Medical research

  • Article |

    Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.

    • Stanley W. K. Ng
    • , Foad J. Rouhani
    •  & Peter J. Campbell
  • Article |

    The viral lineage responsible for the February 2021 outbreak of Ebola virus disease in Guinea is nested within a clade that predominantly consists of genomes sampled during the 2013–2016 epidemic, suggesting that the virus might have re-emerged after a long period of latency within a previously infected individual.

    • Alpha Kabinet Keita
    • , Fara R. Koundouno
    •  & N’. Faly Magassouba
  • Article |

    A robust, cost-effective technique based on whole-exome sequencing data can be used to characterize immune infiltrates, relate the extent of these infiltrates to somatic changes in tumours, and enables prediction of tumour responses to immune checkpoint inhibition therapy.

    • Robert Bentham
    • , Kevin Litchfield
    •  & Nicholas McGranahan
  • Article |

    Alanine-scanning mutagenesis is used to identify the PF4 epitope that is recognized by anti-PF4 antibodies in patients with vaccine-induced immune thrombotic thrombocytopaenia, revealing that the epitope corresponds to the heparin-binding site on PF4.

    • Angela Huynh
    • , John G. Kelton
    •  & Ishac Nazy
  • Article |

    Two malaria vaccines comprising Plasmodium falciparum sporozoites and treatment with either pyrimethamine or chloroquine induced durable protective responses against both the African vaccine strain and a heterologous South American strain of P. falciparum.

    • Agnes Mwakingwe-Omari
    • , Sara A. Healy
    •  & Patrick E. Duffy
  • Article |

    Fibre snacks that target distinct features of the microbiomes of donors with obesity transplanted into gnotobiotic mice also lead to fibre-specific changes in the microbiome and physiology when used in controlled-diet human studies.

    • Omar Delannoy-Bruno
    • , Chandani Desai
    •  & Jeffrey I. Gordon
  • Article |

    Statistical analysis of COVID-19 transmission among users of a smartphone-based digital contact-tracing app suggests that such apps can be an effective measure for reducing disease spread.

    • Chris Wymant
    • , Luca Ferretti
    •  & Christophe Fraser
  • Article |

    Aggressive cerebral cavernous malformations (CCMs) are found to grow through a three-hit cancer-like mechanism, involving gain of function of a gene that promotes vascular growth, and loss of function of genes that suppress it.

    • Aileen A. Ren
    • , Daniel A. Snellings
    •  & Mark L. Kahn
  • Perspective
    | Open Access

    This Perspective discusses how the Somatic Cell Genome Editing Consortium aims to accelerate the implementation of safe and effective genome-editing therapies in the clinic.

    • Krishanu Saha
    • , Erik J. Sontheimer
    •  & Jiangbing Zhou
  • Article |

    Phylogenies of human placental cells based on whole-genome sequencing of bulk samples and microdissections reveal extensive mutagenesis in placental tissue, and suggest that mosaicism is a typical part of normal placental development.

    • Tim H. H. Coorens
    • , Thomas R. W. Oliver
    •  & Sam Behjati
  • Article |

    The 501Y.V2 variant of SARS-CoV-2 in South Africa became dominant over other variants within weeks of its emergence, suggesting that this variant is linked to increased transmissibility or immune escape.

    • Houriiyah Tegally
    • , Eduan Wilkinson
    •  & Tulio de Oliveira
  • Article |

    In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.

    • Shinya Sugimoto
    • , Eiji Kobayashi
    •  & Toshiro Sato
  • Article
    | Open Access

    The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

    • Daniel Taliun
    • , Daniel N. Harris
    •  & Gonçalo R. Abecasis
  • Article |

    Single-stranded, DNA-damage-associated small RNAs generated by a BRCA1–RNA-interference complex promote PALB2–RAD52-mediated DNA repair at transcriptional termination pause sites that contain R-loops and are rich in single-stranded DNA breaks in both quiescent and proliferating cells.

    • Elodie Hatchi
    • , Liana Goehring
    •  & David M. Livingston
  • Article |

    A range of techniques are used to investigate the molecular landscape of chronic kidney disease, and the results suggest that distinct populations of pericytes and fibroblasts are the main source of myofibroblasts in kidney fibrosis.

    • Christoph Kuppe
    • , Mahmoud M. Ibrahim
    •  & Rafael Kramann
  • Article |

    Transgenic K18-hACE2 mice are a useful model of COVID-19 including anosmia; infection of these mice resulted in severe pneumonia and, in some cases, infection in the brain, which was prevented by convalescent plasma.

    • Jian Zheng
    • , Lok-Yin Roy Wong
    •  & Stanley Perlman
  • Article |

    Whole-genome sequencing analyses of African populations provide insights into continental migration, gene flow and the response to human disease, highlighting the importance of including diverse populations in genomic analyses to understand human ancestry and improve health.

    • Ananyo Choudhury
    • , Shaun Aron
    •  & Neil A. Hanchard
  • Article
    | Open Access

    Single-cell and single-nucleus RNA sequencing are used to construct a cellular atlas of the human heart that will aid further research into cardiac physiology and disease.

    • Monika Litviňuková
    • , Carlos Talavera-López
    •  & Sarah A. Teichmann
  • Article |

    In a dose-escalation study of the COVID-19 RNA vaccine BNT162b1 in 45 healthy adults, RBD-binding IgG concentrations and SARS-CoV-2 neutralizing titres in sera increased with dose level and after a second vaccine dose.

    • Mark J. Mulligan
    • , Kirsten E. Lyke
    •  & Kathrin U. Jansen
  • Article |

    Hydroxychloroquine did not confer protection against SARS-CoV-2 infection or reduce the viral load after infection in macaques; these findings do not support the use of hydroxychloroquine as an antiviral drug treatment of COVID-19 in humans.

    • Pauline Maisonnasse
    • , Jérémie Guedj
    •  & Roger Le Grand
  • Article |

    Current outcomes are reported from the ongoing National Lung Matrix Trial, an umbrella trial for the treatment of non-small-cell lung cancer in which patients are triaged according to their tumour genotype and matched with targeted therapeutic agents.

    • Gary Middleton
    • , Peter Fletcher
    •  & Lucinda Billingham
  • Article |

    OpenSAFELY, a new health analytics platform that includes data from over 17 million adult NHS patients in England, is used to examine factors associated with COVID-19-related death.

    • Elizabeth J. Williamson
    • , Alex J. Walker
    •  & Ben Goldacre
  • Article |

    Respiratory syncytial virus enters cells by binding to cell-surface IGFR1, which activates PKCζ and induces trafficking of the NCL coreceptor to the RSV particles at the cell surface.

    • Cameron D. Griffiths
    • , Leanne M. Bilawchuk
    •  & David J. Marchant
  • Article |

    SARS-CoV-2 modulates central cellular pathways, such as translation, splicing, carbon metabolism, proteostasis and nucleic acid metabolism, in human cells; these pathways can be inhibited by small-molecule inhibitors to prevent viral replication in the cells.

    • Denisa Bojkova
    • , Kevin Klann
    •  & Christian Münch
  • Article
    | Open Access

    Pneumococcal and rotavirus vaccines have reduced antibiotic consumption substantially among children under five years old in low- and middle-income countries; however, this effect could be doubled if all countries were to implement vaccination programmes and meet universal vaccine coverage targets.

    • Joseph A. Lewnard
    • , Nathan C. Lo
    •  & Ramanan Laxminarayan