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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.

The authors analyze 162 primary mismatch-repair-deficient gliomas and identify three subgroups underpinned by distinct somatic mutations in replicative DNA polymerases and IDH1.

Early results from the phase 2b VIBRANT-HD trial of the oral splicing modulator branaplam in Huntington’s disease suggested reduced cerebrospinal fluid huntingtin levels, but safety monitoring revealed signs of peripheral neurotoxicity, prompting early termination of the study.

Specific pain-sensing nociceptors and chemosensory tuft cells form a circuit to promote type 2 immune responses in the intestine.

Here, using samples from ~1,100 individuals, the authors define the nasal microbiome linked to Staphylococcus aureus colonization, identifying seven communities- either S. aureus-dominated or dominated by other bacteria.

Transcription in trypanosomatids, such as Trypanosoma brucei, is predominantly polycistronic and involves unconventional RNA polymerase II promoters. This study uses precision gene editing, site-saturation mutagenesis, and expression assays to demonstrate how modified and promoter-associated histone tails impact these polycistronic expression controls in trypanosomes.

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

Roßmann and colleagues report a simple strategy to generate a panel of fluorescent HaloTag Ligands that enable visualisation of cell surface proteins at low concentrations and with brief incubation times. They use these probes to label neuromodulatory receptors in neurons, allowing for the distinction of surface versus internal receptors of the presynaptic terminal.

A pangenome of oat, assembled from 33 wild and domesticated oat lines, sheds light on the evolution and genetic diversity of this cereal crop and will aid genomics-assisted breeding to improve productivity and sustainability.

Synovial sarcoma (SyS) is a cancer driven by a fusion oncoprotein, SS18::SSX, but the mechanism underlying the oncoprotein-mediated tumorigenesis remains unclear. Here, the authors employ transgenic mouse models and multi-omics to show how SS18:SSX modifies the activity and recruitment of BAF-family chromatin remodeling complexes to drive SyS tumorigenesis.

LipoID profiles lipid droplet interactions and identifies interorganelle regulators.

Here, the authors developed a method to precisely measure bulk, chromosome arm- and allele-specific human telomere length using nanopore sequencing. They resolve telomere shortening and differences between telomerase- and ALT-positive cancer cells

The potential roles of viruses in microbial-induced permafrost thaw, which is accelerated by climate change, are unclear. Here, Trubl et al. sample a permafrost thaw gradient and identify thousands of new viruses carrying genes with metabolic-related functions, which might influence the fate of stored carbon.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

The early genetic evolution of uveal melanoma (UM) remains poorly understood. Here, the authors perform genetic profiling of 1140 primary UMs, including 131 small early-stage tumours, finding that most genetic driver aberrations have occurred by the time small tumours are biopsied; in addition, the15-gene expression profile discriminant score can predict the transition from low- to high-risk tumours.

This study investigates a calcium-permeable AMPAR–gated microcircuit in the nucleus accumbens during social bonding in prairie voles. By showing that disrupting calcium-permeable AMPAR signaling impairs ensemble-level encoding despite increasing single-neuron selectivity, the work reveals how coordinated ensemble dynamics transform social interaction into enduring attachment.

Sivanandan, Leitmann, and colleagues present the CellPaint-POSH platform, which combines pooled CRISPR screening with Cell Painting. Using self-supervised deep learning on cell images, the method enables discovery of gene function and biological networks.

Low glume coverage is the preferred for easy threshing in grain production, but the genetic basis remains unclear. Here, the authors report the gene GC1, which encodes an atypical G protein γ subunit, negatively regulates sorghum glume coverage and the naturally truncated alleles can be useful in the naked grain breeding.

Development and application of the integrated linkage disequilibrium score (iLDS) reveals both selective pressures impacting the human gut microbiome and the mechanisms by which gut bacteria adapt to meet them.

This study shows that the mobile genetic elements of Listeria monocytogenes exhibit a structured but interconnected network of genetic exchanges. The authors found dense interconnections of similar sequences among phages, plasmids and transposons.

Two main acceleration mechanisms in the auroral acceleration region are electric potential and Alfvénic acceleration but associated energy dynamics are not completely resolved. Here, the authors show that Alfvén waves power the Earth’s auroral arc through a static potential drop in the auroral acceleration region.

Paul and colleagues report the development and characterization of an antibody–drug conjugate targeting TRBC2 for the treatment of T cell malignancies.

Here the authors show that persistent antigen stimulation drives the generation of CD8⁺ tissue-resident exhausted T cells with distinct developmental origins, function and therapeutic responsiveness when compared to CD8⁺ tissue-resident memory T cells.

NHEJ is the primary repair pathway during class switch recombination. Here the authors show that in absence of NHEJ, Pol θ repairs persistent G1-induced breaks in S-phase resulting in recombination products showing resection and microhomology.

