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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.

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.

Genome-wide ancient DNA data from individuals from the Middle Bronze Age to Iron Age documents large-scale movement of people from the European continent between 1300 and 800 bc that was probably responsible for spreading early Celtic languages to Britain.

Stable carbon and oxygen isotope analysis of mammal teeth associated with stone tools and cut-marked bone dated to between 300,000 and 500,000 years ago reveals that, at the time of the earliest-known hominin presence, the Arabian peninsula was home to productive grasslands similar to modern-day African savannahs.

Here, Layton et al describe a non-invasive method to study intestinal disease by profiling faecal microRNAs, revealing intestinal fibrosis in chronic helminth infection.

Openshaw and colleagues find myeloid inflammation and complement activation signatures in patients with long COVID who were previously hospitalized.

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

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.

Sera from vaccinated individuals and some monoclonal antibodies show a modest reduction in neutralizing activity against the B.1.1.7 variant of SARS-CoV-2; but the E484K substitution leads to a considerable loss of neutralizing activity.

Study shows PTSD predisposition shares distinct genes and genomic regions with several cardiovascular conditions. Here the findings reveal neuronal, immune, and metabolic pathways, and repurposed drug targets that further the understanding of the comorbidity.

COVID-19 can be associated with neurological complications. Here the authors show that markers of brain injury, but not immune markers, are elevated in the blood of patients with COVID-19 both early and months after SARS-CoV-2 infection, particularly in those with brain dysfunction or neurological diagnoses.

In this work, Bay et al describe the construction of the first genome-scale metabolic model for the parasitic whipworm, Trichuris muris and use it to identify novel metabolic pathways and predict critical enzymes and essential metabolites for worm survival.

Kidney transplantation usually relies on hypothermia to safely preserve the graft. Here, the authors show that keeping kidneys at 37°C, using a machine to supply them with blood, oxygen, and nutrition, is feasible for up to 24 hours, and may be useful for testing and treating them pre-transplant.

‘Commercial fisheries have decimated keystone species, including oysters in the past 200 years. Here, the authors examine how Indigenous oyster harvest in North America and Australia was managed across 10,000 years, advocating for effective future stewardship of oyster reefs by centering Indigenous peoples.’

A study of the evolution of the SARS-CoV-2 virus in England between September 2020 and June 2021 finds that interventions capable of containing previous variants were insufficient to stop the more transmissible Alpha and Delta variants.

Archaeological discoveries from Malta suggest that humans were present on the Maltese islands from around 8,500 years ago, providing evidence that Mesolithic hunter-gatherers made sea crossings as long as 100 km.

Remdesivir is under evaluation for treatment of COVID-19 in clinical trials. Here, the authors report results of remdesivir treatment in a patient with COVID-19 and the genetic antibody deficiency XLA. They show a temporally correlated clinical and virological response, suggesting that remdesivir can reduce SARS-CoV-2 replication in patients.

In this Review, Ian Roberts provides a detailed description of the immunohistology and light microscopical features of IgA nephropathy, and highlights the importance of accurate recognition of the various histological lesions for reproducible classification of the disease. The different schemas used for classifying IgA nephropathy are compared, with particular focus on the Oxford classification.

Analysis of whole-genome sequencing data across 2,658 tumors spanning 38 cancer types shows that chromothripsis is pervasive, with a frequency of more than 50% in several cancer types, contributing to oncogene amplification, gene inactivation and cancer genome evolution.

The rapid waning of SARS-CoV-2-specific serum antibodies observed after immunization with COVID-19 mRNA vaccines may be accounted for by the absence of long-lived plasma cells in the bone marrow specific for the virus.

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.

A major challenge in protein design is to augment existing functional proteins with multiple property enhancements. Here the authors use the evolutionary model EVcouplings to computationally design highly mutated variants of TEM-1 ß-lactamase, and characterise these designs experimentally.

In hospitals, surfaces present as a reservoir for bacteria pathogens, potentially leading to nosocomial infections. In this work, authors aim to profile extended-spectrum β lactamase- and carbapenemase-carrying bacterial species colonising neonatal hospital wards and causing neonatal sepsis.

A comprehensive multi-omics reference atlas of prenatal human skin shows that innate immune cells crosstalk with non-immune cells to perform pivotal roles in skin morphogenesis, including the formation of hair follicles.

Chromodomain Helicase DNA-binding (CHD) proteins have been implicated in neurodevelopmental processes. Here, the authors identify missense variants in CHD3 that disturb its chromatin remodeling activities and cause a neurodevelopmental disorder with macrocephaly and speech and language impairment.

Comprehensive integration of gene expression with epigenetic features is needed to understand the transition of kidney cells from health to injury. Here, the authors integrate dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and histone modifications to decipher the chromatin landscape of the kidney in reference and adaptive injury cell states, identifying a transcription factor network of ELF3, KLF6, and KLF10 which regulates adaptive repair and maladaptive failed repair.