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Results for the final phase of the 1000 Genomes Project are presented including whole-genome sequencing, targeted exome sequencing, and genotyping on high-density SNP arrays for 2,504 individuals across 26 populations, providing a global reference data set to support biomedical genetics.

Dense calcium imaging combined with co-registered high-resolution electron microscopy reconstruction of the brain of the same mouse provide a functional connectomics map of tens of thousands of neurons of a region of the primary cortex and higher visual areas.

In this Perspective, the international PAINDIFF Network makes 13 recommendations for studying sex and gender as variables in preclinical, clinical and translational pain research that are applicable across the spectrum of biomedical and psychosocial research.

Nir Hacohen, Bruce Walker, David Sabatini, Eric Lander and colleagues perform a CRISPR–Cas9-based screen for host factors that are required for HIV infection. They identify two known and three novel factors that are necessary for viral infection but that are not required for cell viability, making them potential targets for antiviral therapy.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

A genome-wide association meta-analysis study here shows novel genetic loci to be associated to body fat percentage, and describes cross-phenotype association that further demonstrate a close relationship between adiposity and cardiovascular disease risk.

Past genome-wide associate studies have identified hundreds of genetic loci that influence body size and shape when examined one trait at a time. Here, Jeff and colleagues develop an aggregate score of various body traits, and use meta-analysis to find new loci linked to body shape.

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

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

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.

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.

Doan et al. show that loss of cardiac NAD⁺ is sufficient to drive metabolic derangements, hypertrophic remodeling and lethal arrhythmias in adult mouse hearts, despite maintenance of ejection fraction and bioenergetics.

Siew et al. using multi-omic, physiological & imaging approaches have demonstrated that spaceflight causes kidney remodelling, suggesting a contribution to kidney stone formation, & that space radiation causes kidney damage & early signs of dysfunction.

A representation-learning strategy for machine-learning models applied to medical-imaging tasks improves model robustness and training efficiency and mitigates suboptimal out-of-distribution performance.

In the allohexaploid genome of wheat, meiotic recombination between homoeologues is suppressed through the action of several loci. Here, the authors report the cloning of the long sought-after gene Ph2 and show its function in reduction of homoeologous recombination.

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.

1000 Genomes imputation can increase the power of genome-wide association studies to detect genetic variants associated with human traits and diseases. Here, the authors develop a method to integrate and analyse low-coverage sequence data and SNP array data, and show that it improves imputation performance.

Several mechanisms have been put forward to explain tropical Pacific decadal variability, the contributions of which are debated. This Review outlines the different drivers of tropical Pacific decadal variability, summarizing that tropical pycnocline adjustment to wind forcing and Rossby wave activity is likely the dominant mechanism, albeit with uncertainty.

Lean body mass is a highly heritable trait and is associated with various health conditions. Here, Kiel and colleagues perform a meta-analysis of genome-wide association studies for whole body lean body mass and find five novel genetic loci to be significantly associated.

We report the outcome of an international optical observation campaign of a prototype constellation satellite, AST SpaceMobile’s BlueWalker 3, which features a 64.3 m² phased-array antenna and a launch vehicle adaptor.

A crow-sized stem bird, Falcatakely forsterae, possesses a long and deep rostrum—a beak morphology that was previously unknown among Mesozoic birds and is similar to that of some crown-group birds, such as toucans.

Sequencing data from two large-scale studies show that most of the genetic variation influencing the risk of type 2 diabetes involves common alleles and is found in regions previously identified by genome-wide association studies, clarifying the genetic architecture of this disease.

Data from the NASA GRAIL spacecraft recover the lunar gravity field suggesting preservation of a predominantly thermal anomaly in the nearside mantle, which could influence the spatial distribution of deep moonquakes.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Although Bayesian models provide good accounts of perceptual decisions, it is unclear how their components are represented in the brain. This paper addresses this question by showing that uncertainty decoded from visual cortex helps predict behavior.

It is unclear whether CO₂-stimulation of photosynthesis can propagate through slower ecosystem processes and lead to long-term increases in terrestrial carbon. Here the authors show that CO₂-stimulation of photosynthesis leads to a 30% increase in forest regrowth over a decade of CO₂ enrichment.

Circulating lipoprotein(a) is an important risk factor for cardiovascular disease and shows variability between different ethnic groups. Here, Zekavat et al. perform whole-genome sequencing in individuals of European and African ancestries and find ancestry-specific genetic determinants for lipoprotein(a) levels.

