Search

Structures associated with the final steps of non-homologous end joining (NHEJ) and gap filling present new targets for NHEJ inhibition to enhance efficacy of radiotherapy and accuracy of gene editing.

The study reports the arrival of avian influenza H5N1 virus clade 2.3.4.4b into the Indian Ocean sub-Antarctic archipelagos of Crozet and Kerguelen. Using phylogeographic analyses, the virus likely came from the distant South Georgia islands.

What is the role of disorder in non-homologous end-joining proteins? The authors use nuclear magnetic resonance to reveal that disordered regions mediate a network of multivalent interactions, promoting biomolecular condensation that accelerates DNA ligation kinetics.

Glioma stem-like cells (GSCs) contribute to therapeutic resistance via enhanced capability of DNA damage repair. Here the authors identify that the upregulated transcription factor AATF in GSCs modulates the stability and release of XRCC4 protein to promote DNA repair and resistance to radiotherapy.

DNAPKcs and its kinase activity are required for blunt DNA break end joining when the bridging factor XLF is weakened, but for homologous recombination and radiation resistance, the influence of DNAPKcs is not further enhanced with loss of XLF.

Many factors are involved in end joining (EJ) repair of double strand breaks. Here the authors present a method to identify a chromosomal break repair event that requires classical non homologues end joining (C-NHEJ) using Cas9-based end joining tools, and define a role of CNHEJ factor XLF in repair.

Two polypeptides synthesized by common bacterial strains in human gut microbiota lower body fat and blood glucose and increase bone density, improving the metabolism of rodents.

Polymerase theta is a widely conserved DNA polymerase that mediates Theta Mediated End Joining. Here authors present a synthetic lethal CRISPR screen to identify DDR gene mutations that induce cellular addiction to Pol theta.

Oxygenated bottom water existed transiently on continental shelves with O₂ penetrating into underlying marine sediments by about 2.65 billion years ago, according to a study of thallium isotopes in Archaean shales.

In this work, Planas et al. report that Omicron subvariants BA.2.75.2, BA.4.6, and BQ.1.1 escape neutralization from monoclonal antibodies, and sera from vaccinated individuals with or without Omicron BA.1/2 or BA.5 breakthrough infection.

DNA 5-hydroxymethylcytosine (5hmC) modification is associated with gene transcription and used as a mark of mammalian development. Here the authors report a comprehensive 5hmC tissue map and analysis of 5hmC genomic distributions in 19 human tissues derived from 10 organ systems, thus providing insights into the role of 5hmC in tissue-specific development.

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.

A potent mAb shows promise in monkeys either alone or in a combination therapy for either prophylaxis or treatment of infection with SARS-CoV-2 Omicron BA.1, BA.1.1 and BA.2.

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.

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.

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.

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.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

Mounting evidence suggests that keratin post-translational modifications are crucial for many cellular processes. Now, keratin 18 modified by the addition of an O-linked N-acetylglucosamine residue is shown to be as a critical effector of stress-responsive Akt signalling, providing an important link between keratin glycosylation and cell survival.

Human cerebral organoids exhibit compositional and transcriptomic alterations in both neuronal and non-neuronal cells in the absence of UBE3A.

Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

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.

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.

A generative AI model, Orion, learns a robust and generalizable pattern of non-small cell lung cancer from cancer-specific circulating non-coding RNAs. Orion enhances the performance of liquid biopsy for early cancer detection and tumor subtyping.

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.

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.

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.

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.

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.

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.

Metamaterials show many intriguing properties, which are often limited to a narrow range of frequencies. The demonstration of a low-loss broadband metamaterial at radiofrequencies promises applications as enhanced antennas, for example.

The two homoeologous subgenomes in the allotetraploid frog Xenopus laevis evolved asymmetrically; one often retained the ancestral state, whereas the other experienced gene loss, deletion, rearrangement and reduced gene expression.

Acquired mutations of the gene UBA1 occurring in myeloid cells that result in the expression of impaired isoforms of the enzyme E1 have been described in patients with a severe adult onset auto-inflammatory syndrome called VEXAS. Here the authors profile patients with UBA1 mutations presenting with or without VEXAS disease and show VEXAS disease is characterized by inflammasome activation and monocyte dysregulation.

We identified Tad1, a large family of phage-encoded proteins that inhibit Thoeris immunity, and define the chemical structure of a central immune signalling molecule, showing a new mode of action by which pathogens can suppress host immunity.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.

Phase-resolved mid-infrared observations from JWST of the hot gas giant WASP-43b detect a day–night difference of 659 ± 19 K. Comparison with climate models shows that the observations are compatible with cloudy skies, at least on the nightside, and the lack of methane detection suggests the presence of disequilibrium chemistry.

Amyloid fibrils grow through the recruitment of soluble monomer to the fibril end that propagates the fibril structure. Here the transition state, the rate-limiting conformation, of such a reaction has been characterized by Φ-value analysis. An energy landscape model has been developed and fibril growth rates predicted from first principles.

Andrew Morris, Mark McCarthy, Michael Boehnke and colleagues report a meta-analysis of genome-wide association studies for type 2 diabetes, including 26,488 cases and 83,964 controls from populations of European, east Asian, south Asian and Mexican and Mexican American ancestry. They identify seven loci newly associated with type 2 diabetes and examine the genetic architecture of disease across populations.

A systematic gene deletion screen targeting all predicted transmembrane transporters of the protozoan parasite Leishmania identified forty mutants that had a significant loss of fitness in macrophage and mouse infections. Loss of the V-type H⁺ ATPase was particularly deleterious in vivo.

Pyroelectric materials exhibiting large and nearly constant pyroelectric coefficients over a wide temperature range are highly desirable. Here, the authors develop molecular [FeCo] crystals with continuous pyroelectricity, originating from a transition between three distinct electronic structures.