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GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

Loss-of-function mutations in Myosin Binding Protein C3, MYBPC3, are the most common genetic cause of hypertrophic cardiomyopathy. Here, the authors present an AAV9-based gene therapy system with an optimized expression cassette with minimal promoter and cis-regulatory elements that can ameliorate cardiac functions and prolong survival in a murine MYBPC3-deficient model.

Mutations accumulate with age in the male germline, and can lead to genetic diseases in offspring. Here, the authors collect from individuals sequential sperm samples separated by long timespans, which they profile by high-fidelity sequencing to study germline mutation processes.

The authors identify a neural population in the basal forebrain of mice that is key for maintaining energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.

Genome-wide association studies (GWAS) have become a key tool to discover genetic markers for complex traits; however, environmental factors that interact with genes are rarely considered. Here, the authors conduct a GWAS of obesity traits, and find that smoking may alter genetic susceptibilities.

Ito et al. present CoVFit, an AI model that predicts variant fitness (transmissibility) from spike protein sequences alone. They further demonstrate its utility in forecasting viral evolution via single amino acid mutations.

Erik Ingelsson and colleagues report a large-scale genome-wide meta-analysis for associations to the extremes of anthropometric traits, including body mass index, height, waist-to-hip ratio and clinical obesity. They identify four loci newly associated with height and seven loci newly associated with clinical obesity and find overlap in the genetic structure and distribution of variants identified for these extremes of the trait distributions and for the general population.

The structure of the GABA_B receptor in an inactive state reveals, amongst other features, a latch between the two subunits that locks the transmembrane domain interface, and the presence of large phospholipids that may modulate receptor function.

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.

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

A randomized trial in patients hospitalized with COVID-19 showed no benefit and potentially increased harm associated with the use of convalescent plasma, with subgroup analyses suggesting that the antibody profile in donor plasma is critical in determining clinical outcomes.

The acidophilic fungus Acrodontium crateriforme is present in traps of the carnivorous plant Drosera spatulata and promotes prey digestion.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Catfish represent 6.3% of all vertebrate species, and occupy a phylogenetic position close to the common ancestor of bony fish. Liu et al. present a reference genome of the channel catfish, and reveal a genomic basis for the evolutionary loss of scales in these species.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

In a mouse model of progeria, an adenine base editor delivered with adeno-associated virus corrects the pathogenic mutation in LMNA, rescues vascular pathology and markedly extends the lifespan of the mice.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

Two approaches using an adenine base editor and a Cas9 nuclease prevented the development of hypertrophic cardiomyopathy in mice carrying a pathogenic mutation on the Myh6 gene, highlighting the potential of single-dose genetic therapies for the treatment of cardiac disease.

In vitro library screening is a powerful approach to identify functional biopolymers, but only covers a fraction of possible sequences. Here, the authors use experimental in vitro selection results to train a conditional variational autoencoder machine learning model that generates biopolymers with no apparent sequence similarity to experimentally derived examples, but that nevertheless bind the target molecule with similar potent binding affinity.

BANKSY is an algorithm with R and Python implementations that identifies both cell types and tissue domains from spatially resolved omics data by incorporating spatial kernels capturing microenvironmental information. It is applicable to a range of technologies and is scalable to millions of cells.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

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.

Genome-wide association analysis in over one million individuals of European ancestry identifies 2,103 independent genetic signals (including 113 new loci) associated with blood pressure traits.

Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.

Chiea Chuen Khor, Tin Aung, Francesca Pasutto, Janey Wiggs and colleagues report a global genome-wide association study of exfoliation syndrome and a fine-mapping analysis of a previously identified disease-associated locus, LOXL1. They identify a rare protective variant in LOXL1 exclusive to the Japanese population and five new common variant susceptibility loci.

A multi-ancestry genome-wide association study for age at menarche followed by fine mapping and downstream analysis implicates 665 pubertal timing genes, such as the G-protein-coupled receptor 83 (GPR83) and other genes expressed in the ovaries involved in the DNA damage response.

Cell motion along linear confinements is deterministic. Now a model predicts deterministic oscillations in cellular polarization at a Y junction in a set-up with adhesive patterns.

Fasolino et al. provide insights into ductal cell roles and type 1 diabetes pathogenesis using a pancreatic islet single-cell atlas generated by the Human Pancreas Analysis Program.

The impact of genetic fusions on degrons, which are motifs for ubiquitin-mediated protein degradation, has not been fully explored. Here, the authors analyse fusion genes affecting degrons in pan-cancer genomics data, validate their functional impact and find enrichment for both internal and C-terminal degron losses.

Nitrogen monoxide at low concentrations can promote the formation of highly oxygenated organic molecules, which are crucial precursors to secondary organic aerosol (SOA), rather than inhibit it as traditionally thought.

This analysis of single-cell RNA sequencing data from peripheral blood mononuclear cells for 474 individuals of diverse Asian ancestries in the Asian Immune Diversity Atlas links cell-type-specific splicing variation with autoimmune and inflammatory disease risk.

Few aerobic hyperthermophilic microorganisms are known to degrade polysaccharides. Here, Nou et al. use genomic information to enrich and optical tweezers to isolate an aerobic hyperthermophilic bacterium that can grow at 65–87.5 °C using polysaccharides as sole carbon sources.

An RNA-binding protein on leukemia cells provides an effective target in mouse models.

A metal–organic framework (MOF)–pillar[5]arene hybrid can bind small molecules with long alkyl chains, such that single-crystal structures of the host–guest complexes can be obtained and therefore small molecular structures determined.

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.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Precise and reliable gene delivery remains technically challenging. Here, the authors show that rationally designed frameshifting splicing can be used to express genes only in targeted cell types, with the potential to enhance the specificity AAV gene delivery.

Autonomous hypermutation yeast surface display (AHEAD) mimics the process of somatic hypermutation in animals to enable the rapid in vitro evolution of antibodies, including nanobodies targeting the RBD of SARS-CoV-2.

Atoh7 is essential for retinal ganglion cell (RGC) genesis. Here the authors perform scRNAseq on embryonic mouse retina and conclude that Atoh7 defines a transitional state and that other factors also participate in establishing the RGC lineage.