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The BioDIGS project is a nationwide initiative involving students, researchers and educators across more than 40 research and teaching institutions. Participants lead sample collection, computational analysis and results interpretation to understand the relationships between the soil microbiome, environment and health.

The CommonMind Consortium sequenced RNA from dorsolateral prefrontal cortex of subjects with schizophrenia (N = 258) and control subjects (N = 279), creating a resource of gene expression and its genetic regulation. Using this resource, they found that ∼20% of schizophrenia loci have variants that may contribute to altered gene expression and liability.

Here the authors studied pulmonary arterial endothelial cells (PAEC) under laminar shear stress and show that this physiologic condition markedly changes chromatin accessibility at regulatory regions, when compared to cells grown in a static state. They find that KLF4 organizes chromatin by interacting with the SWI/SNF nucleosome remodeling complex to regulate vasculo-protective gene expression.

Neutralisation assays are key to understanding immune responses to SARS-CoV-2 infection or vaccination. Here, the authors report a surrogate virus neutralization assay called Neu-SATiN, which measures neutralization directly from sera, and allows easy adaptation to variant-specific testing.

An analysis of genome-wide chromatin interactions during human embryonic stem cell differentiation reveals changes in chromatic organization and simultaneously identifies allele-resolved chromatin structure and differences in gene expression during differentiation.

Using high-throughput functional profiling, how disordered regions control mRNA stability and translation is explored.

This study shows that many plants form a second, deeper root layer underground, enabling access to nutrient-rich deep soil. This previously unnoticed rooting pattern adds to the growing recognition that deep soil dynamics are overlooked.

Mechanisms underlying sex associated differences in the role of androgen receptor (AR) in melanoma are unclear. Here the authors show that androgen-activated AR transcriptionally upregulates fucosyltransferase 4, which fucosylates L1CAM and promotes melanoma invasiveness by disrupting adherens junctions.

Nixon-Abell et al. show that ANXA11 condensation on lysosomal membranes causes a coupled phase transition of the underlying lipids and mechanical stiffening of the overall ensemble involved in RNP granule-lysosome tethering and co-trafficking.

The affected cellular populations during Alzheimer’s disease progression remain understudied. Here the authors use a cohort of 84 donors, quantitative neuropathology and multimodal datasets from the BRAIN Initiative. Their pseudoprogression analysis revealed two disease phases.

The authors highlight the role of acyl coenzyme A binding protein (encoded by DBI) in Cushing’s syndrome by using six different inhibition methods and mapping the physiological effects.

Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.

This study shows how different myeloid cell types contribute to damage and repair following cerebrovascular injury, a pathology common to many central nervous system disorders, and offers new therapeutic opportunities to improve clinical outcomes.

Development of targeted MYC inhibitors for cancer therapy remains challenging. Here, the authors design an mRNA medicine which downregulates MYC gene transcription via epigenetic modification of MYC regulatory elements, showing significant antitumor activity in preclinical models of hepatocellular carcinoma.

Serotonin 5-HT_2A receptor signaling mechanisms associated with predicting psychedelic potential remain elusive. Using 5-HT_2A-selective β-arrestin-biased ligands, here the authors show that a threshold level of 5-HT_2A-Gq efficacy and not β-arrestin recruitment is associated with psychedelic potential.

Induction of CD4 T follicular helper (Tfh) cells is important for antibody responses to viral infections. Here, the authors show in a rhesus macaque model of mild COVID-19 that SARS-CoV-2 infection results in transient accumulation of proliferating Tfh cells with a Th1 profile in peripheral blood and generation of germinal center Tfh cells specific for viral proteins.

HIV-1 is a formidable target for vaccine development. Here, Parthasarathy et al. show that envelope glycoproteins of some HIV-1 primary strains exhibit inherent conformational flexibility that may contribute to HIV-1 evasion from neutralizing antibodies.

A cross-reactive antibody and T cell response is identified in a large portion of patients with multisystem inflammatory syndrome in children.

This study challenges the hypothesis that high-quality plant litters form stable, mineral-associated soil organic carbon most efficiently, providing evidence that litter-microbial interactions and soil mineralogy regulate soil organic carbon formation.

Designing efficient and scalable specialized neuromorphic circuits to integrate raw nervous stimuli and respond identically to biological neurons remains a challenge. Here, the authors propose an analog programming strategy to emulate biological neurons in silico.

Using well-calibrated statistical methods the authors jointly analyze Undiagnosed Diseases Network genomes, identifying known and novel disease genes. Software is publicly available to support future cross-cohort rare disease discovery efforts.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

Severe SARS-CoV-2 infection has been associated with extensive diffuse alveolar damage and fibrin formation. Here, Erickson et al describe an infection-induced coagulation mechanism which involves activation of prothrombin by members of TMPRSS genes.

Active responses to stressors involve motor planning, execution, and feedback. The authors identify a neuronal projection from the insular cortex to the bed nucleus of the stria terminalis that is activated during motor struggling in response to restraint stress as a potential active coping response.

Interoception, the perception of internal bodily signals, is crucial for mental and physical well-being, yet the origins of disruptions in interoception are not well understood. Here the authors conduct a meta-analysis of 17 studies, revealing that childhood maltreatment, particularly emotional maltreatment, is linked to reduced body trust, potentially impacting long-term health outcomes.