The mechanism of collagen heterotrimer folding is difficult to recapitulate synthetically. Now an ABC collagen mimetic heterotrimer has been designed that employs pairwise amino acid interactions, validated by X-ray crystallography, to promote composition- and register-specific assembly. The high specificity of its assembly leads to an increased rate of folding compared with similar collagen heterotrimers.

A study that tracked mammal populations before, during and after a severe storm in Mozambique’s Gorongosa National Park finds that behavioural responses and survival are linked to body size, with increased mortality of small species owing to limited mobility and changes in food availability.

The origin of the photoemission replica bands in monolayer FeSe/SrTiO₃ remains controversial. Here, the authors perform angle-resolved photoemission spectroscopy with polarized photon on FeSe/SrTiO₃ and observe high-order replica bands with high intensity from various Fe 3d bands, suggesting a mixed mechanism.

Genome-wide analysis of tandem DNA repeats in the genomes of individuals with autism spectrum disorder and control participants reveals a strong contribution of tandem repeat expansions to the genetic aetiology and phenotypic complexity of autism spectrum disorder.

Common genetic variants associated with plasma lipids have been extensively studied for a better understanding of common diseases. Here, the authors use whole-genome sequencing of 16,324 individuals to analyze rare variant associations and to determine their monogenic and polygenic contribution to lipid traits.

Molnupiravir is an antiviral that forces lethal error catastrophe in SARS-CoV-2 RNAs. Here, the authors confirm the mechanism of action of molnupiravir in humans using samples obtained from the UK’s AGILE phase IIa clinical trial investigating the antiviral efficacy of the drug against SARS-CoV-2. No treatment-associated SARS-CoV-2 mutations were identified.

Sensory data about most natural task-relevant variables are entangled with task-irrelevant nuisance variables. Here, the authors present a theoretical framework for quantifying how the brain uses or decodes its nonlinear information which indicates near-optimal nonlinear decoding.

Biomphalaria glabrata is a fresh water snail that acts as a host for trematode Schistosoma mansoni that causes intestinal infection in human. This work describes the genome and transcriptome analyses from 12 different tissues of B glabrata, and identify genes for snail behavior and evolution.

Whole-exome sequencing in a large autism study identifies over 100 autosomal genes that are likely to affect risk for the disorder; these genes, which show unusual evolutionary constraint against mutations, carry de novo loss-of-function mutations in over 5% of autistic subjects and many function in synaptic, transcriptional and chromatin-remodelling pathways.

Glycolytic enzymes are challenging drug targets due to their highly conserved active sites and phosphorylated substrates. Here, the authors identify fast acting allosteric inhibitors of Trypanosoma brucei phosphofructokinase that block trypanosome glycolysis and provide cure evidence in murine model.

Humans are exposed to millions of chemicals but mass spectrometry (MS)-based targeted biomonitoring assays are usually limited to a few hundred known hazards. Here, the authors develop a workflow for MS-based untargeted exposome profiling of known and unidentified environmental chemicals.

Multi-omics analyses of faecal, urine and blood samples from women with and without recurrent urinary tract infections reveal that gut dysbiosis and differential immune responses may play a role in risk of infection via the gut–bladder axis.

Harnessing information from whole genome sequencing in 185 individuals, this study generates a high-resolution map of copy number variants. Nucleotide resolution of the map facilitates analysis of structural variant distribution and identification of the mechanisms of their origin. The study provides a resource for sequence-based association studies.

Transcriptomic analyses of acute phase whole blood from a large cohort of patients with COVID-19 identify molecular determinants of post-infection long-term sequelae.

Mark McCarthy and colleagues identify twelve new risk loci for type 2 diabetes through a large-scale genome-wide association and replication study in individuals of European ancestry. The identified loci affect both beta-cell function and insulin action and are enriched for genes involved in cell cycle regulation.

Tropical teleconnections can influence polar climates through the generation of stationary Rossby waves. This Review outlines the dynamics and impacts of long-term tropical–polar connections on the Antarctic climate, which include warming trends and ice mass loss in West Antarctica.

Sporadic surface melt over the West Antarctic Ice Sheet is not fully understood. Here, the authors report on an extensive melting episode in the Ross Ice Shelf area in 2016 and use comprehensivein situobservations and model simulations to highlight the role of the strong El Niño event.