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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.

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.

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.

Alternative splicing generates diverse protein isoforms, yet the functions of most exons remain unknown. Here, the authors introduce scCHyMErA-Seq, a scalable single-cell CRISPR exon-deletion platform that maps exon-specific transcriptional functions shaping gene expression and cell-cycle states.

The authors released NSD-synthetic, a dataset of 7T fMRI responses from the same eight NSD participants for 284 out-of-distribution synthetic images, to facilitate the development of more robust models of visual processing.

Saturation genome editing of a cancer mutation hotspot in CTNNB1, the gene encoding β-catenin, reveals a gradient of effects of missense mutations on Wnt signaling.

Measurement of the 2S–6P transition in cryogenic atomic hydrogen using laser spectroscopy reveals a proton radius value that is 2.5-fold more precise than previous determinations and in excellent agreement with the muonic value, and tests the Standard Model to 0.7 parts per trillion.

A follow-up analysis of a clinical trial that evaluated anti-PD-1 therapy in patients with cancer who are living with HIV provides mechanistic insights into transcriptomic, cellular and cytokine changes related to immune checkpoint inhibitor treatment and identifies a signature associated with clinical response.

Spatial transcriptomics technologies are still too restrictive for widespread clinical use, and methods that have been designed to bridge them with histopathology carry important limitations. Here, the authors develop MISO, a deep learning framework that allows inferring tissue spatial organisation and gene expression with near single-cell resolution from histopathology images.

Keshishian, Mischler et al. report that a recurrent automatic speech recognition system aligns closely with brain organization: model layers map to distinct cortical regions and naturally learn to encode a parallel progression from acoustic to phonetic, lexical and semantic content.

Predicting gene expression from H&E slides is a cost-effective alternative to Spatial Transcriptomics for clinical use. Here the authors introduce a Multiple Instance Learning approach to infer single-cell expression, unlike prior methods which operate at coarser patch level.

Jacquemyn et al. identify key lipid determinants controlling ectosome shedding from neurons. They find that ectosomes are a major route for the intercellular transport of misfolded α-synuclein, with relevance to Parkinson’s disease pathology.

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.

A measurement strategy is described that is able to read out the parity of minimal two-site Kitaev chains in real time, by coupling two Majoranas and resolving their quantum capacitance.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

He and colleagues develop a METTL3-based RNA base-editing screening strategy to identify functional N⁶-methyladenosine (m⁶A) sites that are important for prostate cancer cells and validate the role of a top m⁶A target, CHD9, in this context.

Wei et al. perform spatial transcriptomic profiling on synovial tissue biopsy samples from individuals with recent-onset rheumatoid arthritis, finding TGFβ signaling and fibrogenic fibroblast activation drive a treatment-refractory tissue phenotype.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

The identification of cellular targets for natural products that potently inhibit the growth of cancer cell lines implicates oxysterol-binding proteins in the growth of cancer cells. These natural products, termed ORPphilins, also affect sphingomyelin biosynthesis.

Crohn’s disease is associated with disturbances in the B-cell compartment and secreted antibodies. Here, the authors reveal impaired colonic dimeric IgA responses in patients with Crohn’s disease and verify this phenotype in murine models, demonstrating that mitochondrial dysfunction drives defective mucosal humoral immunity.

Capsular polysaccharides are bacterial virulence factors, yet their transport mechanism remains unclear. Here, the authors reveal the structure and dynamics of the Wza–Wzc complex, uncovering how a trans-envelope channel assembles to guide capsular polysaccharide synthesis and export.

The PhenoSphere is a unique plant cultivation facility in which field-like environments can be simulated. Here, the authors find that a single season simulation is superior to an averaged season and to a climatized glasshouse cultivation to elicit field-like phenotypes evaluated in 11 maize lines.

Different agonists produce equilibria of at least four distinct active states of the G-protein-bound M2 muscarinic acetylcholine receptor, each with a different ability to activate G proteins.

Analysis of a placebo-controlled trial of a BCMA-targeting CAR-T cell therapy in patients with myasthenia gravis shows that CAR-T cell infusion selectively remodels the systemic immune environment, with elimination of BCMA-high plasma cells and activated plasmacytoid dendritic cells and changes in the autoreactive B cell repertoire.

