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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.

Available wheat genomes are annotated by projecting Chinese Spring gene models across the new assemblies. Here, the authors generate de novo gene annotations for the 9 wheat genomes, identify core and dispensable transcriptome, and reveal conservation and divergence of gene expression balance across homoeologous subgenomes.

Common bean is an evolutionary model for studying adaptive diversity in legumes. Here, the authors present the common bean pangenome based on five high-quality genomes and whole-genome reads of 339 wild and domesticated genotypes, and reveal adaptive gene loss during expansion and domestication.

The Sc2.0 consortia is reengineering the yeast genome. To expand the Sc2.0 genetic repertoire, the authors build a neo-chromosome comprising variable loci from diverse yeast isolates, providing phenotypic plasticity for use in synthetic backgrounds.

Global analysis of obesity trends from 1980 to 2024 in 200 countries and territories using data from 4,050 population-based studies reveals that framing obesity as a single global epidemic masks the highly varied dynamics across countries and age groups.

Castro-Dopico et al. report the design of reagents to bridge F-actin and Fcγ receptors, endowing a range of antigen-presenting cells with the ability to cross-present antigens from dead tumor cells and boosting antitumor immunity in preclinical models.

Promiscuous interactions underpin natural protein evolution, but ways to harness such promiscuity to design new functions remain underexplored. Now it is shown that mapping this promiscuity with geometric precision in a de novo protein can guide its redesign into a fluorophore binder and an efficient enzyme approaching the diffusion limit.

DNA-sequencing data from primary tumours and paired metastases from participants in the TRACERx lung study and PEACE autopsy programme are used to analyse the metastatic diversity of advanced non-small cell lung cancer and the seeding patterns that underpin it.

Nitazenes are potent synthetic opioids that are difficult to detect. Here, authors computationally redesign a plant receptor to create sensitive sensors capable of detecting diverse nitazenes and their metabolites in biological samples.

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.

The authors show how Vγ1⁺ γδ T cells produce IL-4 to drive early CD8⁺ T cell and dendritic cell responses to malaria infection in mice.

Timothy Chan and colleagues show that the PARK2 tumor suppressor is a master regulator of G1 and S phase cyclins and is critical for proper cell cycle regulation. PARK2 genetic alterations are common across many human cancers as well as in hereditary Parkinson's disease.

A meta-analysis of studies on chimpanzees and bonobos across Africa shows that their conspecific aggression is the normal and expected product of adaptive strategies to obtain resources or mates and has no connection with the impacts of human activities.

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.

IMiD-based PROTACs may degrade IKZF1/3 with hematologic effects. This study profiles these liabilities using hematopoietic assays showing stem cell rewiring and interferon activation and introduces a CRBN ligand that reduces them.

A reference genome from the coccolithophore Emiliania huxleyi is presented, along with sequences from 13 additional isolates, revealing a pan genome comprising core genes and genes variably distributed between strains: E. huxleyi is found to harbour extensive genetic variability under different metabolic repertoires, explaining its ability to thrive under a diverse range of environmental conditions.

Correcting organizational errors of the Brassica A, B and C genomes reveals the conserved structure of each genome across species and genome evolutionary pathways. Genus-wide pan-genomes were constructed, helping to elucidate the genomic impacts of alien introgressions.

JWST has produced some of the first spatially resolved spectroscopic observations of massive quiescent galaxies less than 2 Gyr after the Big Bang, revealing a kinematically unique galaxy that shows little-to-no rotational support.

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.

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.

There are limited vaccines available for Ebola virus and none for broad protection from filoviruses. Here, the authors rationally design vaccines using nanoparticles and stabilized Ebola virus and other filovirus glycoproteins, characterize antibody epitopes and profile lymph node and antibody responses in mice.

The authors show that aberrant epithelial GREM1 expression remodels intestinal stroma to form ectopic stem cell niches in mice. Anti-GREM1 reversed these changes, highlighting a potential strategy for preventing polyposis in patients with HMPS.

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 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 tolerogenic activity of type 1 conventional dendritic cells (cDC1s) is determined by EPOR, which is preferentially expressed in cDC1s and induces antigen-specific FOXP3-expressing regulatory T cells.

A centimetre-scale convolutional spectrometer offers high performance, low cost and ~500-nm bandwidth. The system classifies diverse solid samples and quantifies concentrations of solutions with detection accuracy surpassing commercial benchtop spectrometers.

The Sanitation-related Quality of Life index (SanQoL-5) combines answers to five questions (disgust, privacy, disease, shame and safety) into a score ranging from 0 to 1. This study found good evidence for the validity and cross-cultural comparability of SanQoL-5.

Despite extensive genetic heterogeneity, nearly half of all multiple myeloma (MM) cases are driven by cyclin D2 (CCND2) over-expression. Here the authors dissect the chromatin landscape of MM to provide insights into the transcriptional regulatory landscape driving MM and divergent transcriptomes corresponding to different MM genetic subtypes.

Multi-ancestry genome-wide analyses identify 95 loci associated with post-traumatic stress disorder and implicate candidate genes, pathways and neurobiological systems underlying its pathophysiology.

The human pelvis exhibits distinct spatiotemporal ossification patterns and an ilium cartilage growth plate that is shifted perpendicularly compared with those of other mammals and non-human primates—two key adaptations that underlie bipedalism.

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.

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

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.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Here, the authors perform large trans-ancestry fine-mapping analyses identifying large numbers of association signals and putative target genes for colorectal cancer risk, advancing our understanding of the genetic and biological basis of this cancer.

A multiancestry phenome-wide analysis of copy number variants in the UK Biobank genomes increases power to detect genetic associations with complex traits across human populations.

Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations.

There is an unmet clinical need for simple, accessible biomarkers to select patients who are more likely to respond to immune checkpoint therapy. Here the authors show that a lower neutrophil-to-lymphocyte ratio is associated with better overall and progressive-free survival, as well as higher rate of response, in a multi-cancer cohort of patients treated with immune checkpoint inhibitors.

The susceptibility of mouse and human T cells to ferroptosis is determined by the balance of systemic polyunsaturated and monounsaturated fatty acids, highlighting a key role for lipid metabolism and dietary composition in regulating T cell function.