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At single-cell resolution, Tarkhov et al. delineate stochastic and co-regulated components of epigenetic aging, revealing a simultaneous loss of regulation at the epigenetic and transcriptional levels in aging.

Researchers reveal that TNF alpha unmasks a metabolic impairment in the enteric malate-aspartate shuttle. This dysfunction acts as a key pathological bridge linking intestinal inflammation to the neurodegeneration seen in Parkinson’s disease.

Massively parallel reporter assays across five cell types identify thousands of causal, noncoding regulatory variants among 220,000 loci, revealing diverse regulatory mechanisms shaping complex traits and disease.

Preclinical studies have evaluated murine double minue 2 (MDM2) inhibitors as a treatment for adenoid cystic carcinoma (ACC). Here the authors present a phase I clinical trial reporting tolerability and efficacy preliminary data for the MDM2 inhibitor alrizomadlin (APG-115) in patients with TP53 wild type salivary gland cancers, especially adenoid cystic carcinoma.

Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

AlphaGenome, a deep learning model that inputs 1-Mb DNA sequence to predict functional genomic tracks at single-base resolution across diverse modalities, outperforms existing models in variant effect prediction and enables comprehensive genomic analysis.

T-prolymphocytic leukemia (T-PLL) is an aggressive T-cell malignancy, but 15–25% of cases are diagnosed at a primarily indolent stage. Here, the authors use single-cell RNA sequencing and whole genome sequencing to study the molecular changes underlying the indolent-to-active evolution of T-PLL, finding patient-specific and common mechanisms of disease progression.

Saturation genome editing of RNU4-2 identifies the functional and clinical impact of variants across the entire gene and delineates variants that cause a new recessive neurodevelopmental disorder distinct from ReNU syndrome.

This study uses the inception loop framework to map neuronal invariances in mouse V1, revealing a bipartite receptive-field organization linked to segmentation and a synaptic-level hierarchy of increasing invariance supported by the MICrONS dataset.

How the brain supports speaking and listening during conversation of its natural form remains poorly understood. Here, by combining intracranial EEG recordings with Natural Language Processing, the authors show broadly distributed frontotemporal neural signals that encode context-dependent linguistic information during both speaking and listening..

The CMS experiment at CERN reports one of the highest-precision measurements of the W boson mass, finding it in line with standard model predictions and at odds with recent anomalous measurements.

Robustness checks and reproduction of analyses with existing and updated data based on 110 articles in economics and political science journals with data and code-sharing requirements found high levels of robustness and reproducibility and determined that robustness was not dependent on author characteristics or data availability.

The Mouse Cancer Cell line Atlas (MCCA) provides major advances towards a mechanistic understanding of cancer genomes.

Czernilofsky et al. identified factors that reprogram stromal cells into an inflammatory, dysfunctional state, leading to the structural disorganization of lymph nodes in B cell lymphoma at single-cell and spatial resolutions.

Lazarevic et al. reveal a shared loss of a TBX5-dependent atrial gene network in cardiomyocytes and a disease-specific network gain in activated fibroblasts across atrial fibrillation and heart failure models.

Improved red and green indicators for norepinephrine and their characterization are reported. These indicators allow detection of norepinephrine release in awake behaving mice in dual-color fiber photometry and two-photon imaging applications.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

Analysis of sequencing data from rare disease cohorts identifies biallelic variants in RNU2-2 underlying a developmental and epileptic encephalopathy associated with reduced U2-2 abundance and clinically distinct from the dominant RNU2-2 disorder.

Sepsis is a heterogeneous inflammatory disease and it is believed treatment requires suitable stratification based on the underlying disease pathology and immunology. Here the authors show genetic variation in the regulatory elements of MTOR can impact neutrophil-T cell cross talk in the context of pneumonia associated sepsis, highlighting a genetic framework for targeted patient stratification.

A comprehensive atlas platform integrating transcriptional and epigenetic data enables more precise engineering of T cell states, accelerating the rational design of more effective cellular immunotherapies.

MAU2’s role in Cornelia de Lange syndrome was unclear. Here, the authors identify pathogenic MAU2 variants that disrupt NIPBL–MAU2 function, define MAU2‑specific episignatures, and show variable CdLS‑related phenotypes, supported by a Mau2 knockout mouse model.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

The 4D Nucleome Project demonstrates the use of genomic assays and computational methods to measure genome folding and then predict genomic structure from DNA sequence, facilitating the discovery of potential effects of genetic variants, including variants associated with disease, on genome structure and function.

Antarctic sea ice declined sharply between 2015 and 2017, and this study uses ocean observations and atmospheric data to determine contributing factors. The authors show that thinning of Winter Water in the previous decade, followed by strong winds, brought warm deep water into contact with sea ice.

It has been proposed that language meaning is represented throughout the cerebral cortex in a distributed ‘semantic system’, but little is known about the details of this network; here, voxel-wise modelling of functional MRI data collected while subjects listened to natural stories is used to create a detailed atlas that maps representations of word meaning in the human brain.

