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The APOE-ε4 allele is the strongest genetic risk factor for late-onset Alzheimer’s disease, but it is not deterministic. Here, the authors show that common genetic variation changes how APOE-ε4 influences cognition.

Environmental justice and drinking water in the US: Higher proportions of Hispanic/Latino, American Indian/Alaskan Native, and non-Hispanic Black residents were associated with higher public water arsenic and uranium at the county-level, findings differed by region.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Kinematic measurements of the Perseus galaxy cluster reveal two drivers of gas motions: a small-scale driver in the inner core associated with black-hole feedback and a large-scale driver in the outer core powered by mergers.

Extrachromosomal DNA (ecDNA) drives oncogene amplification, tumour evolution and therapy resistance across cancers. This Review summarizes advances in ecDNA biology, highlights emerging therapeutic vulnerabilities and outlines strategies to improve ecDNA detection and translate ecDNA-targeted approaches from bench to bedside.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

CAR-T cell therapy has been shown to be effective in immunotherapy for treatment of several different tumours. Here the authors show pre-specified interim outcomes from a P-BCMA-ALLO1 trial with BCMA targeted CAR-T therapy in multiple myeloma.

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.

The first Nature Index table on the field shows how research in the East is focused on industrial strategy.

Nagano et al. identify the third mitotic cohesin complex, STAG3–cohesin, which, with its unique biophysical properties, weakens insulation and rewires regulatory interactions of spermatogonial stem cells, shaping the male germline nucleome.

Saur, Lesage et al. report that RNA:DNA hybrids arise at double-strand breaks in transcribed genes, independently of de novo recruitment of RNA polymerase II/III, as a result of DSB-induced transcriptional repression.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

Economic inequality is on the rise, and children will bear its burden. Yet children’s perspectives are rarely considered. We urgently need interdisciplinary research to better understand how inequality gets into children’s heads and under their skins, and to inform policies that center children’s lived experiences.

Impacts from a climate event can cascade through natural, anthropogenic and socio-economic systems. Here the authors assess cascading climate impacts on the EU and identify intervention points for adaptation related to water, livelihoods, agriculture, infrastructure and economy, and violent conflict.

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.

Large language models (LLMs) are emerging as powerful tools in healthcare, with a growing role in global health, particularly in low- and middle-income countries. This Perspective examines the current progress, challenges and prospects of LLMs in addressing health system disparities and supporting achievement of the Sustainable Development Goals.

Planting diverse forests is widely promoted as a way to counter climate change and improve ecosystem functioning. This study finds that the spatial arrangement of tree species matters: forests with higher spatial mixing of tree species yield greater biomass, faster nutrient cycling, and thus enhanced ecosystem functioning.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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).

Resistance mutations are challenging to characterize because their effects are highly context dependent. Here, authors present a quantitative mutant screening technique that deconstructs how factors like antibiotic mechanism and genetic background interact to govern resistance evolution.

The transition to sustainable diets is challenging for countries that face malnutrition and limited resources. Now a study explores how various dietary transformations in China can improve public health, make food affordable and reduce environmental impacts, while evaluating the feasibility of the diet changes.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

Integrating incomplete multi-omics data remains a key challenge in precision oncology. IntegrAO, an unsupervised framework that integrates diverse omics, enables accurate patient classification even with incomplete datasets.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

Segal and colleagues identify a population of immature neutrophils as having regenerative properties on injured neurons and being capable of inducing axon regeneration. These findings suggest potential strategies for restoring lost neurological functions in central nervous system disorders.

What is the state of trust in scientists around the world? To answer this question, the authors surveyed 71,922 respondents in 68 countries and found that trust in scientists is moderately high.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

Control of HIV and SIV infection is largely thought to be achieved through direct lysis of target cells. Here, using mathematical modelling of viral load data from rhesus macaques, the authors propose that virus control is best explained by the combination of cytolytic and non-cytolytic effects.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Humanized mice are an enabling technology to explore human immunity and disease. Here, Douam et al. provide an in-depth comparison of immune responses to yellow fever vaccine in human vaccinees, conventional and second-generation humanized mice and define a workflow to evaluate and refine these models.

The use of time-bin entangled qudits is hindered by the phase instability, timing inaccuracy and low scalability of current interferometric schemes. Here, the authors show a fiber-pigtailed photonic chip for generating and processing picosecond-spaced time-bin entangled qudits and utilize the system to implement a quantum key distribution protocol.

Study of human heart failure is limited by access to human tissue. Here, the authors apply multi-omic screening in human ischaemic and dilated myocardial tissue and matched controls to determine molecular changes common and unique to each aetiology and to reveal differences between male and female hearts.

For water-bear enthusiasts, it’s the creature’s legs that make it stand out.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

Kidney injury progression involves complex changes in cellular composition and spatial organization. Here, the authors use multimodal spatial transcriptomics to reveal fibro-inflammatory niche with Runx2 and integrin beta-2 driving fibrotic remodeling.

Aeneas, a generative neural network trained on ancient texts, helps historians contextualize inscriptions and perform epigraphic tasks, offering an improved starting point for historical research.

Ochre, a strain of Escherichia coli engineered to have a single stop codon, enables reassignment of four codons for non-degenerate functions, such as incorporation of non-standard amino acids into proteins.

Data collected from more than 2,000 taxa provide an unparalleled opportunity to quantify how extreme wildfires affect biodiversity, revealing that the largest effects on plants and animals were in areas with frequent or recent past fires and within extensively burnt areas.

Surprisingly consistent replication failure of gray matter correlates of childhood maltreatment raises questions about publication bias in prior literature and about prevailing models linking maltreatment to brain structure in adult populations.

Preece et al. show that B6SPRTF1 hybrid males between C57BL/6J and Mus spretus are suitable for the generation of pseudopregnant female mice for embryo transfer. By providing an alternative to vasectomized males, the method shows clear 3R benefits.

Machine-learning algorithms trained on 25,000 geolocated soil samples are used to create high-resolution global maps of mycorrhizal fungi, revealing that less than 10% of their biodiversity hotspots are in protected areas.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.