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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.

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.

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.

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.

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.

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 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.

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.

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.

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.

Centrosome dynamics play a central role in immune regulation. Here, the authors demonstrate that centrosome integrity as well as centriole numbers and spatial organisation emerge as critical determinants of effective T cell responses.

A wearable paper-based microfluidic device tracks cortisol in sweat via gold nanoflower colorimetric assays and captures circadian rhythms, stress responses and jet lag disruptions.

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.

One of three back-to-back papers to show dosage of BACH2 can modulate T cell differentiation and function and how we might apply this to enhance chimeric antigen receptor T cell therapies for cancer.

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.

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.

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.

Uropathogenic Escherichia coli infection of a murine prostate organoid model reveals a bacterial FimH–host prostatic acid phosphatase adhesin-receptor interaction enabling invasion and replication within the host tissue.

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.

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

Vassy, Dornisch and colleagues developed a genomics-based prostate cancer risk model to support a randomized clinical trial of precision screening in a national healthcare system.

Ginhoux, Dutertre and colleagues provide a comprehensive analysis of dendritic cell subsets and states across human tumoral and juxtatumoral tissues.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

While the emergence of immune checkpoint inhibitors has improved outcomes in patients with small cell lung cancer (SCLC), tumour that develop means of immune evasion become resistant. Here, the authors report that ERBB2 signalling induces loss of MHC Class I expression and subsequently immune evasion in preclinical models of SCLC.

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.

Wegner et al. apply machine learning to video recordings of walking tasks in people with ataxia and healthy controls using sensor-free motion capture. Their models replicate clinical ratings and detect subtle longitudinal gait changes that are challenging to capture in standard assessments, supporting improved monitoring of disease progression.

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.

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.

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.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.

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.

Joller and colleagues show that the co-inhibitory receptor TIGIT induces the expression of the tissue growth factor amphiregulin (Areg) in regulatory T cells and contributes to tissue repair in response to viral infection.

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.

Linking prior epigenetic status to future outcomes remains a challenge. Here, authors show recording neuronal enhancer activity across postnatal development in mice reveals loci that predict and can be manipulated to modify acute seizure response.

In vivo loss-of-function CRISPR screens were performed to identify genes influencing CAR T cell persistence and function in human multiple myeloma, highlighting CDKN1B as a promising target.

Caspase 8 protein expression is largely absent in small cell lung cancer (SCLC) patients. Here, the authors generate a caspase 8 deletion SCLC mouse model and show that it promotes a neuronal progenitor-like cell state and pre-tumoral immunosuppression triggered by necroptosis that promotes metastasis.

Exercise has considerable health benefit, including modulation of the immune system. Here the authors compare the molecular make-up of peripheral blood immune cells at resting state and upon a single bout of two different aerobic exercise modes by proteomics and show that although both exercise modes trigger similar changes, the effect is more pronounced after high intensity interval training.

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.

This study associates p53 loss and brain metastasis in breast cancer. Mechanistically, p53-null tumors recruit astrocytes that provide substrates for enhanced fatty acid synthesis via upregulated SCD1 expression, representing a targetable axis in the disease.

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.

Ying, Paulson and collagues have developed an open-source framework, Biolearn, to harmonize and systematically evaluate 39 aging biomarkers across diverse populations, enabling standardized validation and facilitating development of robust aging biomarkers.

Engineered DNA recombinases efficiently and specifically insert genetic cargos without the use of landing pads.

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.

CFAP20 has a key role in rescuing RNA polymerase II complexes that have arrested during DNA transcription, limiting the accumulation of R-loops and preventing collisions between the transcription and replication machinery.

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.

Xie and colleagues show that MRI-based brain function maps can identify patient-specific abnormalities in temporal lobe epilepsy, track how they spread along brain networks, and help diagnose, lateralize seizure focus, and predict surgical outcomes.

Improved understanding of the tumor ecosystem in glioblastoma is critical for developing new treatment strategies for the disease. Here, the authors identify pericytes as an active paracrine signaling hub within the tumor parenchyma that orchestrates a tumor-suppressive microenvironment, suggesting pericyte preservation as a key feature of future therapeutic regimens for glioblastoma.

This work uses gene expression and single cell analyses to group extrapulmonary tuberculosis patients into three immune types, revealing immune pathways driving pathogenesis and markers that could improve diagnosis and guide tailored treatments.