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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.

This study identifies protein signatures of pediatric obesity linked to cardiometabolic risk, shows treatment-related changes, and highlights a three-protein panel predictive of steatotic liver disease for early diagnosis

An analysis involving the shotgun sequencing of more than 300 ancient genomes from Eurasia reveals a deep east–west genetic divide from the Black Sea to the Baltic, and provides insight into the distinct effects of the Neolithic transition on either side of this boundary.

While the photoreceptor outer segments in the bird outer retina have access to oxygen, the inner retina operates under chronic anoxia, supported by anaerobic glycolysis in the retinal neurons.

Genome-wide analyses identify 13 loci associated with susceptibility to infection with SARS-CoV-2 Omicron variants, including variation in ST6GAL1, previously associated with influenza susceptibility, and other genes involved in glycosylation processes.

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.

Integrated data, including 100 human genomes from the Mesolithic, Neolithic and Early Bronze Age periods show that two major population turnovers occurred over just 1,000 years in Neolithic Denmark, resulting in dramatic changes in the genes, diet and physical appearance of the local people, as well as the landscape in which they lived.

Large-scale genome-wide analyses identify hundreds of genetic loci associated with hypothyroidism and thyroid hormone levels, demonstrating the potential of using polygenic risk scores to predict disease onset and progression.

This large meta-analysis of 11 GWAS identified 7 genetic loci associated with strabismus, esotropia and exotropia. Mendelian randomisation provided genetic evidence of the causal link between maternal smoking to increased strabismus risk in offspring.

Ancient DNA analyses reveal that Viking Age migrations from Scandinavia resulted in differential influxes of ancestry to different parts of Europe, and the increased presence of non-local ancestry within Scandinavia.

Muscle mass is lost in patients with diabetes, which is associated with mitochondrial disfunction. Here they show that SLIRP maintains muscle mitochondria and that exercise training can compensate for SLIRP loss, improving mitochondrial function and quality control in muscle.

Microflora Danica—an atlas of Danish environmental microbiomes—reveals that although human-disturbed habitats have high alpha diversity, species reoccur, revealing hidden homogeneity.

Analysis of two-million-year-old ancient environmental DNA from the Kap København Formation in North Greenland shows there was an open boreal forest with diverse plant and animal species, of which several taxa have not previously been detected at the site, representing an ecosystem that has no present-day analogue.

In plants and fungi, cellular ion homeostasis is powered by the proton pump, a member of the P-type ATPase family. The first X-ray structure of the H⁺-ATPase is presented, and insight into the mechanism by which protons are transported against an electrochemical gradient is provided.

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.

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.

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.

Leveraging four large, longitudinal, prospectively-followed mother–child cohorts, this study shows that a western diet in early–mid-pregnancy is associated with neurodevelopmental disorders in the offspring.

Here the authors show how the DNA-sensing cGAS–STING pathway activates NF-κB and inflammatory gene expression with delayed kinetics via post-Golgi endolysosomal signaling.

Trained and validated on multimodal data from 14.5 million images from multicountry datasets, a foundation model is shown to increase diagnostic and referral accuracy of clinicians when used as an assistant in a trial involving 16 ophthalmologists and 668 patients.

The first genome sequence of an ancient human is reported. It comes from an approximately 4,000-year-old permafrost-preserved hair from a male from the first known culture to settle in Greenland. Functional single-nucleotide polymorphism (SNP) assessment is used to assign possible phenotypic characteristics and high-confidence SNPs are compared to those of contemporary populations to find those most closely related to the individual.

Two polypeptides synthesized by common bacterial strains in human gut microbiota lower body fat and blood glucose and increase bone density, improving the metabolism of rodents.

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.

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.

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.

Genome-wide association meta-analyses identify more than 350 loci associated with atrial fibrillation. A polygenic score derived from these results improves atrial fibrillation risk prediction compared to published clinical and polygenic scores.

Sequences of 137 ancient and 502 modern human genomes illuminate the population history of the Eurasian steppes after the Bronze Age and document the replacement of Indo-European speakers of West Eurasian ancestry by Turkic-speaking groups of East Asian ancestry.

The free EMOPEC web tool enables precise tuning of bacterial protein expression on the basis of small changes to the Shine-Dalgarno sequence; oligos can be generated to engineer expression of any Escherichia coli gene.

Industrial bioethanol production is driven by ecological interactions within the microbial community rather than the interactions within yeast population. Here, the authors identify bacteria affecting ethanol production and reveal temperature as the major driving force for strain-level dynamics.

A high proportion of confirmed SARS-CoV-2 cases in Denmark were sequenced during the pandemic and linked to demographic, spatial and temporal data. Here, the authors analyse 290,000 genomes sampled in 2021 to demonstrate the value of this high coverage, detailed data set.

Transition state theory has proven to be a powerful tool for the analysis of a number of processes, perhaps most commonly chemical reactions. Here, the authors use transition state theory to model a directly observable, micron scale process—the transport of DNA molecules in a confined environment.

Combining a large-scale dataset of 23 ungulate species (in which newborns follow contrasting tactics of predator avoidance) with continuous-time stochastic movement models, the authors reveal that there are multiple dimensions of maternal movement behaviour and space use.

An X-ray crystal structure of sarcoplasmic reticulum Ca²⁺-ATPase (SERCA) in the presence of sarcolipin, a SERCA regulator, is presented; the structure shows that sarcolipin traps SERCA in a previously unidentified ‘open’ state in which its high-affinity Ca²⁺-binding sites are unoccupied, but accessible from the cytoplasm.

Coastal seaweed transported to the open ocean contributes up to 3–4% of the particulate organic carbon sinking into the deeper ocean, according to combined ecological and biogeochemical modelling.

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

Robust genome-wide association study (GWAS) methods that can utilise time-to-event information such as age-of-onset will help increase power in analyses for common health outcomes. Here, the authors propose a computationally efficient time-to-event model for GWAS.

Substrate and fibre availabilities determine whether the gut microbiota generates beneficial or detrimental tryptophan metabolites.

Genome-wide association analyses identify 93 risk loci for venous thromboembolism (VTE). A polygenic score derived from these results identifies individuals at increased VTE risk equivalent to monogenic forms of the disease.

By exploiting the unique structural motifs and self-recognition properties of DNA, it is possible to generate self-assembled DNA nanostructures of specific shapes. Here, a previously described DNA 'origami' method has been extended into three dimensions to create an addressable DNA box on the nanometre scale that can be opened by an externally supplied DNA key'.

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.

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.

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.

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.

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.