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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.

JADE is a subunit of human acetyltransferase complex HBO1 that is essential in transcriptional regulation. Gaurav et al. characterize the molecular mechanism by which JADE mediates genomic association and enzymatic and pathological activities of the HBO1 complex.

Hedgehog signaling is essential for bone formation. Here, the authors show that the transmembrane protein SLITRK5 is a negative regulator of hedgehog signaling in osteoblasts, suggesting it may be a potential therapeutic target to enhance bone formation.

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.

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.

A genome-wide association study in large cohorts of patients with different types of cancer treated with immune checkpoint inhibitors identifies genetic variants associated with immune-related adverse events.

Ligands that activate GPCRs generally do so by stabilizing a particular conformation of the transmembrane helices. Here, the authors reveal a distinct activation mechanism where a ligand instead stabilizes a particular intracellular loop conformation.

Common-variant and rare-variant association analyses combining datasets from multiple populations yield insights into the genetic architecture of all-cause heart failure across the allele-frequency spectrum.

Post-traumatic stress disorder (PTSD) is a common mental health problem. Here, the authors report a GWAS from the Psychiatric Genomics Consortium in which they identify two risk loci in European ancestry and one locus in African ancestry individuals and find that PTSD is genetically correlated with several other psychiatric traits.

Jayavelu, Samaha et al., apply machine learning models on hospital admission data, including antibody titers and viral load, to identify patients at high risk for Long COVID. Low antibody levels, high viral loads, chronic diseases, and female sex are key predictors, supporting early, targeted interventions.

Here, the authors present multi-ancestry genome-wide meta-analyses of uterine fibroids, identifying 11 new gene associations, and demonstrating that heritability is higher in African ancestries.

Pathogen diagnostics are strong determinants of azithromycin effects on diarrhea duration, but host factors may better predict benefits for severe outcomes. In this work, authors utilise a machine learning-based approach to evaluate personalized rules for the decision to treat watery diarrhea with azithromycin.

Here, the authors show that the skin microbiome of a remote hunter-gatherer Yanomami community harbors environmental microbes that help maintain skin barrier integrity and combat oxidative stress—functions that are reduced by industrial lifestyles.

Analysis of 273 ancient horse genomes reveals that modern domestic horses originated in the Western Eurasian steppes, especially the lower Volga-Don region.

Analyses of the exposomes of populations across 40 countries found global disparities in healthy aging attributed to diverse biological, socioeconomic and political factors, with accelerated aging seen in populations from Egypt, South Africa, and Latin American and Caribbean regions.

This Viewpoint compares MammoSite^® brachytherapy with other forms of partial breast irradiation. Although very few reports on clinical efficacy have been published, indications so far are that the MammoSite^®catheter is technically simple, adequately spares normal tissues, and is associated with a favorable cosmetic outcome and toxicity profile. The choice of the optimal irradiation method remains complex and requires input from both treating physicians and their patients.

Integrated analysis of clinical, serological and behavioral data estimates that current clinical surveillance systems detect only 1 of 3,280 true community infections in a cholera-endemic region of Bangladesh.

The number of ligand binding sites in the dopamine transporter is enigmatic due to conflicting data from structures and molecular pharmacology. Here, force spectra reveal the position and dynamics of a previously invisible transient site.

Bild and colleagues identify convergent clonal evolution mechanisms through single-cell genomic analyses, explaining therapy resistance in patients with early-stage breast cancer treated with endocrine and CDK4/6 therapy in the FELINE trial.

In this Consensus Statement, an international panel of experts present an overview of the latest developments in the field of cholangiocarcinoma. A set of consensus recommendations and research priorities is provided.

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.

Grimes and colleagues integrate multiomic features to create a framework that allows the isolation of discrete cell states across hematopoiesis and exploit the underlying gene regulatory networks to identify lineage restriction within multilineage progenitors.

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Here the authors use the evolutionary model EVcouplings to computationally design highly mutated variants of TEM-1 ß-lactamase, and characterise these designs experimentally.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A diverse, multidisciplinary panel of 386 experts in COVID-19 response from 112 countries provides health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Analyses of pretransplant omics data from different cohorts of African American recipients found that genetic polymorphisms at the LILRB3 gene are associated with kidney graft loss.

Multi-ancestry genome-wide analyses identify new risk loci for age-related macular degeneration. Ancestry-specific analyses identify distinct effects at major risk loci, including smaller effect sizes for CFH risk alleles in haplotypes of African ancestry.

A combination of cell-based and biochemical approaches reveals how oncogenic fusion protein SS18-SSX directs BAF complexes to H2AK119Ub-modified nucleosomes to remodel chromatin at cancer-specific gene targets.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

A study identifies three dominant genomic archetypes of breast cancer induced by discrete mutational processes, describing a continuum of genomic profiles and detailing the mechanisms underlying the progression of breast cancer.

Adoro and colleagues report the involvement of the IRE1α–XBP1 signaling axis in protecting hematopoietic stem and progenitor cells from proteomic stress and as a safeguard against leukemic transformation.

Fouling of solid surfaces is a problem when designing microchannel systems for applications such as bioassays and drug delivery. Here Hou et al. propose a way to overcome this issue by controlling fluid flow by means of an immiscible functional liquid partly infiltrated in a porous solid matrix.

In this Perspective, authors from the Polygenic Risk Methods Development (PRIMED) Consortium highlight the ethical and analytical impact of population descriptors in polygenic risk score development and advocate for documenting detailed justifications.

Observations and samples from the central Himalayas show that a giant rockslide occurring around 1190 ad in the Annapurna massif led to the collapse of an elevated palaeo-summit, illustrating the episodic mode of erosion of the glaciated high relief by mega-rockslides.

A proteomic risk score for cardiorespiratory fitness, comprising as few as 21 proteins, is dynamic with exercise training and helps predict the risk of mortality and a range of cardiovascular, metabolic and neurological conditions.

The proton insertion mechanism in α-molybdenum trioxide remains incompletely elucidated. Herein, the authors uncover a three-proton intercalation mechanism within α-molybdenum trioxide using a specially designed electrolyte, which endows α-molybdenum trioxide with an improved specific discharge capacity.

How SARS-CoV-2 enters cells and causes COVID-19 is still under intensive investigation. Here, the authors identify unexpected crosstalk between human coronavirus and filovirus entry and discover pan-inhibitors for these highly pathogenic viruses.

Solid organ transplant recipients are at increased risk of infectious disease and have unique molecular pathophysiology. Here the authors use host-microbe profiling to assess SARS-CoV-2 infection and immunity in solid organ transplant recipients, showing enhanced viral abundance, impaired clearance, and increased expression of innate immunity genes.

Analysis of ground-sourced and satellite-derived models reveals a global forest carbon potential of 226 Gt outside agricultural and urban lands, with a difference of only 12% across these modelling approaches.

This study identifies temporal and coordinately regulated cell-state-specific super-enhancers driving the expression of transcription factors that control circuits needed to switch neuroblastoma tumor cells from self-renewal to differentiation.

A multi-ancestry genetic meta-analysis identifies 12 new loci associated with preeclampsia and gestational hypertension and proposes the integration of polygenic scores and clinical factors for disease prediction