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Both rare and common variants contribute to the aetiology of complex traits such as type 2 diabetes (T2D). Here, the authors examine the effect of coding variation on glycaemic traits and T2D, and identify low-frequency variation in GLP1Rsignificantly associated with these traits.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

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.

RMC-7977, a multi-selective RAS(ON) inhibitor, exhibits potent tumour-selective activity in multiple pre-clinical models of pancreatic ductal adenocarcinoma through a combination of pharmacology and oncogene dependence.

A large, open dataset containing parallel recordings from six visual cortical and two thalamic areas of the mouse brain is presented, from which the relative timing of activity in response to visual stimuli and behaviour is used to construct a hierarchy scheme that corresponds to anatomical connectivity data.

This study examines the impact of destructive wildfires on human migration in the contiguous United States, showing that only the most extreme events affected existing migration trends. Migration in response to wildfire building destruction was rare, while immobility was a more common response.

Two doses of the coronavirus disease 2019 vaccine ChAdOx1 nCoV-19 boost antibody responses and functions in phase 1/2 trial participants.

The authors summarize the data produced by phase III of the Encyclopedia of DNA Elements (ENCODE) project, a resource for better understanding of the human and mouse genomes.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Mutations of ESR1, the gene encoding the estrogen receptor alpha, are associated with acquired resistance to therapy in luminalbreast cancer. Here the authors show that ESR1 mutant tumors gain basal-like features with increased expression of basal cytokeratines and immune activation.

Neuroendocrine differentiation of epithelial tumor cells can contribute to cancer cell resistance and survival. Here, the authors show that dysregulated c-Myc promotes neuroendocrine differentiation in pancreatic ductal adenocarcinoma, leading to poor survival and chemoresistance.

In a re-analysis of a cluster-randomized trial on malaria-control measures, the combined intervention reduces infections up to 3 km from the point of intervention, increasing efficacy and cost-effectiveness of the intervention.

There is an unmet need to improve the response to immune checkpoint blockade in patients with head and neck squamous cell carcinoma (HNSCC). Here the authors show that aberrant HER3 activation sustains the proliferation of PIK3CA wild type HNSCC cells and that HER3 inhibition increases response to PD-1 blockade in HNSCC preclinical models.

Detailed clinical and virologic characteristics of the first 12 individuals with COVID-19 in the United States from the US Centers for Disease Control and Prevention.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

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.

The heterogeneity of whole-exome sequencing (WES) data generation methods presents a challenge to joint analysis. Here, the authors present a bioinformatics strategy to generate high-quality data from processing diversely generated WES samples, as applied in the Alzheimer’s Disease Sequencing Project.

A first-in-human study of an antisense oligonucleotide targeting hepatitis B virus (HBV) RNA provides initial insights into this potential new therapeutic modality for individuals with chronic HBV infection.

Expression of the Epstein–Barr virus protein LMP1 in B cells increases expression of—and promotes T cell responses to—tumour-associated antigens, delineating a mechanism of infection-induced anti-tumour immunity, which could inform immune-based approaches to cancer treatment.

Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

A family of calcium-dependent protein kinases (CDPK), containing a calcium-binding ___domain, is present in apicomplexan parasites, ciliates and plants, but not in animals. Now crystal structures of CDPKs from Toxoplasma gondii and Cryptosporidium parvum in their apo or calcium-bound states reveal the structural reorganization induced by calcium that results in activation.

Body axis elongation from head to tail is essential for animal development, however, the spatial cues that direct cell rearrangements relative to the anterior–posterior axis were unknown; this Drosophila study of convergent extension reveals that three Toll family receptors, expressed in overlapping stripes, modulate the contractile properties of cells to generate the polarized cell rearrangements that lead to body axis elongation.

The CNV analysis group of the Psychiatric Genomic Consortium analyzes a large schizophrenia cohort to examine genomic copy number variants (CNVs) and disease risk. They find an enrichment of CNV burden in cases versus controls and identify 8 genome-wide significant loci as well as novel suggestive loci conferring either risk or protection to schizophrenia.

This study uses gene expression predictors for the dorsolateral prefrontal cortex and other brain regions to perform a transcriptomic imputation analysis of schizophrenia, identifying 413 genic associations across 13 brain regions and 36 significantly enriched pathways.

After two doses of the BNT162b2 vaccine, virus-specific antibodies and T cells were reduced in patients with solid tumors as compared to individuals without cancer, but neutralizing antibodies increased in most patients who received a third vaccine dose.

The Human Microbiome Project Consortium has established a population-scale framework to study a variety of microbial communities that exist throughout the human body, enabling the generation of a range of quality-controlled data as well as community resources.

Determining progress in adaptation to climate change is challenging, yet critical as climate change impacts increase. A stocktake of the scientific literature on implemented adaptation now shows that adaptation is mostly fragmented and incremental, with evidence lacking for its impact on reducing risk.

A single dose of the ChAdOx1 nCoV-19 vaccine elicits antibodies and cytokine-producing T cells that might help control or prevent SARS-CoV-2 infection.

Results from a phase 1 clinical trial show that a broadly neutralizing, HIV-specific antibody is durably expressed in vivo from a viral vector, highlighting an alternate approach for the delivery of antibodies in humans.

First-in-human trial of a self-assembling, ferritin nanoparticle-based influenza vaccine shows evidence that this new platform can elicit neutralizing and cross-reactive antibodies and has potential for further vaccine development.

By comparing neural responses to diverse visual stimuli measured with a standardized two-photon imaging pipeline, the authors reveal response specializations within the mouse visual cortex.

Relatives of patients with amyotrophic lateral sclerosis have an unexpectedly high incidence of schizophrenia. Here, the authors show a genetic link between the two conditions, suggesting shared neurobiological mechanisms.

The authors defined a roadmap for investigating the genetic covariance between structural or functional brain phenotypes and risk for psychiatric disorders. Their proof-of-concept study using the largest available common variant data sets for schizophrenia and volumes of several (mainly subcortical) brain structures did not find evidence of genetic overlap.

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.

Schizophrenia is a highly heritable genetic disorder, however, identification of specific genetic risk variants has proven difficult because of its complex polygenic nature—a large multi-stage genome-wide association study identifies 128 independent associations in over 100 loci (83 of which are new); key findings include identification of genes involved in glutamergic neurotransmission and support for a link between the immune system and schizophrenia.

Detection of structural variants in the human genome is facilitated by a benchmark set of large deletions and insertions.

The neural mechanisms through which neurons represent simultaneously presented stimuli are not well understood. Here the authors demonstrate that the two stimuli are alternately encoded through fluctuations in the activity patterns of single neurons.

Genomic characterization of the SARS-CoV-2 Omicron lineages BA.4 and BA.5, responsible for the fifth COVID-19 pandemic wave in South Africa, shows continued viral diversification and provides insights into the potential mechanisms underlying the ability of the new lineages to outcompete their predecessors.

The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community.