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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.

Walmsley and colleagues report that systemic hypoxia induces persistent loss of histone H3K4me3 marks and epigenetic reprogramming in neutrophil progenitors, resulting in long-term impairment of subsequent neutrophil effector functions.

Long COVID has heterogeneous presentation and clinical trajectories are not well defined. Here, the authors define trajectories using data from a prospective cohort study in the United States involving symptom questionnaires from acute infection up to 15 months.

Artifact mutations from FFPE are a major barrier blocking WGS adoption in clinical oncology. FFPErase, a machine learning framework, eliminates these with high accuracy in multiinstitutional datasets, delivering clinical-grade variant reports.

GPSeq is a genome-wide method for probing the radial organization of the genome in cells or nuclei by progressive in situ digestion of chromatin with a restriction enzyme diffusing inward from the periphery followed by high-throughput sequencing.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Here the authors develop a novel statistical method for quantifying mutation burden from whole genome sequencing data and use it to discover the genetic, genomic, and phenotypic correlates of clonal hematopoiesis without known driver genetic lesions.

The role of rare pathogenic/likely pathogenic (P/LP) germline variants in pediatric central nervous system (CNS) tumour development remains poorly understood. Here, the authors investigate the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumour patients.

Polygenic risk scores can help identify individuals at higher risk of type 2 diabetes. Here, the authors characterise a multi-ancestry score across nearly 900,000 people, showing that its predictive value depends on demographic and clinical context and extends to related traits and complications.

Targeting TGFBR1 in transplantable mouse colorectal tumor organoids improves response to anti-PD-L1 therapy. Mechanistically, TGF-β abrogates clonal expansion of T effector and memory phenotypes and indirectly inhibits T cell activity by regulating immunosuppressive tumor-associated macrophage activity.

Breast cancer has been associated with long term negative personal and household level economical impact in survivors. Here the authors find that while financial losses exist across the population, they are mitigated by robust social safety nets however, certain subgroups including students and individuals with poor baseline health, experience a disproportionate economic burden that persists long after diagnosis.

Despite improving therapeutic options, the prognosis for patients with metastatic castration-resistance prostate cancer (mCRPC) remains poor. Here, the authors identify MCL1 copy number alterations as a prognostic and predictive biomarker, demonstrating its therapeutic potential as a drug target, either alone or in combination, in patients with mCRPC.

Mussels produce a dynamic bio-interface between their living tissue and their non-living byssus attachment, relevant for design of implant devices. Here, authors discover a mechanoresponsive protein that may mediate mechanosensing at the interface.

The influence of pregnancy on Long COVID is not well understood. Here, the authors use electronic health record data from the United States to compare the incidence of Long COVID in females after infection in pregnancy with matched non-pregnant females of reproductive age.

Here the authors perform a trans expression quantitative trait locus meta-analysis study of over 3,700 people and link a USP18 variant to expression of 50 inflammation genes and lupus risk, highlighting how genetic regulation of immune responses drives autoimmune disease and informs new therapies.

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.

New research finds that policymakers coleading energy scenario design has the potential both to better align scenarios with policymakers’ priorities and to question current policy, by substantially reducing energy use at half of the cost of technology-focused approaches.

Despite being consumers, nitrite-oxidizing bacteria contribute to the accumulation of nitrite in marine oxygen minimum zones through interactions with other microbes, in particular denitrifiers, according to ecosystem and regional ocean modelling.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Otopetrins form proton channels in animals ranging from nematodes to humans. Here, authors identify small molecule inhibitors and characterize their binding in the intrasubunit interface region, thus highlighting the area for pharmacological targeting for channel modulation.

A new strategy that uses prime editing to convert an endogenous tRNA into a suppressor tRNA shows therapeutic potential for multiple genetic diseases that are caused by premature stop codons.

A recombinant antivenom composed of eight nanobodies provides broad protection against venom-induced lethality and dermonecrosis in mice challenged with venoms from cobras, mambas and rinkhals snakes.

