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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.

Feuerer and colleagues use multiomic analyses to identify DNA methylation, chromatin accessibility and gene expression programs that govern the tissue adaptation of human skin T_reg cells.

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.

This work demonstrates a nonlinearity-enhanced combination of dispersive and dissipative coupling in photon-pressure circuits, a circuit-QED analog of optomechanics, and reveals how transparency and backaction are modified by coupling-interference. The results hold relevance for radiation-pressure systems, (quantum) control protocols and Hamiltonian simulation.

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 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.

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.

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.

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.

Using proximity-based screening, protein engineering, and structural analysis, this study describes the development of a p62-based biodegrader for the clearance of organelles and aggregated proteins by autophagy-targeted degradation.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Analyses of genomes from 914 children, adolescents, and young adults provide a comprehensive resource of genomic alterations across a spectrum of common childhood cancers.

RNA binding proteins are important regulators of RNA function. Here the authors describe a method for isolation of RNA-protein complexes that does not rely on a specific RNA sequence or motif, and demonstrate the approach by providing the global RNA-bound proteomes of human HEK293 cells and Salmonella Typhimurium.

The immune response is key in determining disease severity of COVID19. Here Nouailles et al., apply bulk proteomics and scRNA-Seq of lung and blood samples of SARS-CoV-2 infected Syrian hamsters and provide a temporal atlas of the systemic and pulmonary cellular responses.

Burkitt lymphoma (BL) is the most common pediatric B-cell lymphoma. Here, within the International Cancer Genome Consortium, the authors performed whole genome and transcriptome sequencing of 39 sporadic BL, describing the landscape of mutations, structural variants, and mutational processes that underpin this disease how alterations on different cellular levels cooperate in deregulating key pathways and complexes.

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.

Methane formation by a ROS-mediated process is linked to metabolic activity and is identified as a conserved feature across living systems.

Primary lymphomas of the central nervous system (PCNSL) are defined as diffuse large B-cell lymphomas (DLBCL) confined to the CNS. Here, the authors complete whole genome sequencing and RNA-seq to characterize 51 PCNSLs, and find common mutations in immune pathways and upregulated TERT expression and find distinct pathway differences between DLBCL and other primary CNS lymphomas.

Rare mutations in the high requirement temperature protein A1 (HTRA1) cause cerebral vasculopathy. Here, authors establish mechanistically distinct protein repair approaches to reverse the deleterious effects of pathogenic mutations interfering with the assembly and protease function of HTRA1.

An investigation using various methods reports an association between adeno-associated virus 2 and paediatric hepatitis of unknown aetiology.

Local pH alterations can be manifestations of pathologies such as cancer, inflammation and ischaemia. Here Düwelet al. show hyperpolarized ¹³C-labelled zymonic acid can be used as a non-invasive probe to map and measure pH in vivo, suggesting it as a candidate for clinical imaging and a diagnostic tool.

This study characterizes the interaction between the clinical candidate anle138b and Aβ₄₀ fibrils in a lipid environment. The compound reduced fibril formation by approximately 75%, providing insights relevant to Alzheimer’s drug development.

TRPV4 dominant mutations cause neuropathy. Here, the authors show that TRPV4 binds and interacts with RhoA, modulating the actin cytoskeleton. Neuropathy-causing mutations of TRPV4 disrupt this complex, leading to RhoA activation and impairment of neurite extension in cultured cells and flies.

Elevator transporters, like SLC23 proteins, transport solutes by a mechanism involving a reorientation of two rigid domains. Here, the authors show that linkers connecting these domains control the carrier’s conformational space and thus its function.

Proteins rich in phenylalanine-glycine (FG) repeats can phase separate through FG–FG interactions. The molecular interactions of an important FG-repeat protein, nucleoporin 98, have now been studied in liquid-like transient and amyloid-like cohesive states. These interactions underlie the behaviour of FG-repeat proteins and their function in physiological and pathological cell activities.

Natural killer (NK) cells are important immune cells for mediating antiviral immunity. Here the authors show that chronic hepatitis C virus infection in human can imprint lasting functional phenotypes in NK cells to increase their inter-individual but decrease intra-individual diversity.

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.

Pro-inflammatory signals trigger innate immune pathways with consequential metabolic remodeling. Here authors show that a rate-limiting enzymes of glycolysis, PFKL, is directly regulated by innate stimuli via phosphorylation at Ser775, which modification in turn influences pro-inflammatory cytokine production.

Higher-order TCRs have been postulated to maintain high antigen sensitivity and trigger signaling. Huppa and colleagues use various investigative techniques and find exclusively monomeric TCR–CD3 complexes that drive the recognition of antigenic pMHC.