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Longitudinal metatranscriptomics in a prospective cohort of 1,164 adults hospitalized for COVID-19 reveals that azithromycin offered no apparent anti-inflammatory benefit but enriched the respiratory microbiome with potential pathogens and antimicrobial resistance genes.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Genome-wide association studies (GWAS) have improved our understanding of the genetic basis of lung adenocarcinoma but known susceptibility variants explain only a small fraction of the familial risk. Here, the authors perform a two-stage GWAS and report 12 novel genetic loci associated with lung adenocarcinoma in East Asians.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

The authors determine the synaptic wiring diagram of a vertebrate circuit and reveal behaviorally associated modules. A model based on this connectome predicts neural coding and dynamics that are verified with calcium imaging data.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

Wastewater-based surveillance tends to focus on specific pathogens. Here, the authors mapped the wastewater virome from 62 cities worldwide to identify over 2,500 viruses, revealing city-specific virome fingerprints and showing that wastewater metagenomics enables early detection of emerging viruses.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Prophylactic HPV vaccines are provisionally recommended as a one-dose schedule in girls. Here, the authors report sustained immune memory and increased IgG1 and IgG3 antibodies six years following one dose of quadrivalent HPV vaccine in Fijian girls.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

The authors use artificial intelligence approaches to explore the predictive value of whole exome sequencing in forecasting clinical outcomes following surgery for congenital heart defects. Findings include that damaging genotypes in chromatin-modifying and cilia-related genes are associated with an increased risk of adverse post-operative outcomes such as mortality, cardiac arrest, and prolonged mechanical ventilation.

Geographic location can be a key determinant of human health outcomes. Here, the authors show that in large-scale trials, randomization that is pair matched by geography can lead to substantial improvements in statistical efficiency and enable insights into spatially varying intervention effects.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

Antibody responses to SARS-CoV-2 are critical in the immune response to infection, but the potential cross-reactivity to other human corona viruses is poorly appreciated. Here the authors apply a systems based approach to characterise the antibody response in pre-pandemic cohorts and assess heterotypic reactivity to SARS-CoV-2.

Three electron microscopy datasets are combined to provide a complete connectomic description of the neural circuitry that makes up the neck connective in Drosophila, including the descending neurons, ascending neurons and sensory ascending neurons.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

For many neurodevelopmental disorder (NDD) risk genes, the significance for mutational burden is unestablished. Here, the authors sequence 125 candidate NDD genes in over 16,000 NDD cases; case-control mutational burden analysis identifies 48 genes with a significant burden of severe ultra-rare mutations.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Kedzierska et al. report an association between low production of receptor-binding domain antibodies after mRNA vaccination and altered glycosylation of IgG before vaccination in people with comorbidities, and show that this condition disproportionately affects Australia’s First Nations peoples because of the high burden of comorbidities in this population.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

An analysis of the Drosophila connectome yields all cell types intrinsic to the optic lobe, and their rules of connectivity.

It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk

Patricia Munroe, Christopher Newton-Cheh, Andrew Morris and colleagues perform association studies in over 340,000 individuals of European ancestry and identify 66 loci, of which 17 are novel, involved in blood pressure regulation. The risk SNPs are enriched for cis-regulatory elements, particularly in vascular endothelial cells.

The study reveals the Acinetobacter baumannii T6SS Rhs effector, Tse15, uses its clade domain as an internal chaperone to facilitate toxin delivery and the Rhs cage is not secreted.

In this study, Uldrich and colleagues describe the crystal structure of the Vγ9Vδ2 T cell antigen receptor (TCR) interacting with BTN2A1 and demonstrate the existence of a second ligand that co-binds to a distinct epitope on Vγ9Vδ2 TCR. Using these data, the authors suggest a model of Vγ9Vδ2 TCR activation in which BTN2A1 and BTN3A1 are tethered to each other at the steady state, and must disengage to allow TCR binding.

Soft electronic patches worn on the skin of infants or children in intensive-care units have a wide range of capabilities in aiding critical care, including monitoring of hemodynamic parameters, cardiac activity, movement and crying.

In this work, authors show that randomized water, sanitation, hygiene and nutrition interventions reduced child antibiotic use in Bangladesh (in parallel with high intervention uptake and reduced infections) but not Kenya (in parallel with lower uptake and no effect on infections).

The immune response to SARS-CoV-2 infection is variable but has been linked to prognosis and the development of severe immunopathology. Here the authors assess a range of immune parameters in both peripheral blood and respiratory samples, providing a comparative assessment of the immune response between these compartments and their potential impact on immune-pathogenesis.

Allele-preferential transcription factor binding can influence pancreatic ductal adenocarcinoma risk loci function. Here, the authors show allele-specific JunB and JunD binding at chr1p36.33 and propose a role for KLHL17 in protein homeostasis by mitigating inflammation.

Luis Pérez-Jurado, Stephen Chanock and colleagues detect clonal chromosomal abnormalities in peripheral blood or buccal samples from individuals in the general population. They show that the frequency of such events increases with age and is associated with elevated risk of developing subsequent hematological cancers.

Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.

Children with SARS-CoV-2 infection are more likely to have mild symptoms and may be asymptomatic, but underlying reasons remain unclear. Here, the authors show cellular, cytokine and antibody response to SARS-CoV-2 infection in three children who repeatedly tested negative for the virus by PCR, despite high exposure in the household.

Longitudinal analyses are needed to show how the immune response to Sars-Cov-2 infection changes over time. Here, the authors use multiple strategies to profile the change in immune cell responses from patients with convalescent COVID-19 over the course of ~5 months, showing that although neutralizing antibody responses drop off after ~4 months, B cell immune responses strengthen.

A study reports the distribution, replication and persistence of SARS-CoV-2 throughout the human body including in the brain at autopsy from acute infection to more than seven months following symptom onset.

In this immunological ancillary study of the PREVAC trial, the authors show that approved Ebola virus vaccines induce memory T-cell responses that persist during the five year follow-up after initial vaccination.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.

Current guidelines recommend stereotactic radiosurgery for brain metastasis measuring less than 3 cm but there is significant variability in outcomes following treatment. This study shows that in treatment naïve brain metastasis less than 3 cm, intrinsic biological differences across multiple histologies may influence response to stereotactic radiosurgery.

Heart failure is a complex syndrome that is associated with many different underlying risk factors. Here, to increase power, the authors jointly analyse cases of heart failure of different aetiologies in a genome-wide association study and identify 11 loci of which ten had not been previously reported.

Here, by performing an integrative multi-omics analysis coupled to clinical features of COVID-19 patients prospectively followed for up to 6 month, the authors identify specific gut microbiome patterns associated with disease severity and development of post-acute COVID-19 syndrome.

Rocks and dust from the asteroid Bennu contain some of the molecular building blocks of life on Earth, such as amino acids and nucleobases. They also carry ammonia that formed billions of years ago in cold, distant regions of our Solar System.

Understanding the emergence, evolution, and transmission of antibiotic resistance genes (ARGs) is essential to combat antimicrobial resistance. Here, Munk et al. analyse ARGs in hundreds of sewage samples from 101 countries and describe regional patterns, diverse genetic environments of common ARGs, and ARG-specific transmission patterns.