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Generalizable Pathology Foundation Model (GPFM) consolidates expertise from a variety of existing models for use in a broad spectrum of computational pathology tasks.

Tetrandrine is one of the most potent inhibitors of Ebola Virus infection. Here the authors identify LIMP-2 as a direct cellular target of Tetrandrine and establish a functional connection between lysosomal sphingosine homeostasis and calcium regulation.

Here, the authors perform plaque reduction neutralization (PRNT) assays quantitating SARS-CoV-2 specific neutralizing antibodies from 195 patients in different disease states and find that patients with severe disease exhibit higher peaks of neutralizing antibody titres than patients with mild or asymptomatic infections and that serum neutralizing antibody persists for over 6 months in most people.

An analysis of data from the Sherlock-Lung study provides insight into the mutational processes that contribute to lung cancer in never smokers, and looks at the possible role of factors such as air pollution and passive smoking.

PAPD5 is responsible for adenylation of microRNAs. Here, the authors show that elevated level of PAPD5 enhances the adenylation and reduced expression of miR-7-5p. As a result, expression of TAB2, a target of miR-7-5p, is induced triggering neuronal apoptosis in Huntington’s disease.

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.

Machine learning prediction of electronic structure remains a general challenge. Here, the authors have developed a model with high accuracy and transferability by treating the electron density as a 3D greyscale image and adapting techniques from the image super-resolution computer vision field.

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.

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.

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.

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.

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.

Stereotactic needle biopsies are currently performed for diagnosis only in glioblastoma; this study highlights the depth of information available through multi-omics analysis.

The authors present a 3D map of nearly all cells in C. elegans embryos, revealing how cell shape, size, and fate change over time. They show how Notch and Wnt signaling, along with mechanical forces, influence development, including organ formation.

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.

Coronaviruses exploit the host caspase-6 to cleave coronavirus nucleocapsid protein into fragments with interferon-antagonizing activity to facilitate virus replication.

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.

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.

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.

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.

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.

There hasn’t been much experimental attention to the interaction of chiral active particles with complex environments. Chan et al. propose an interesting granular particle system based on natural plant seeds to examine the transport of chiral active matter in complex surroundings.

The anti-leprosy drug clofazimine inhibits coronavirus replication in several cell models and shows potent antiviral activity against SARS-CoV-2 infection in a hamster model, particularly when used in combination with remdesivir.

Here, using lung epithelial cells and ex vivo tissue explants, the authors show that, in addition to ACE2, host heparan sulfate is directly involved in SARS-CoV-2 attachment and entry and provide data suggesting that host sialic acids may act as viral restriction factor in lung tissues.

The authors present a material-specific ab initio understanding of doped cuprates. Their method correctly captures two known experimental trends: the pressure effect, where the pairing order and gap increase with intra-layer pressure, and the layer effect, where the pairing order and gap vary with the number of copper-oxygen layers.

Viruses rely on host cell metabolism for replication, making these pathways potential therapeutic targets. Here, the authors show that AM580, a retinoid derivative and RAR-α agonist, affects replication of several RNA viruses by interfering with the activity of SREBP.

Metabolomics data quality is limited by ion suppression effects. Here, the authors present an IROA-based workflow that corrects these issues across diverse analytical conditions and reveals previously unknown metabolic changes in cancer therapy.

Generative AI holds promise for creating novel compounds. Here, authors introduce TamGen, a GPT-like model designed to generate molecules tailored to specific target proteins. TamGen identified 14 potent compounds against the Tuberculosis ClpP protease, showing its potential for drug discovery.

Structural variations (SV) contribute to inter-individual variability. Here, the authors describe a first-generation multi-ancestry Asian SV catalogue containing 73,035 SVs from 8392 Singaporeans to provide insights into Asian SV diversity.

In a previous study, the authors developed a next-generation sequencing-based method for tracking SARS-CoV-2 infection dynamics. Here, they describe integration of this technology into a clinical pipeline and use it to describe the dynamics of SARS-CoV-2 variants in Toronto, Canada from 2020 to 2023.

Somatic mutational loads in cancer genomes change with chromatin domain boundaries. Different mutational processes lead to distinct somatic mutation distributions in active versus inactive domains, including during tumor evolution.

The second Global Amphibian Assessment finds that the status of amphibians is continuing to deteriorate globally, driven predominantly by climate change, disease and habitat loss.

Using deep single-nucleus multi-omics profiling, Fink et al. report transition states between crypt epithelial cells and a revival stem cell lineage. They find that the TGFβ and Hippo signalling pathways cooperatively drive intestinal regeneration.

The mechanisms allowing early disseminated cancer cells colonize other tissues remain largely unknown. Here, authors show that GPRC5A axis drives esophageal squamous cell carcinoma lung seeding and metastasis, in a mechanism resembling trophoblast behavior during embryo implantation.

Immune lymphocyte estimation from nucleotide sequencing (ImmuneLENS) infers B cell and T cell fractions from whole-genome sequencing data. Applied to the 100,000 Genomes Project datasets, circulating T cell fraction provides sex-dependent and prognostic insights in patients.

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.

Analysing data from seven countries, this study found that unmarried individuals had a higher depression risk than married individuals. This risk was higher in Western countries, among males and among those with higher educational attainment.