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An empty room can be intimidating. But with some thoughtful planning, you can create a thriving scientific community.

Here the authors perturb genes linked to schizophrenia risk in human neurons. They find that single perturbations share common downstream effects on gene networks, while joint perturbations result in downstream effects being saturated.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

Targeting neurons that regulate energy balance may offer new approaches for obesity treatment. Here, authors show that chemogenetic and pharmacological manipulation of GABAergic neurons in the DRN/vlPAG increases adaptive thermogenesis and reduces weight gain in mice fed a highfat diet.

K11/K48 branched ubiquitin chains regulate protein degradation and cell cycle progression. Here, the authors report the structural basis of how such a branched ubiquitin chain is recognized by the human 26S proteasome, revealing a multivalent binding mode that underlies selective recognition.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

PU.1^low CD28-expressing microglia may act as suppressive cells in Alzheimer’s disease, mitigating its progression by reducing neuroinflammation and amyloid plaque load, indicating potential immunotherapeutic approaches for treatment.

The early postnatal roles of dendrite-targeting interneurons in primary visual cortex (V1) remain elusive. Here, the authors find that somatostatin interneurons in mouse V1 exhibit a uniquely delayed developmental trajectory for innervation and sensory responses, highlighting a window for the emergence of a key mechanism for normalization in cortical circuits.

Transcriptomic screening identifies pairs of cell-surface proteins that mediate repulsive interactions between axons and dendrites of non-cognate partner neurons, thereby contributing to correct synaptic partner matching.

Using a new analytical method for tracking gamma band events in mouse visual cortex, flexible encoding of visual information according to behavioural context is shown.

Using a mouse model enabling an inducible ‘switch’, Golden et al. show that an astrocyte-specific replacement of the Alzheimer’s risk gene APOE4 with protective APOE2 alters metabolism and gene expression, reducing amyloid pathology and gliosis.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

The medium-resolution transmission spectrum of the exoplanet WASP-39b, described using observations from the Near Infrared Spectrograph G395H grating aboard JWST, shows significant absorption from CO₂ and H₂O and detection of SO₂.

An integrated analysis of de novo and inherited coding variants in 42,607 individuals with autism spectrum disorder identifies 60 risk genes of which five have not previously been associated with neurodevelopmental disorders.

Astrocytes are important players in brain development, homeostasis, and disease. Here, the authors compare the transcriptional profiles of human and mouse astrocytes. They report species-specific susceptibility to oxidative stress and response to hypoxic and inflammatory conditions.

Together with a companion paper, the generation of a transcriptomic atlas for the mouse lemur and analyses of example cell types establish this animal as a molecularly tractable primate model organism.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

An integrated data and sample repository for clinical, cellular and multi-omics research from diverse spaceflight missions known as Space Omics and Medical Atlas (SOMA) is presented.

Integral equations are used in science and engineering to model complex systems with non-local dependencies; however, existing traditional and machine-learning-based methods cannot yield accurate or efficient solutions in several complex cases. Zappala and colleagues introduce a neural-network-based method that can learn an integral operator and its dynamics from data, demonstrating higher accuracy or scalability compared with several state-of-the-art methods.

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.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Machine learning can be used to identify subtypes of psychiatric disease. Here the authors identified two neurostructural subgroups in schizophrenia, each showing reproducibility and generalizability across different collection locations and illness stages, using the SuStain algorithm.

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.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Progranulin deficiency causes untreatable neurodegenerative diseases. Here, the authors show that hematopoietic stem cell transplantation and optimized brain conditioning correct the disease phenotype in progranulin-deficient mice.

Somatic mutations accumulate with age; however, the role they have in cardiac aging is unclear. Here Choudhury et al. describe the somatic mutation landscape of human heart muscle cells by single-cell whole-genome sequencing and report mutational signatures indicative of increased oxidative DNA damage and failed repair.

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.

Bacterial AB₅ toxins, such as cholera toxin, bind to oligosaccharides on the host cell surface and play key roles in the pathogenesis of diarrheal disease. Here, Patry et al. show that these toxins bind also to bacterial oligosaccharides and inhibit the growth of Campylobacter jejuni and gut commensal bacteria.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Cell migration through narrow constrictions during cancer metastasis significantly deforms the nucleus, creating mechanical stress on chromatin. Here, the authors reveal that such chromatin deformations lead to changes in nuclear condensates, affecting their assembly and phase behavior.

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.

Addressing the mental health of graduate and postdoctoral trainees in the biosciences will substantially benefit the scientific community at large.

Surveys from 2,584 sites across the Indo-Pacific identify key climate, socioeconomic and environmental drivers associated with hard coral assemblages. This informs a strategic approach to protect, recover or transform coral reef management.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

The influence of X chromosome genetic variation on blood lipids and coronary heart disease (CHD) is not well understood. Here, the authors analyse X chromosome sequencing data across 65,322 multi-ancestry individuals, identifying associations of the Xq23 locus with lipid changes and reduced risk of CHD and diabetes mellitus.

An antibody–drug conjugate that targets the pan-haematopoietic marker CD45 combined with transplanted stem cells engineered to be shielded from it can eradicate leukaemic cells while preserving haematopoiesis.

Hosseinzadeh et al. demonstrate use of a publicly accessible automated machine learning platform to differentiate between a common benign tumor and malignant transformation of it within the paranasal sinuses. This AI algorithm beat prior human prediction, and showed that physicians with no coding background can effectively utilize this tool.

Transmission spectroscopy observations from the James Webb Space Telescope show the detection of carbon dioxide in the atmosphere of the gas giant exoplanet WASP-39b.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

In macaque motor cortex, moment-to-moment fluctuations in neurally derived decision variables are tightly linked to decision state and predict behavioural choices with better accuracy than condition-averaged decision variables or the visual stimulus alone, and can be used to distinguish between different models of decision making.

Observations from the JWST show the presence of a spectral absorption feature at 4.05 μm arising from SO₂ in the atmosphere of the gas giant exoplanet WASP-39b, which is produced by photochemical processes and verified by numerical models.

Endocrinologists have traditionally focused on studying one hormone or organ system at a time. Here the authors use transcriptomic data from the mouse lemur to globally characterize primate hormonal signaling, describing hormone sources and targets, identifying conserved and primate specific regulation, and elucidating principles of the network.

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.

Stabilization of DNA quadruplex structures (G4) is lethal for cells with a compromised DNA repair pathway. Here, the authors show that CX-5461, a small molecule in clinical trials as RNA polymerase inhibitor, has G4-stablization properties and can be repurposed to target DNA repair-defective cancers cells.

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.