Search

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.

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.

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 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.

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.

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.

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

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.

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.

Expanding the scope of materials for spin caloritronics enhances the opportunity to achieve more energy efficient memory and sensor devices. Here the authors report the tunnel magneto-Seebeck effects in magnetic tunnel junctions with Co₂FeAl and Co₂FeSi Heusler compounds.

This article presents NAPstars, a family of genetically-encoded biosensors that enable real-time monitoring of NADP redox dynamics across species. The sensors reveal robust NADP redox regulation, cell-cycle-linked NADP oscillations, and glutathione as the major conduit for anti-oxidative electron flux.

Photosynthesis occurs at the thylakoid membrane, which acts as a scaffold, precisely arranging functional proteins and electron carriers. Sunet al.synthesize hollow photosynthetic nanospheres that function as light-harvesting antennae and structured scaffolds that improve photoredox catalysis.

Urinary albumin-to-creatinine ratio (UCAR) is associated with various clinical outcomes such as kidney disease and cardiovascular disease. Here, the authors report genome-wide meta-analysis in over 500,000 individuals and find 68 UACR loci, followed by statistical fine-mapping, gene prioritization and experimental validation in flies.

Olfactory perception shows marked sexual dimorphism, yet its genetic basis remains underexplored. Here, the authors show sex-specific and shared genetic loci for odour identification, implicating olfactory receptor clusters and links to Alzheimer’s disease risk.

X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases such as chronic kidney disease (CKD). Here, the authors perform a sex-stratified, cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits, with results including identification of four novel loci associated with the CKD-defining trait eGFR.

In the Tumor Profiler proof-of-concept observational study, a multiomics approach for profiling tumors from patients with melanoma was feasible, returning data within 4 weeks and informing treatment recommendations in 75% of cases.

Understanding asteroid materials is critical for determining deflection methods for planetary defense. Here the authors show, via experiments performed in High-Radiation to Materials facility at CERN, that iron-rich asteroid materials can absorb more energy without structural failure than standard material parameters would suggest.

Ion transport through nano channels can exhibit intriguing non-linear behaviour. Here, Chen et al. fabricate a hierarchical system of sandwiched carbon membranes of wide and narrow pores with substantial enhancement in rectification ratio of the ionic current, adjustable by optical triggers.

Quantifying intermolecular coupling and local morphology is important to understand soft matter systems. Pollard et al. show how multispectral vibrational near-field optical microscopy can be used to image molecular-scale morphology and intermolecular interactions with nanometre spatial resolution.

A genome-wide association meta-analysis study of blood lipid levels in roughly 1.6 million individuals demonstrates the gain of power attained when diverse ancestries are included to improve fine-mapping and polygenic score generation, with gains in locus discovery related to sample size.

Imine reductases have been regarded as one of the most promising enzymes by the pharmaceutical industry—but their industrial application is still lacking. This work reports the successful industrial application of an imine reductase, enabled by directed evolution.

Two-dimensional conjugated metal-organic frameworks (2D c-MOFs) are emerging candidates for organic 2D crystal materials, but the precise implantation of chirality has yet to be demonstrated. Here, the authors report a side chain-induced chirality amplification strategy to achieve tunable chiral expression in 2D c-MOFs.

Species’ traits and environmental conditions determine the abundance of tree species across the globe. Here, the authors find that dominant tree species are taller and have softer wood compared to rare species and that these trait differences are more strongly associated with temperature than water availability.

In two-dimensional spin-polarized systems, the valleys in the conduction bands could be useful for spintronics applications if they can be efficiently spin polarized. Here, the authors exploit the Rashba effect to achieve 100% spin-polarized valleys on a silicon surface loaded with thallium.

Hydro-responsive plant movements have provided inspiration for the design of adaptive materials. Harringtonet al. investigate the hydration-dependent unfolding of ice plant seed capsules and find an origami-like folding pattern, which could aid the development of biomimetic folding structures.

Emerged sustainable techniques for nitrogen fixation still lack ammonia yield rate to be practically relevant. Here, the authors demonstrate a laser–induced method to deliver a yield rate of 30.9 µmol s-1 cm−2 at ambient conditions, which is two orders of magnitude higher than other methods.

BepiColombo mission had its first Mercury flyby on 1 October 2021. Here, the authors show plasma measurements taken during this flyby, which reveals that electron injections and subsequent energy-dependent drift is a universal mechanism generating aurorae in the planetary magnetospheres.

Typical quantum error correcting codes assign fixed roles to the underlying physical qubits. Now the performance benefits of alternative, dynamic error correction schemes have been demonstrated on a superconducting quantum processor.

An integrated structural biology approach encompassing solid-state NMR and molecular dynamics simulations was implemented to obtain an atomic view of the ordered polyglutamine core and fuzzy coat of the amyloid-like protein aggregates implicated in Huntington’s disease.

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Bergel et al. show that an infraslow rhythm connecting the brain and body during sleep is shared by lizards, mammals and birds, revealing an ancestral process and reshaping our understanding of the evolution of sleep states.

Expression of TMPRSS2—a protease that activates SARS-CoV-2 for entry into cells—renders SARS-CoV-2 insensitive to chloroquine.

NaHCO₃ production is energy- and cost-intensive. Here the authors report an operando electrosynthesis system by embedding nitrate reduction reaction into Solvay system, achieving high NaHCO₃ productivity even up to 4.58 times of benchmark industrial route.

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.

Exome sequencing within a structured diagnostic process for rare diseases in Germany shows how facial image analysis and machine learning can guide variant prioritization and uncover many ultrarare diseases.

Here, the authors compared measurements between 34 laboratories from 19 countries, to quantify by mass spectrometry four ceramides of clinical relevance in human blood plasma Standard Reference Materials. The main goals were to evaluate concordance obtained in a large inter-laboratory trial and to report absolute concentrations of four circulating lipids in a publicly available standard.