Search

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

There are many proposals for new forms of quantum matter in frustrated magnets but in practice disorder prevents the realisation of theoretically-tractable idealised models. Kimchi et al. show that recently observed scaling behavior common to several disordered quantum magnets can be understood as the emergence of a universal random-singlet regime.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

The unoccupied electronic levels of graphene are modified by corrugation, doping and presence of impurities. Here, the authors map discrete electronic domains within a single graphene sheet using scanning transmission X-ray microscopy and provide insight into the modification of unoccupied levels.

The structure of human TIP60-C uncovers a molecular machine that modifies and exchanges histones in the nucleosome, illustrating how vertebrates merge these activities, which are carried out by two independent assemblies in yeast.

Here, the authors use cryo-EM, biochemical and yeast assays of the HAT NuA4–Tip60 to reveal its mechanism of acetylating distant nucleosomes through the Epl1 linker establishing long-range chromatin interactions.

This study shows that climate change is expected to result in a 41% increase in the frequency of lightning worldwide. This increase has the potential to amplify the risk of lightning-induced wildfires.

Structural studies on the yeast transcription coactivator complex SAGA (Spt–Ada–Gcn5–acetyltransferase) provide insights into the mechanism of initiation of regulated transcription by this multiprotein complex, which is conserved among eukaryotes.

Cryo-electron microscopy structures of the human Integrator complex in three different functional states shed light on how Integrator terminates RNA polymerase II (Pol II) transcription by disengaging Pol II from the DNA template.

Carey and colleagues reveal 35 major latent constructs (factors) in the phenotype data of unrelated individuals with predominantly estimated European genetic ancestry from UK Biobank.

Cryo-EM structures of the transcription preinitiation complex in the presence of the +1 nucleosome show how the general transcription factor TFIIH can interact with the nucleosome at several positions.

Transcription preinitiation complex assembly begins with the recognition of the gene promoter by the TATA-box Binding Protein-containing TFIID complex. Here the authors present a Cryo-EM structure of promoter-bound yeast TFIID complex, providing a detailed view of its subunit organization and promoter DNA contacts.

The transcription co-activator complex SAGA is recruited to promoters by transcriptional activators and promotes the formation of the pre-initiation complex. Here, the authors present the cryo-EM structure of the SAGA complex and resolve the major target of activator binding, the 430 kDa Tra1 protein.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

The structures of three distinct human transcription factor IID (TFIID) protein assemblies are solved using cryo-electron microscopy; by incorporating TAF8 and TAF10, the key structural changes that remodel TFIID during assembly are determined, particularly the transition from a symmetric core-TFIID to an asymmetric holo-complex.

Analysis of mitochondrial genomes (mtDNA) by using whole-genome sequencing data from 2,658 cancer samples across 38 cancer types identifies hypermutated mtDNA cases, frequent somatic nuclear transfer of mtDNA and high variability of mtDNA copy number in many cancers.

Efficient, large-scale genomic analysis is facilitated on the cloud by a computational tool with error-diagnosing and self-healing capabilities.

Eukaryotic RNA polymerase I (Pol I) is responsible for the transcription of rRNA genes. Here the authors determine the cryo-EM structure of the Pol I-Rrn3 complex, providing insight into how Rrn3 stabilizes the monomeric initiation competent Pol I to drive pre-initiation complex formation.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

TFIID is an essential transcription factor complex that controls the expression of most protein-coding genes in eukaryotes. Here the authors identify and characterize a complex containing TAF2, TAF8 and TAF10, which assembles in the cytoplasm before integration into the nuclear holo–TFIID complex.

Here, the authors show that a single substitution in mouse P1, outside of its arginine core and independently of its charge, suffices to alter sperm chromatin structure and associated developmental outcomes.

Direct coupling of aliphatic C–H nucleophiles to aryl electrophiles is described, through the combination of light-driven polyoxometalate hydrogen atom transfer and nickel catalysis.