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

Identifying jets originating from heavy quarks plays a fundamental role in hadronic collider experiments. In this work, the ATLAS Collaboration describes and tests a transformer-based neural network architecture for jet flavour tagging based on low-level input and physics-inspired constraints.

Here, a combination of forward genetics and genome-wide association analyses has been used to show that variation at a single genetic locus in Arabidopsis thaliana underlies phenotypic variation in vegetative growth as well as resistance to infection. The strong enhancement of resistance mediated by one of the alleles at this locus explains the allele's persistence in natural populations throughout the world, even though it drastically reduces the production of new leaves.

DNA double-strand breaks endanger genome stability. Here, the authors present cryo-EM structures showing how Ku70/80 and DNA-PK bind DNA ends on nucleosomes, offering a mechanistic model for break recognition within chromatin.

Data obtained from the MicroBooNE liquid-argon time projection chamber are used to exclude the single light sterile neutrino interpretation of the LSND and MiniBooNE anomalies at the 95% confidence level.

PD-L2 can bind the immune checkpoint PD-1. However, its potential as a therapeutic target for immune checkpoint blockade in cancer has not been extensively explored. Here, the authors demonstrate that αPD-L2 is effective in aged, but not young, melanoma murine models.

Laser cooling is a powerful technique that enables precision measurements and quantum control, yet its implementation in molecules remains challenging due to their complex structures. Here, the authors apply 2D transverse laser cooling to a focused beam of cold barium monofluoride (138Ba19F) molecules to significantly increase beam brightness.

A dataset of coding variation, derived from exome sequencing of nearly one million individuals from a range of ancestries, provides insight into rare variants and could accelerate the discovery of disease-associated genes and advance precision medicine efforts.

Cytosine modifications within genomic DNA can serve as important epigenetic markers, but sequencing them at single-base resolution requires chemical modification-selective C-to-T code conversion with potential complex analysis. Now an unnatural base pair enables the sequencing of an epigenetic modification—5-formylcytosine—at single-base resolution within a Sanger sequencing format.

The origin of intertwined electronic orders in transition-metal dichalcogenides has long been debated. Here, Bawden et al. report that the normal state, from which these phases emerge, is unexpectedly spin-polarized, with spins locked to both valley and layer pseudospins.

A 3.05 Å cocrystal structure of BWC0977, a pyrazino-oxazinone-based novel bacterial topoisomerase inhibitor (NBTI) in Phase 1 clinical trials, with topoisomerase IV from Klebsiella pneumoniae reveals features that underpin BWC0977’s antibacterial potency.

Cellular niches are highly heterogenous in triple negative breast cancer. Here, the authors utilise imaging mass cytometry and spatial transcriptomics to characterise the microenvironment in Black American and White American patients.

5-Formylcytosine (5fC) is implicated in active DNA demethylation and has been proposed to act as an epigenetic signal. Balasubramanian and colleagues now report that this base modification imparts a unique, previously undescribed conformation to DNA.

In this work, the authors probe the efficacy of BWC0977, a bacterial topoisomerase inhibitor, in pre-clinical animal models, also demonstrating that BWC0977 is safe and well tolerated in healthy human volunteers, in a phase 1 trial.

Synthetic nanomotors convert chemical energy into motion. Here, they have been implemented in a motion-based assay that allows specific DNA and ribosomal RNA detection. The technique is fast, simple and sensitive, and the concentration-dependant distance signals of the magnetically aligned nanomotors are detected by optical microscopy.

Puddu et al. investigate the role of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) as biomarkers for early-stage colorectal cancer (CRC) detection in cell-free DNA (cfDNA). 6-base genome sequencing, using both 5mC and 5hmC biomarkers, increases the detection of stage I CRC.

Quantum gates based on geometric phase shifts offer a promising approach for the realization of fault-tolerant quantum computing. Using nitrogen-vacancy centre qubits in diamond, this study experimentally realises a high-fidelty, non-adiabatic, non-Abelian holonomic single-qubit gate at room temperature.

Identifying DNA sequences that adopt alternative structures within the context of genomic DNA presents a major challenge. Pyridostatin, a G-quadruplex–specific chemical probe, was shown to induce DNA damage at specific genomic sites, including the proto-oncogene SRC, leading to cell cycle arrest in human cancer cells.

Dynamic gene expression is crucial for coordinating diverse cellular activities, but challenging to modulate with high spatiotemporal precision. Now, a photoswitchable DNA structure-specific, small-molecule ligand enables reversible, light-controlled regulation of gene expression and cell proliferation in live cells.