Decoding cell identity from DNA alone is a challenge. Here, the authors demonstrate that counting transcription factor motifs in regulatory DNA can forecast cell-type specificity outperforming deep-learning models.

Findings from a tectonically active mountain range show that soil production is driven by bottom-up rock weakening rather than by soil thickness, challenging long-held top-down models.

Seagrass genomes of the deep-water Zostera pacifica and shallow-water Z. marina from the Eastern Pacific Ocean provide evidence for low-light adaptation exemplified in the wild hybrid Z. marina × pacifica subjected to low-light stress in aquaria.

Genome-wide CRISPRi screens for modulators of androgen receptor (AR) protein levels using live-cell quantitative endogenous AR fluorescence reporters identify PTGES3 as a new regulator of AR stability and function in prostate cancer.

Pancreatic cancer progression is driven by a switch from HNF4G-driven transcriptional activity in primary disease to FOXA1-mediated transcription in the metastatic setting.

A previously uncharacterized microbial enzyme is responsible for the production of molecular hydrogen in the gut, which drives the growth of other bacteria and has implications for human health.

This study reconstructs the evolution of leaf venation networks, describing the transition from fewer, corrugated veins to high vein density and smoother loops. It also suggests herbivory as a potential driver of venation architectural changes.

Potthoff and colleagues present a MALDI-MSI-based method that integrates in-source brightfield and fluorescence microscopy, which allows for spatially-resolved analysis of lipids and metabolites at the (sub)cellular level.

Eggplants are important vegetables worldwide. Here, the authors report 40 genome assemblies of Solanum melongena, its progenitor S. insanum and the allied species S. incanum to construct two pangenomes, and identify loci associated with multiple traits via pangenome-wide association analysis.

Living plant collections hold an immense wealth of plant diversity and have critical educational, scientific and conservation roles. This Perspective examines current data management practices of living collections and advocates for higher data standards and a robust and inclusive global data ecosystem.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Stem cell differentiation is controlled by manipulating RNA condensates.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

Hepatitis C virus (HCV) variability and its phenotypic consequences aren’t well studied in relation to viral replication fitness and disease severity. Here, the authors identify a replication-enhancing domain in non-structural protein 5A, linking high replication fitness to severe disease outcomes, with implications for understanding HCV pathogenesis in immunocompromised patients.

The roles of distinct dopaminergic neuron subpopulations and the circuit projections driving their activity during threat behaviors remain incompletely understood. Here, the authors demonstrate that substantia nigra pars lateralis dopamine neurons receive selective, robust excitation from auditory and temporal association cortices, which, combined with rapid action potential firing, contributes to auditory threat conditioning.

The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of inactivating many tumor suppressor genes, which may contribute to the deceleration in cancer incidence with extreme age in humans.

Gene expression programs underlying memory are not well understood in Drosophila. Here, authors use mushroom body-specific RNA sequencing to characterize the transcriptional trace of long-term memory and key TFs that may regulate it.

The authors identify defective viral particles, in people with non-suppressible HIV-1, that can replicate through superinfection and interfere with the wild-type virus. However, they show no evidence of these preventing disease progression in the individuals studied.

JWST data show that the exoplanet WASP-18b has thermally distinct regions of its dayside. The authors mapped the sizes of these regions, measured their temperatures and potentially identify water destruction in the hottest region.

NextBrain is an open source, probabilistic atlas of the entire human brain, assembled using artificial-intelligence-enabled registration and segmentation methods to reconstruct the multimodal serial histology of five human half brains, and which can be used to automatically segment brain MRI scans into 333 regions.

Epiphytic plants are a highly biodiverse group of tropical species at high risk of extinction from climate change. In this study, a multi-year transplant experiment, paired with distributional surveys in Central America, shows that many of these species may not survive projected changes in climate, providing empirical evidence for hypotheses raised by previous studies.