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

The combination of neoadjuvant nivolumab, ipilimumab and chemotherapy showed promising efficacy in patients with resectable non-small cell lung cancer, with higher tumor immune cell infiltration and tertiary lymphoid structures after treatment compared with neoadjuvant nivolumab plus chemotherapy.

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.

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.

Structure-based generative chemistry is crucial in computer-aided drug discovery. Here, authors propose PMDM, a conditional generative model for 3D molecule generation tailored to specific targets. Extensive experiments demonstrate that PMDM can effectively generate rational bioactive molecules

Here, a draft sequence of the giant panda genome is assembled using next-generation sequencing technology alone. Genome analysis reveals a low divergence rate in comparison with dog and human genomes and insights into panda-specific traits; for example, the giant panda's bamboo diet may be more dependent on its gut microbiome than its own genetic composition.

The authors show that LARP4 drives T cell dysfunction in tumors by promoting hypertranslation of oxidative phosphorylation-related mRNAs, resulting in mitochondrial dysfunction. They also target LARP4 to enhance T cell persistence and anti-tumor activity and provide a CAR T cell strategy for treating solid and liquid tumors.

Producing methanol — useful as both a fuel and a synthetic building block — from carbon monoxide and carbon dioxide has been achieved using homogeneous catalytic hydrogenation of carbonates, carbamates and formates. The catalyst is a dearomatized ruthenium(II) pincer complex and the reaction proceeds efficiently under mild conditions.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

A comparison of alpha diversity (number of plant species) and dark diversity (species that are currently absent from a site despite being ecologically suitable) demonstrates the negative effects of regional-scale anthropogenic activity on plant diversity.

Blood eosinophil (EOS) counts may serve as risk factors for human coronary heart diseases. Here the authors show that increased circulating and myocardial EOS after myocardial infarction play a cardioprotective role by reducing cardiomyocyte death, cardiac fibroblast activation and fibrosis, and endothelium activation-mediated inflammatory cell accumulation.

A multi-ancestry genome-wide gene–smoking interaction study identifies 13 new loci associated with serum lipids.

While Bell inequalities have been violated several times—mostly in photonic systems—their violations within particle physics experiments are less explored. Here, the BESIII Collaboration showcases Bell-violating nonlocal correlations between entangled hyperon pairs.

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.

Going from model development to a pilot implementation study, a deep learning model shows that acute aortic syndrome can be diagnosed directly from noncontrast CT, increasing accuracy and decreasing time to diagnosis.

A comprehensive analysis of the cell-specific molecular regulatory mechanisms underlying post-traumatic stress disorder in the human prefrontal cortex.

Meta-analyses in up to 1.3 million individuals identify 87 rare-variant associations with blood pressure traits. On average, rare variants exhibit effects ~8 times larger than the mean effects of common variants and implicate candidate causal genes at associated regions.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

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.

In decision-making, choice stochasticity can arise at multiple stages in the brain. Here, the authors show that noise arising early and late relative to a nonlinear neural computation leads to opposing contextual effects on choice accuracy.

The semileptonic decay channels of the Λc baryon can give important insights into weak interaction, but decay into a neutron, positron and electron neutrino has not been reported so far, due to difficulties in the final products’ identification. Here, the BESIII Collaboration reports its observation in e+e- collision data, exploiting machine-learning-based identification techniques.

m⁶A RNA modifications are quantified in cancer patient samples and cell lines using nanopore sequencing.

Light-emitting diodes with suppressed efficiency roll-off can be created by intercalating oxygen plasma into few-layer molybdenum disulfide and tungsten disulfide.

Neck dissection and/or elective nodal irradiation (ENI) are commonly performed in patients with head and neck squamous cell carcinoma (HNSCC) to minimize local and regional recurrence. However, here the authors show that ENI blunts the immune response to combined radiation and immunotherapy, increasing local and distant tumor growth in HNSCC preclinical models.

Observations of SN 2021yfj reveal that its progenitor is a massive star stripped down to its O/Si/S core, which remarkably continued to expel vast quantities of silicon-, sulfur-, and argon-rich material before the explosion, informing us that current theories for how stars evolve are too narrow.

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.

In mice, the neural mechanisms underlying aversive social learning, specifically avoidance and fear after defeat, involve oxytocin signalling in the anterior subdivision of the ventromedial hypothalamus, ventrolateral part.

Together with an accompanying paper presenting a transcriptomic atlas of the mouse lemur, interrogation of the atlas provides a rich body of data to support the use of the organism as a model for primate biology and health.

The mechanisms behind acquired resistance to the proteasome inhibitor bortezomib in multiple myeloma remain to be elucidated. Here, the authors show that the histone methyltransferase NSD2 stabilized SRC-3 protein levels, promotes its phase separation and alters H3K36me2 at certain gene promoters resulting in a transcriptional profile that favors resistance of myeloma cells to bortezomib.

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.

Cave art from the island of Sulawesi in Indonesia, consisting of human hand stencils and animal paintings, is at least 40,000 years old, raising the question of why rock art traditions appeared at more or less the same time at opposite ends of the Late Pleistocene human world.

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.

Sustainable management of soil organic carbon (SOC) in farmland is critical for mitigating climate change and improving soil health. Degradable film mulching is a promising alternative to plastic film mulching, sequestering SOC and reducing C loss in dryland agroecosystems under climate change.

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.

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.

The expansion of China’s waste-to-energy combustion capacity offers great carbon and energy benefits over landfills but remains a carbon-intensive process due to plastic waste and low efficiency. Enhanced waste sorting and the adoption of high-efficiency devices could decarbonize the power generated by these facilities to match that generated by natural gas by 2060.

The cytosolic ubiquitin ligase Nedd4-1 is known to promote autophagy. Here, the authors characterize a primate-specific splice isoform, Nedd4-1(NE), that is localized to late endosomes in the presence of amino acids, where it inhibits autophagy.

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 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.

The presence of phenotypic heterogeneity in collectively invading cells suggests cooperation amongst distinct subtypes of cells to promote invasion and metastasis. Here, the authors use chemical biology tools and report metabolic heterogeneity within the lung cancer collective invasion pack.

Timothy Frayling, Joel Hirschhorn, Peter Visscher and colleagues report a meta-analysis of genome-wide association studies for adult height in 253,288 individuals. They identify 697 variants in 423 loci significantly associated with adult height and find that these variants cluster in pathways involved in growth and together explain one-fifth of the heritability for this trait.