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cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The BNT162b2 COVID-19 vaccine has been shown to reduce viral load of breakthrough infections (BTIs). Here, analyzing viral loads of BTIs post third vaccine shot, Levine-Tiefenbrun et al. show waning of the booster’s effectiveness in reducing infectiousness within months, mirroring the rate and magnitude of decline observed post the second shot.

uPAR is a senescence-associated protein, and CAR T cells targeting uPAR exert senolysis. Here Eskiocak et al. identify uPAR⁺ cells as key targets of intestinal aging and show that CAR T-mediated elimination prevents and restores age-related decline in intestinal regeneration and barrier function.

High entanglement fidelity between neutral atoms is achieved using highly excited Rydberg states. The unique electron structure provided by alkaline-earth atoms makes it a promising platform for various quantum-technology-based applications.

Survey data collected across ten low-income and middle-income countries (LMICs) in Asia, Africa and South America compared with surveys from Russia and the United States reveal heterogeneity in vaccine confidence in LMICs, with healthcare providers being trusted sources of information, as well as greater levels of vaccine acceptance in these countries than in Russia and the United States.

The trihydrogen cation (H3+) plays a key role in the interstellar chemistry. Here the authors, using state of the art experiments and computation, identify factors that govern H3+ formation from doubly ionized small organic molecules, offering guidelines for examining alternative sources of H3+ in the universe.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

Breakthrough infections of SARS-CoV-2 occurring 12 or more days after the first dose of the BNT162b2 mRNA vaccine were associated with lower viral loads than those found in unvaccinated individuals, suggesting that the vaccine might reduce infectiousness.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

About 15,000 pairwise interactions within S. epidermidis from 18 people in 6 families reveal the antagonism and molecular trade-offs that shape the skin microbiota.

Early alcohol drinking confers greater risk for alcohol use disorder in women than men. Here authors show that ovarian-derived estrogen rapidly drives binge alcohol drinking via signaling with membrane-associated estrogen receptors in the extended amygdala.

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.

Vaccination with BNT162b2 is associated with lower viral load in breakthrough infections of SARS-CoV-2, but this effect wanes at 2 months and vanishes at 6 months after vaccination. A third vaccine dose—or booster—restores the reduction in viral load.

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.

Observations from the Lucy spacecraft of the small main-belt asteroid (152830) Dinkinesh reveals unexpected complexity, with a longitudinal trough and equatorial ridge, as well as the discovery of the first contact binary satellite.

Large-scale sequence-based analyses identify novel risk variants and susceptibility genes for Crohn’s disease, and implicate mesenchymal cell-mediated intestinal homeostasis in disease etiology.

The accumulation of senescent cells drives age-related diseases. In this study, the authors show that senolytic CAR T cells can rejuvenate metabolic function and fitness in old mice and that a single dose is sufficient to lead to long-term preventive effects.

A new tool to visualize high-dimensional single-cell data, when integrated with mass cytometry, reveals phenotypic heterogeneity of human leukemia.

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.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

The direct detection of metabolites secreted by cells can indicate how cellular dynamics affects population development. Here, the authors present an integrated circuit-based method for electrochemical imaging of redox-active signalling molecules with spatial resolution within bacterial colonies.

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.

Analyses of the proportions of individuals who have completed key levels of schooling across all low- and middle-income countries from 2000 to 2017 reveal inequalities across countries as well as within populations.

High-resolution subnational mapping of child growth failure indicators for 105 low- and middle-income countries between 2000 and 2017 shows that, despite considerable progress, substantial geographical inequalities still exist in some countries.

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.

Palantir uses single-cell RNA-seq data to generate continuous models of differentiation, infer developmental trajectories, and calculate the probabilities of cell fate choices.

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.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

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

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

A genome-wide association study identifies 17 genetic loci that are associated with the risk of myeloproliferative neoplasms (MPNs), and shows that the modulation of haematopoietic stem cell function drives MPN risk.

High tree species diversity in tropical forests is driven by reduced interspecific competition relative to intraspecific competition, as a result of the asynchronous timing of tree recruitment permitted by long and stable growing seasons.

Rich evidence of the potential co-benefits and trade-offs of natural climate solutions is available but remains poorly understood. Assessing the literature with machine learning methods, this study maps and analyses the growing evidence of trade-offs in natural climate solutions globally.

Acute myeloid leukemia (AML) is genetically a very heterogeneous disease. Here, Erdem et al. uncover heterogeneity in the metabolic landscape of AML and identify Pyruvate dehydrogenase kinase 1 (PDK1) as a targetable determinant of different metabolic states in distinct subtypes of AML.