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.

Single-neuron recordings in humans reveal largely separate content and context neurons whose coordinated activity flexibly places memory items in context.

Plant roots elongate under mild nitrogen deficiency as part of a foraging response that facilitates nutrient uptake. Here the authors show that natural variation in this response among Arabidopsis accessions depends on the brassinosteroid (BR) signaling kinase BSK3, which can enhance BR sensitivity and root growth.

CDK4/6 inhibitors are promising treatments for ER+ breast cancer, however resistance remains a challenge. Here, the authors analyse the NeoPalANA cohort and indicate that a 33 gene signature was predictive of response to neoadjuvant anastrozole and palbociclib.

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.

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.

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.

The genetic distance between parents influences hybrid performance in plants. Here Miller et al. show that Arabidopsishybrids produced from diverse parental ecotypes have reduced expression of stress responsive genes at certain times of the day and this correlates with greater biomass production.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

Li and colleagues describe a monocyte-specific transcriptional state along with a persistent elevation of inflammatory markers specifically found in individuals with long COVID who had mild-to-moderate disease during acute SARS-CoV-2 infection.

A multilevel pattern-learning framework investigates the effects of genome-wide protein-coding mutations on brain organization and behaviour in the Adolescent Brain Cognitive Development cohort.

A 3-wave study of 1427 climate-action supporters tests predictors of conventional versus radical climate activism. Radical intentions were rare and linked most strongly to youth, personality and collective victimhood rather than ideology or efficacy.

Individual-level prediction is critical for precision medicine, but many neuroimaging prediction studies are underpowered. Here the authors present a simple yet powerful approach that effectively translates predictive models from big to small data.

Climate change can alter when and how animals grow, breed, and migrate, but it is unclear whether this allows populations to persist. This global study shows that shifts in seasonal timing are key to helping vertebrate species maintain population growth under global warming.

CLASSIC is a high-throughput genetic profiling platform that combines long- and short-read next-generation-sequencing modalities to quantitatively assess pools of constructs of arbitrary length containing diverse genetic part compositions.

Several recent publications have attempted to detect novel unannotated microproteins using mass spectrometry proteomics. Here, the authors reassess these claimed microprotein detections, finding that many are poorly supported, while a subset represents likely genuine discoveries of novel proteins.

Five-year survival data and biomarker analysis of the PRADO extension cohort of the phase 2 OpACIN-neo trial, in which patients with high-risk stage III melanoma received neoadjuvant ipilimumab and nivolumab and underwent pathologic response-directed surgery and adjuvant therapy, show 71% event-free survival and 88% overall survival, with tumor mutational burden, IFNγ signature and PD-L1 expression associated with favorable outcomes.

Melanoma cells lacking SOX10 are tolerant to MAPK inhibition (MAPKi) due to elevated TAZ-driven TEAD signaling. Here, the authors develop two inhibitors of TEAD, capable of resensitising SOX10 knockout melanoma cells to MAPKi and offering a strategy to overcome drug tolerance and improve treatment response.

Using 1,425 UK Biobank participants, we show for the first time that morphological brain asymmetry exhibits evidence of plasticity changes throughout adulthood, which tracks individual variation ~1,000 lifestyle factors and ~4,500 disease ICD codes.

Rare loss-of-function mutations in SETD1A are associated with schizophrenia, but how SETD1A haploinsufficiency leads to disease phenotypes remains unknown. Here, authors show that SETD1A regulates genes at common schizophrenia risk loci regulating genomic stability and synaptic function.

Microbial community-scale metabolic modelling predicts person-specific short-chain fatty acid profiles and can be used to estimate the impact of dietary, prebiotic and probiotic interventions.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.

Hussain et al. build multivariate machine-learning models integrating brain MRI with genetic, clinical and socioeconomic data to infer 15 neurocognitive test scores in adolescents and young adults with congenital heart disease. The models achieve moderate accuracy and highlight joint brain, genetic, and contextual contributions.

Mitochondrial DNA heteroplasmy associates with context-specific nuclear CpG methylation, supported by a cell model. Heteroplasmy–CpG scores relate to mortality and cardiovascular risk, though direction and mechanisms remain unclear.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.