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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.

Unveiling the regulation of mitotic protein degradation is crucial for cancer therapy. Here, the authors reveal that a reciprocal inhibition of PIN1-APC/C^CDH1 controls the cell cycle and mitotic protein degradation, offering a synergistic anti-tumor strategy.

Here the authors report a low-cost method to fabricate flexible Ag2Se thermoelectric films with high performance and durability, enabling efficient energy harvesting and cooling in wearable and portable thermoelectric devices.

Xu et al. identify the MondoA–TXNIP signalling axis as a regulator of antitumour immune surveillance in response to lactic acid in the tumour microenvironment.

Human cortical functions rely on intricate spatial arrangements and interactions among neuronal cell types. Here, authors show a comprehensive cellular atlas illustrating detailed neuron distribution and communication patterns across cortical regions.

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.

Triangle-beam interference structured illumination microscopy leverages radially polarized beams to generate two-dimensional lattice illumination patterns. The technique enables a temporal resolution of 242 Hz, spatial resolution of 100 nm and continuous imaging of neuronal growth for up to 13 h.

The authors propose a targeted doping strategy that enables copper atoms to occupy specific positions within the material’s crystal structure, avoiding the unwanted defects typically introduced by conventional methods.

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.

This study shows how auditory cortex activation and cognitive function develop during a six-month follow-up after gene therapy in children with congenital deafness.

Slope inspection is crucial for preventing landslide hazards. In this work, authors develop a LiDAR-based quadrotor with assisted obstacle avoidance, achieving efficient slope inspection under dense vegetation.

Macrocyclic compounds hold promise as therapeutic agents, yet their structural optimization is hindered by a scarcity of bioactive candidates. Here, the authors present CycleGPT, a generative chemical language model that enhances macrocycle design through innovative transfer learning and sampling strategies, leading to potent JAK2 inhibitors with promising in vivo efficacy.

The authors report a flexible thermoelectric film, comprising Ag₂Se and reduced graphene oxide, achieving a power factor of 37 μW cm⁻¹ K⁻² in the film and a normalized power density of over 9.8 μW cm⁻² K⁻² in the out-of-plane device.

Zhang, Peng, and colleagues benchmark metabolic RNA labelling chemistries for time-resolved single-cell RNA sequencing, improving in vivo detection of newly synthesized RNA during zebrafish embryogenesis.

Enhancing the arsenal of E3 ligases is important for PROTACs development. Here, the authors identify a non-inhibitory aptameric ligand to CRL2^ZYG11B E3 ligase, and develop a general, modular, and straightforward aptamer-based PROTAC platform, termed ZATAC, providing insights for untapped E3 ligases.

In contrast to the well-established palladium-catalyzed version, the nickel-catalyzed carbonylative coupling is underdeveloped. Here the authors report a nickel-catalyzed allylic carbonylative coupling with alkyl zinc reagents, allowing for preparation of β,γ-unsaturated ketones in a linear-selective fashion.

Upstream pathways regulating Brg1 stability and their role in carcinogenesis are unknown. Here they show Brg1 to be phosphorylated by CK1δ to promote its ubiquitination by SCF^FBW7 (FBW7), Brg1 stabilization to promote gastric cancer metastasis, and suggest targeting Brg1 in FBW7 compromised gastric cancer.

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

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 sodium storage mechanism of K-containing polyanion compounds is intricate and unclear. Here, the authors reveal that the residual K⁺ pillars uphold K-containing polyanion structure upon sodium storage, enabling long-term cycling stability.

The mechanisms underlying the invasiveness and aggressiveness of pituitary neuroendocrine tumours (PitNETs) remain poorly understood. Here, the authors perform single-cell RNA sequencing and spatial transcriptomics to characterise the tumour microenvironment of PitNETs and identify potential therapeutic targets.

The Dark sectioning algorithm removes the background and provides single-frame optical sectioning in fluorescence microscopy. It offers improved quantitative analysis and deep-tissue segmentation accuracy and is compatible to diverse modalities.

Abundance of PD-L1, the ligand of the anti-cancer immunotherapy target PD-1, is negatively regulated by poly-ubiquitination via the cyclin D–CDK4/cullin 3–SPOP axis and PD-1 blockade treatment in mice improved survival when combined with CDK4/6 inhibitors.

Laser-capture microdissection and mini-bulk exome sequencing are combined to analyse somatic mutations in morphologically normal tissues from nine organs from five donors, revealing variation in mutation burdens, mutational signatures and clonal expansions.

The authors report a wet-chemical selenization-based anisotropy optimization to control the orientation of the Ag₂Se thin film, achieving a power factor of 30.8 μW cm⁻¹ K⁻² in the thin film and a normalized power density of 1.8 μW cm⁻² K⁻² in the device.

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.

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.

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.

The authors introduce nanoscale titanium layers to boost the flexibility of flexible thermoelectric device with 162 thin-film legs (p-Bi0.5Sb_1.5Te₃/n-Bi₂Te_2.7Se_0.3), achieving a high normalized power density >4 μW cm⁻² K⁻² and offering good flexibility.

Here the authors show that the E3 ligase GID4 can be harnessed for targeted protein degradation and present the crystal structure of the GID4–PROTAC–BRD4 ternary complex to elucidate the underlying molecular mechanisms.

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.

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.

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.

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.

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 multistep processes involved in the evolution of inflammation to invasive esophageal squamous cell carcinoma (ESCC) is unclear. Here, the authors report a mouse model of ESCC and the role of interplay between carcinogen-transformed epithelial cells and their microenvironment in ESCC development.

N-degron pathways play an important role in maintaining protein homeostasis. Here, Li et al. demonstrates an additional non-Ac/N-degron pathway, in which N-terminal non-acetylated small residue degrons (Ser, Ala, or Cys) are recognized by CRL2^ZER1/ZYG11B and targeted for protein degradation.

The authors introduce SelectID, an approach combining CRISPR-guided targeting with methylation-sensitive labeling to identify proteins interacting with methylated repetitive sequences. They suggest that CHD4 directly binds young LINE-1 retrotransposons, suppressing their activity.

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.

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.

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.

Porphyrins are produced at scale through metabolic engineering and optimization of CPIII purification.