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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.

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.

Designing synthetic biomolecular condensates offers biological insights and is valuable for cellular and metabolic engineering. Here, the authors express orthogonal, unnatural condensates with protein binding aptamers in E. coli, which can dissolve and reassemble upon thermal cycling.

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.

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.

In a screen of 324 human cancer cell lines and utilising a systematic target prioritization framework, the Werner syndrome ATP-dependent helicase is shown to be a synthetic lethal target in tumours from multiple cancer types with microsatellite instability, providing a new target for cancer drug development.

McGrail and colleagues report that high intratumoral bacteria abundance is associated with an immunosuppressive microenvironment and resistance to immune checkpoint blockade in head and neck squamous cell carcinoma.

Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI studies of psychedelics.

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.

Statistically unbiased prediction utilizing spatiotemporal information in imaging data (SUPPORT) is a self-supervised deep learning approach to accurately denoise voltage and calcium imaging data while preserving true dynamic signals.

This study introduces two new measures of brain function at the gray–white matter boundary, revealing distinct patterns of signal transmission and metabolic activity that deepen our understanding of brain organization and development.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

A cavity-array microscope is realized using intra-cavity lenses to create a two-dimensional array of over 40 modes, each coupled to a single atom in free-space.

Engineering stabilized proteins is essential for industrial and pharmaceutical biotechnologies. Here, authors present Stability Oracle, a Graph-Transformer framework trained on protein masked microenvironments to predict protein thermodynamic stability, using less training data while achieving improved generalization.

Clonal hematopoiesis becomes increasingly common with age. Here the authors track stem cell dynamics in monozygotic twins and provide evidence that clonal hematopoiesis in later life reflects weak selection conferred by stem cell variation before birth.

Here, the authors examine the mechanisms behind cheatgrass’s successful invasion of North American ecosystems. Their genetic analyses and common garden experiments demonstrate that multiple introductions and migrations facilitated cheatgrass local adaptation.

The authors show that brain inflammation in COVID-19 correlates with viral load, systemic inflammation and virus-sensing pattern recognition receptors. Microglial dysfunction occurs at sites of vascular inflammation with myelin injury and synapse loss.

Recently published results from a Phase I trial showed the blood brain barrier could be transiently opened in glioblastoma patients using low-intensity ultrasound and microbubbles. Here, the authors develop a microfluidic chip to capture tumour-derived extracellular vesicles and particles in response to paclitaxel treatment.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

Quantifying the impact of copy-number alterations (CNAs) on gene expression at the subclone level in cancer remains a challenge. Here, the authors develop TreeAlign, a method that integrates sample-matched single-cell DNA and RNA sequencing data to infer the impact of CNAs on subclonal gene expression.

Here the authors develop a probabilistic model for single-cell DNA sequencing of aneuploid tumors that infers clone-specific replication timing and S-phase fractions, unveiling their relationships with copy number evolution and clonal fitness.

Hoang et al. developed a deep-learning framework called ENLIGHT–DeepPT that predicts therapy response based on imputed transcriptomics and shows predictive power across patient cohorts and cancer types.

Amplification-free single-cell whole-genome sequencing shows that genomic, evolutionary and biophysical factors collectively drive cell-to-cell variation in mitochondrial DNA copy number.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Time-series data from tropical forests tracking weather and declines in arthropod diversity and function show that fluctuations in species were largely dependent on their El Niño sensitivity and ecological specialization.

Skin prick testing for allergy diagnosis is limited by variability due to differences in test setting and operator expertise. Here, the authors develop and validate an AI-assisted readout method for reading allergy skin test results, and find that integrating AI enhances standardization throughout the skin prick testing process.

The role of rare pathogenic/likely pathogenic (P/LP) germline variants in pediatric central nervous system (CNS) tumour development remains poorly understood. Here, the authors investigate the prevalence and clinical significance of germline P/LP variants in cancer predisposition genes across 830 CNS tumour patients.

A 1,024-channel microelectrode array is delivered to the brain cortex via a minimally invasive incision in the skull and dura, and allows recording, stimulation and neural decoding across large portions of the brain in porcine models and human neurosurgical patients.

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.

Spatial gene expression provides insights into disease mechanisms. Here, authors benchmark eleven methods predicting spatial gene expression from histology images across five datasets and external validation, providing insights into clinical utility, challenges, and future directions.

The epigenetic mechanisms underlying phenotypic diversity across different metastatic sites in castration-resistant prostate cancer (CRPC) remain to be characterised. Here, multi-omic profiling across metastatic lesions identifies regulatory networks driving tumour lineage programs and potential therapeutic targets.

Self-supervised learning (SSL) is increasingly used to train pathology foundation models. Here, the authors introduce a pathology benchmark set generated during standard clinical workflows that includes multiple cancer and disease types; then leverage it to assess the performance of multiple public SSL pathology foundation models and to provide best practices for model training and selection.

This paper describes the Simons Sleep Project, an open resource designed to accelerate research into the sleep and daily behaviors of autistic children using synchronized recordings from multiple wearable and nearable devices for >3,600 days and nights.

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.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

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.

Here, Wong et al investigate the cell-free DNA landscape of individuals with Li-Fraumeni syndrome (LFS), a cancer predisposition, and find altered composition compared to non-LFS individuals which can be used to detect and track cancer development.

This study demonstrates that brain functional network imbalance appears linked to progressive brain atrophy and cognitive decline across the dementia spectrum.

Human cortical maturation is organized along the sensorimotor-association axis. Here, the authors investigate in multiple cohorts if the development of functional connectivity during adolescence conforms to this hierarchy.

Integrated multi-omic analyses using samples from the TRACERx study highlight cross-talk between DNA hypermethylation and genomic lesions in non-small cell lung cancer.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Reframing of arousal as a latent dynamical system can reconstruct multidimensional measurements of large-scale spatiotemporal brain dynamics on the timescale of seconds in mice.

Analysis of copy number alterations in 1,451 patient-derived xenografts (PDXs) and matched patient tumor samples shows strong conservation from patient tumors through late-passage PDXs and a lack of systematic copy number evolution driven by the mouse host.