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Antibiotic resistance is biologically driven by antibiotic use but other social, environmental, demographic, economic and behavioural factors also contribute. Here, the authors conduct a cross-sectional study to identify risk factors jointly associated with multidrug resistant urinary tract infection in East Africa.

The inclusion of abundance data in global surveys of reef fishes reveals new hotspots of functional biodiversity, not all of which show high species richness. The findings may influence conservation priorities. See Letter p.539

The Omicron variant evades vaccine-induced neutralization but also fails to form syncytia, shows reduced replication in human lung cells and preferentially uses a TMPRSS2-independent cell entry pathway, which may contribute to enhanced replication in cells of the upper airway. Altered fusion and cell entry characteristics are linked to distinct regions of the Omicron spike protein.

Antigenic characterization of new SARS-CoV-2 variants is important to evaluate population immunity and the need for vaccine updates. Here, neutralizing antibodies against newly emerged Omicron variants were analysed in bivalently boosted individuals.

Here, Tisza, Dekker, and colleagues perform large scale analysis of genome methylation in the gut commensal and pathogen, Bacteroides fragilis group, revealing immense methyl motif diversity and evidence of widespread methyltransferase exchange among phages.

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.

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.

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.

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.

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.

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.

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.

Insect toxins with tandem repeats of neurotoxin domains have been found with enhanced receptor avidity. Here, the authors describe a bivalent toxin from remipede venom that targets ryanodine receptors, a rare target for animal venoms.

Retrosynthetic pathway design using promiscuous enzymes can provide a solution to the biosynthetic production of natural products. Here, the authors design a pathway for the production of cis-α-irone with a promiscuous methyltransferase using structure-guided enzyme engineering strategies.

T cell responses can be generated to either pathogen infection or from priming with a vaccine. Here the authors compare T cell generation, phenotype and single cell transcriptome of participants vaccinated with a mpox vaccine or infected with the virus showing that the virus induced T cells showed more effective function and phenotype.

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Here the authors analyze data from COVAIL trial participants receiving an mRNA second COVID-19 vaccine boost and show that, while neutralizing antibody titer is correlated with Omicron COVID-19 risk, the correlation is weak in naïve individuals compared to previously infected ones.

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Genome-wide association analyses of 41,917 bipolar disorder cases and 371,549 controls of European ancestry provide new insights into the etiology of this disorder and identify novel therapeutic leads and potential opportunities for drug repurposing.

The authors find subtype-specific influenza cross-reactivity patterns, including rapid declines for A(H3N2) within 6 years, sustained responses for A(H1N1)pdm09 and increased cross-reactive responses in humans after repeated A(H3N2) exposure.

Analysis of antibody responses to COVID-19 vaccines encoding variant-specific spike, with or without ancestral spike, suggests no loss of neutralization of the ancestral virus with variant-only vaccines, which may simplify future vaccine updates.

Genetic and testing data from England show that the SARS-CoV-2 variant of concern B.1.1.7 has a transmission advantage over other lineages.

A systematic census at 1,636 sites around Australia from 2008 to 2021 finds that more than 30% of shallow invertebrate species in cool latitudes exhibit a high extinction risk due to declining populations and oceanic barriers, but tropical coral species remain relatively stable.

ATE1 is a highly specific enzyme hijacking tRNA from ribosomal pathways to install an arginine onto proteins as a post-translational modification. Here, the authors describe the structures of yeast ATE1 with or without its tRNA cofactor. ATE1 recognizes and selects tRNA in a unique mechanism.

A genome-wide association study of critically ill patients with COVID-19 identifies genetic signals that relate to important host antiviral defence mechanisms and mediators of inflammatory organ damage that may be targeted by repurposing drug treatments.

A new specific, small-molecule activator of the PI3Kα isoform (UCL-TRO-1938) identified through high-throughput screening can transiently activate PI3K signalling and biological responses in cells and tissues, with potential therapeutic applications in tissue protection and regeneration.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Proferroptotic activity of 7-dehydrocholesterol reductase is shown along with an unexpected prosurvival function of its substrate, 7-dehydrocholesterol, indicating a cell-intrinsic mechanism that could be used by cancer cells to protect phospholipids from oxidative damage and escape ferroptosis.

Post-international travel quarantine has been widely implemented to mitigate SARS-CoV-2 transmission, but the impacts of such policies are unclear. Here, the authors used linked genomic and contact tracing data to assess the impacts of a 14-day quarantine on return to England in summer 2020.

In this study, Aggarwal and colleagues perform prospective sequencing of SARS-CoV-2 isolates derived from asymptomatic student screening and symptomatic testing of students and staff at the University of Cambridge. They identify important factors that contributed to within university transmission and onward spread into the wider community.

Hawkey et al. provide insights into the spatio-temporal distribution and genetic diversity of Salmonella Paratyphi B — the agent of paratyphoid B fever — and report a genotyping scheme facilitating the international surveillance of this pathogen.

Integrative analysis in patients with diffuse large B-cell lymphoma uncovers that biallelic mutations on TMEM30A are associated with a favorable outcome and enhanced sensitivity to CD47 blockade.