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Self-healing polymer materials based on metal–ligand coordination bonds have been extensively utilized for their advantages of rich metal–ligand species and functionalities but the strength of the metal bonds is not easily tunable. Here, the authors introduce coordination metals into liquid metals leveraging the inherent fluidity of multi-component liquid metals to convert common metal-ligand coordination into reversible interfacial coordination.

A 3D soft electronic mesh allows high-resolution electrical recording and stimulation across the full surface of neural organoids, enabling long-term studies, drug testing and optogenetic control without compromising their viability owing to its porous design.

In situ cryo-electron microscopy structures show the spatial arrangement of flagellin proteins and provide insight into mechanisms of assembly and rotation of the sheathed flagellum in Vibrio cholerae.

Humanity’s Last Exam, a multi-modal benchmark at the frontier of human knowledge, is designed to be an expert-level closed-ended academic benchmark with broad subject coverage.

Large-effect variants in autism remain elusive. Here, the authors use long-read sequencing to assemble phased genomes for 189 individuals, identifying pathogenic variants in TBL1XR1, MECP2, and SYNGAP1, plus nine candidate structural variants missed by short-read methods.

Glycine sensing in the dorsal vagal complex (DVC) regulates hepatic glucose production in rodents. Here the authors show that pharmacological and molecular inhibition of glycine reuptake in the DVC potentiates NMDA receptors, and improves metabolic homeostasis in animal models of obesity and diabetes.

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

Chai et al. use cryo-electron microscopy to systematically interrogate the conformational landscape of motor protein dynein. The reported structures reveal intermediate states in the mechanochemical cycle of dynein, the role of adenosine triphosphate and the communication mechanism with microtubules.

Minimally invasive oral vaccine delivery is a desired approach. Here, the authors report on an engineered probiotic-based oral vaccine system that enables controlled mucosal delivery of ferritin-displayed dual antigens, eliciting robust mucosal and systemic antitumor immune responses.

Mosquito saliva can affect transmission of Plasmodium to mammalian hosts, but active saliva components or mechanisms are poorly understood. Here, the authors identify a mosquito saliva protein that binds Plasmodium sporozoites and inhibits cell traversal in vitro and sporozoite speed in mice.

Analyses of 2,658 whole genomes across 38 types of cancer identify the contribution of non-coding point mutations and structural variants to driving cancer.

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.

Using genome-wide association studies and meta-analyses on dimensions of personality from large existing datasets, Gupta et al. find novel genomic loci that refine our understanding of the genetic architecture of complex traits.

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.

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.

Disparities in risk and outcomes of pediatric acute lymphoblastic leukemia (ALL) are apparent between different ancestries. Here the authors identify genetic variants with African ancestry-specific risks for developing pediatric B-cell ALL that are also linked to greater 5-year mortality risk.

Here, authors solve cryo-EM structures of the central apparatus of motile cilia and analyze its dynamic conformations to elucidate the mechanism of ciliary beating.

Outer-arm dyneins (OADs) assemble in large arrays on the ciliary axoneme to drive rhythmic beating. Cryo-EM structures of microtubule-bound Tetrahymena thermophila OAD arrays reveal details of this complex assembly and suggest a model for its mechanism of coordinated action.

In somatic cells the mechanisms maintaining the chromosome ends are normally inactivated; however, cancer cells can re-activate these pathways to support continuous growth. Here, the authors characterize the telomeric landscapes across tumour types and identify genomic alterations associated with different telomere maintenance mechanisms.

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.

A pan-cancer genomic analysis reports the effects of structural variations on chromatin domains (TADs). Most TAD disruptions do not result in appreciable changes in expression of nearby genes.

An analysis of 2,954 genomes from 38 cancer subtypes identified 19,166 retrotransposition events in 35% of samples. Aberrant LINE-1 retrotranspositions can lead to the deletion of tumor-suppressor genes as well as the amplification of oncogenes.

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.

Conductive polymer electronics often require high loads of conductive fillers, making it challenging to design these materials. Here the authors use electromagnetic waves to cohere microparticles to optimize conductivity.

How post-translational SUMOylation regulates the SRF activity in cardiovascular disease is unclear. Here, the authors report that SRF SUMOylation increased by SENP1 deficiency switches vascular smooth muscle cells from a healthy contractile phenotype to a disease-associated synthetic phenotype.

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.

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.

The flagship paper of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium describes the generation of the integrative analyses of 2,658 cancer whole genomes and their matching normal tissues across 38 tumour types, the structures for international data sharing and standardized analyses, and the main scientific findings from across the consortium studies.

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.

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.

Whole-genome sequencing data for 2,778 cancer samples from 2,658 unique donors across 38 cancer types is used to reconstruct the evolutionary history of cancer, revealing that driver mutations can precede diagnosis by several years to decades.

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.

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

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 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.

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.

This study identifies four distinct polycystic ovary syndrome (PCOS) subtypes using unsupervised clustering analysis on data from 11,908 women and validated across five diverse cohorts. The subtypes show unique clinical features and suggest that subtype-specific management could enhance treatment precision for PCOS.

LIS1 is a critical activator of dynein-mediated retrograde transport. Ton et al. reveal that microtubule binding by dynein initiates a cascade of structural changes that trigger LIS1 dissociation from dynein prior to transport, providing insights into dynein activation.

This study reveals that population aging intensifies heat- and cold-related deaths, more so than climate change, in 50 countries. At 1.53 °C global warming, aging contributes to rising heat-related deaths, offsetting declines in cold related death.

Isotope tracing, kinetics and transcriptomics show how members of the four AOM lineages employ different nitrogen use strategies that minimize competition for nitrogen substrates.

The role of caspase-12 in viral immunity has not been characterized yet. Fikrig and colleagues now show that it positively regulates the response to West Nile Virus through control of ubiquitinylation of the viral RNA receptor RIG-I.

A genome-wide association study meta-analysis combined with multiomics data of osteoarthritis identifies 700 effector genes as well as biological processes with a convergent involvement of multiple effector genes; 10% of these genes express the target of approved drugs.

The health impacts of air pollution at low concentrations are unclear. Here, using a double negative control approach to capture omitted confounders, the authors show increased cardiovascular risk associated with long-term air pollution exposure below US regulatory standards, suggesting the need to tighten the current standards.

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.

Zong et al. reveal that genetic and pharmacologic inhibition of TRPM7 channel function prevents the activation of Ca²⁺–CaM–calcineurin–KLF4 signaling, the phenotypic switch of vascular smooth muscle cells and the formation of abdominal aortic aneurysms.

Brain structural traits are highly heritable and have been linked to disease. Here the authors have used gene expression data to perform a transcriptome-wide association study on 211 brain structural traits, discovering 273 associated genes.