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Circulating tumour DNA profiling in early-stage non-small-cell lung cancer can be used to track single-nucleotide variants in plasma to predict lung cancer relapse and identify tumour subclones involved in the metastatic process.

A transancestral exome-wide association study for body-fat distribution identifies protein-coding variants that are significantly associated with waist-to-hip ratio adjusted for body mass index.

Using cryo-EM, SAXS and HDX–MS, the authors mechanistically delineate dimerization-induced autoinhibition of the HECT-type ligase HACE1 and the selectivity of the active ligase monomer for GTP-bound RAC1.

ASCC3 is a multi-functional helicase that contains two consecutive Ski2-like helicase units. Here, the authors show that ASCC3 can unwind DNA by threading one strand of a substrate duplex through both helicase units, supported by the TRIP4 protein.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

TAGAP gene variants are linked to human autoimmunity. Here the authors identify TAGAP as a Dectin-1 and EphB2-binding protein mediating antifungal innate immune signaling and cytokine production, and demonstrate TAGAP in non-T cells promotes Th17 response in mouse models of infection and autoimmunity.

This study used fine-mapping to analyze genetic regions associated with bipolar disorder, identifying specific risk genes and providing new insights into the biology of the condition that may guide future research and treatment approaches.

Multiplexable barcodes for electron microscopy are applied to brain imaging.

Point spread function (PSF) splitting with the ‘Circulator’, which encodes the fluorophore emission band into the PSF, improves the information content of fluorescence microscopy and enables improved super-resolution imaging and single-particle tracking.

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.

Adult pluripotent stem cells, called neoblasts, are considered a defining feature of all flatworms. This manuscript shows that canonical neoblasts are absent in an early branching flatworm lineage, raising important questions about the evolution of neoblasts.

This study shows that brain connectivity changes in Huntington’s disease begin decades before symptoms, shifting from hyper- to hypoconnectivity, with links to specific neurotransmitter systems specially in granular and infragranular cortical layers.

Roeck et al. show that ferroptosis spreads between neighboring cells via lipid peroxidation across adjacent membranes. Cell contact and extracellular iron are key factors, highlighting a potential mechanism for tissue necrosis propagation.

Different facets of an orthorhombic substrate can stabilize different ordering patterns in a perovskite oxide, even in the absence of differences in strain and polarity mismatches.

Batki, Hetzel et al. report a lineage-tracing strategy to track extraembryonic gut endoderm cells over development. They find that these cells are eventually eliminated in a p53-dependent manner and neighbouring embryonic cells clear their remnants.

Autophagosome tethering compounds (ATTECs) are small molecule degraders hijacking the autophagy system. Here, the authors show that current ATTEC ligands did not bind to their designated targets but establish good ligandability of ATG8 isoforms through fragment screening and docking.

Bernhard Radlwimmer and colleagues report whole-genome bisulfite sequencing of 13 Burkitt lymphomas and nine follicular lymphomas. They find that both types of germinal center B cell lymphomas show global hypomethylation compared to normal germinal center B cell precursors and identify regions of differential methylation that correlate with somatic mutations and differential gene expression.

Coupling distances between synaptic vesicles and Ca²⁺ channels determine the efficacy of neurotransmission. Böhme et al. find that presynaptic scaffold complexes spatiotemporally control Unc13 isoforms to establish two independent release pathways at subsynaptic active zones: Unc13B defines nascent, loosely coupled synapses whereas Unc13A facilitates release at mature synapses by tight coupling between Ca²⁺ channels and synaptic vesicles.

The N₂-fixing symbiont ‘Candidatus Celerinatantimonas neptuna’ lives inside the root tissue of the seagrass Posidonia oceanica, providing ammonia and amino acids to its host in exchange for sugars and enabling highly productive seagrass meadows to thrive in the nitrogen-limited Mediterranean Sea.

Mode-selective vibrational excitations can be used to transiently induce a range of phenomena in strongly correlated states of matter. It is now shown that by exciting apical oxygen distortions in the cuprate system YBa₂Cu₃O_6.5, an unusual photoconductive effect is induced both at low and at high temperatures.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

A high-resolution, global atlas of mortality of children under five years of age between 2000 and 2017 highlights subnational geographical inequalities in the distribution, rates and absolute counts of child deaths by age.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

A liver-intrinsic mechanism is presented that suppresses effective anti-hepatitis virus B responses in mice and humans by rendering virus-specific CD8 T cells refractory to activation causing loss of effector functions.

Stratified medicine promises to tailor treatment for individual patients, however it remains a major challenge to leverage genetic risk data to aid patient stratification. Here the authors introduce an approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue-specific gene expression levels, and highlight its ability to identify biologically meaningful and clinically actionable patient subgroups, supporting the notion of different patient ‘biotypes’ characterized by partially distinct disease mechanisms.

This study shows atomic-scale observations of geometric reconstruction in a fluorine-intercalated infinite layer nickelate superlattice, highlighting how fluorine influences the material’s structure and electronic properties.

Defects of a passive nematic liquid crystal made from actin filaments pattern the collective behaviour of active microtubules, creating macroscopic polar patterns and chiral loops.

High-pressure synthesis is used to stabilize superconducting (Ba,K)SbO₃, whose properties provide a fresh perspective on the origin of superconductivity in these types of materials.

Zhang et al. use single-cell RNA sequencing and functional analyses to describe the hyaluronic acid–GPRC5C signalling axis as an essential component controlling the state of dormancy for human and mouse haematopoietic stem cells.