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A cross-ancestry genomic and transcriptomic cohort of gastric cancer highlights significantly mutated genes and mutational signatures, some of which are ancestry-specific.

While hepatoblastoma is the most common pediatric liver cancer, its molecular background has not been fully characterised. Here, the authors perform genomic and epigenomic profiling of 163 untreated pediatric liver tumours and suggest the upregulation of ASCL2 and methylation patterns of IGF2 promoters in driving hepatoblast carcinogenesis.

Hidewaki Nakagawa and colleagues report a comprehensive genome-wide mutational landscape of 300 liver cancers from Japanese individuals. They identify candidate driver mutations, including ones in noncoding regions, and structural mutations affecting the expression of nearby genes.

A close-up look at the action of space weathering on carbonaceous asteroids, provided by Ryugu’s returned samples, highlights its role on the dehydration of the first micrometre-thick layer of the surface, possibly hiding a water-rich interior. The depth of the 2.7 µm hydration band may be an indication of the level of space weathering withstood by a C-type asteroid.

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.

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.

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.

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.

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.

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.

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.

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.

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 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.

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 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.

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.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a complex lung disease caused by abnormal surfactant homeostasis. Here, the authors carry out a genome-wide association study of aPAP in a Japanese cohort, finding variants in the MHC and suggesting predisposition to abnormal antibody production.

Diabetes is known to increase the risk of nonalcoholic steatohepatitis (NASH) and hepatocellular carcinoma (HCC). Here, the authors show in a mice model that insulin action in the gut may play a protective role in the development of NASH and HCC in diabetes.

How PDZD8 acted in Mitochondria-ER contact formation was unclear. Here, the authors show that binding to mitochondrial FKBP8 slows PDZD8’s rapid motion, enhancing contacts and mitochondrial complexity.

The innate antiviral immune response is an important defense against infection. Here, the authors show that leukocyte cell-derived chemotaxin 2 (LECT2) promotes RIG-I-mediated innate immune responses by preventing its degradation, and inhibits lymphocytic choriomeningitis virus replication in the liver.

Right ventricular (RV) failure is clinically crucial, but there is no specific therapy. Here, the authors show that the complement alternative pathway is activated in RV failure and that blockade of the pathway ameliorates RV failure in mice.

Electron holography discovered nonmagnetic framboids and many iron nanoparticles with a vortex magnetic flux formed by magnetite reduction due to a micrometeoroid impact on asteroid Ryugu, providing a new way to study the Solar System magnetic field.

Thermal imaging data obtained from the spacecraft Hayabusa2 reveal that the carbonaceous asteroid 162173 Ryugu is an object of unusually high porosity.

The catalytic activity of a noble metal nanocluster is tied to its atomicity. Here, the authors report an atom-precise, fully scalable synthesis of platinum clusters from molecular ring precursors, and show that a variation of only one atom can dramatically change a cluster’s reactivity.

Tatsuhiro Shibata, David Wheeler, Hiroyuki Aburatani and colleagues report the genomic, exomic and oncoviral sequencing of hundreds of liver cancers from the United States and Japan. The authors analyzed mutation patterns and identified signatures unique to the Asian cases.

How enhancers transition from a hypoacetylated primed state to a hyperacetylated-active state in response to differentiation stimuli is incompletely understood. Here the authors show that SETD5 forms a complex with NCoR-HDAC3 co-repressor to prevent histone acetylation of master adipogenic gene enhancers, while SETD5 degradation triggers enhancer hyperacetylation and transition to active state.

Limited oxidative weathering of crustal sulfide before the Gowganda glaciation suggests low atmospheric oxygen levels persisted long before the final Huronian glaciation, according to a geochemical and isotopic analysis of the upper Espanola and Serpent formations in Canada.

Ru is one of the most active metals for oxygen evolution reaction, but it quickly dissolves in acidic electrolyte particularly in nanosized form. Here, the authors show that coral-like solid-solution Ru‒Ir consisting of 3 nm-thick sheets with only 6 at% Ir is a long-lived catalyst with high activity.

The Hayabusa2 spacecraft returned 5.4 g of material from the asteroid Ryugu. A first analysis of the samples found an estimated density of 1,282 ± 231 kg m⁻³, considerably lower than even the most porous meteorites. Together with preliminary spectral analysis, these results indicate that Ryugu is similar to CI chondrites, but darker, more porous and more brittle.

Sexual dimorphism describes physical differences between males and females of the same species and is partly shaped by the action of hormones. Maekawa and colleagues construct mixed-sex chicken brain chimeras and find that the female reproductive cycle is largely destroyed in female chimeras with male brains.

The crystal structure of a solid-solution alloy is generally determined by its elemental composition, limiting synthetic control over the alloy’s properties. Here, the authors are able to selectively control the crystal structure of Au–Ru alloy nanoparticles by rationally tuning the reduction speed of the metal precursors.

Surface-enhanced Raman spectroscopy (SERS) visualizes fingerprints of intermolecular vibrations of many metabolites. Here the authors report a SERS imaging technique that enables the visualization of metabolites distribution and automated extraction of tumour boundaries in frozen tissues.

Understanding blood and lymphatic vasculature networks is currently limited by existing imaging systems and quantification methods. Here the authors use the tissue clearing method CUBIC to generate 3D images, machine learning to capture the signals, and extract geometric features by topological data analysis.

Hiraike et al. identify nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat. NFIA activates cell-type-specific enhancers prior to differentiation and facilitates PPARγ binding to regulate the brown fat gene program.