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Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Variant-to-gene-to-program is a new approach to building maps of genome function to link risk variants to disease genes and to convergent signalling pathways in an unbiased manner; its strength is demonstrated in coronary artery disease.

A genome-wide association meta-analysis of individuals with clinically assessed or self-reported depression identifies 44 independent risk loci. Comparisons with other psychiatric disorders and candidate gene analyses provide new insights into major depressive disorder.

An amplicon-based sequencing protocol that includes synthetic DNA spike-ins improves the quality and efficiency of SARS-CoV-2 high-throughput sequencing and detects common errors in genomic data.

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.

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

An adversarial domain translation framework is presented for scalable integration of single-cell atlases across samples, technical platforms, data modalities and species.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Lightbody et al. present SWIFT-seq, a single-cell RNA sequencing approach to profile circulating tumor cells from patients with multiple myeloma and its precursor conditions and leverage it to derive clinical and biological insights into the disease.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

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.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

A pan-cancer epigenetic and transcriptomic atlas identifies epigenetic drivers associated with cancer transitions.

The use of organic photoactive materials in direct solar water-splitting devices has been limited by recombination losses and their instability in aqueous media. Daboczi et al. report that stable and efficient devices based on organic photoactive layers can be achieved through the application of catalyst-functionalized protective graphite sheets.

The Human Microbiome Project Consortium reports the first results of their analysis of microbial communities from distinct, clinically relevant body habitats in a human cohort; the insights into the microbial communities of a healthy population lay foundations for future exploration of the epidemiology, ecology and translational applications of the human microbiome.

Recent studies integrating multi-omics data with cell atlases across development for brains of humans and model organisms are revealing conserved and divergent patterns of brain development at the molecular and cellular levels, and linking these to complex behavioural and neuropsychiatric phenotypes.

Somatic mutations accumulate with age; however, the role they have in cardiac aging is unclear. Here Choudhury et al. describe the somatic mutation landscape of human heart muscle cells by single-cell whole-genome sequencing and report mutational signatures indicative of increased oxidative DNA damage and failed repair.

The non-coding RNA RNU4-2, which is highly expressed in the developing human brain, is identified as a syndromic neurodevelopmental disorder gene, and, using RNA sequencing, 5′ splice-site use is shown to be systematically disrupted in individuals with RNU4-2 variants.

Genome-wide analysis of chronic obstructive pulmonary disease identifies 82 loci, 35 of which are new. Integration of gene expression and genomic annotation data shows enrichment of signals in lung tissue, smooth muscle and several lung cell types.

There is currently no licensed SARS-CoV-2 vaccine. Here, the authors generate an optimized DNA vaccine candidate encoding the SARS-CoV-2 spike antigen, demonstrating induction of specific T cells and neutralizing antibody responses in mice and guinea pigs. These initial results support further development of this vaccine candidate.

A case–control study investigating the causes of recent cases of acute hepatitis of unknown aetiology in 32 children identifies an association between adeno-associated virus infection and host genetics in disease susceptibility.

Conditional deletion of the transcriptional co-activator Brd4 in infiltrating Cx3cr1⁺ mouse macrophages ameliorates heart failure and substantially reduces fibroblast activation.

Phenotypic variation and diseases are influenced by factors such as genetic variants and gene expression. Here, Barbeira et al. develop S-PrediXcan to compute PrediXcan results using summary data, and investigate the effects of gene expression variation on human phenotypes in 44 GTEx tissues and >100 phenotypes.

Results from a comprehensive evaluation of the function of BRCA2 variants, particularly variants of uncertain significance, provide a useful resource to improve the clinical management of individuals who carry such genetic variants.

An oligodendrocyte-specific genomic silencer element determines the cell type specificity for a fatal neurological disorder caused by a widely expressed nuclear protein (Lamin B1) and suggests a role for silencer elements in disease causation.

The Bladder Cancer Advocacy Network established the UC-GENOME study in order to create a biobank and data repository for metastatic urothelial carcinoma. Here, the authors present the first characterization and analysis of DNA and RNA sequencing data from the 218 patients included in the UC-GENOME.

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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Isolation and optimization of antibodies targeting the malaria parasite may offer the potential for immediate protection as a prophylactic intervention to prevent severe disease.

Glutathione has pleiotropic functions in different organs. Here the authors specifically examine deletion of a glutathione synthetic enzyme in the liver of adult mice and show that lack of glutathione affects lipid abundance through repressing NRF2.

Here the authors show that ventrally derived oligodendrocytes (OLs) can myelinate areas usually populated by dorsally derived OLs but cannot functionally compensate, as animals populated only by ventrally derived OLs show locomotor and cognitive deficits.

An expanded GWAS of birth weight and subsequent analysis using structural equation modeling and Mendelian randomization decomposes maternal and fetal genetic contributions and causal links between birth weight, blood pressure and glycemic traits.

Sexual dimorphism in genetic vulnerability to schizophrenia, systemic lupus erythematosus and Sjögren’s syndrome is linked to differential protein abundance from alleles of complement component 4.

A catalogue of predicted loss-of-function variants in 125,748 whole-exome and 15,708 whole-genome sequencing datasets from the Genome Aggregation Database (gnomAD) reveals the spectrum of mutational constraints that affect these human protein-coding genes.

Space interferometry reveals the hidden and filamentary internal structure of the relativistic jet in 3C 279 at microarcsecond angular resolution. These details challenge previous assumptions on the morphology and radio variability of blazars.

As phase 1 of the Earth Microbiome Project, analysis of 16S ribosomal RNA sequences from more than 27,000 environmental samples delivers a global picture of the basic structure and drivers of microbial distribution.

A combination of genetic strategies and tools is used to define and fate-map different subtypes of glutamatergic pyramidal neurons according to their developmental and molecular programs, providing insight into the assembly of cortical processing networks.

Although T cells proliferate at an exceptionally fast rate following activation, the mechanisms sustaining such fast proliferation remain unclear. Here, the authors demonstrate that c-Myc upregulates the E3 ubiquitin ligase Cul4b to reduce replication stress in CD8⁺ T cells, allowing massive clonal expansion and viral clearance.

Schief and colleagues show that germline-targeting epitope scaffolds can elicit responses from rare broadly neutralizing antibody precursor B cells with predefined binding specificities and genetic features.

Collateral sensitivity-inducing mutations in methicillin-resistant Staphylococcus aureus strains lead to re-sensitization of bacteria to penicillin–clavulanic acid combinatorial treatment.

A strategy for inferring phase for rare variant pairs is applied to exome sequencing data for 125,748 individuals from the Genome Aggregation Database (gnomAD). This resource will aid interpretation of rare co-occurring variants in the context of recessive disease.

A genomic constraint map for the human genome constructed using data from 76,156 human genomes from the Genome Aggregation Database shows that non-coding constrained regions are enriched for regulatory elements and variants associated with complex diseases and traits.

Med-PaLM, a state-of-the-art large language model for medicine, is introduced and evaluated across several medical question answering tasks, demonstrating the promise of these models in this domain.