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Here, Koster et al., model human papillomavirus and Chlamydia coinfection dynamics in patient-derived ectocervical organoids, and characterize the effects of multiple infections in the cellular microenvironment, potentially contributing to neoplasia.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Materials typically break down in response to the repeated mechanical forces that they experience during use. Now, it has been shown that a mechanochemically active polymer can respond to shear forces by forming more bonds than are broken, leading to improved mechanical properties under conditions that would otherwise be destructive.

Polymer mechanochemistry can trigger a wide range of often unanticipated reactivity, but the focus of these systems typically falls on the structure of the mechanophore rather than the intervening polymer backbone. Now, it has been shown that a poly(norbornene) backbone has a substantial impact on a mechanochemical ring-opening reaction, despite having only a minor effect on the force-free reaction.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Climate change is warming freshwater fish thermal habitats. Here, the authors examine daily temperature profiles from 12,688 lakes and thermal habitats of 60 fish species, finding that cold-water fishes are losing preferred thermal habitats at a faster rate than warm-water fishes are gaining them.

Microbes structure biogeochemical cycles and food webs in the marine environment. Here, the authors sample coral reef-associated microbes across a 24-hour period, showing clear day–night patterns of microbial populations and thus calling for more studies to consider temporal variation in microbiomes at this scale.

A subcortical circuit that regulates food consumption in mice is described, involving neurons in the ventromedial hypothalamus that are directly linked to motor centres that regulate feeding and jaw movements.

Complete sequences of chromosomes telomere-to-telomere from chimpanzee, bonobo, gorilla, Bornean orangutan, Sumatran orangutan and siamang provide a comprehensive and valuable resource for future evolutionary comparisons.

Conditional Degron Tags are a valuable tool to validate and study novel therapeutic targets. Here, the authors compared 5 orthogonal tags across 16 unique proteins and provide a panel of vectors for users to systematically screen the tags with their own protein of interest.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Zachary Lippman, Dani Zamir and colleagues report that the flowering gene, SINGLE FLOWER TRUSS, displays heterosis for fruit yield in tomato. Heterozygosity at this gene in several distinct genetic backgrounds leads to increases of up to 60% in fruit yield.

Foragers hunted small game locally and procured most large prey in riparian habitats and Afromontane grasslands to the southeast of the Kasitu Valley of northern Malawi, suggesting that migratory behavior in large grazers was absent, according to strontium isotopic analysis.

This Consensus Statement presents the standards for technical reporting in environmental and host-associated microbiome studies (STREAMS) guidelines.

Artificial reefs provide important ecosystem services in marine environments. Accurate knowledge of the area covered by such reefs can help evaluate benefits and risks of such structures. This study describes the physical footprint of artificial reefs deployed in coastal waters of the United States.

Reference assemblies of great ape sex chromosomes show that Y chromosomes are more variable in size and sequence than X chromosomes and provide a resource for studies on human evolution and conservation genetics of non-human apes.

Phylogenomic analysis of 7,923 angiosperm species using a standardized set of 353 nuclear genes produced an angiosperm tree of life dated with 200 fossil calibrations, providing key insights into evolutionary relationships and diversification.

Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

The impact of various immune statuses on SARS-CoV-2 transmission is unclear. Here, the authors used transmission chain experiments in hamsters to show better transmission prevention after intranasal vaccination and previous infection. Higher humoral responses against Delta may provide a competitive advantage to Omicron.

The genomic and epigenomic landscape during metastasis in osteosarcoma remains to be investigated. Here, functional and pharmacological studies identify the dynamic epigenomic changes and gene vulnerabilities during the formation of osteosarcoma tumours in the lung microenvironment.

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.

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.

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.

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.

Subsidies for coastal management and tax advantages for high-income property owners dampen the negative effects of climate risks on coastal property values. Without subsidies or tax advantages market prices better reflect climate risks, but coastal gentrification could accelerate.

Pannexin-1 ion channels on endothelial cells regulate vascular inflammation and remodeling to mediate aortic aneurysm formation. Pharmacological blockade of Pannexin-1 channels may offer translational therapeutic mitigation of aneurysmal pathology.

Roughly 10% of Cystic Fibrosis (CF) patients still have no effective medicine to take. Lung Selective Organ Targeting (SORT) Lipid Nanoparticles can efficiently deliver Cas9 mRNA, sgRNA, and donor ssDNA templates for precise homology-directed repair-mediated gene correction in ex vivo and in vivo CF models.

Multitrait genome-wide association analyses identify hundreds of risk loci for primary open-angle glaucoma. Integration with other data types highlights potential new drug targets, including proteins likely to act via the optic nerve.

Paul Pharoah and colleagues report the results of a large genome-wide association study of ovarian cancer. They identify new susceptibility loci for different epithelial ovarian cancer histotypes and use integrated analyses of genes and regulatory features at each locus to predict candidate susceptibility genes, including OBFC1.

The enzyme autotaxin (ATX) produces the lipid mediator LPA to stimulate cell migration and proliferation. The crystal structures of rat ATX, in its apo and inhibitor-bound forms, along with functional work, offer insight into substrate specificity and show that ATX interacts with integrins through one of its SMB domains.

The intercalated disc (ICD) is a membrane structure of the cardiac muscle involved in normal heart function. Here the authors report that knockdown of the ICD-bound transmembrane protein 65 results in impaired ICD structure, abnormal cardiac electrophysiology and cardiomyopathy in mice.