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The characterization of 4,645 whole-genome and 19,184 exome sequences, covering most types of cancer, identifies 81 single-base substitution, doublet-base substitution and small-insertion-and-deletion mutational signatures, providing a systematic overview of the mutational processes that contribute to cancer development.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Tissue-resident macrophages (TRM) are important mediators of local immunity. Here the authors show that the deficiency or inhibition of a kinase, WNK1, unlinks macrophage colony-stimulating factor signaling and resulted macropinocytosis with the downstream, potentially IRF8-mediated genetic program to bias progenitor differentiation to neutrophil instead of TRM.

Birds have an excellent ability to learn to discriminate harmless insects from those that they mimic on the basis of subtle differences in appearance.

A high-bandwidth neuromotor interface offers performant out-of-the-box generalization across people.

A mix-and-go system enables the rapid prototyping of antibody formulations, allowing control of their orientation on the surface of LNPs for specific cell targeting, significantly improving the ex vivo and in vivo deliveries of mRNA.

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.

Whole-genome sequencing data from more than 2,500 cancers of 38 tumour types reveal 16 signatures that can be used to classify somatic structural variants, highlighting the diversity of genomic rearrangements in cancer.

Single-cell multimodal data has the potential to unveil noncoding disease mechanisms. Here, authors introduce GrID-Net, a graph-based Granger causal approach that links noncoding variants to genes by exploiting the time lag between epigenomic and transcriptional cell states.

Insufficient oxygen limits the efficacy of cell encapsulation therapies for type 1 diabetes. Here, the authors develop an implantable system that continuously generates oxygen to support high-density islet cell survival and function, enabling diabetes reversal in rats without immunosuppression.

Analysis of snRNA genes in individuals with rare disorders identifies de novo and recurrent variants in RNU5B-1 and RNU5A-1, in addition to previously unreported cases with pathogenic or likely pathogenic variants in RNU4-2.

In this study, the authors assess the global response to the toxic aldehyde glyoxal (GO) in Pseudomonas aeruginosa, suggesting that GO controls quorum sensing during infection through a mechanism involving a novel protein, ArqI.

A Telluride Science Workshop on electrochemical separations was convened in early 2025. In this Feature, 17 of the workshop participants share their perspectives and future outlooks on this rapidly growing research area.

Bacterial peptidoglycan fragments (PGNs) are potent inducers of Candida albicans invasive hyphal growth in the host. Here, the authors reveal that surface sensing of PGNs by Candida albicans cell surface protein Ssy1 is a key prerequisite for PGN-induced hyphal growth, highlighting Ssy1 as a potential promising target for anti-virulence strategies.

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.

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.

An in-depth microbiological and metagenomic analysis of Colombian farm and fermentation facilities resulted in the design of a defined microbial community that can reproduce the flavour of fine chocolate.

Using a combination of radical retrosynthesis, biocatalysis and C–H functionalization logic, a concise and scalable approach to the synthesis of saxitoxin and derivatives thereof in fewer than ten steps is presented.

Using a trapped-ion quantum simulator of up to 50 spins, researchers explore new universal scaling laws in non-equilibrium dynamics, revealing unique critical behaviors following a sequence of quenches in a long-range 1D Ising model.

Commercial investment in enhanced rock weathering for carbon dioxide removal on agricultural lands is growing rapidly. This Review explores the potential of large-scale deployment, outlining the challenges faced in science, policy and governance to scale the technology.

The ability to sequence oligonucleotides which consist entirely of artificial bases will facilitate their ongoing development and use. Here authors demonstrate de novo nanopore sequencing of DNA oligomers composed of “P” “Z” “S” and “B” bases with high sequencing accuracy.

Cellular spatial organisation is crucial for shaping tissue functions and phenotypes. Here, authors present TrimNN, a graph-based deep learning framework to identify conserved cellular community motifs, revealing links between spatially distributed cell-type patterns and diverse phenotypes.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

A connectome of the right optic lobe from a male fruitfly is presented together with an extensive collection of genetic drivers matched to a comprehensive neuron-type catalogue.

Nardone et al. identify a metazoan protein complex (mRAVE) that assembles V-ATPases from two subcomplexes, enabling lysosome acidification, neurotransmitter vesicle loading and a lysosome damage response pathway.

This Perspective from Summerfield et al. considers the impacts of advanced artificial intelligence systems on the process and function of democracy. The authors explore a wide range of potential risks and opportunities.

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.

The neural circuits that transmit cool signals remain not fully understood. Here, authors identify a spinal circuit in mice that transmits cool sensations from the skin to the brain, revealing a dedicated neural pathway for detecting innocuous cool temperatures.

PARP inhibitor treatment triggers histone release from the chromatin in cancer cells; consequently, targeting the histone chaperone NASP renders cells vulnerable to PARP inhibition.

Measuring the bulk power laws of Luttinger liquids in semiconductors remains challenging. Here, the authors demonstrate the dominance of the end-tunneling effect in two fairly distinct Luttinger liquids coexisting in a single quantum wire.

Bruton tyrosine kinase (BTK) inhibitors can interrupt the crosstalk between follicular lymphoma FL cells and macrophages thereby inducing downregulation of pro-survival pathways in FL cells. Here this group reports a phase 2 single-arm trial evaluating the regimen of acalabrutinib with lenalidomide plus rituximab on twenty four patients with previously untreated FL.

Genome-wide analyses identify 30 independent loci associated with obsessive–compulsive disorder, highlighting genetic overlap with other psychiatric disorders and implicating putative effector genes and cell types contributing to its etiology.

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.

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.

An expert-elicitation process identifies current methodological barriers for monitoring terrestrial biodiversity, and how technological and procedural development of robotic and autonomous systems may contribute to overcoming these challenges.

Using single-molecule analysis, the authors establish that direct competition between eIF1 and eIF5 governs accurate yet flexible translation initiation in humans, providing a biophysical framework with broad relevance to health and disease.

An image analysis framework makes use of rotation-invariant autoencoders and point clouds for morphology-appropriate representation learning to better understand the organization of complex subcellular structures.

By developing a functional nuclear import system and correlative imaging workflow, this study reveals that HIV-1 nuclear entry relies on the elasticity of both the viral capsid and the nuclear pore to enable the selective passage of small HIV-1 cores.

The authors report resonant soft x-ray scattering and polarimetry measurements on epitaxial thin films of La3Ni2O7. They find a diagonal bicollinear double spin stripe order, with no evidence of charge modulation.

Most metabolic studies using traditional procedures fail to reveal the spatial patterning associated with metabolic flux and cellular metabolism within tissue microenvironments. Here, the authors show the application of multi-scale microscopy, machine learning-based image segmentation and spatial analysis to map the fate of nutrient-derived ¹³C across spatiotemporal scales.

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.

Analysis of cancer genome sequencing data has enabled the discovery of driver mutations. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium the authors present DriverPower, a software package that identifies coding and non-coding driver mutations within cancer whole genomes via consideration of mutational burden and functional impact evidence.

City pedestrians must look out for road traffic, especially at busy intersections. This study finds that New York City’s leading pedestrian interval program gives people a head start over turning traffic that improves safety.