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Multiple molecular profiling methods are required to study urothelial non-muscle-invasive bladder cancer (NMIBC) due to its heterogeneity. Here the authors integrate multi-omics data of 834 NMIBC patients, identifying a molecular subgroup associated with multiple alterations and worse outcomes.

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

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

GPR25 and its ligand define the core chemoaffinity axis GPR25–CXCL17 of the integrated extraintestinal mucosal immune system, regulating how immune responses disseminate to non-intestinal barrier tissues and with implications for understanding and manipulating immunity and inflammation.

Metformin may serve as a non-toxic intervention to inhibit mitochondrial metabolism and slow DNMT3A-R882 clonal haematopoiesis expansion, thus delaying or averting progression to acute myeloid leukaemia.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Caveolae in arteriolar endothelial cells—but not those in neighbouring smooth muscle cells—have a key role in neurovascular coupling, an essential function for meeting acute brain energy demand.

Observations of a luminous quasar from the high-resolution spectrometer Resolve aboard XRISM revealed highly inhomogeneous wind structure outflowing from a supermassive black hole, which probably consists of up to a million clumps.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

In this article, Batten and colleagues measure fast neurotransmitter release in patients undergoing awake brain surgery. As volunteers play an economic game with human and computer partners, dopamine and serotonin track social context and value statistics.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

Multi-modal analysis is used to generate a 3D atlas of the upper limb area of the mouse primary motor cortex, providing a framework for future studies of motor control circuitry.

Hintiryan, Foster et al. present an online mouse cortico-striatal projectome describing projections from the entire cortex to dorsal striatum. Computational neuroanatomic analysis of these projections identified 29 distinct striatal domains. This connectomics approach was applied to characterize circuit-specific cortico-striatal connectopathies in a mouse model of Huntington disease and in monoamine oxidase (MAO) A/B knockout mice.

Direct elevation of heart rate using noninvasive optogenetics in mice influences anxiety-like behaviours in specific environmental contexts, and the posterior insular cortex is implicated in this integration of signals from the heart with environmental risk information.

BiomedParse is a foundation model for image analysis that uses a joint learning approach to jointly conduct segmentation, detection and recognition and offer state-of-the-art performance across a wide range of datasets and nine modalities.

Although the origin of jaws is one of the key episodes in the evolution of vertebrates, the jaw bones of modern bony fishes and limbed vertebrates differ so much from those in any other groups that the individual evolutionary steps in the transition are still unknown; here Entelognathus is described, an early placoderm fish with full body armour, but with marginal jaw bones similar to those of modern bony fishes and limbed vertebrates.

Selective disruption of adjacent splice acceptor and donor sites identifies cryptic exons involved in recursive splicing in Drosophila, thus unifying the mechanism of recursive splicing in flies and mammals.

Combined patch clamp recording, biocytin staining and single-cell RNA-sequencing of human neurocortical neurons shows an expansion of glutamatergic neuron types relative to mouse that characterizes the greater complexity of the human neocortex.

A multi-ancestry meta-regression study analyses diverse genome-wide association studies and genome loci associated with tobacco and alcohol use.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Unimolecular integration of NMDA receptor antagonism with GLP-1 receptor agonism effectively reverses obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

X-ray spectroscopic observations of the Centaurus galaxy cluster with the X-Ray Imaging and Spectroscopy Mission satellite show that the hot gas flows along the line of sight relative to the central galaxy.

Upper tract urothelial carcinoma (UTUC) is an aggressive cancer and largely uncharacterised cancer. Here, Faltas and colleagues report its distinctive molecular and immune landscape compared to urothelial carcinoma of the bladder and explore the role of FGFR3 signaling in UTUC biology.

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

A multi-ancestry genome-wide association meta-analysis of kidney cancer identifies 63 regions associated with disease susceptibility including one locus that was associated with increased risk in individuals with African ancestry.

Analysis of 46 newly sequenced or re-sequenced Tausch’s goatgrass (Aegilops tauschii) accessions establishes the origin of the bread wheat (Triticum aestivum) D genome from genetically and geographically discrete Ae. tauschii subpopulations.

The superior colliculus (SC) receives diverse cortical inputs to drive many behaviors. Here, based on comprehensive mapping of cortico-tectal projections, the authors refined the superior colliculus into medial, centromedial, centrolateral, and lateral zones, and characterized the input-output connectivity and morphology of neurons in each zone that serve the role of SC in goal-directed behaviors.

Epidemics of whooping cough caused by Bordetella pertussis have been seen and are linked to waning immunity globally. Here the authors explore responses to inactivated poliovirus (IPV) in the Tdap-IPV vaccine and show it stimulates early antiviral responses in monocytes and dendritic cells that are associated with long-lived pertussis antibody responses.

While heterogeneous catalysts can act as tangible, efficient materials for energy conversion, understanding the active catalytic sites is challenging. Here, authors engineer specific catalytic sites into molybdenum sulfide to improve and elucidate hydrogen evolution electrocatalysis.

Marginal zone lymphoma (MZL) is a common subtype of B-cell non-Hodgkin lymphoma. Here the authors carry out a two-stage genome-wide association study in over 8,000 Europeans and identify two new MZL risk loci at chromosome 6p, implicating the major histocompatibility complex in the disease for the first time.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Toll-like receptor 7 (TLR7) normally recognizes exogenous single-stranded RNA for the activation of innate immunity. Here the authors show that TLR7 may also contribute, via the modulation of mast cell functions, to experimental, cigarette smoke-induced mouse models of emphysema, thereby hinting TLR7 as a potential therapeutic target for human lung inflammation.

A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.

A description is given of the ENCODE effort to provide a complete catalogue of primary and processed RNAs found either in specific subcellular compartments or throughout the cell, revealing that three-quarters of the human genome can be transcribed, and providing a wealth of information on the range and levels of expression, localization, processing fates and modifications of known and previously unannotated RNAs.

STAAR is a powerful rare variant association test that incorporates variant functional categories and complementary functional annotations using a dynamic weighting scheme based on annotation principal components. STAAR accounts for population structure and relatedness and is scalable for analyzing large whole-genome sequencing studies.

Ibanez et al. introduce multimodal diversity, a synergistic framework integrating multimodal brain metrics, whole-body health, and exposomic data through neurosyndemic computational modeling to advance context-sensitive precision brain health across global settings.

The PSA (KLK3) genetic variant rs17632542 is associated with reduced prostate cancer risk and lower serum PSA levels, although the underlying reasons are unclear. Here, the authors show that this PSA variant reduced proteolytic activity and leads to smaller tumours, but also increases invasion and bone metastasis, indicating its dual risk association depending on tumour context; the variant is associated with both lower risk and poor clinical outcomes.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.