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Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Interleukin 9 secretion contributes to allergic inflammation. Kaplan and colleagues identify the transcription factor PU.1 as being necessary for T_H9 differentiation and as a contributing factor in allergic airway inflammation.

Whole genome sequences enable discovery of rare variants which may help to explain the heritability of common diseases. Here the authors find that ultra-rare variants explain ~50% of coronary artery disease (CAD) heritability and highlight several functional processes including cell type-specific regulatory mechanisms as key drivers of CAD genetic risk.

Whether multimorbidity accelerates brain Aβ deposition in humans remains largely unknown. Here, the authors demonstrate that higher self-reported multimorbidity burden predicts increased brain Aβ accumulation rates in the ADNI cohort.

Genome-wide association analysis of gout and urate identifies 148 new loci, implicating biological pathways and prioritizing candidate genes involved in inflammatory processes.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

A cell-based phenotypic screen led to the discovery of compounds called NVS-STGs, which bind to the N-terminal domain of STING and act as a molecular glue to induce higher-order oligomerization and activation.

The ATLAS Collaboration reports a measurement of the ratio of the decay rates of W bosons to τ leptons and muons, in agreement with universal lepton couplings as postulated in the standard model of particle physics.

Lung adenocarcinoma is often curable when diagnosed at an early stage, but a subsection of patients will progress. Here, the authors use multi-omics profiling to show that gene expression data can predict clinical outcome.

Cuprate superconductors are created by adding electrons or holes to a ‘parent’ compound. They have dissimilar phase diagrams and the asymmetry is further highlighted by unexpected collective modes measured using resonant inelastic X-ray scattering.

The immunostimulatory properties of TLR7/8 agonists, such as resiquimod, have been exploited for cancer immunotherapy. Here, the authors design platelet membrane-cloaked nanoparticles for selective intratumoral delivery of resiquimod, resulting in potent anti-tumor immune response in a range of preclinical solid tumors.

Whole-genome sequencing and association analysis of 270 Epstein–Barr virus (EBV) isolates from China identify two non-synonymous EBV variants within BALF2 that are strongly associated with the risk of nasopharyngeal carcinoma.

Metabolic dysregulation in the development of clear cell renal cell carcinoma (ccRCC) remains to be understood. Here the authors identify that a carnitine synthesis enzyme BBOX1, which inhibits TBK1-mTORC1 signaling and glycolysis, is often lost in ccRCC.

The ATLAS Collaboration reports the observation of the electroweak production of two jets and a Z-boson pair. This process is related to vector-boson scattering and allows the nature of electroweak symmetry breaking to be probed.

This work integrates duplex sequencing with cost-effective Ultima sequencing to enhance the accuracy of whole-genome circulating cell-free DNA profiling.

Longitudinal sampling is used to map the evolution of an HIV-1 virus from the time of infection, and the co-evolution of a broadly neutralizing antibody in the same infected patient; the findings have important implications for HIV vaccine development.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

PD-1 blockade can enhance antitumor responses in a subset of cases. Khleif and colleagues demonstrate that PD-1 blockade in the context of suboptimal T cell activation engenders a state of non-responsiveness but not when there is strong stimulation by vaccination.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.

The authors use long-term ground and satellite data to reveal the impact of drought on autumn date of foliar senescence (DFS). They link increased drought impacts to precipitation changes and plant functional traits and project earlier DFS by the end of the century, particularly at high latitudes.

The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

Shamsi et al. identify vascular smooth muscle cells marked by expression of Trpv1 as a part of the cellular lineage of brown and beige fat. Cold stimulates the expansion and differentiation of Trpv1-expressing progenitors to highly thermogenic adipocytes.

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.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

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.

Here the authors use cryo-EM to determine the structures of three bacterial flagellar filaments, revealing distinct outer domains. Upon further analysis of all AlphaFold predicted flagellar outer domains, they show that the outer domains of flagella are highly diverse.

To understand the contribution of variants to transcript expression regulation, long-read transcriptome data are generated from the GTEx resource, and a new software package to perform allele-specific analysis is developed.

Hydrogen-doping driven metal to ferroelectric phase transition in a complex oxide NdNiO₃ is demonstrated. Transient negative differential capacitance and implementation of polarization decay into neural network for learning are then presented.

Ruth Loos and colleagues report a meta-analysis of genome-wide association studies in 181,171 individuals identifying 14 new loci associated with heart rate and test these for association with cardiac conduction, rhythm disorders and cardiovascular disease. Their experimental studies in Drosophila melanogaster and zebrafish models provide support for a role for 20 candidate genes at 11 of these loci in regulation of heart rate.

An extended nonlinear recharge oscillator model shows skilful and explainable El Niño–Southern Oscillation forecasts at lead times up to 16–18 months, better than global climate models and comparable to the most skilful artificial intelligence forecasts.

The nature of the excitations in the pseudogap regime and their relation to superconductivity remain core issues in cuprate high-T_c superconductivity. Here, using resonant inelastic x-ray scattering, the authors find that high-energy excitons in optimally-doped Bi₂Sr₂CaCu₂O_8+δ are enhanced by the onset of superconductivity, an effect possibly explained in terms of electron fractionalization.

In Arabidopsis roots, NaCl induces the translocation of AtCLCf from the Golgi to the plasma membrane, mediated by the small GTPase AtRABA1b, where AtCLCf functions as a Cl⁻ efflux channel and confers salinity tolerance to the plant.

Lipid concentration in the serum is one of the most important risk factors for coronary artery disease and can be targeted for therapeutic intervention. A genome-wide association study in >100,000 individuals of European ancestry now finds 95 significantly associated loci that also affect lipid traits in non-European populations. Among associated loci are those involved in cholesterol metabolism, known targets of cholesterol-lowering drugs and those that contribute to normal variation in lipid traits and to extreme lipid phenotypes.

A multi-omic analysis of pancreatic cancer identifies spatially resolved, heterogeneous cell populations including transitional cell types. Analysis of primary samples identifies treatment-related changes in cross-talk between tumor and stromal cells.

The energy alignment at organic-metal interface has a strong influence on the performance of organic-based electronic devices. Lin et al.show this alignment can be tuned by varying the thickness of a uniform metallic thin film, which is confined between organic active layers and the substrate.

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.

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.

Genome-wide association analyses based on whole-genome sequencing and imputation identify 40 new risk variants for colorectal cancer, including a strongly protective low-frequency variant at CHD1 and loci implicating signaling and immune function in disease etiology.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.

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.

Using degron approaches, the authors show that cancer cells experiencing prolonged DNA methylation loss—without substantial DNA damage—undergo non-canonical senescence. This has important potential implications for cancer treatment.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Tree rings retain information of sudden variations of ancient radiocarbon (¹⁴C) content, however the origin and exact timing of these events often remain uncertain. Here, the authors analyze a set of Arctic tree rings and link a rapid increase in ¹⁴C to a solar event that occurred during the spring of AD 774.