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Here the authors functionally test and resolve the spatial genome organization of cis-regulatory elements and genetic variants in atrial, ventricular, and failing human cardiomyocytes and linked them to heart disease traits, including QT syndrome.

Koina is an open-source, online platform that simplifies access to machine learning models in proteomics, enabling easier integration into analysis tools and helping researchers adopt and reuse ML models more efficiently.

A genome-wide study by the Long COVID Host Genetics Initiative identifies an association between the FOXP4 locus and long COVID, implicating altered lung function in its pathophysiology.

By combining left- and right-handed DNA-PAINT probes, Unterauer et al. achieve simple, robust, and highly multiplexed super-resolution. They show 13-plex neuronal maps, revealing nanoscale organization of cytoskeleton, organelles, and synapses.

Complex traits associate with genetic variation and environment and their interaction. Here, the authors study the influence of different diets on trait variability in 1154 outbred mice from an advanced intercross line and find gene-diet interactions associated with spontaneous autoimmunity development in these animals.

In this study, 591 mice from an advanced-intercross mouse line were used to provide evidence that fungi are regulated by host genetics, while uncovering a regulatory role of diet on the composition of fungi in the murine gut.

The nanoscale organization of the antigen-antibody complexes influences the therapeutic action of monoclonal antibodies. Here, the authors present a multi-target 3D RESI imaging assay for the nanometer spatial analysis of CD20 in complex with therapeutic monoclonal antibodies within intact cells, to analyse the interdependency between the mode of antibody binding and the therapeutic function.

In a phase 1/2a umbrella trial in patients with glioblastoma matching targeted therapies according to tumor molecular profiling, temsirolimus plus radiotherapy improved PFS compared to standard of care in patients with phospho-mTOR activation.

Cell fate choices, including developmental cell death, are often driven by asymmetric cell division, though what determinants drive these choices remain unclear. Here they show that the evolutionarily conserved CMG complex, best known for its role in unwinding DNA during chromosome replication, is also required for cell fate divergence during asymmetric cell divisions in C. elegans development.

Myocardin-related transcription factors (MRTFs) increase muscle growth and regeneration. Here, Hinkel et al. show that MRTFs also promote microvessel growth and maturation in chronic ischaemic disease of the heart or peripheral muscle by increasing the expression of the pro-angiongenic factors, CCN1 and CCN2.

Borna disease virus 1 (BoDV-1) is a zoonotic pathogen endemic in bicoloured white-toothed shrews in Central Europe that can cause fatal encephalitis in humans and other mammals. Here, the authors investigate the molecular epidemiology and phylogeography of BoDV-1 using newly collected and archived samples.

Multiomic factor analysis of blood multiomic data, including single-cell transcriptomics, for individuals with either acute or chronic coronary syndrome identifies immune cell signatures that correlate with treatment outcomes.

Infection with SARS-COV-2 can result in self-limited upper airway infection or progress to a more systemic inflammatory condition including pneumonic COVID-19. Here the authors utilise a multi-omics approach to interrogate the immune response of patients with self-limiting upper respiratory SARS-CoV-2 infection and reveal a temporal immune trajectory they associate with viral containment and restriction from pneumonic progressive disease.

Integrin-linked kinase (ILK) is an important mediator of integrin signaling. Here Park et al. show that mice with endothelial-specific deletion of Ilk develop vascular defects that resemble familial exudative vitreoretinopathy, and identify mutations in ILK in patients with exudative vitreoretinopathy suggesting a potential role in human pathogenesis.

Extracting quantitative information on biomolecular oligomerisation with high resolution remains a significant challenge. Here, the authors propose SPINNA, a framework that compares nearest-neighbour distances from experimental single-protein position data with those obtained from simulations based on a model of protein oligomerisation.

Understanding how biosilica forms is crucial to our knowledge of this important biomaterial. Now, the role of collagen as structuring agent for the metre-long spicules of a primitive glass sponge has been revealed and found to have an unusual peptide motif.

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.

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.

By combining bioorthogonal metabolic labelling and resolution enhancement through sequential imaging of DNA barcodes, the molecular organization of individual sugars in the native glycocalyx has been resolved at a spatial resolution of 9 ångström.

This work finds a systematic offset of 5.5 ± 1.1 Myr between estimates of the ages of stars made with two popular techniques: isochronal fitting and dynamical traceback. This offset is proposed to represent the time a young star remains bound to its parental cloud before dispersing and could help to improve stellar evolutionary models.

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.

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.

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.

Steve Brown and colleagues report an analysis of 20 phenotyping tests, including 413 data parameters, across 449 mutant mouse alleles. They identify widespread pleiotropy and assign putative functions to genes that lacked previous phenotypic annotation.

Crystal structures of a localization element of ASH1 mRNA alone, in complex with its nuclear shuttling protein She2p, and in the cytoplasmic complex with She2p and She3p reveal a step-wise maturation pathway.

The human leukocyte antigen (HLA) haplotype DRB1*15:01 is the major risk factor for multiple sclerosis (MS).  Here the authors find that DNA methylation at HLA-DRB1 gene mediates the effect of DRB1*15:01 and of a protective HLA variant on HLA-DRB1 expression and the risk of MS.

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.

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.

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.

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.

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.

Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.