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In this clinical study, the authors show that fecal microbiota transplantation is feasible and safe in adult women with anorexia nervosa, shifting gut bacteria toward a healthy donor profile and improving stool consistency after a single treatment.

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.

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.

PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

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.

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.

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.

Genomic analyses applied to 14 childhood- and adult-onset psychiatric disorders identifies five underlying genomic factors that explain the majority of the genetic variance of the individual disorders.

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.

Unimolecular integration of NMDA receptor antagonism with GLP-1 receptor agonism effectively reverses obesity, hyperglycaemia and dyslipidaemia in rodent models of metabolic disease.

An analysis of 101 ancient human genomes from the Bronze Age (3000–1000 bc) reveals large-scale population migrations in Eurasia consistent with the spread of Indo-European languages; individuals frequently had light skin pigmentation but were not lactose tolerant.

Intracytoplasmic sperm injection, usually reserved for cases of male infertility, was found to be nonsuperior to conventional in vitro fertilization in couples without male infertility concerns.

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.

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.

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.

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.

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.

Phage engineered with tail fibers and CRISPR–Cas reduce Escherichia coli load in animals.

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.

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.

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.

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.

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.

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.

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.

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.

Sortilin is a neuronal receptor involved in sorting and signal transduction. The crystal structure of the mature Sortilin ectodomain bound to one of its ligands, neurotensin, reveals a binding tunnel formed by the Sortilin β-propeller domain. Combined with binding and mutagenesis studies, the findings suggest that Sortilin substrates compete for access to the tunnel so that only one ligand binds at a time.

A critical determinant of tumor eradication by adoptive immunotherapy is the tumor associated antigen recognized by cytotoxic T lymphocytes. Here the authors generate ex vivo autologous cytotoxic T lymphocytes by exposure to antigens induced by DNA demethylation and report the results of a phase 1 trial of 25 patients with recurrent glioblastoma multiforme with tumor regression in three patients.

Drivers of physiological aging are also linked to the etiology of chronic obstructive pulmonary disease (COPD), including inflammation and senescence, both influenced by nicotinamide adenine dinucleotide (NAD⁺) metabolism. Norheim et al. performed a randomized controlled trial in patients with COPD, testing whether boosting NAD⁺ levels reduces airway inflammation.

Establishing methods to access the chemical space that lies beyond canonical terpenoid biosynthesis will increase the applications of isoprenoids. Here, the authors reconstruct the modular structure of terpene biosynthesis on 16-carbon backbones by engineered yeast and synthesize 28 different unique terpenes.

SNC1 is an intracellular NLR immune receptor controlled by the E3 ubiquitin ligase SCF^CPR1. A reverse genetic screen in Arabidopsis identified three clustered NLR partners of SNC1 named SIKICs, which are themselves regulated by novel E3 ubiquitin ligases MUSE1 and MUSE2.

Genome analysis of the pico-eukaryotic marine green alga Prasinoderma coloniale CCMP 1413 unveils the existence of a novel phylum within green plants (Viridiplantae), the Prasinodermophyta, which diverged before the split of Chlorophyta and Streptophyta.

Mutations in potassium and calcium channel genes have been associated with cardiac arrhythmias. Here, Jensen et al. show that an anion transporter chloride-bicarbonate exchanger AE3 is also responsible for the genetically-induced mechanism of cardiac arrhythmia, suggesting new therapeutic targets for this disease

Genome-wide analyses identify eight independent loci associated with anorexia nervosa. Genetic correlations implicate both psychiatric and metabolic components in the etiology of this disorder, even after adjusting for the effects of common variants associated with body mass index.