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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.

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, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Automated pathotyping of synovial tissue in arthritis is a major unmet need. Here, the authors develop and demonstrate the efficacy of an automated tissue and cellular pathotyping tool for inflammatory arthritis.

The transmission of quantum information through channels is a fundamental step for future quantum communication technologies. Cubitt et al.now show that there exist channels whose potential for transmitting quantum information requires an unbounded number of usages to be detected.

Kim and colleagues propose a curvature-controlled organ chip array to monitor how geometric stress drives corneal disease progression. The authors show that geometric stress triggers cellular changes that replicate keratoconus pathology and they identify dysregulated molecular pathways for potential therapeutic approaches.

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.

Malnutrition during pregnancy has lasting effects on maternal and offspring health. Its adverse impacts are modified by the maternal microbiome and attenuated by gestational treatment with select microbial metabolites.

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.

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.

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.

Cell surface attachment factors, such as glycans, play an important role in viral infection. Here, Petitjean et al. show that SARS-CoV-2 specifically binds to 9-Oacetylated sialic acid and have designed novel inhibitors based on multivalent derivatives.

Chronic Kidney Disease affects 1 in 10 people worldwide with prevalence continuing to rise, thus there is a need to identify novel biomarkers that can add value to existing clinical and biochemical risk predictors. Here the authors identify miR190a-5p as potential indicator of kidney health and disease progression in patients with chronic kidney disease.

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.

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.

Uncorrected noise prevents quantum computers from running deep algorithms and outperforming classical machines. A method is now reported that allows noisy shallow quantum algorithms to be used to solve classically hard problems.

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.

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.

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.

Viral proteins can achieve high multifunctionality, but mechanisms are poorly understood. This study shows structural flexibility of rabies virus P protein enables RNA binding and phase separation to expand functions by infiltrating host condensates.

By collecting nearly 50,000 perceptual estimates of smell, a reliable physicochemical measure that links odorant structure to odorant perception at a resolution that enables the creation of olfactory metamers was derived.

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.

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.

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.

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 state of a single photon can be stored as a Rydberg excitation using electromagnetically induced transparency, and this enables nonlinear interactions at the single-photon level. Here, the authors store a paired photon emitted by a quantum memory in an ensemble-based, highly nonlinear medium.

Ethanol-induced fructose metabolism, mediated by KHK-A/C, drives excessive alcohol consumption and pathogenesis of alcoholic liver disease.

The authors report on an experimental study of attosecond time delays of photoelectrons emitted from CO₂ molecules. This clarifies the role of internal dynamics of ions and ionelectron entanglement on the photoionization dynamics.

Qutrits, or quantum three-level systems, can provide advantages over qubits in certain quantum information applications, and high-fidelity single-qutrit gates have been demonstrated. Goss et al. realize high-fidelity entangling gates between two superconducting qutrits that are universal for ternary computation.

Universal quantum logic operations with fidelity exceeding 99%, approaching the threshold of fault tolerance, are realized in a scalable silicon device comprising an electron and two phosphorus nuclei, and a fidelity of 92.5% is obtained for a three-qubit entangled state.

Chronic infection with SARS-CoV-2 leads to the emergence of viral variants that show reduced susceptibility to neutralizing antibodies in an immunosuppressed individual treated with convalescent plasma.

The degradation of dead wood by basidiomycete fungi relies on Fenton chemistry under aerobic conditions. Here, Röllig et al. show that these fungi can also thrive and degrade wood in anoxia, switching from a Fenton chemistry-based process to the secretion of plant cell wall-active enzymes.

Geospatial estimates of the prevalence of anemia in women of reproductive age across 82 low-income and middle-income countries reveals considerable heterogeneity and inequality at national and subnational levels, with few countries on track to meet the WHO Global Nutrition Targets by 2030.

An atomic force microscope and confocal microscope set-up that allows nanomechanical mapping of virus binding under cell culture conditions shows that the first binding steps of a virus to a cell surface receptor are specific and weak, but affinity increases as more bonds are formed between the virus and cell surface receptors.

TIRTL-seq is a high-throughput method for paired T cell receptor sequencing at the cohort scale.