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A single dose of a small-molecule HIV capsid inhibitor provides long-term protection from repeated simian–human immunodeficiency virus challenges in macaques and might serve as a novel strategy for HIV prevention in humans.
Whole-transcriptome sequencing of a subset of 75 non-small-cell lung cancer specimens in a multi-institutional genome screening study identified a fusion of the CLIP1 and LTK genes with transformational potential due to constitutive LTK kinase activity.
Whole-exome sequencing analysis of 454,787 individuals in the UK Biobank is used to examine the association of protein-coding variants with nearly 4,000 health-related traits, identifying 564 distinct genes with significant trait associations.
A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.
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.
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.
Virus-induced senescence is a central pathogenic feature in COVID-19, and senolytics, which promote apoptosis of senescent cells, can reduce disease severity in hamsters,mice, as well as humans infected with SARS-CoV-2.
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.
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.
In many European countries, more than half of the SARS-CoV-2 lineages circulating in late summer 2020 resulted from new introductions, highlighting the threat of viral dissemination when restrictions are lifted.
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.
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.
Single-cell RNA sequencing and imaging of macrophages in human non-small cell lung cancer and in a mouse model of lung adenocarcinoma show that tissue-resident macrophages have a key role in early tumour progression.
In a phase-I/II trial in healthy adults, the BNT162b2 vaccine induces neutralizing antibodies and poly-specific T cells against SARS-CoV-2 epitopes that are conserved in a wide range of currently circulating variants.
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.
A trio-binning approach is used to produce a fully haplotype-resolved diploid genome assembly for the common marmoset, providing insight into the heterozygosity spectrum and the evolution of the sex-differentiation region.
Trial Pathfinder uses data from electronic health records of patients with cancer to evaluate eligibility criteria and broaden restrictive criteria, which facilitates the design of more-inclusive trials while maintaining safeguards for patient safety.
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.
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.
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.
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.
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.
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.
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.
Heart atria produce a large pool of calcitonin (previously well-recognized as a thyroid-secreted hormone with roles in calcium and bone metabolism) that in the heart acts as a paracrine signal controlling atrial fibrosis and fibrillation.
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.
Single-nucleus RNA sequencing in mouse and human adipose tissue identifies a subpopulation of adipocytes that regulates thermogenesis in neighbouring adipocytes in a paracrine manner by modulating acetate signalling.
By integrating healthcare and exome-sequencing data from parent–offspring trios of patients with developmental disorders, 28 genes that had not previously been associated with developmental disorders were identified.
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.
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.
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.