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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.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.

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.

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.

While experiments in younger trees support increased production under higher CO₂, it is unclear whether more mature trees can respond similarly. Here, the authors show increased production of biomass in a 180-year-old Quercus robur L. woodland under 7 years of free-air CO₂ enrichment (FACE).

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.

Some individuals present with multiple synchronous colorectal tumours, but the genetic understanding of this is unclear. Here, the authors use a sequencing strategy to show that the synchronous tumours are genetically independent and the patients harbour rare germline damaging mutations in genes associated with the immune system.

This study identifies a clade of archaea that is the immediate sister group of eukaryotes in phylogenetic analyses, and that also has a repertoire of proteins otherwise characteristic of eukaryotes—proteins that would have provided the first eukaryotes with a ‘starter kit’ for the genomic and cellular complexity characteristic of the eukaryotic cell.

A new version of nanorate DNA sequencing, with an error rate lower than five errors per billion base pairs and compatible with whole-exome and targeted capture, enables epidemiological-scale studies of somatic mutation and selection and the generation of high-resolution selection maps across coding and non-coding sites for many genes.

Two related studies describe a newly discovered cranium of Australopithecus anamensis, the environment in which this hominin would have lived approximately 3.8 million years ago and how it is related to Australopithecus afarensis.

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.

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.

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.

SUMO modification regulates protein function, with SENP enzymes controlling SUMO removal. Here, the authors present crystal structures of SENP5 bound to SUMO1 and SUMO2, revealing how structural features drive its preference for SUMO2 and offering insights into SUMOylation regulation.

Social determinants of health can have a considerable impact on patient outcomes. Here, the authors examine how social determinants of health contribute to the growing global burden of acute kidney injury and its inequities, and discuss key strategies for tackling disparities in acute kidney injury care and outcomes.

Metal-based nanostructures offer a solution to scale down photonics to the nanoscale. Sorgeret al. directly demonstrate waveguiding of ultra-small propagating waves at visible and near-infrared frequencies using NSOM imaging, with the potential for nanoscale photonic applications such as bio-sensing.

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.

A large genome-wide association study of more than 5 million individuals reveals that 12,111 single-nucleotide polymorphisms account for nearly all the heritability of height attributable to common genetic variants.

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.

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.

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.

At the mucosal interface of the gut and microbiome immune cells play pivotal roles to regulate between commensalism, colonisation and pathogenic invasion. Here, Lo et al. show CTLA-4 expression in innate lymphoid cells is linked to mucosal homeostasis in a microbiome dependent manner.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

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.

A national prospective study of patients requiring hospitalization for COVID-19 demonstrates global cognitive deficits at 1 year, associated with elevated brain injury markers and reduced gray matter volume.

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.

A combined modelling and tumour analysis approach is used to study the temporal and spatial patterns of subclone evolution in the TRACERx renal study. Studying the tumour shape and spatial features of clonal diversity in early-stage tumours may allow the prediction of tumour progression and patterns of subclone diversification over time.

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Sleeping sickness caused by African trypanosome parasites induces a chronic, and potentially lethal, infection in humans. Here, the authors uncover a conserved protein, Q586B2, playing an important regulatory role in Trypanosomatid infection establishment.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

There is limited epidemiological data on PRRSV sublineage 8.7 in Asia. Using national PRRSV surveillance data, the authors compiled a genomic dataset showing a geographically centralized spread, the likely impact of human-related activities on PRRSV spread and regional variability in interlineage recombination likelihood.

Using multi-ancestry genome-wide association study and fine-mapping, 298 loci and 36 credible genes are identified in the aetiology of bipolar disorder.

An apparent redundant role with EZH2 has rendered EZH1 as a secondary player in PRC2-mediated homeostasis regulation. Here, the authors report that gain- and loss-of-function variants in EZH1 cause neurodevelopmental disorders, highlighting its functional relevance.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

Comparative analysis of whole-genome sequencing of six zokor species that live at different altitudes show the contribution of deletions and inversions to adaptation to high altitude in these subterranean rodents.