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Whole-genome sequencing of more than 2,000 colorectal carcinoma samples provides a highly detailed view of the genomic landscape of this cancer and identifies new driver mutations.

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.

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.

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.

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.

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.

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.

Experiments under upper-tropospheric conditions map the chemical formation of isoprene oxygenated organic molecules (important molecules for new particle formation) and reveal that relative radical ratios control their composition

A consensus cell type atlas for the fly brain provides both an intellectual framework and open-source toolchains for brain-scale comparative connectomics.

Drug-target residence time is viewed as a predictor of the clinical efficacy of small-molecule drugs. A pharmacodynamic model, taking into account the target binding kinetics of antibacterial compounds, leads to accurate predictions of cellular and in vivo efficacies of the inhibitors.

5-hydroxymethylcytosine, the sixth DNA base, plays a key role in brain aging and Alzheimer’s disease. Here, the authors study over 1000 deceased brains to identify genes with 5-hydroxymethylcytosine alterations linked to Alzheimer’s pathology.

A description is given of the ENCODE consortium’s efforts to examine the principles of human transcriptional regulatory networks; the results are integrated with other genomic information to form a hierarchical meta-network where different levels have distinct properties.

Automated recommender systems need to put some jokers in the pack, if we're not going to end up with narrow-minded tastes, says Philip Ball.

Whole-genome sequencing, transcriptome-wide association and fine-mapping analyses in over 7,000 individuals with critical COVID-19 are used to identify 16 independent variants that are associated with severe illness in COVID-19.

Tumor cell in the peritoneum are often exposed to shear forces generated by ascitic flow during metastasis. Here, the authors show that metastatic cancer stem cells tether more and roll slower than the non-metastatic counterparts, and that sialyl-Lewis^x -P-selectin axis mediates peritoneal metastasis.

Cell type labelling in single-cell datasets remains a major bottleneck. Here, the authors present AnnDictionary, an open-source toolkit that enables atlas-scale analysis and provides the first benchmark of LLMs for de novo cell type annotation from marker genes, showing high accuracy at low cost.

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.

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

Whole-genome sequencing and phenotype data sharing are introduced in a national health system to streamline diagnosis and to discover coding and non-coding variants that cause rare diseases.

The authors achieve precise strain control of freestanding SrTiO₃ membranes, enabling reversible ferroelectric transition. In-situ X-ray absorption spectroscopy unveils classical-to-quantum crossover in ferroelectric phase transition at low temperatures.

Inbreeding depression has been observed in many different species, but in humans a systematic analysis has been difficult so far. Here, analysing more than 1.3 million individuals, the authors show that a genomic inbreeding coefficient (FROH) is associated with disadvantageous outcomes in 32 out of 100 traits tested.

SaprotHub is a community repository for protein language models.

Lipid nanoparticles (LNPs) delivering mRNA after intratumoral administration could be a promising cancer treatment strategy. Here this group reports the intratumoral delivery of mRNA with LNPs inducing the expression of purine nucleoside phosphorylase and inhibiting the progression of head and neck squamous cell carcinoma in vivo.

Parkin plays a role in mitophagy and has been shown to control adipose tissue browning and thermogenesis. Here the authors report that Parkin coordinates mitophagy with Pgc1α-mediated mitochondrial biogenesis in white adipocytes to regulate adiposity.

Investigation of variation in three cohorts has identified multiple genetic signals associated with the pregnancy-specific liver disorder, intrahepatic cholestasis of pregnancy, giving insight into the disease which can cause preterm birth and stillbirth.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Cryo-electron microscopy studies show that dynamic coordination of Na⁺ in the ion channel of Dispatched homologue 1 and the transmembrane Na⁺ gradient have key roles in exporting lipid-modified Hedgehog protein signal.

The role of impaired lung function in lung cancer etiology is complex due to the relation of cigarette smoking to both conditions. Here, supported by Mendelian randomization analysis the authors find a link between pulmonary function impairment and lung cancer risk beyond smoking, implicating immune-related pathways

A simple model of the tribulations of hostel shower systems highlights the benefits of human diversity, says Philip Ball.

Toll-like receptor 7 (TLR7) normally recognizes exogenous single-stranded RNA for the activation of innate immunity. Here the authors show that TLR7 may also contribute, via the modulation of mast cell functions, to experimental, cigarette smoke-induced mouse models of emphysema, thereby hinting TLR7 as a potential therapeutic target for human lung inflammation.

X-ray crystallography, cryo-EM and biochemical analysis provide insight into the assembly of the bacterial Gabija complex, an anti-phage system, and reveal how viruses can evade this defence mechanism.

Here, twisted boron nitride is demonstrated to be a versatile moiré substrate for band structure engineering.

Developing biointerfaces that combine the advantages of both monolithic and focal elements remains challenging. Now, a hydrogel that releases surface-modified granules and shows biointerface transition capability has been developed. This granule-releasing hydrogel manages colitis, accelerates wound healing, and facilitates cardiac tissue regeneration and mapping of cardiac activity with bioelectronic devices.

The 26S proteasome is a protein degradation machine composed of a 20S core particle (CP) flanked at one or both ends by a 19S ATPase regulatory particle (RP). Here the authors reconstitute asymmetric archaeal proteasomes and reveal allosteric coupling between the conformations of gates in the α-rings positioned at opposite ends of the CP, which modulates RP assembly and substrate entry.

Whole-genome sequencing analysis of individuals with primary immunodeficiency identifies new candidate disease-associated genes and shows how the interplay between genetic variants can explain the variable penetrance and complexity of the disease.

Exome-sequencing analyses of a large cohort of patients with type 2 diabetes and control individuals without diabetes from five ancestries are used to identify gene-level associations of rare variants that are associated with type 2 diabetes.

Heat from sliding rocks created pressure-cooker effect.

Antibody diversification relies on the intentional mutagenesis of immunoglobulin genes for adaptive immune responses. Here, the authors identified a CTLH E3 ubiquitin ligase complex that co-opts FAM72A to recruit and degrade the UNG2 base excision repair factor to permit mutagenesis.

Wastewater treatment plants are important reservoirs of antibiotic resistance genes (ARGs). Here, the authors analyze ARGs in a global collection of samples from wastewater treatment plants across six continents, providing insights into biotic and abiotic mechanisms that appear to control ARG diversity and distribution.

The genetic basis of atopic dermatitis is not fully understood. Here, the authors find 91 genetic loci associated with atopic dermatitis in a GWAS of >1million individuals, which highlight the importance of systemic immune regulation.