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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.

Chemical language models trained on known metabolites can identify previously unknown metabolites from mass spectrometry-based metabolomics data with high accuracy.

Semiconductor-based, non-optical DNA sequencing technologies such as Ion Torrent sequencing offer speed and cost advantages compared with alternative techniques. Cheng et al. demonstrate a protocol allowing the use of Ion Torrent technology to sequence DNA from chromatin immunoprecipitation experiments.

Foundation models trained on DNA sequences have the potential to transform genomics, but systematic evaluations are scarce. Here, the authors benchmark five DNA foundation models across diverse genomic tasks, revealing key factors influencing their performance and practical application.

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.

In this study the authors consider the structural variants (SVs) present within cancer cases of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. They report hundreds of genes, including known cancer-associated genes for which the nearby presence of a SV breakpoint is associated with altered expression.

Following spinal cord injury, gamified physical therapy that incorporates closed-loop vagus nerve stimulation can aid restoration of arm and hand function.

Self-supervised learning (SSL) is increasingly used to train pathology foundation models. Here, the authors introduce a pathology benchmark set generated during standard clinical workflows that includes multiple cancer and disease types; then leverage it to assess the performance of multiple public SSL pathology foundation models and to provide best practices for model training and selection.

Jails are high-risk settings for transmission of pathogens. Here, the authors use genomic and epidemiological data to investigate the bacterial and clinical factors affecting transmission of MRSA in jails and impacts on wider community transmission dynamics.

The functions of small nucleolar RNAs (snoRNAs) in cancer remain to be studied. Here the authors show that the snoRNA Snord67 promotes lymph node metastasis of breast cancer cells through guiding modifications of the spliceosome and regulating the splicing landscape.

RNA translation is a core cell process that is deregulated in cancer. Here, the authors show that a machine learning approach, RiboTIE, can reconstruct RNA translation in cancer and non-cancer cells. In medulloblastoma, a brain cancer, RiboTIE enables discovery of subtype-specific microproteins.

Pan-cancer proteomics analysis enables the analysis of protein expression across multiple cancer types. Here, the authors compare proteomics from 14 cancer types and show 11 distinct subtypes across multiple cancer types. Proteome data could link higher pathway activity levels with somatic alteration of specific genes in the pathway.

Here the authors show inducible genes and enhancers are regulated mainly by transcriptional burst frequency and that this is coordinated in single cells and individual alleles. Cohesin, which is important for inducible gene expression, is largely dispensable for regulating enhancer burst frequencies; however, it is required for coupling burst frequencies of inducible enhancers and promoters.

Drawing on 51,269 participants across 9 independent, geographically diverse datasets, an AI model identifies the etiologies contributing to dementia in individuals, harnessing a broad array of data, including demographics, medical history, medication use, neuropsychological assessments, functional evaluations, and multimodal neuroimaging.

Mucosal influenza vaccines promise enhanced protection but lack defined immune correlates of protection. Here, the authors conduct a phase I trial of an intranasal recombinant influenza A/H5 vaccine with a nanoemulsion adjuvant, demonstrating successful mucosal priming and broad cross-clade immune responses, advancing the development of intranasal influenza vaccines.

PIWI-interacting RNAs (piRNAs) are regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity. Here the authors characterized their binding specificity and reveal the 5′ nucleotide bias of the Drosophila Piwi protein, through mutation of its specificity loop.

Rooftop solar and battery storage can reduce energy costs and provide affordable back-up power for over 60% of US households, but benefits often bypass the high outage risk and disadvantaged communities most in need.

How expectations of reward influence spatial memories remains unclear. Here, the authors reveal a dopamine pathway to the hippocampus that increases activity with proximity to expected rewards, thus stabilizing spatial representations of trajectories that lead to rewards.

The authors show that loss-of-interaction with the nuclear importer, TNPO3, causes cytoplasmic mislocalization of RBM20 variants linked to severe cases of dilated cardiomyopathy. Restoring their nuclear localization alleviates the disease phenotype.

Candida auris is a fungal pathogen notorious for persistent skin colonization and transmission in healthcare settings. Here, Zhao et al. explore the mechanisms driving pathogen’s adherence to skin, involving a conserved adhesin, as well as the potential of collagen coatings as a strategy to reduce C. auris adherence to abiotic surfaces.

Obtaining data on antimicrobial resistance (AMR) from healthy human populations is difficult. Here, Hendriksen et al. use metagenomic analysis to obtain AMR data from untreated sewage from 79 sites in 60 countries, finding correlations with socio-economic, health and environmental factors.

Resistance to first line treatment is a major hurdle in cancer treatment, that can be overcome with drug combinations. Here, the authors provide a large drug combination screen across cancer cell lines to benchmark crowdsourced methods and to computationally predict drug synergies.

PBK is a mitotic kinase implicated in cancer. This study reveals how PBK evicts key C2H2-zinc finger transcription factors such as Ikaros, Aiolos and CTCF from DNA as cells divide, regulating mitotic chromatin accessibility and chromosome compaction.

In a silent trial involving 197 patients with lung cancer over a span of 4 months, a fine-tuned pathology foundation model was able to identify the presence of EGFR mutations with high accuracy, potentially preventing further genetic testing in 43% of cases.

The largest harmonized proteomic dataset of plasma, serum and cerebrospinal fluid samples across major neurodegenerative diseases reveals both disease-specific and transdiagnostic proteomic signatures, including a robust plasma profile associated with the APOEε4 genotype.