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.

A combined sequencing technique assesses 18 patients with high-grade serous ovarian cancer over a multi-year period from diagnosis to recurrence and shows drug resistance typically arises from selective expansion of one or a few clones present at diagnosis.

Neuromorphic computing processes data faster and with less energy than electronics. Here, authors demonstrate a reconfigurable photonic reservoir computer that performs multiple machine learning tasks in parallel at ultrafast rates while using extremely low energy per operation.

Recently, various computational tools have emerged for detecting mRNA isoforms using long-read sequencing data. Here, the authors systemically evaluate and compare the performance of these tools.

The mechanisms that impact tumorigenesis during aging are incompletely understood. Here Shuldiner et al. show that in mice, aging represses KRAS-driven lung tumorigenesis and dampens the impact of inactivating many tumor suppressor genes, which may contribute to the deceleration in cancer incidence with extreme age in humans.

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 fetal globin gene repressors BCL11A and ZBTB7A directly bind γ-globin gene promoter regions. Repressor binding is disrupted by naturally occurring point mutations located upstream of the transcriptional start site that are associated with hereditary persistence of fetal hemoglobin.

Plant mitoribosomes are crucial for mitochondrial protein synthesis. Here, authors use cryo-EM to determine high-resolution structures of cauliflower mitoribosomes, and combined with sequencing and mass spectrometry, identified 19 rRNA base modifications.

Moral-Sanz, Fernández-Carrasco and colleagues identify senolytic properties of sea anemone-derived pore-forming toxins, with selectivity mediated by senescence-associated lipid profiles. An optimized senotoxin improves the efficacy of chemotherapy in mouse models.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

High-throughput chemical ligand discovery is challenged by false positives. Here, authors introduce a scalable enantioselective affinity-selection mass spectrometry approach for proteome-wide ligand discovery with high sensitivity and selectivity

An exploratory analysis of the phase 3 ECOSPOR III trial shows that a higher dosage of the oral microbiome therapeutic VOWST led to enhanced pharmacokinetics, increased species engraftment and altered microbiome and metabolite profiles, providing mechanistic insights into how it may prevent Clostridioides difficile infection recurrence.

With rich, multi-layered baseline data and long-term follow-up through linkage, the HELIOS Study provides a resource to investigate the behavioural, environmental, genomic, and molecular factors impacting health in Asian populations.

DiMeLo-seq uses native long-read sequencing to examine protein–DNA interactions by mapping exogenous methylation marks generated by a nonspecific DNA methyltransferase, as well as profile endogenous CpG methylation simultaneously.

Colorectal cancer is often diagnosed at later stages, leading to poor prognosis. Here, the authors utilise analysis of rectal mucus specimens using host and microbial analysis to detect cancer lesions.

PPARγ regulates glucose and lipid metabolism, yet safer PPARγ-targeted insulin sensitizers are needed to treat metabolic disorders. Here, Kuang-Ting et al. elucidate structure–function relationships of non-covalent inverse agonists that enhance receptor binding and improve insulin sensitivity, providing a framework for next-generation drug design.

Single-cell transcriptomic analyses of Plasmodium falciparum and Anopheles gambiae reveal key developmental stages, processes and factors in parasite–mosquito interactions and identify potential targets for blocking malaria transmission.

Genomic, transcriptomic and metabolomic analyses from a population of 295 diverse sweet-corn inbred lines provide insights into kernel quality formation mechanisms and the divergence of sweet corn and field corn.

Long-read sequencing enables high-quality genome assemblies, but challenges remain. Here, the authors introduce Cornetto, a method that improves assembly quality, enables genome sequencing from saliva, and accurately resolves medically-relevant repetitive genes.

The Sargasso Sea is a natural laboratory for understanding future conditions of warmer oceans and associated nutrient limitation. Here, the authors combined short- and long-read sequencing to survey Sargasso Sea viral communities.

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.

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.

Roles of of viruses in ocean subsurface oxygen maxima are unclear. Here, the authors analyse Bermuda Atlantic Time Series data to show that viruses may drive SOM in stratified oceans by boosting nutrient recycling and phytoplankton productivity linking virus activity to oxygen buildup and a stronger microbial loop.

Distinguishing treatment failure from reinfection is crucial for assessing antimalarial efficacy in endemic regions. Here the authors introduce the probabilistic classifier PfRecur, a software utilizing Bayesian analysis to improve accuracy in identifying treatment failures in polyclonal infections, and apply it to data from Angola.

High-depth sequencing of non-cancerous tissue from patients with metastatic cancer reveals single-base mutational signatures of alcohol, smoking and cancer treatments, and reveals how exogenous factors, including cancer therapies, affect somatic cell evolution.