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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.

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.

iGluSnFR4f and iGluSnFR4s are the latest generation of genetically encoded glutamate sensors. They are advantageous for detecting rapid dynamics and large population activity, respectively, as demonstrated in a variety of applications in the mouse brain.

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.

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.

Tan and colleagues conducted a single-cell multiomic analysis of T cell acute lymphoblastic leukemia and identified a treatment-resistant subpopulation of bone marrow progenitor-like blasts associated with poor outcomes.

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.

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.

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.

Multielectron quantum dots offer a promising platform for high-performance spin qubits; however, previous demonstrations have been limited to single-qubit operation. Here, the authors report a universal gate set and two-qubit Bell state tomography in a high-occupancy double quantum dot in silicon.

Additions to alkenes and alkynes are useful routes for generating highly functionalized products. Here the authors report the 1,1-difunctionalization of alkynes through a CuH-catalysed asymmetric hydroboration/hydroamination cascade.

Computationally designed genetically encoded proteins can be used to target surface proteins, thereby triggering endocytosis and subsequent intracellular degradation, activating signalling or increasing cellular uptake in specific tissues.

A combination of high-resolution spatial imaging, spatial proteomics and transcriptional data reveals sparse and heterogeneous bacterial signals in gliomas and brain metastases.

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.

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.

Bacterial enzymes synthesize androgens that could promote cancer cell progression interfering with the efficacy of steroid-targeted prostate cancer therapies.

The feasibility of satellite-assisted quantum communication is demonstrated by a field test on the ground. To supress noise due to sunlight the wavelength of 1,550 nm is chosen, and spectrum and spatial filtering technology developed.

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.

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.

Scanning tunnelling microscopy shows that electrons in twisted bilayer graphene are strongly correlated for a wide range of density. In particular, a correlated regime appears near charge neutrality and theory suggests nematic ordering.

A diverse collection of potent neutralizing antibodies against the SARS-CoV-2 spike protein have been isolated from five patients with severe COVID-19 and high serum neutralization titres.

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.

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.

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.

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.

Genetic predictors of health outcomes often drop in accuracy when applied to people dissimilar to participants of large genetic studies. Here, the authors investigate the root causes and highlight open questions underlying this problem.

The authors mapped the dendritic morphology of thousands of striatal D1-type and D2-type medium spiny neurons in healthy and Huntington’s disease mouse brains, revealing dendritic modules with distinct neuronal shapes, spatial distributions and cortical inputs.

Previous work has realized a superconducting switch in heterostructures of superconductors and ferromagnetic insulators, but the effect has been smaller than originally predicted. Here, the authors report an absolute superconducting switch by inserting a heavy metal layer in the EuS/Nb/EuS heterostructure.

Epichaperomics allow the study of protein-protein interactions and their alterations, but probes have been limited to capturing HSP90 epichaperomes. Here, the authors introduce and validate a toolset of HSP70 epichaperome ligands, and use them in epichaperomics to identify a mechanism with which cancer cells can enhance the fitness of mitotic protein networks.

Wearable sensors typically require innovative methods of energy harvesting for low-power electronics. Here, the authors present an adaptive power management system with a trimodal energy harvesting approach.

The bactericidal action of some antibiotics is associated with increased ATP consumption, cellular respiration, and reactive oxygen species formation. Here, Li et al. show that constitutive hydrolysis of ATP and NADH (or ‘bioenergetic stress’) potentiates the evolution of antibiotic resistance and persistence in E. coli.

Amyloid fibrils can adopt a range of distinct conformations, yet it is challenging to rapidly discriminate between these polymorphs. Now methods have been developed to screen large, diverse libraries of turn-on fluorescent dyes to rapidly identify probes that recognize fibril subsets.

Single-cell data analysis is challenging due to inherent noise and sparsity. Here, authors introduce scMINER, a mutual information-based integrative tool to enhance clustering and reveal regulatory networks and hidden biological drivers by transforming scRNA-seq expression into activity profiles.

Directed evolution is a powerful method to optimize protein fitness. Here, authors develop an active learning workflow using machine learning to more efficiently explore the design space of proteins.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

The transient reactivation of ETV2 in adult human endothelial cells reprograms these cells to become adaptable vasculogenic endothelia that in three-dimensional matrices self-assemble into vascular networks that can transport blood and physiologically arborize organoids and decellularized tissues.

The crystal structure of V1/V2, the only unresolved portion of the HIV-1 gp120 envelope glycoprotein, is reported in complex with human antibody PG9 and reveals a paradigm of antibody recognition with implications for vaccine development.

CAR-T cells engineered with αPD-L1–IL-12 fusion proteins show antitumour activity in mouse models of prostate and ovarian cancer.

Yang et al. show that transcription–replication collisions lead to large tandem duplications, which are frequent in female-enriched, upper gastrointestinal tract and prostate cancers and are associated with poor survival and mutations in specific genes, such as CDK12.

Melanoma is a cancer that responds relatively well to immunotherapy but resistance does ensue. Here, the authors show that loss of IFNGR2 or JAK1 in a melanoma cell line enhances T cell mediated lysis, however these cells are paradoxically more sensitive to immune-mediated tumor control in vivo due to the loss of PD-L1.

Using large-scale multimodal retinal and brain imaging data, the authors map eye-brain connections and uncover underlying genetic factors, suggesting the retina as a window into brain structure, function, and disorders.

A dataset of the genomes of 363 species from the Bird 10,000 Genomes Project shows increased power to detect shared and lineage-specific variation, demonstrating the importance of phylogenetically diverse taxon sampling in whole-genome sequencing.

An analysis of 24,202 critical cases of COVID-19 identifies potentially druggable targets in inflammatory signalling (JAK1), monocyte–macrophage activation and endothelial permeability (PDE4A), immunometabolism (SLC2A5 and AK5), and host factors required for viral entry and replication (TMPRSS2 and RAB2A).

A remora-inspired mechanical underwater adhesive device adheres securely to a range of soft substrates and maintains performance under extreme pH and moisture conditions, with potential applications in biosensing and drug delivery.

A complementary metal–oxide–semiconductor (CMOS) imager that has a 512-pixel silicon image sensor post-processed into a 4.1-mm-long, 120-μm-wide shank with a collinear fibre for illumination can be used to record transient fluorescent signals in deep brain regions at 400 frames per second.

A new Cretaceous arachnid fossil encased in Burmese amber sheds light on the evolution of spiders, as it preserves both primitive and derived features, suggestive of a basal Araneae position.