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The intestinal microbiome is shaped by genetics and environment. Here, the authors show in rats that host genetic effects, including indirect social effects, influence microbiome composition, identify replicated loci, and reveal mechanisms contributing to microbiome heritability.

Multi-omics and genetic models show that CGG repeat toxicity in GABAergic neurons drives FXTAS pathology and identify PRKCG as a critical modifier and potential therapeutic target.

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.

Li and colleagues present CellScope, a tree-structured framework that reveals multi-level cellular hierarchies and gene functions in single-cell data. This approach provides clear clustering, intuitive visualization, and deep biological views into cell types and functions.

Tan and colleagues develop DNA nanodevices to detect the pH of the lysosomal outer surface, observing an acidic layer generated by TMEM175 that regulates lysosome positioning in response to changes in juxta-lysosomal pH.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Researchers studied the blood-based metabolome of over 23,000 people from ten ethnically diverse cohorts. They identified 235 metabolites associated with future risk of type 2 diabetes (T2D). By integrating genetic and modifiable lifestyle factors, their findings provide insights into T2D mechanisms and could improve risk prediction and inform precision prevention.

The Taiwan Precision Medicine Initiative recruited and genotyped more than half a million Taiwanese participants, almost all of Han Chinese ancestry, and performed comprehensive genomic analyses and developed polygenic risk score prediction models for numerous health conditions.

Vitamin K-dependent carboxylation is vital for human health. Here, authors present cryo-EM structures of the relevant γ-glutamyl carboxylase, uncovering substrate recognition, processive modification, and a bicarbonate-mediated CO₂ fixation mechanism.

Mi et al. use de novo protein design to address bystander and off-target editing in base editing, resulting in a highly precise mitochondrial cytosine base editor that is valuable for studying and treating mitochondrial diseases.

The rapid expansion of agricultural irrigation raises concerns about exacerbating water scarcity, but land–atmosphere interactions are often overlooked. This study isolates irrigation impacts from other drivers using a multi-model framework to reveal that historical irrigation expansion substantially reduces net atmospheric water influx, intensifying drying trends and accelerating terrestrial water storage depletion, urging immediate mitigation strategies.

Polygenic scores for body mass index and obesity constructed using data from 5 million people with different ancestries were associated with distinct weight gain trajectories from early childhood to adulthood.

The CMS Collaboration reports the measurement of the spin, parity, and charge conjugation properties of all-charm tetraquarks, exotic fleeting particles formed in proton–proton collisions at the Large Hadron Collider.

Machine learning is increasingly used to support IVF pretreatment prognostic counseling. Here, the authors find that center-specific models improved IVF live birth predictions over a US registry model, and draw conclusions for improving IVF access, affordability and patient-centric counseling.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

An atomic stencilling method based on the co-adsorption of iodide and 2-naphthalenethiol on gold is described, yielding more than 20 different types of nanoparticle with masked and painted regions and patchy particle morphologies not reported previously.

The mechanisms linking neuropsychiatric and metabolic disorders remain unclear. The authors show a pancreas–hippocampus feedback loop whereby metabolic and circadian factors drive behavioral fluctuations, with potential relevance for bipolar disorder.

Genome-wide analysis in individuals of African ancestry identifies a nonsense variant in CD36 associated with increased risk of dilated cardiomyopathy (DCM), partly accounting for the higher incidence of DCM in African-ancestry populations.

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.

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.

Zaxinone is a novel ligand of the strigolactone (SL) receptor DWARF14 (D14) in Arabidopsis. It competitively binds the active site of D14 and acts as a long-lasting, non-hydrolysable antagonist of SL by blocking the interaction between D14 and MAX2.

A meta-analysis of genome-wide association studies of type 2 diabetes (T2D) identifies more than 600 T2D-associated loci; integrating physiological trait and single-cell chromatin accessibility data at these loci sheds light on heterogeneity within the T2D phenotype.

The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

The conventional focus on pore size distribution overlooks the role of surface charge homogeneity in ion separation by polymeric membranes. This study proposes a surface charge engineering strategy for fabricating highly ion-selective membranes.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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

This study reports an extended 2D gastruloid system for spatially modeling human mesoderm development.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

Targeting CD8⁺ T cell exhaustion is a strategy to enhance immune checkpoint inhibition and to fight cancer. Here the authors show a NRF2-dependent role for the prostaglandin I₂ receptor PTGIR in controlling T cell exhaustion.

This work presents SCIGEN, a machine learning framework integrating geometric constraints into material generation. The framework enables the discovery of stable quantum material candidates, and the authors synthesize two predicted magnetic materials.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

The authors present a process that boosts the piezoelectric properties of ScAlN thin films by 3.5 times, enhancing their performance for use in acoustic devices. The technique is scalable, cost effective, and could enable advanced sensors, clocks, and communication technologies.

Correlated errors coming from leakage out of the computational subspace are an obstacle to fault-tolerant superconducting circuits. Here, the authors use a multi-level reset protocol to improve the performances of a bit-flip error correcting code by reducing the magnitude of correlations.

Cosmic rays flying through superconducting quantum devices create bursts of excitations that destroy qubit coherence. Rapid, spatially resolved measurements of qubit error rates make it possible to observe the evolution of the bursts across a chip.

In a randomized controlled trial involving patients with heart failure with reduced ejection fraction, treatment with Qiliqiangxin, a traditional Chinese medicine derived from 11 types of plants, decreased the incidence of cardiac events, as compared to placebo.

Association analyses in over 1 million individuals identify 535 new loci influencing blood pressure traits. The results provide new insights into blood pressure regulation and highlight shared genetic architecture between blood pressure and lifestyle exposures.

Genome-wide association and fine-mapping analyses in ancestrally diverse populations implicate candidate causal genes and mechanisms underlying type 2 diabetes. Trans-ancestry genetic risk scores enhance transferability across populations.

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.