Search

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

By comparing newly produced RNA in the nucleus with mature RNA in the cytosol, genetic variants that control gene expression showed striking differences in localization and biological mechanisms, helping explain how they contribute to disease.

Daratumumab, an anti-CD38 monoclonal antibody, was recently approved for patients with high-risk smoldering myeloma to prevent progression to overt myeloma. Here, the authors present results on a Phase II trial of daratumumab in patients of earlier stage to determine response and safety in that population.

Global Burden of Disease analysis found that in 2023, suboptimal diet was estimated to be responsible for 4 million deaths and 97 million morbidity burdens from ischemic heart disease.

Electrocatalytic CO₂ reduction is often hindered by the competing hydrogen evolution reaction, reducing selectivity for the desired products. Here the authors demonstrate that helical chiral copper electrodes can suppress hydrogen evolution by generating spin-polarized carriers through the chiral-induced spin selectivity effect.

A technique called condense-seq has been developed to measure nucleosome condensability and used to show that mononucleosomes contain sufficient information to condense into large-scale compartments without requiring any external factors.

Genome-wide analyses identify genetic loci and plasma proteins associated with polycystic ovary syndrome (PCOS). This study highlights the hormonal and metabolic foundations of the disease and explores the impact of polygenic risk for PCOS in both sexes.

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.

Snyder et al. analyze two population-based birth cohorts to test associations of newborn metabolite concentrations and childhood respiratory outcomes. C4, C10:1, C18:2, and citrulline are associated with early-life wheezing and asthma, with C18:2 specifically associated with increased non-allergic asthma risk.

A brief digital CBT self-help programme paired with screening improved mental health and service use among college students, offering a scalable way to support diverse populations and reduce symptoms across multiple conditions.

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.

In a first-in-human trial combining the transplantation of CD33-negative CRISPR-edited hematopoietic cells with the CD33-targeted antibody–drug conjugate gemtuzumab ozogamicin, all transplanted patients achieved primary engraftment, and the treatment was well tolerated.

Here the authors show in a longitudinal cohort with up to 3 years follow-up that paediatric long COVID comprises temporally structured immunometabolic subgroups shaped by disease phase, EBV imprinting and autoreactivity. Recovery-associated features track with milder impairment and support stratification.

This study explores the clonal architecture of aplastic anemia across age using single-cell approaches. Somatic inactivation of specific human leukocyte antigen risk alleles is a frequent event and often occurs in multiple independent events.

An analysis of 5,778 domains 28–64 amino acids in length reveals hidden variation in conformational fluctuations, even between sequences sharing the same fold and global folding stability.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Exposome analyses across 34 countries showed that social exposures were associated with faster functional brain aging and physical exposures with faster structural brain aging.

In photosynthesis, cytochrome c₆ (Cyt c₆) has been evolutionarily replaced by plastocyanin as the electron donor to Photosystem I (PSI). Here, the authors present the cryo-EM structure Cyt c₆: PSI complex from green algae, revealing both novel and ancestral features of donor:PSI interactions.

Decreased brain volumes and increased NfL levels can be observed earlier than disease diagnosis in short-tandem-repeat-associated neurological diseases.

Plasma phosphorylated tau 217 levels predict future accumulation of Alzheimer’s disease pathology in cognitively unimpaired older adults without elevated brain amyloid-β (“A-”) on positron emission tomography.

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).

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

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.

Peripartum cardiomyopathy (PPCM) is a potentially fatal heart condition with poorly understood molecular causes. Here, the authors show that loss of the protein PTRH2 in female mice leads to postpartum heart failure, identifying it as a potential therapeutic target.

Viruses exploit host cell machinery for replication, but their spatial cues remain elusive. Using nanochip-enabled membrane shaping, the authors discover saddle curvature association of viral proteins, revealing a new spatial regulation mechanism.

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.

Mass-wasting deposits that accumulated against mid-ocean ridge faults have high porosity in which calcium carbonate precipitated, storing seawater carbon dioxide, as revealed by cores of a 61-million-year-old seafloor talus deposit.

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

Genome-wide association meta-analysis identifies 58 independent risk loci for major anxiety disorders among individuals of European ancestry and implicates GABAergic signaling as a potential mechanism underlying genetic risk for these disorders.

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.

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.

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.

Macrophage-dependent phagocytosis elicits robust antitumor immunity. Nevertheless, therapeutic strategies harnessing phagocytosis have been met with limited success. Here the authors demonstrate that dual-phagocytosis checkpoint blockade, achieved by simultaneously targeting CD47 and CD24, greatly enhances tumor cell phagocytosis thus increasing antigen-presentation capacity, cGAS-STING activation and T cell infiltration into the tumor microenvironment, ultimately fostering robust antitumor immunity in preclinical mouse models of glioblastoma.

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.

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.

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.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

Annotating regulatory elements in domestic animal genomes is important to understand the mechanisms underlying gene regulation. Here, the authors use multi-omics data from sheep to map regulatory elements in the sheep genome.

Gestational exposure of mice to the obesogen tributyltin alters 3-D chromatin interactions in primordial germ cells leading to stable reduction of hepatic Ide expression and predisposing male descendants to insulin dysregulation and obesity.

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.

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.

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.

A study of several longitudinal birth cohorts and cross-sectional cohorts finds only moderate overlap in genetic variants between autism that is diagnosed earlier and that diagnosed later, so they may represent aetiologically different conditions.

Snow loss and warming reduce runoff and alter the relative contributions of old and young groundwater to streamflow in the Upper Colorado River Basin headwaters, according to a data–model analysis.

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.

mRNA–lipid-nanoparticle vaccines do not require type 1 conventional dendritic (cDC1) cells or the WDFY4-dependent cross-presentation pathway for CD8⁺ T cell priming but, instead, engage both cDC1 and cDC2 cells redundantly.

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.