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Affinity-proteomics platforms often yield poorly correlated measurements. Here, the authors show that protein-altering variants drive a portion of inter-platform inconsistency and that accounting for genetic variants can improve concordance of protein measures and phenotypic associations across ancestries.

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.

GluFormer, a generative foundation model, uses continuous glucose monitoring data to accurately forecast glycaemia-related health responses, particularly for long-term outcomes.

This study detects Chlamydia pneumoniae in human retina and brain, increasing with AD severity. Retinal pathogen load with Aβ₄₂ may predict AD stage. In models, infection drives Aβ deposition and NLRP3 activation, worsening pathology and cognition.

Vocal fold cancer tumours lose some of their malignant traits when mechanically stimulated by physiological stretch or vibrations, mimicking the opening and closing of vocal folds and phonation.

Mucosal administration of a multivalent, adjuvanted vaccine against Clostridioides difficile promoted bacterial clearance and protected against morbidity, mortality, tissue damage and recurrence in mice.

Post-transcriptional regulation of mRNA translation was explored using Ribo-STAMP and single-cell RNA sequencing to reveal cell-type-specific and isoform-specific translation patterns across hippocampal neuronal and non-neuronal cell types, highlighting functional differences between CA1 and CA3.

Here they demonstrate a therapeutic intervention elevating levels of CYP450-derived lipids to control the expansion of intermediate monocytes in tissue and peripheral blood, presenting a first in class therapeutic approach for treating chronic inflammatory disease.

Genome-wide analyses in the Norwegian HUNT study with replication in Swedish and Finnish cohorts identify host genetic variants associated with gut microbiome features and provide evidence of a causal effect of body mass index on gut microbiota composition.

A covariate-aware analysis reveals that microbiome changes in the gut of patients with chronic kidney disease are better explained by intestinal transit time than by kidney function.

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.

The functions of the vast majority of brain-expressed spliced isoforms are unknown. Here the authors describe an isoform-resolution perturbation system coupled to a single cell transcriptomics read-out, and through this approach identify neuronal microexons that control autism-linked signatures underlying neuronal maturation and function

The therapeutic relevance of telomere maintenance mechanisms in cancer, remains to be explored. Here, the authors integrate multi-omic data and functional readouts, generate a resource of telomere biology metrics and identify potential molecular vulnerabilities.

The impact of variants of uncertain significance (VUS) on protein function and cancer risk remain unclear. Here, the authors focus on the functional impact of VUS of the PALB2 gene and identify defects in DNA damage repair by homologous recombination associated with increased risk of breast cancer.

DNA methylation and gene expression data integration identify aging-related genes in blood that predict health outcomes, offering new insights into aging biology and potential therapeutic targets.

Li et al. propose a conceptual framework to study the phenomenon of falling asleep based on electroencephalogram data. They show that a tipping point marks the brain’s nonlinear wake-to-sleep transition and that the unfolding process can be tracked in real time.

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.

The study shows that nitrogenase enzymes have maintained stable isotope signatures over billions of years, revealing how ancient microbes shaped Earth’s nitrogen cycle and offering a new experimental framework for probing early life.

Disease heterogeneity complicates precision medicine, which focuses on single conditions and ignores shared mechanisms. Here the authors introduce ‘pan-disease’ analysis using a deep learning model on multi-organ data, identifying 11 AI-derived biomarkers that reveal new therapeutic targets and pathways, enhancing patient stratification for disease risk monitoring and drug discovery.

The substantia nigra and all Parkinson’s disease deep-brain stimulation targets are selectively connected to the somato-cognitive action network rather than to effector-specific motor regions.

Thendral et al. describe a mitophagic programme that removes deleterious mtDNA during the oocyte-to-zygote transition in Caenorhabditis elegans, promoting mitochondrial health and offspring survival. Loss of this mitophagy leads to mutant mtDNA accumulation.

Understanding the mechanisms underlying the survival of drug tolerant persister cells following chemotherapy remains elusive. Here, multi-omics analysis and experimental approaches show that the germ-cell-specific H3K4 methyltransferase PRDM9 promotes metabolic rewiring in glioblastoma stem cells.

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.