Using blood-based genome sequence data, non-genetic and genetic factors associated with control of Epstein–Barr virus during persistent infection are reported.

Schober and colleagues show that effector CD8⁺ T cells undergo metabolic shutdown, CD8⁺ central memory T cells are the most metabolically active, and naive-like memory T cells are quiescent during the acute phase of the immune response and represent the dominant population of memory CD8⁺ T cells after yellow fever vaccination in humans.

Idiopathic pulmonary fibrosis is characterised by the accumulation of fibroblasts, which deposit excessive extracellular matrix impairing respiratory functions. Here, the authors show that fibroblast-expressed versican, a chondroitin sulphate proteoglycan, suppresses fibroblasts’ ability to invade and further grow the underlying matrix, thus limiting their accumulation and attenuating pulmonary fibrosis.

CRISPR activators are powerful tools for controlling gene expression, but they suffer from inconsistent efficacy and high toxicity. Here, authors develop a high-throughput method to test thousands of CRISPR activators, revealing distinct principles of activator biology and delivering improved tools.

Rudensky and colleagues demonstrate a context-dependent differential requirement for Foxp3 for T_reg cell transcriptional and functional programs.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

Deconvolution methods infer levels of immune infiltration from bulk expression of tumour samples. Here, authors assess 6 published and 22 community-contributed methods via a DREAM Challenge using in vitro and in silico transcriptional profiles of admixed cancer and healthy immune cells.

scooby achieves DNA sequence-based single-cell level modeling of RNA-sequencing coverage and ATAC-sequencing insertion profiles by adapting a deep learning model that predicts bulk RNA-sequencing coverage.

Analyses of leukocyte telomere length in All of Us identify associations with various lifestyle, socioeconomic and disease traits. Genome-wide analyses combining All of Us with UK Biobank data discover new loci contributing to telomere length variation.

89ZED88082A is a zirconium-89-labeled one-armed anti-CD8α antibody for the non-invasive whole-body visualization of CD8 + T-cells by positron emission tomography (PET). Here the authors report the results of a phase 2 study of 89ZED88082A for whole-body CD8 + T-cell PET imaging in patients with large B-cell lymphoma before and during CD19-directed CAR T-cell therapy.

This study shows that during the first wave of SARS-CoV-2 infection in England, residents of long-term care facilities who survived infection developed a robust and stable immunity against the virus that did not negatively impact responses to other seasonal viruses.

Analysis of clinical trial data suggests that CDK4/6 inhibitors prevent the expansion of TP53-mutant clones in the blood, potentially mitigating the risk of secondary myeloid neoplasms in patients treated with cytotoxic drugs.

Here, the authors provide evidence that marine viruses spread via aerosolization and rain through the natural water cycle. Hosts from the first centimeters of the marine water column show signs of immunity against rain viruses. Those have DNA adaptations facilitating their stay in the air.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

Risk stratification in non-small cell lung cancer (NSCLC) remains challenging. By combining multiplex immunofluorescence, H&E histology, and AI, the study identifies spatial “cell-niche” patterns that enhance survival prediction beyond UICC8 staging. These patterns reclassify many stage I patients as high risk, revealing potentially undertreated cases and establishing spatial tumor microenvironment features as clinically actionable biomarkers.

Single-cell multimodal data has the potential to unveil noncoding disease mechanisms. Here, authors introduce GrID-Net, a graph-based Granger causal approach that links noncoding variants to genes by exploiting the time lag between epigenomic and transcriptional cell states.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

LINE-1 activity was quantified in a large, pan-cancer dataset, finding locus-specific heterogeneity and new associations using a computational pipeline. A mathematical mediation model of p53 and L1 interactions was inferred. Somatic retrotransposition was seen in Li-Fraumeni Syndrome with heritable TP53 mutations.

Via high-throughput imaging and tracking over 140 million single mycobacteria, the authors show that drug- and strain-specific killing predict treatment outcomes, with potential to improve drug development and personalized therapy.

How inflammation spreads from the skin to the joints in psoriatic disease is unclear. Here, the authors show that joint-resident fibroblasts can control differentiation of infiltrating skin-derived myeloid precursors that can become inflammatory macrophages.

A nanoscale 3D DNA tracing workflow visualizes Cohesin-dependent loops in single, structurally well-preserved cells. Computer simulations based on the tracing data give further insight into how Cohesin folds compact domains in the genome.

Experimental measurements of high-order out-of-time-order correlators on a superconducting quantum processor show that these correlators remain highly sensitive to the quantum many-body dynamics in quantum computers at long timescales.

Fusion genes involving KMT2A rearrangements are frequent oncogenic drivers of acute myeloid leukaemia (KMT2A-r AML) but the cell of origin remains unclear. Here, using preclinical models of EVI1 positive KMT2A-r AML the authors investigate the cell of origin and find that the presence of exogenous factors influences AML initiation and the resulting phenotype.

Aberrant redox homeostasis links lipid metabolism and cell death programs. Here, authors reveal how cell stress reduces growth factor signaling, enriching polyunsaturated fatty acids in phospholipids and sensitizing membranes to oxidative damage.