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Here, Wulczynski et al. find fewer small-intestinal fiber-degrading bacteria in CeD patients, independent of the gluten-free diet, while inulin-supplemented diet in gluten-sensitized mice facilitates microbial saccharolytic function and SCFAs, accelerating mucosal healing in the small intestine.

The authors observe strong coupling between valley excitons in a monolayer WS2 and intrinsically chiral photons shaped by a metasurface. The polaritons display enhanced chiral emission with their spin configuration controlled by the light source.

Analyses of large-scale, multitaxa and long-term thermophilization patterns in forests, grasslands and alpine summits across Europe provide insight into shifts in community composition among different ecosystems in a warming world.

Chemical programming on a modular Chemputer digital chemistry platform couples automated synthesis with Drosophila phenotypic screening, yielding AP4-43, a multi-kinase inhibitor lead that improved survival in a KRAS-mutant colorectal cancer model.

The advantage of living in cities compared with rural areas with respect to height and BMI in children and adolescents has generally become smaller globally from 1990 to 2020, except in sub-Saharan Africa.

This Resource paper presents a global SARS-CoV-2 phylogenetic tree of 4,471,579 high-quality genomes consistently constructed by Viridian, an efficient amplicon-aware assembler.

A non-destructive DNA isolation method for the stepwise release of DNA trapped in ancient tooth and bone artefacts is developed.

High-coverage and low-coverage genomic data for some of the earliest modern humans in Europe provide insights into recent admixture with Neanderthals and familial relationship links with distant communities approximately 45,000 years ago.

Energy storage offers potential to support a changing electricity sector, but investors remain uncertain about its attractiveness. Analysis now shows that this can be overcome for battery technology by providing more than one storage service in a single facility.

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.

BRCA1 and BRCA2 are well known breast cancer predisposition genes, however, many variants have not yet been classified for their pathogenicity. Here, the authors analyse a large combined cohort to provide evidence of variant pathogenicity.

Certo, Pontarini et al. provide insight into the metabolic requirements of ectopic lymphoid structure (ELS) assembly in the context of autoimmunity, and show that blocking lactate uptake by SLC5A12 offers therapeutic benefits in a mouse model of Sjögren’s disease.

A cross-ancestry meta-analysis of genome-wide association studies identifies association signals for stroke and its subtypes at 89 (61 new) independent loci, reveals putative causal genes, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as potential drug targets, and provides cross-ancestry integrative risk prediction.

Krapić, Kavazović and colleagues dissect the mechanism by which natural killer cells drive adipose tissue remodelling during viral infection, thus fuelling antiviral immune responses.

Reduced glomerular filtration rate (eGFR) is a hallmark of chronic kidney disease. Here, Pattaro et al. conduct a meta-analysis to discover several new loci associated with variation in eGFR and find that genes associated with eGFR loci often encode proteins potentially related to kidney development.

Ancient mitochondrial DNA from sediments reveals the sequence of Denisovan, Neanderthal and faunal occupation of Denisova Cave, and evidence for the appearance of modern humans at least 45,000 years ago.

Through archaeological excavation, morphological and proteomic taxonomic identification, mitochondrial DNA analysis and direct radiocarbon dating of human remains, a study reports the presence of Homo sapiens in Germany north of the Alps more than 45,000 years ago.

In this Stage 2 Registered Report, Buchanan et al. show evidence confirming the phenomenon of semantic priming across speakers of 19 diverse languages.

Fine-mapping of causal variants and integration of epigenetic and chromatin conformation data identify likely target genes for 150 breast cancer risk regions.

Cryo-electron microscopy analysis of the extracellular flagellum structure, including the hook–filament junction and filament cap complex, reveals mechanisms of flagellin incorporation into the growing filament and filament stabilization.

Inflammasome assembly promotes the cleavage and oligomerisation of gasdermin D (GSDMD) and subsequent pore formation. Here the authors raise nanobodies to human gasdermin and characterize the pore formation process mediated by GSDMD and how antagonistic nanobodies prevent pyroptosis.

Genetic data for 13 Neanderthals from 2 Middle Palaeolithic sites in the Altai Mountains of southern Siberia presented provide insights into the social organization of an isolated Neanderthal community at the easternmost extent of their known range.

In breast cancer the contribution of different genetic variants to disease heritability is complex and not fully understood. Here, the authors present a network-based analysis in 84,567 patients studying ~7.3 million variants, identifying gene modules associated with breast cancer survival.

Hibernating brown bears maintain their muscle mass, which is due to a drastic reduction in metabolic rate. Here, De Napoli et al. show that this is partly due to a reduction of energy consumption by the motor protein myosin in resting skeletal muscle that increases the super relaxed state stability.

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.

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.

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 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.

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.

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.

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.

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.

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.

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

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.