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Increasing dietary carbohydrate-to-fat ratio in a randomized controlled feeding study altered circulating small molecules (metabolites), including ones associated with diabetes risk, underscoring important metabolic effects of dietary composition.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Understanding collective behaviour is an important aspect of managing the pandemic response. Here the authors show in a large global study that participants that reported identifying more strongly with their nation reported greater engagement in public health behaviours and support for public health policies in the context of the pandemic.

This study demonstrates the capability of deep learning protein design models in generating functionally validated β-strand pairing interfaces, expanding the structural diversity of de novo binding proteins and accessible target surfaces.

Global Burden of Disease estimates show that between 1990 and 2023, the prevalence and burden of drug use disorders, inclusive of amphetamine, cannabis, cocaine and opioid use, have been increasing in high-income countries, particularly in the USA.

NatD is an acetyltransferase responsible for N-α-terminal acetylation of the histone H4 and H2A and has been linked to cell growth. Here the authors show that NatD-mediated acetylation of histone H4 serine 1 competes with the phosphorylation by CK2α at the same residue thus leading to the upregulation of Slug and tumor progression.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

This work identifies ERECTA–EPFL genes as major regulators of maize meristem activity and the development of maize shoots and ears. The findings highlight genetic targets that influence kernel row number and plant architecture to increase maize yield.

The xylosyltransferase isoenzymes XT1 and XT2 catalyze the first glycosylation step in the biosynthesis of proteoglycans. Now, bump-and-hole engineering of XT1 and XT2 enables substrate profiling and modification of proteins as designer proteoglycans to modulate cellular behavior.

Multi-trait genome-wide analyses identify variants associated with comorbid lung diseases. Polygenic scores leveraging shared components of heritable risk improve prediction of asthma, chronic obstructive pulmonary disease and lung cancer in a multi-ancestry cohort.

Two-dimensional poly(arylene vinylene) frameworks are promising polymer semiconductors, yet obtaining highly crystalline materials is a major challenge. Now a series of 11 highly crystalline or single-crystalline 2D poly(arylene vinylene)s have been prepared—from 2D imine-linked covalent organic frameworks through a Mannich-elimination strategy—with diverse lattices, enhanced conjugation and specific surface areas up to 2,000 m² g⁻¹.

Pyramidal neuron-driven mechanisms actively promote the survival and terminal differentiation of their associated interneuron subtypes.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

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.

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.

Seasonal variation in K isotopes of rivers that drain the Chinese Loess Plateau indicates that riverine K isotopes can trace changes in silicate weathering intensity over time, offering a tool to track Earth’s climate–rock interactions.

Tools to identify who will develop Crohn’s disease in the future are limited. Here, the authors develop and validate a proteomics-based model that predicts disease onset up to 16 years before clinical diagnosis.

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.

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.

Natural disasters induce power outages with unequal impacts on poverty and non-poverty counties in China. Climate change will further exacerbate this disparity.

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.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

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.

China’s crowded coasts must balance seafood demand with conserving migratory shorebirds that rely on tidal flats along the East Asian–Australasian Flyway. This study suggests that well-managed mariculture feeds shorebirds and limits overharvest, benefiting seafood production and biodiversity.

Proton-exchange membrane water electrolysers rely on iridium to catalyse their anodic reaction, and while ruthenium is a less costly alternative due to its similar activity, it is not as stable. Now, a hierarchical machine-learning catalyst discovery workflow, termed mixed acceleration, is put forward to predict catalyst synthesis, activity and stability, and identify promising RuO_x-based water oxidation catalysts.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

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

Mapping of the neutrophil compartment using single-cell transcriptional data from multiple physiological and patological states reveals its organizational architecture and how cell state dynamics and trajectories vary during health, inflammation and cancer.

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.

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.

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.

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.

An architecture inspired by Hopfield networks based on a programmable, stable, room-temperature optoelectronic oscillator-based photonics Ising machine is introduced that can be used to efficiently address optimization and combinatorics problems.

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.

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.

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.

Vaccinations against the SARS-CoV-2 KP.2 variant were introduced for the 2024-25 season in the United States. Here, the authors investigate the effectiveness of these vaccines up to April 2025 through a target trial emulation study using electronic health record data.

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.

SLFN11 is a predictive marker of chemosensitivity that results in elevated replication stress, but how it regulates replication fork dynamics remains unclear. Here, the authors use super-resolution microscopy to determine how SLFN11 inhibits the function of RFWD3- PRIMPOL to suppress fork restart.

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.

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.

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.

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.