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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.

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.

Multimodal large language models (MLLMs) hold promise for a range of medical applications. Here, the authors use MLLMs for 3D brain CT radiology report generation, demonstrating that combining anatomy-aware model fine-tuning with robust evaluation metrics establishes a comprehensive and effective framework.

Han et al. identify the long non-coding RNA LIPTER as a key mediator of lipid droplet transport and metabolism in human cardiomyocytes. LIPTER overexpression mitigates cardiomyopathy and preserves cardiac function in obese and diabetic mouse models.

Insulating thin films with a random structure can undergo a nanoscale metal–insulator transition by making the film thickness size less than or more than the electron diffusion distance.

This article presents a polymeric membrane-enclosed insulin crystal equipped with physiological signal-sensing microdomains, dubbed ‘smart drug crystals’, that enables long-term, glucose- and β-hydroxybutyrate-dually responsive drug release for type 1 diabetes therapy.

RNA binding protein Quaking (QKI) is known for its broad function in pre-mRNA splicing and modification and its association with several neurodevelopmental disorders. Here the authors reveal that QKI-mediated regulation of RNA splicing is indispensable to cardiac development and contractile physiology.

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.

The authors propose a hydrogen bond modification method to achieve introduction of polarization and enhancement of phase transition temperature in molecular ferroelectrics, exploring the piezoelectric prototype devices of the molecular ferroelectric.

This study examines the history of North Atlantic deep-water masses, as recorded in marine sediments. Major lithological changes and increased rate of deposition reveal that stronger deep-ocean circulation initiated 3.6 million years ago.

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.

Macrophages are abundant in the microenvironment of diffuse large B-cell lymphoma (DLBCL). Here, the authors use spatial transcriptomics to characterize macrophages in DLBCL and reactive lymphoid tissues, and propose six spatially-derived macrophage signatures that are associated with features like cell of origin and clinical outcomes.

Here the authors find that farrerol directly binds to UCHL3 and activates its deubiquitinase activity, and that farrerol promotes development of SCNT embryos by enhancing HR repair and restoring epigenetic networks in a UCHL3-dependent manner.

In this study, the authors use metabolic modelling and isotope labelling to show that archaea can reverse the anaerobic breakdown of butane, turning CO₂ back into the gas, which could help explain how some natural gases form providing new insights into Earth’s hidden microbial activities.

Cooperation is not merely a dyadic phenomenon, it also includes multi-way social interactions. A mathematical framework is developed to study how the structure of higher-order interactions influences cooperative behavior.

CD8⁺ T cell–macrophage interactions have a central role in impairing alveolar regeneration and driving fibrotic sequelae after acute viral pneumonia in a mouse model of long COVID.

The electronic and optical properties of polymer semiconductors are largely dictated by their chemical structure. This study examines the nature of the photoexcited states generated in donor–acceptor polymers, and uncovers the dynamics of polaron pairs generation and recombination.

Chromosome-scale genome assemblies of triploid Cavendish and Gros Michel reveal the banana cultivars’ origins, disease resistance and fruit ripening mechanism.

The authors report the chiral inversion of exceptional points (EPs) through a structural mirror-symmetric operation, extending the application of EP to any desired polarization states, surpassing the inherent limitation of conventional EP systems.

It is unclear whether 2D metal dichalcogenides (TMD) alone can cause ferroptotic cell death. Here, the authors show TMD nanosheets induced ferroptosis in mammalian cell lines and in a mouse model after aspiration of TMD materials into lungs, causing ferroptotic cell death.

Ferroptosis is lipid peroxidation-dependent cell death that has potential to be harnessed as a cancer therapeutic. Here, the authors show that the translation initiation factor eIF4E can repress ALDH1B1 independent of translation, increasing lipid peroxidation levels to promote ferroptosis.

Hybridization-type band gaps are known to persist in phononic crystals, but their fabrication remains challenging for all-solid hypersonic composites. Here, the authors utilize the elastic anisotropy at the interface of polymer-tethered colloidal particles to control phonon propagation in GHz regime.

Electrophysical processes are used to create third-order nanoscale circuit elements, and these are used to realize a transistorless network that can perform Boolean operations and find solutions to a computationally hard graph-partitioning problem.

A versatile hydrothermal approach in an operando acidic environment created ferromagnetic single-atom spin catalysts (SASCs). Ni-based SASC exhibits a giant magnetic field enhancement of OER activity, boosting both water and saline water electrolysis.

In situ reduction deposition is a scalable method for fabricating metal/MXene composites, but rational control remains difficult. Now an in situ reduction strategy for synthesizing metal/MXene composites with precise control over metal size, deposition site and nanostructure has been demonstrated.

As the sample size goes down to the nanoscale, the surface-related mechanism plays an important role in the deformation of nanoscale crystals. Here, the authors report breakdown of the traditional Hall-Petch-like relation in nanoscale Ag attributed to diffusion-involved nucleation behaviors.

The flightless emu wings have a striking resemblance to immobilization phenotypes. Here, authors report that cell death of dual-identity muscle progenitors during embryonic development contributes to distal muscle absence, linked to skeletal shortening and asymmetry in this vestigial structure.

Mass cytometry with signal amplification enables measurement of low-abundance proteins.

The authors show PTEN mutations, which can cause both congenital hydrocephalus and autism spectrum disorder, disrupt CSF homeostasis and brain connectivity in mice. Reducing mTORC1 activation ameliorates ventricular enlargement and neuronal deficits.

The Enzyme Commission (EC) number is a commonly used method for defining enzyme function. Here, authors propose GraphEC, a geometric graph learning-based EC number predictor to identify unannotated enzyme functions, predict their active sites, and determine their optimal pH.

First-generation light-driven rotary molecular motors received considerable interest in various areas of chemistry, but those driven by benign visible light remain less explored. Here the authors describe all-visible-light-driven first-generation molecular motors which show an adaptive behaviour and explore application in multistate photoluminescence.

Battiston et al. discuss the emerging paradigm of higher-order network science and its applications to social systems and human dynamics.

High-content screening of a natural diterpenoid library identified a highly potent anti-liver fibrosis lead, 12-deoxyphorbol 13-palmitate (DP), which targets apolipoprotein L2 (APOL2) and impairs APOL2–SERCA2–PERK–HES1 signaling.