescence in situ hybridization and live-cell imaging are used to study the contribution of transcriptional noise to stem cell heterogeneity, revealing that stochastic transcription dynamics are conducive to concomitant stem-cell maintenance and tissue homeostasis.

    • Justin C. Wheat
    • , Yehonatan Sella
    •  & Ulrich Steidl
  • Article |

    An advanced proteomics workflow is used to identify 340,000 proteins from 100 taxonomically diverse species, providing a comparative view of proteomes across the evolutionary range.

    • Johannes B. Müller
    • , Philipp E. Geyer
    •  & Matthias Mann
  • Article |

    Insights into the interactions between pro- and anti-vaccination clusters on Facebook can enable policies and approaches that attempt to interrupt the shift to anti-vaccination views and persuade undecided individuals to adopt a pro-vaccination stance.

    • Neil F. Johnson
    • , Nicolas Velásquez
    •  & Yonatan Lupu
  • Article |

    A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

    • David E. Gordon
    • , Gwendolyn M. Jang
    •  & Nevan J. Krogan
  • Article |

    A human binary protein interactome map that includes around 53,000 protein–protein interactions involving more than 8,000 proteins provides a reference for the study of human cellular function in health and disease.

    • Katja Luck
    • , Dae-Kyum Kim
    •  & Michael A. Calderwood
  • Article |

    Single-cell RNA sequencing is used to generate a dataset covering all major human organs in both adult and fetal stages, enabling comparison with similar datasets for mouse tissues.

    • Xiaoping Han
    • , Ziming Zhou
    •  & Guoji Guo
  • Article |

    A single-cell, spatially resolved analysis of breast cancer demonstrates the heterogeneity of tumour and stroma tissue and provides a more-detailed method of patient classification than the current histology-based system.

    • Hartland W. Jackson
    • , Jana R. Fischer
    •  & Bernd Bodenmiller
  • Article |

    A new computational framework, novoSpaRc, leverages single-cell data to reconstruct spatial context for cells and spatial expression across tissues and organisms, on the basis of an organization principle for gene expression.

    • Mor Nitzan
    • , Nikos Karaiskos
    •  & Nikolaus Rajewsky
  • Letter |

    In two patient-derived xenograft models of colorectal cancer and a mouse model of autochthonous soft-tissue sarcoma, dietary restriction of methionine influences the outcome of cancer and interacts with antimetabolite and radiation therapies, through effects on one-carbon metabolism.

    • Xia Gao
    • , Sydney M. Sanderson
    •  & Jason W. Locasale
  • Article
    | Open Access

    The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.

    • Jason Lloyd-Price
    • , Cesar Arze
    •  & Curtis Huttenhower
  • Article |

    High-fidelity convergent total synthesis is used to produce Escherichia coli with a 61-codon synthetic genome that uses 59 codons to encode all of the canonical amino acids.

    • Julius Fredens
    • , Kaihang Wang
    •  & Jason W. Chin