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Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Kagome lattices exhibit notable rich physics, however, there has been only limited study of the influence of magnetic ordering on the electronic structure. Here, by combining angle-resolved photoemission spectroscopy and first principles calculations, Lou et al. find that the spin reorientation transition has an orbital-selective effect on the Dirac fermions of the kagome material, Fe₃Ge.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

Topological semimetals with space-inversion and time-reversal symmetry breaking have attracted attention recently. Here, using a combination of experimental techniques and calculations, the authors demonstrate the tunability of the Weyl nodes via magnetism and pressure in the ferromagnetic Weyl semimetal CeAlSi.

In a GWAS study of 32,438 adults, the authors discovered five novel loci for intracranial volume and confirmed two known signals. Variants for intracranial volume were also related to childhood and adult cognitive function and to Parkinson's disease, and enriched near genes involved in growth pathways, including PI3K-AKT signaling.

Maintaining genomic integrity is essential for the survival of organisms. Here, the authors identify FTO as an endogenous negative regulator of PARP1 and the DNA damage response in cells beyond its role as an RNA demethylase.

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Integrative analyses of transcriptome and whole-genome sequencing data for 1,188 tumours across 27 types of cancer are used to provide a comprehensive catalogue of RNA-level alterations in cancer.

Some cancer patients first present with metastases where the location of the primary is unidentified; these are difficult to treat. In this study, using machine learning, the authors develop a method to determine the tissue of origin of a cancer based on whole sequencing data.

Multi-omics datasets pose major challenges to data interpretation and hypothesis generation owing to their high-dimensional molecular profiles. Here, the authors develop ActivePathways method, which uses data fusion techniques for integrative pathway analysis of multi-omics data and candidate gene discovery.

Cancers evolve as they progress under differing selective pressures. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, the authors present the method TrackSig the estimates evolutionary trajectories of somatic mutational processes from single bulk tumour data.

Post-acute sequelae of SARS-CoV-2 (PASC) is still not well understood. Here the authors provide patient reported outcomes from 590 hospitalized COVID-19 patients and show association of PASC with higher respiratory SARS-CoV-2 load and circulating antibody titers, and in some an elevation in circulating fibroblast growth factor 21.

Deregulation of BCL-2 proteins ensures resistance to apoptosis. Here, the authors describe cytosolic BAX dimers, which in cancer cells inhibit BAX activation and they develop a strategy to modulate BAX dimers to potentiate BAX-mediated apoptosis.

Understanding deregulation of biological pathways in cancer can provide insight into disease etiology and potential therapies. Here, as part of the PanCancer Analysis of Whole Genomes (PCAWG) consortium, the authors present pathway and network analysis of 2583 whole cancer genomes from 27 tumour types.

There’s an emerging body of evidence to show how biological sex impacts cancer incidence, treatment and underlying biology. Here, using a large pan-cancer dataset, the authors further highlight how sex differences shape the cancer genome.

Viral pathogen load in cancer genomes is estimated through analysis of sequencing data from 2,656 tumors across 35 cancer types using multiple pathogen-detection pipelines, identifying viruses in 382 genomic and 68 transcriptome datasets.

Many tumours exhibit hypoxia (low oxygen) and hypoxic tumours often respond poorly to therapy. Here, the authors quantify hypoxia in 1188 tumours from 27 cancer types, showing elevated hypoxia links to increased mutational load, directing evolutionary trajectories.

The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke.

This study reports unexpected structural diversity in computationally designed protein assemblies due to subunit flexibility. Fixing flexibility in one design restores the intended architecture, suggesting a strategy to design dynamic assemblies.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

As vesicles fuse to the plasma membrane, they form intermediate Ω-shaped structures followed by either closure of the pore or full merging with the plasma membrane. Here Wen et al. show that dynamic actin assembly provides membrane tension to promote Ω merging in neuroendocrine cells and synapses.

Accurate identification of sub-compartments from chromatin interaction data remains a challenge. Here, the authors introduce an algorithm combining graph embedding and unsupervised learning to predict sub-compartments using Hi-C data.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

A 3.5 μm robotic device featuring plasmonic nanomotors and tweezer can deliver, capture, and release a single 70 nm nanodiamond. In this study, the authors develop and demonstrate such a microrobotic device.

