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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.

Galland et al. present soSMARt, a method for in-depth single molecule localisation microscopy using microfabricated devices, which enables single-objective light-sheet microscopy, adaptive optics correction, real-time registration, and axially extended volume reconstruction with nanometer precision.

Rizzollo et al. show that BDH2 participates in iron distribution between cellular compartments, which sets the threshold for the ferroptosis vulnerability of the melanoma cell phenotypes, ultimately affecting their metastatic capacity

Single-agent maintenance PARP inhibition may represent an effective strategy for advanced/metastatic endometrial cancer treatment. Here this randomized phase IIb UTOLA trial evaluates the efficacy and safety of orally administered olaparib in female patients (n = 145) without progression following front-line platinum-based chemotherapy for advanced/metastatic endometrial cancer.

Chronic care manages long-term, progressive conditions, while acute care handles short-term ones. Here, authors show chronic conditions account for most of the global health burden, with 68% of DALYs and 93% of YLDs attributed to chronic care needs.

This study examines the function of G-quadruplex DNA secondary structures in mammalian promoters, revealing that they represent core promoter elements contributing to gene regulation by nucleosome exclusion and by promoting RNA polymerase II pause–release.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

The JAK inhibitor ruxolitinib has been used for treatment of myeloproliferative neoplasms (MPN) and its association with clonal evolution requires further investigation. Here the authors report accumulation of RAS pathway mutations in ruxolitinib-treated myelofibrosis patients, stemming from RAS clonal selection induced by JAK2 inhibition.

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.

Trees come in all shapes and size, but what drives this incredible variation in tree form remains poorly understood. Using a global dataset, the authors show that a combination of climate, competition, disturbance and evolutionary history shape the crown architecture of the world’s trees and thereby constrain the 3D structure of woody ecosystems.

Iceberg calving can act as a submarine melt amplifier through excitation of transient internal waves.

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.

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.

Tanner’s law describes the spreading dynamics of droplets made of Newtonian viscous fluids. Here, the authors demonstrate that this law remains valid for phase-separated binary liquids close to their critical point, and thus for all the associated universality class.

The electrons and holes in a semiconductor can bind together to form excitons, which in turn couple together at higher carrier densities to create biexcitons. Here, the authors show, contrary to expectation, that biexcitons can outlive excitons at carrier densities close to the appearance of unbound electrons and holes.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

Biomembranes can transmit forces over cellular length scales. Now, however, their active role in generating stress is demonstrated. The adhesion and spreading of a liposome that has no active cytoskeletal machinery are shown to contract the substrate, exerting traction stresses that are comparable with those of living cells.

Targeting cancer stem cells (CSCs) has great potential in anti-cancer treatment. Here this group reports the role of antibiotic Nifuroxazide as a potent anti-CSC compound and fabricates it into an anti-breast CSC prodrug using click chemistry strategy.

Here the authors identify GPATCH11 variants responsible for retinal dystrophy with neurological impairment and facial dysmorphy. They explore its function using a mouse model and demonstrate GPATCH11’s involvement in RNA regulation and splicing.

Enhanced control of the nuclear spin orientation of rare isotopes has now been demonstrated. This technique is considerably more efficient than traditional methods and significantly broadens the domain of accessible nuclei, promising insights in nuclear physics and applications in material science.

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.

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 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.

Borcoman and colleagues present the efficacy and safety results of the phase 2 PEVOsq basket trial investigating the combination of pembrolizumab with the epidrug vorinostat in patients with recurrent and/or metastatic squamous cell carcinoma.

This study identified two plant synaptonemal complex central element proteins—SCEP1 and SCEP2. Mutant versions of these proteins do not synapse, have more crossovers but lose crossover interference and show reduced heterochiasmy.

From 1980 to 2018, the levels of total and non-high-density lipoprotein cholesterol increased in low- and middle-income countries, especially in east and southeast Asia, and decreased in high-income western countries, especially those in northwestern Europe, and in central and eastern Europe.

Effective treatments for myelin repair are currently lacking. Here, the authors show that two FDA-approved drugs, leucovorin and dyclonine, identified through pharmacogenomic screening, promote oligodendrocyte formation and brain repair in myelin injury models.

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.

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.

Resistance to anti-EGFR therapy is a clinical issue for patients with advanced head and neck cancers. Here, the authors show that therapy-resistant cancer cells enhance fatty acid metabolism, which can be therapeutically targeted by inhibiting peroxisome proliferator-activated receptor alpha (PPARα).

Spatial entanglement in many-body systems is fully characterized by the entanglement Hamiltonian, but its measurement has remained challenging. Here the authors realize this for a topological quantum Hall system using ultracold gases of dysprosium atoms.

Modelling of the evolution of atmospheric methane emissions from the 2022 Nord Stream subsea pipeline leaks shows that the event emitted the largest recorded amount of methane from a single transient event.

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.

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.

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.

Understanding ligated metal clusters’ reactivities is challenging. Now, a methodology has been developed to explore dynamic mixtures of metal clusters. Interrelated cluster populations are constructed through organometallic precursor chemistry. Structural information on mixed-metal systems is obtained with a bias-free computational framework, and reactivities towards CO₂ and alkynes are investigated in situ.

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 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.

A large dataset of 6 million trees from 193 taxa is used to map the floristic and functional composition of central African forests and predict their vulnerability to climate change.

Immune cells contribute to adverse remodeling following myocardial infarction. Here the authors show in mice and pigs that CD8⁺ lymphocytes release Granzyme B in the infarcted heart leading to cardiomyocyte death, enhanced inflammation and deterioration of cardiac function.

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.

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.

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.

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.

Here, the authors describe biallelic loss-of-function variants in human SHARPIN in individuals with autoinflammation and immunodeficiency, termed sharpenia. They also successfully treat one of these individuals with TNF inhibitors.