Single-cell data analysis is challenging due to inherent noise and sparsity. Here, authors introduce scMINER, a mutual information-based integrative tool to enhance clustering and reveal regulatory networks and hidden biological drivers by transforming scRNA-seq expression into activity profiles.

A study comparing the pattern of single-nucleotide variation between unique and duplicated regions of the human genome shows that mutation rate and interlocus gene conversion are elevated in duplicated regions.

Organellar transport is carefully regulated, and endolysosome localized ARL8 is important for kinesin recruitment and anterograde movement. Here, the authors show that RUFY3 and RUFY4 promote retrograde transport of endolysosomes by mediating interaction of ARL8 with dynein-dynactin.

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.

Type 2 inflammation drives the formation of pathologic mucus in patients with asthma. Here, authors reveal a role for intelectin-1 in IL-13-induced mucus properties, and that an ITLN1 eQTL is associated with protection from the formation of mucus plugs in T2-high asthma.

He et al. develop a network-based metric of amyloid-β burden by integrating individualized brain connectomes with amyloid-PET imaging. This approach improves prediction of future cognitive decline in older adults and may support earlier identification of individuals at risk of dementia.

Why do certain individuals learn faster than others, and how does the acquired information take shape within their brains? Tang and colleagues show that fast learners encode information in a particularly compact, efficient and space-saving manner.

The most common protein modification in eukaryotes is N-terminal acetylation, but its functional impact has remained enigmatic. Here, the authors find that a key role for N-terminal acetylation is shielding proteins from ubiquitin ligase-mediated degradation, mediating motility and longevity.

Here, the authors perform a large-scale, high-throughput biochemical assay to determine the compatibility of over 300,000 domain recombination variants of the inward rectifier K⁺ channel Kir2.1. They derive rules for designing domain insertion variants that fold and traffic to the cell surface and conclude that the insertion of domains at protein termini is evolutionary favoured.

Tumour profiling with next-generation sequencing is challenging due to the low amounts of diagnostic material in cytology samples that are obtained through non-invasive procedures. Here, the authors report on the optimization of this process across 4,871 cancer cytology samples profiled by MSK-IMPACT, with emphasis on the successful use of supernatant cell-free DNA.

With the generation of large pan-cancer whole-exome and whole-genome sequencing projects, a question remains about how comparable these datasets are. Here, using The Cancer Genome Atlas samples analysed as part of the Pan-Cancer Analysis of Whole Genomes project, the authors explore the concordance of mutations called by whole exome sequencing and whole genome sequencing techniques.

ATG9A is transmembrane autophagic machinery protein that delivers phospholipids to expanding autophagosomes. Mailler et al. show that ATG9A is required to mobilize lipids from lipid droplets for autophagosome expansion as well as mitochondrial fatty acid import and β-oxidation.

The relevance of non-coding somatic mutations in cancer remains elusive. Here, the combination of mass spectrometry-based proteomics and whole genome sequencing data across multiple cancer types helps to assess the effects of somatic structural variant breakpoint patterns on protein expression of nearby genes.

An initial draft of the human pangenome is presented and made publicly available by the Human Pangenome Reference Consortium; the draft contains 94 de novo haplotype assemblies from 47 ancestrally diverse individuals.

Lung squamous carcinomas (LUSC) are poorly molecularly characterized, but sub-populations show promising response to immune checkpoint inhibitors. Here, the authors identify a subset of LUSC characterized by infiltration of inflammatory monocytes, where metastasis is linked to Factor XIIIA promoting fibrin cross-linking.

The enzyme ABHD18 is shown to have a key role in cardiolipin metabolism in mitochondria, offering a potential route for a small-molecule treatment of the rare genetic disease Barth syndrome.

This study describes the integrative analysis of 111 reference human epigenomes, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression; the results annotate candidate regulatory elements in diverse tissues and cell types, their candidate regulators, and the set of human traits for which they show genetic variant enrichment, providing a resource for interpreting the molecular basis of human disease.

Aregger et al. provide an approach to study genetic interactions in mammalian cells and describe genetic interaction maps that characterize genes involved in lipid metabolism. They identify the role of C12orf49, a previously uncharacterized gene, in regulating lipid uptake in human cells.

Urological cancers have disparate tissues and cells of origin but share many molecular features. Here, the authors use multidimensional and comprehensive molecular characterization to classify urological cancers into nine major genomic subtypes, highlighting potential therapeutic targets.

Antibody responses to SARS-CoV-2 may be important biomarkers for assessing the risk for viral transmission. Here the authors present serological antibody profiling results of COVID-19 patients using a new multiplex assay to show distinct kinetics and dynamics of IgG, IgM and IgA responses in patients with different disease severity.

This study finds that sST2 is a disease-causing factor for Alzheimer’s disease. Higher sST2 levels impair microglial Aβ clearance in APOE4⁺ female individuals. A genetic variant, rs1921622, is associated with a reduction in sST2 level and protects against AD in APOE4⁺ female individuals.

The phenotype and function of immune cells could change during spaceflight. Here the authors use simulated microgravity, coupled to validation with spaceflight data, to assess whether there are distinct gene expression changes in resting and TLR 7/8 stimulated PBMCs and found conserved changes in IFN signalling, the cytoskeleton, IL-6 and sirtuin signalling.

A first-in-human phase I clinical trial demonstrates the feasibility and safety of non-viral precision genome-engineering of a personalized adoptive cell transfer anticancer therapeutic.