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Kv7.4 channels regulate auditory function. Here, authors use electrophysiological, optical and computational methods to investigate the structural changes that drive Kv7.4-channel opening, and how these are impaired by a deafness-causing mutation

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.

Analysis combining multiple global tree databases reveals that whether a location is invaded by non-native tree species depends on anthropogenic factors, but the severity of the invasion depends on the native species diversity.

While CDK4/6 inhibitors (CDK4/6i) are often initially successful in many breast cancer subtypes, often resistance develops and other subtypes like triple-negative breast cancer (TNBC) fail to respond. Here, the authors demonstrate that the CDK2 inhibitor BLU-222, alone or with CDK4/6i, restores cell-cycle control via p21/p27 induction overcoming resistance in preclinical models of breast cancer, including TNBC.

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.

Preventing endosomal damage sensing or using lipids that create reparable endosomal holes reduces inflammation caused by RNA-lipid nanoparticles while enabling high RNA expression.

A global network of researchers was formed to investigate the role of human genetics in SARS-CoV-2 infection and COVID-19 severity; this paper reports 13 genome-wide significant loci and potentially actionable mechanisms in response to infection.

Entanglement was observed in top–antitop quark events by the ATLAS experiment produced at the Large Hadron Collider at CERN using a proton–proton collision dataset with a centre-of-mass energy of √s  = 13 TeV and an integrated luminosity of 140 fb⁻¹.

A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.

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.

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 advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

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.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

Development of probes specific for human β-cells could aid in delivery of therapeutics and monitoring β-cells mass during diabetes progression or islet transplantation. Here the authors identify two RNA aptamers specific for β-cells that allow efficient transfection of human islets and β-cell quantification of human islet grafts in immunodeficient mice.

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.

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.

Foundation models enable rapid adaptation to various downstream tasks and are hence about to become a new paradigm in biomedicine. Here, the authors develop LLaVA-Rad, a small AI that bests larger models in chest X-ray interpretation, and CheXprompt, a radiologist-aligned factuality metric, to enable scalable, privacy-preserving image analysis.

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.

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.

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.

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

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.

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.

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.

Cycling of the sulfur compound DMSOP by dimethylsulfoniopropionate lyase enzymes in the most abundant marine bacteria, algae and fungi is diverse and prevalent in Earth’s oceans and sediments and probably impacts climate-active gas production.

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.

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.

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.

Ten years after the discovery of the Higgs boson, the ATLAS  experiment at CERN probes its kinematic properties with a significantly larger dataset from 2015–2018 and provides further insights on its interaction with other known particles.

Iron deficiency is the leading cause of anaemia and is known to compromise immune function. Here, the authors identify several new genes associated with iron status in European populations and provide insight into how iron levels may be linked to the risk of metabolic disease.

A meta-analysis of associations between human genetic variation and gut microbial structural variations shows that ABO genotype differentially affects the presence of Faecalibacterium prausnitzii strains containing GalNAc utilization pathway in the gut.

Multisystem inflammatory syndrome in children (MIS-C) onsets in COVID-19 patients with manifestations similar to Kawasaki disease (KD). Here the author probe the peripheral blood transcriptome of MIS-C patients to find signatures related to natural killer (NK) cell activation and CD8+ T cell exhaustion that are shared with KD patients.

Wood density is an important plant trait. Data from 1.1 million forest inventory plots and 10,703 tree species show a latitudinal gradient in wood density, with temperature and soil moisture explaining variation at the global scale and disturbance also having a role at the local level.

Swanton and colleagues present a clonal expression signature, ORACLE, which, in combination with clinicopathological and molecular risk factors, can predict survival of patients with lung adenocarcinoma, and they prospectively validate its prognostic value.

Bacigaluppi and colleagues report that the accumulation of atypical mature and immature neutrophil subsets and a dysregulated emergency granulopoiesis response in aged mice and humans affect the outcome of stroke.

EGFR inhibition and lenvatinib treatment of liver cancer cells in vitro and in in vivo mouse models has potent anti-proliferative effects, and lenvatinib plus gefitinib treatment of 12 patients with advanced liver cancer resulted in meaningful clinical responses.

Lipid nanoparticles carrying plasmid DNA and an inflammation inhibitor enable longer transgene expression than mRNA nanoparticles.

The analysis of radial velocity variations of O-type stars in the Small Magellanic Cloud reveals a large fraction of close binaries, suggesting that binary physics also plays a prominent role in the low-metallicity environment of the distant Universe.

The number and diversity of organisms known to produce the environmentally important sulfur compound dimethylsulfoniopropionate (DMSP) is expanded with the discovery of a family of DMSP synthesis enzymes.

The hepatocyte growth factor receptor MET is a receptor tyrosine kinase involved in cellular processes such as proliferation, migration, and survival. Here the authors combine molecular dynamics simulations and smFRET in cells, to investigate the early stages of MET activation.