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Genetic variants of TREX1, a negative regulator of type I interferon responses, have been linked previously to non-monogenic systemic lupus erythematosus (SLE). Here the authors analyze UK Biobank multi-omics data to show that, while a derived oligoprotein interferon signature associates with increased SLE risk, TREX1 variants do not.

Membrane bioreactors play a pivotal role in protecting the water environment and achieving a sustainable urban water cycle, but their operational stability faces great challenges due to membrane fouling. A study now provides an intelligent strategy to enable early warning of fouling events.

The transcription factor ATF4 and its effector lipocalin 2 (LCN2) have a key role in immune evasion and tumour progression, and targeting the ATF4–LCN2 axis might provide a way to treat several types of solid tumour by increasing anti-cancer immunity.

This study demonstrated that distinct antidepressant therapies act on a common brain network. It explains previous heterogeneous findings across therapies and may be adopted to guide precision repetitive transcranial magnetic stimulation.

Using two-photon microscopy with a panoramic virtual reality setup, how head direction cells in larval zebrafish integrate visual landmarks and optic flow to track orientation is revealed.

The predicted increase in frequency of droughts and rising temperatures in Europe will lead core populations of a temperate plant to an evolutionary dead-end unless they acquire genetic alleles that are present only in extreme edge Mediterranean, Scandinavian, or Siberian populations.

A global synthesis of >600 studies finds that across agro-ecosystems, grasslands and forests in temperate and tropical zones, increasing plant diversity has a consistently positive effect on plant performance and the suppression of antagonists.

Bruijns et al. present a modeling tool that enables the tracking of learning dynamics across subjects to reveal how behaviors emerge and adapt. Applying the tool to a decision-making task in mice uncovers similarities and differences across individuals.

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.

Extending their previous findings of brain changes in a first pregnancy, the authors show that a second pregnancy uniquely alters women’s brains, involving both a further fine-tuning of first-pregnancy effects and distinct changes in other networks.

This study presents MAOSS, a multimodal AI model that repurposes non-contrast CT scans and leverages clinical features to detect and stage liver steatosis and fibrosis. Here the authors show MAOSS accurately stratifies cirrhosis progression risk when embedded into the standard clinical workflow, enabling scalable, opportunistic screening for early intervention of steatotic liver disease.

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.

The MOUNTAINEER phase 2 trial demonstrated the efficacy and safety of tucatinib (HER2-targeted TKI) and trastuzumab (anti-HER2 antibody) in patients with HER2 + , RAS wildtype unresectable or metastatic colorectal cancer that had progressed on chemotherapy, resulting in the approval of the regimen. Here, the authors report the updated analysis of the MOUNTAINEER trial.

SleepGPT is a time-frequency foundation model for sleep decoding, built on a generative pretrained transformer, achieving superior performance in various downstream tasks across datasets.

The microbiomes associated with reef corals are complex and diverse. Here, the authors investigate fire coral clones naturally occurring in distinct habitats as a model system to disentangle the contribution of host genotype and environment on their microbiome, and predict genomic functions based on taxonomic profiles.

The evolutionary dynamics of aneuploidy in solid tumors are challenging to study. Here the authors introduce a method, ALFA-K, which estimates karyotype fitness and predicts emergent karyotypes before experimental detection, and test its performance on synthetic and empirical data.

Using the single-cell Deep Visual Proteomics technique, the authors develop a resource providing spatially resolved proteomic analysis of individual cells in human liver tissue.

Temporal variability of structural-functional coupling (SFC) remains poorly understood. Here, authors show such variability is underpinned by specific transcriptomic and chemoarchitectural signatures, thereby supporting neurocognitive specialization.

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.

ENTRAP-seq systematically links protein sequence to transcriptional output in a native plant context.

MMCLKin is a multimodal and multiscale contrastive learning framework for kinase-inhibitor affinity prediction, kinase inhibitor selectivity profiling, virtual screening for known, unknown, and mutated kinases, and interpretable analysis.

Terrestrially derived dissolved organic carbon is pervasive in the Arctic Ocean, especially within the Transpolar Drift current, and changing inputs could impact future marine carbon cycling, according to a dissolved organic carbon inventory.

A benchmarking competition improves tools that predict how regulatory regions control gene expression.

Extrachromosomal circular DNAs (ecDNAs) are prevalent in human cancers and are thought to drive tumor evolution and drug resistance by amplifying oncogenes. Here, authors develop ec3D to reconstruct three-dimensional ecDNA structures, revealing how their spatial organization rewires regulatory circuits.

Lung adenocarcinomas bearing the ID2 mutational signature display increased LINE-1 retrotransposon activity, which contributes to their fast evolutionary dynamics and aggressive phenotype.

This work presents a global wind power simulation tool that uses high-resolution data and extensive validation to improve accuracy. It corrects wind speed biases and validates against real-world data, enhancing reliability for wind energy assessments across various scales and regions.

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.

Evolutionarily related ‘proto-point’ centromeres providing resolution to the evolutionary origins of point centromeres are identified in yeast, and comparison shows they evolved in an ancestor with retrotransposon-rich centromeres and that long-terminal-repeat retrotransposons are the genetic substrate.

Current mapping of fork progression in the human genome suffers from drastically low throughput. Here, the authors introduce ForkML, a nanopore sequencing-based method automatically positioning thousands of individual fork velocities by tracking BrdU incorporation into asynchronously growing cells.

Metabolomics, metagenomics, proteins and genetics were combined with clinical data to define a metabolic signature of obesity.

Women of reproductive age may have specific concerns relating to perceived impacts on fertility and menstrual cycles that make them hesitant to receive COVID-19 vaccination. In this study, the authors explore COVID-19 vaccine uptake rates in women of reproductive age using linked data for ~13 million women in England.

Capsular polysaccharides are bacterial virulence factors, yet their transport mechanism remains unclear. Here, the authors reveal the structure and dynamics of the Wza–Wzc complex, uncovering how a trans-envelope channel assembles to guide capsular polysaccharide synthesis and export.

This study shows that WDR5 remodels NANOG condensates to control transcriptional programs. Disrupting their interaction compromises stem cell identity and suppresses leukemia stem cell expansion.

Compiling data on floral introductions and European colonial history of regions worldwide, the authors find that compositional similarity of floras is higher than expected among regions once occupied by the same empire and similarity increases with the length of time the region was occupied by that empire.

A multilevel pattern-learning framework investigates the effects of genome-wide protein-coding mutations on brain organization and behaviour in the Adolescent Brain Cognitive Development cohort.

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.

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.

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.

The relocalization of the vacuolar calcium pump Cdt1 to the plasma membrane contributes to fluconazole adaptation in Candida auris.

This study reveals a hierarchical development of the brain’s structural connectome from infancy to childhood, characterized by distinct sensorimotor-association trajectories and alignment with multiple neurobiological hierarchies.

Luppi et al. identify transcriptomic and connectomic controllers of information integration and its breakdown induced by anaesthesia in humans, macaques, marmosets and mice.

Dyskalemia is a dangerous potassium imbalance requiring rapid treatment. Here, the authors show, in a randomized trial of 14,989 patients, that real-time AI-ECG alerts increased hyperkalemia (69.1% vs. 41.6%, HR 2.23, 95% CI 1.44–3.46) but not hypokalemia treatment (HR 1.14, 95% CI 0.74–1.77).

While alternative splicing is known to drive oncogenesis and be a source of potential therapeutic targets, identifying such drivers on a genome-wide scale has proven difficult. Here, the authors present a computational approach to identify potential cancer-driver exons and evaluate applicability as therapeutic targets.

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.