MultiSuSiE is an extension of the Sum of Single Effects fine-mapping model that allows causal effect sizes to vary across ancestries. Applying MultiSuSiE to quantitative traits in All of Us identifies fine-mapped variants not implicated by other methods.

How white matter develops along the length of major tracts in humans remains unknown. Here, the authors identify fundamental patterns of human white matter development along distinct axes that reflect brain organization.

Hematoxylin and eosin (H&E) staining is a widely used method in histopathology, but it cannot directly inform about specific molecular markers. Here, the authors present ROSIE, a deep-learning framework that computationally imputes the expression and localisation of dozens of proteins from H&E images.

Astrocytes in the basolateral amygdala dynamically track fear state and support fear memory retrieval and extinction.

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.

Native state proteomics of PV interneurons revealed unique molecular features of high translational and metabolic activity, and enrichment of Alzheimer’s risk genes. Early amyloid pathology exerted unique effects on mitochondria, mTOR signaling and neurotransmission in PV neurons.

This study demonstrates that the reduced serum serine in patients with chemotherapy or women with poor sleep, is linked to the decline of ovarian function. Serine supplementation prevented ovarian damage in mice by inhibiting ferroptosis in ovarian granulosa cells, without affecting chemotherapy efficacy.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

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.

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.

Denz et al. show that loss of the antiviral protein IFITM3 allows human SARS-CoV-2 variants to adapt more rapidly in mice while preserving distinct, variant-specific patterns of infection and disease.

Around 20% of synonymous sites are conserved in placental mammal genomes, but the evolutionary forces determining this is unclear. This study show that a combination of GC-biased gene conversion, functional constraint, and mutation rate variation has likely shaped synonymous site evolution.

RNAi therapy has huge potential but effective delivery to target location is a major issue. Here, the authors report on the delivery of RNAi to tumors using self-agglomerating nanohydrogels that can overcome the different delivery barriers and supply multiple RNAi payloads.

Metagenomes from prairie soils in Kansas, USA, show how historical exposure to water stress impacts soil microorganisms and subsequently drought responses in plants.

Genome-wide association studies incorporating data for populations of African ancestry provide an expanded view of the genetic basis of schizophrenia, which has previously been studied mainly in European and East Asian cohorts.

Npm1 promotes tumor formation via attenuating the integrated stress response and p53 activation in mouse WNT-driven intestinal and liver tumorigenesis.

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.

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.

Proton-exchange membrane water electrolysers rely on iridium to catalyse their anodic reaction, and while ruthenium is a less costly alternative due to its similar activity, it is not as stable. Now, a hierarchical machine-learning catalyst discovery workflow, termed mixed acceleration, is put forward to predict catalyst synthesis, activity and stability, and identify promising RuO_x-based water oxidation catalysts.

Phosphorylation-dephosphorylation and ubiquitination tune TCR signaling to avoid self-reactivity. Kim and colleagues show that acetylation also modulates TCR signaling.

Juvenile idiopathic arthritis (JIA) associated uveitis can cause vision loss in children, but mechanisms remain unclear. The authors here identify elevated CD19⁺IgD^-CD27^- double negative type 1 B cells in JIA-uveitis and show that targeting B-T cell interactions suppresses disease in mouse models of uveitis.

Systematic evaluation of Procrustes alignment shows how using more functional gradients alters principal gradients and affects identifiability, highlighting key implications for individual-level fMRI analyses.

In young, estrogen-deprived female mice, the authors show that daily low-intensity vibration protected bone, muscle and fat metabolism. This treatment also enhanced bisphosphonate outcomes, strengthening the skeleton to counter adverse effects of cancer therapy on musculoskeletal tissue.

Proximity-dependent biotinylation maps protein locations using multiple bait proteins, limiting scalability. Here, the authors present GENBAIT, a computational tool that selects optimal baits to reduce the number of experiments required while preserving subcellular organization.

Although the number of participants is important for phenotypic prediction accuracy in brain-wide association studies using functional MRI, scanning for at least 30 min offers the greatest cost effectiveness.

When stem cells develop into tissues intracellular signalling is rewired, errors in this process lead to cancer. Here, authors applied tools from differential geometry made by Albert Einstein’s General Relativity to understand and predict biological network rewiring in health and disease.