A two-step Bayesian model improves small area population estimates by integrating health campaign data or household surveys with incomplete satellite settlement maps. It reduces errors by up to 73%, offering a practical solution in regions where traditional methods face limitations.

Ji et al. identify an idiopathic generalised epilepsy network that links heterogeneously distributed brain abnormalities to a common brain network and deep brain stimulation sites which reduce generalised seizures.

COVID-19 is often characterized by a hyperinflammatory syndrome. Wang and colleagues show that low levels of IgG fucosylation enhance interactions with activating Fcγ receptors, boosting the inflammatory cytokines associated with severe COVID-19.

An atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain unravels the transcriptional regulatory programs that drive the heterogeneity and complexity of brain structure and function.

An improved, single-cell lineage-tracing system, based on deep detection of naturally occurring mitochondrial DNA mutations with simultaneous readout of transcriptional states and chromatin accessibility, is used to define the clonal architecture of haematopoietic stem cells.

Multiomic analysis of blast-phase myeloproliferative neoplasms identifies a chromosome 21 amplicon harboring DYRK1A as a clonal and therapeutically targetable event in around a quarter of cases.

Integration of GWAS and single-cell transcriptomic data from the entire nervous system systematically identifies cell types underlying brain complex traits and provides insights into the etiology of Parkinson’s disease.

The nuclear pore complex (NPC) is known to regulate p53 signaling and this has mainly been linked to peripheral NPC subunits. Here the authors show that Nup155 from the NPC inner ring regulates the p53 pathway by controlling p21 translation while also being a target of p53-mediated repression.

The possibility of banking cryopreserved organs could make transplantation medicine much more accessible. Here, the authors show that vitrification and nanowarming—cooling organs to an ice-free state followed by rapid rewarming using nanoparticles and magnetic fields—enables organ cryopreservation, long-term banking, and recovery of full function in a rat kidney transplant model.

This analysis presents the results of a community-based evaluation of existing software for large-scale glycopeptide data analysis.

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.

Shi et al. report a sulfonation-dependent vulnerability of liver tumors expressing the sulfotransferase SULT1A1 by showing their sensitivity to the small molecule YC-1 and identifying structurally related compounds that can be modified by SULT1A1.

Egyptian rousette bats (ERBs) are natural reservoirs for Marburg virus (MARV), but these bats have not been linked to the MARV Angola strain that caused the largest and deadliest outbreak on record. Here, Amman et al., in a multi-institutional surveillance effort, identify and isolate Angola-like MARV in ERBs in West Africa.

Lowering the levels of disease-promoting proteins is generally assumed to be beneficial. The authors developed a two-step strategy to integrate protein-level tuning, noise-aware synthetic gene circuits into a well-defined human genomic locus. This approach was used to study the effect of BACH1 levels on MDA-MB-231 human breast metastatic cells.

Microglia clearance activity in adult brain is regulated epigenetically and region-specifically to match neuronal attrition rates. Uncoupling this activity from neural apoptosis leads to aberrant microglia activation & neurodegenerative-like changes.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

HYPOMAP integrates single-nucleus RNA sequencing and spatial transcriptomic data to create a comprehensive spatio-cellular map of the human hypothalamus.

scHLApers is an analysis pipeline that quantifies single-cell expression of HLA genes using a personalized genomic reference. Mapping of HLA expression quantitative trait loci at single-cell resolution identifies dynamic effects across cell states.

Atherosclerosis is caused by low-density lipoprotein (LDL) buildup in the vessel wall, a process thought to be mediated by LDL receptor alone. Here, the authors show that the endothelium can uptake LDL via ALK1, a TGFβ signalling receptor, suggesting new therapies for blocking LDL accumulation in the vessel wall.

Gonzalez-Gallego et al. developed a fully iPS-cell-based human three-dimensional blood–brain barrier (BBB) model and used it to study roles of the stroke risk gene FOXF2 in BBB dysregulation, demonstrating its applicability for mechanistic research and drug development.

Reprogramming of somatic cells to induce pluripotent cellular properties that closely resemble those of embryonic stem (ES) cells has important therapeutic potential. The first whole genome single-base resolution profiling of the DNA methylomes of several human ES cell, induced pluripotent stem cell (iPSC) and somatic progenitor lines shows that iPSCs are fundamentally distinct from ES cells, insofar as they manifest common, quantifiable epigenomic differences. These 'hotspots of aberrant reprogramming' might be potentially useful as diagnostic markers for incomplete iPSC reprogramming, for the characterization of the efficacy of different reprogramming techniques, and for screening the potential propagation of altered methylation states into derivative differentiated cells.

Evolutionarily conserved gene modules mediate neurodegenerative dementia in a variety of mouse models and in postmortem brain tissue from patients.

Global trends in biodiversity are subject to regionally heterogeneous diversification processes. Here, the authors examine Late Cretaceous ammonoids, modelling the impact of sampling bias and potential biotic and abiotic drivers on our understanding of their biodiversity trends towards the Cretaceous-Paleogene boundary.