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PCNA–PAF15 has a key role in determining replisome dynamics during genome replication and protecting against genome instability.

This resource highlights the compositional and transcriptional remodelling of abdominal subcutaneous adipose tissue (SAT) in humans undergoing initial lifestyle-induced weight loss followed by bariatric surgery, with implications for modulating tissue function, systemic metabolism and inflammation.

Here they show that PPARα-dependent mitochondrial programming promotes the differentiation of pluripotent stem cell-derived β cells. Targeting mitochondria has the potential to improve β cell replacement efforts for the treatment of type 1 diabetes.

Batch integration is a critical yet challenging step in many single-cell RNA-seq analysis workflows. Here, authors present JOINTLY, a hybrid linear and non-linear NMF-based algorithm, providing interpretable and robust cell clustering against over-integration.

The antigen-B-cell-receptor interaction is the driving force of terminal B cell development that spans from B cell activation to antibody secreting plasma cells. Here authors determine, using DNA-PAINT super-resolution microscopy, how antigen affinity and valency define antigen binding to BCR in an in vitro system allowing precision control of these parameters.

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.

The authors combine tracking and body mass data from five migratory waterfowl species to understand their capacity to accelerate migration in response to earlier spring. They show considerable scope for faster migration by reducing the fuelling time before departure and subsequently on stopovers

Rare variant analyses identify a new type 2 diabetes risk allele near the LEP gene, which encodes leptin, and other risk alleles of intermediate penetrance in genes previously implicated in monogenic forms of diabetes.

An investigation of plant receptor-like kinases identifies regions of these proteins that control whether immune or symbiotic signalling pathways are activated, with minimal changes to specific residues in one of these regions being sufficient to alter signalling specificity.

The light concentrating properties of single p-i-n GaAs nanowires are shown to result in far greater photocurrent densities than expected under one sun illumination. The results suggest that such cells could in principle operate with power conversion efficiencies beyond the Shockley–Queisser limit.

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.

The authors present SVclone, a computational method for inferring the cancer cell fraction of structural variants from whole-genome sequencing data.

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.

Biologics are delivered by a pill that pricks the stomach wall.

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.

Non-active site mutations such as L50F are crucial for restoring the viral fitness of SARS-CoV-2 main protease. Here, the authors use full-length Mpro protein as substrate and demonstrate that L50F can promote the formation of enzyme-substrate complex and thus contribute to nirmatrelvir resistance.

Transcriptional and epigenomic profiling of osteoblast and adipocyte differentiation shows that adipogenesis is driven by de novo activation of enhancers, whereas osteogenesis involves preestablished enhancers and depends on the activation of pro-osteogenic and antiadipogenic transcription factors.

Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

High-throughput chromosome conformation enhancer capture identifies dynamic enhancer networks that regulate differentiation of human mesenchymal stem cells. Transcription factors (TFs) at baited enhancers appear to stabilize TF binding at target enhancers.

The authors demonstrate a holographic light engine enabling volumetric 3D printing with high precision and flexibility. Enhanced light projection efficiency and speckle noise mitigation enable rapid fabrication of millimetric objects, including soft cell-laden hydrogels, with 31 µm resolution.

Methicillin-resistant strains of Staphylococcus aureus appeared in European hedgehogs in the pre-antibiotic era as a co-evolutionary adaptation to antibiotic-producing dermatophytes and have spread within the local hedgehog populations and between hedgehogs and secondary hosts.

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.

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 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.

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.

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.

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.

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.

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.

In this work, the authors report NMR lipids Databank to promote decentralised sharing of biomolecular molecular dynamics (MD) simulation data with an overlay design. Programmatic access enables analyses of rare phenomena and advances the training of machine learning models.

Detection of circulating tumor DNA using MRD-EDGE, a machine-learning-guided single-nucleotide variant and copy-number variant detection platform for signal enrichment, enables monitoring of minimal residual disease and immunotherapy response in settings of low tumor burden.

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.

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.

Molecular analysis of archival formalin-fixed clinical tissues can be difficult. Here, researchers have developed MethCORR, an approach that infers gene expression from DNA methylation data and use the approach for molecular characterization and prognostication of colorectal cancer using archival samples.

Bioactive peptides regulate many physiological functions but progress in discovering them has been slow. Here, the authors use a machine learning framework to predict mammalian peptide candidates from the global and local structure of large-scale tissue-specific mass spectrometry data.

Peptide and oligonucleotide systems are known to self-assemble both in nature and artificial systems. Here, the authors combine both forms of self-assembly through the synthesis of peptideoligonucleotide conjugates and show formation of a three-helix structure that dimerises at higher concentrations.

β-Adrenergic signaling is a core regulator of brown adipocyte function. Here, the authors provide unbiased insight into the transcriptional network controlled by lipolysis in brown adipocytes, showing that lipolysis is required for much of the thermogenic gene program activated by β-adrenergic signals.

Synthetic polymer wires, which contain short oligonucleotides extending from each repeat, can assemble into predesigned routings on two- and three-dimensional DNA origami templates.