Understanding the spin texture of topological insulator surface states is crucial for applications in spintronics and nanodevices. Here, Neupane et al. report systematic spin- and angle-resolved photoemission spectroscopy on ultrathin Bi₂Se₃films for the first time.

An exome-wide association study of six smoking phenotypes in up to 749,459 individuals identifies associations of rare coding variants in CHRNB2 that may reduce the likelihood of smoking.

A structure-specific antibody generated and employed to visualize DNA G-quadruplex structures in human cells shows that these structures are modulated during the cell cycle and can be stabilized by a small-molecule ligand. This provides substantive evidence for endogenous DNA G-quadruplex formation in mammalian cells.

Half-Heusler compounds are predicted to bear topological properties, which is yet to be experimentally evidenced. Here, Logan et al.report experimental evidence of a topological surface state in epitaxially grown thin films of the half-Heusler compound PtLuSb, providing a candidate for new spintronic devices.

In this multicentered observational study, Rotavac, an indigenous, monovalent, live, attenuated, oral rotavirus vaccine, had an adjusted vaccine efficacy of 54% and protected against severe gastroenteritis in Indian children during its rollout between 2016 and 2020.

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.

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.

Caielli and colleagues performed single-cell RNA sequencing on blood CD4⁺ T cells from pediatric patients with systemic lupus erythematosus and healthy donors, identifying naive, memory, T_reg, proliferative and interferon-stimulated gene-high cell subsets. Follicular and peripheral helper T cells, including T_H10 cells, and cytotoxic memory cell populations were expanded, along with dysfunctional T_reg cells marked by aberrant TLR5 and FCRL3 expression, pointing to links between microbial dysbiosis and impaired immune regulation.

Ultrack leverages candidate segmentations from multiple algorithms and temporal consistency across time points for robust, long-term 3D segmentation in challenging samples such as densely packed zebrafish, fruit fly and nematode embryos.

Ziwen Liu et al. report Cytoland, an approach to train robust models to virtually stain landmark organelles of cells and address the generalization gap of current models. The training pipeline, models and datasets are shared under open-source permissive licences.

Here, the authors report on the thermal and mechanical properties of Ruddlesden-Popper phases (Ban+1ZrnS3n+1, n = 2 and 3) of a perovskite chalcogenide (BaZrS3) that push to extreme limits and defy the century-old relation between thermal conductivity and interatomic bond strength.

Whether G-quadruplexes (G4s) regulate stem cell self-renewal and fate determination during embryonic development is not well understood. Here, the authors reveal that the embryonic stem cell state is defined by very high G4 abundance. G4s are progressively lost during differentiation as cells transit to lower lineage potential while artificial G4 stabilisation leads to delayed differentiation.

Gasdermin D Cys191 is S-palmitoylated, and palmitoylation is required for pore formation.

Genotype and exome sequencing of 150,000 participants and whole-genome sequencing of 9,950 selected individuals recruited into the Mexico City Prospective Study constitute a valuable, publicly available resource of non-European sequencing data.

The ESCRT pathway is crucial for membrane remodelling in eukaryotes. Here, Hatano et al. explore the phylogeny, structure, and biochemistry of homologues of the ESCRT machinery and the associated ubiquitylation system in Asgard archaea, the closest living relatives of eukaryotes.

Genomic studies often lack representation from diverse populations, limiting equitable insights. Here, the authors show that the BIG Initiative captures extensive genetic diversity and reveals ancestry-linked health disparities in a community-based Mid-South cohort.

Overexpression of the FOXM1 transcription factor occurs in several cancer and correlates with poor prognoses. Here, the authors identify a novel small molecule capable of displacing FOXM1 from its DNA consensus motif in vitro, displace it from target promoters and downregulate the expression of its target genes cancer cells.

The authors report that tensile strain applied to CsV₃Sb₅ strongly suppresses the charge-density-wave (CDW) gap, increases the mass of the fermions at the higher-order van Hove singularity (HO-VHS) and drives the energy of the HO-VHS towards the Fermi energy. Further, they suggest an important role of the HO-VHS in superconducting pairing.

The lead-free chalcogenide perovskite BaZrS3 is shown to exhibit piezoelectricity. The loosely packed structure of BaZrS3 allows for an extended displacement of the ions, resulting in symmetry breaking and an enhanced dipole moment.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

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.