Van Nerum et al. show that dimethyl α-ketoglutarate enhances the production and functional maturation of human trophectoderm-like cells from embryonic stem cells by regulating histone acetyltransferase activity and the pluripotency network.

Multiancestry genome-wide association analyses identify new risk loci for stroke and stroke subtypes. Fine mapping and bioinformatics analyses of these risk loci point to mechanisms not previously implicated in stroke pathophysiology.

Sun et al. report human lifespan changes in the brain’s functional connectome in 33,250 individuals, which highlights critical growth milestones and distinct maturation patterns and offers a normative reference for development, aging and diseases.

The role of IgG glycosylation in the immune response has been studied, but less is known about IgM glycosylation. Here the authors characterize glycosylation of SARS-CoV-2 spike specific IgM and show that it correlates with COVID-19 severity and affects complement deposition.

This report by the Consortium for Refractive Error and Myopia uses gene-environment-wide interaction study (GEWIS) to identify genetic loci that affect environmental influence in myopia development, and identifies ethnic specific genetic loci that attribute to eye refractive errors.

Fernando Rivadeneira and colleagues in the Genetic Factors for Osteoporosis Consortium report a large-scale meta-analysis identifying new loci associated with bone mineral density (BMD) and risk of fracture. Thirty-two new loci are found to be associated with BMD, and 6 loci confer higher risk for low-trauma bone fracture.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Selectable markers are widely used in cell engineering but there is only a limited variety to choose from. Here the authors split markers using inteins, allowing up to six transgene integration events to be selected for with one marker.

Soil contamination is a pressing environmental concern due to increasing anthropogenic activity. Here, the authors developed a rapid and energy-efficient electrothermal process that simultaneously removes heavy metals and organic pollutants in soil.

Cheng et al. show that smooth muscle cell (SMC)-specific deletion of Smad3 influences the fate of de-differentiated SMCs in atherosclerotic plaques in vivo, promoting both a pro-remodeling SMC transition phenotype and expansion of the SMC-derived chondromyocyte population. These cellular changes are associated with increased outward remodeling and plaque calcification.

The effect of noncoding genetic variation on acute lymphoblastic leukemia treatment response is not fully understood. Here, the authors functionally evaluated variants associated with pharmacological traits and validate the role of rs1247117 in gene regulation impacting therapeutic response.

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

John Chambers, Jaspal Kooner, Pim van der Harst, Shyong Tai, Paul Elliott, Jiang He, Norihiro Kato and colleagues performed a genome-wide association study of blood pressure phenotypes in individuals of European, East Asian and South Asian ancestry. They find trait-associated SNPs at 12 loci, some of which are associated with methylation at nearby CpG sites.

DNA methylation plays an important role in regulating a wide variety of cellular processes and is implicated in a range of diseases. Here the authors present Casilio-ME to assemble protein complexes to demethylate target loci.

Signet-ring cell carcinoma (SRCC) is a unique type of gastric cancer with no prognostic features. Here, the authors report a CLDN18-ARHGAP26/6 gene fusion in patients with a high signet-ring cell content, poor survival outcomes, and who experience no benefit from platinum/fluoropyrimidines-based chemotherapy.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Complex diseases often share genetic determinants and symptoms, but the mechanistic basis of disease interactions remains elusive. Here, the authors propose a network topological measure to identify proteins linking complex diseases in the interactome, and identify mediators between COPD and asthma.

The pilot phase of PigGTEx, re-analyzing 5,457 published RNA-seq samples, presents a pan-tissue catalog of molecular quantitative trait loci. Cross-species comparisons identify traits with shared genetic regulation in humans.

A study leveraging transsynaptic tracing demonstrates rapid and extensive integration of human glioblastoma organoids into the mouse brain.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Temporal information that is useful for episodic memory is encoded across a wide range of timescales in the lateral entorhinal cortex, arising inherently from its representation of ongoing experience.