7,874 results match your criteria: "Sanger Institute[Affiliation]"
J Pathol
December 2024
Department of Pathology and Molecular Pathology, University Hospital and University of Zurich, Zurich, Switzerland.
Tumour content plays a pivotal role in directing the bioinformatic analysis of molecular profiles such as copy number variation (CNV). In clinical application, tumour purity estimation (TPE) is achieved either through visual pathological review [conventional pathology (CP)] or the deconvolution of molecular data. While CP provides a direct measurement, it demonstrates modest reproducibility and lacks standardisation.
View Article and Find Full Text PDFCell Rep
December 2024
Department of Biochemistry, University of Cambridge, Cambridge CB2 1QW, UK. Electronic address:
Pseudomonas aeruginosa produces a wealth of virulence factors whose production is controlled via an intricate regulatory systems network. Here, we uncover a major player in the evolution and regulation of virulence that enhances host colonization and antibiotic resistance. By characterizing a collection of mutants lacking the stringent response (SR), a system key for virulence, we show that the loss of the central regulator MexT bypasses absence of the SR, restoring full activation of virulence pathways.
View Article and Find Full Text PDFAm J Hum Genet
December 2024
Division of Evolution, Infection and Genomics, School of Biological Sciences, the University of Manchester, Manchester M13 9PL, UK; Manchester Centre for Genomic Medicine, St Mary's Hospital, the University of Manchester NHS Foundation Trust, Manchester M13 9WL, UK. Electronic address:
The mitochondrial ribosome (mitoribosome) synthesizes 13 protein subunits of the oxidative phosphorylation system encoded by the mitochondrial genome. The mitoribosome is composed of 12S rRNA, 16S rRNA, and 82 mitoribosomal proteins encoded by nuclear genes. To date, variants in 12 genes encoding mitoribosomal proteins are associated with rare monogenic disorders and frequently show combined oxidative phosphorylation deficiency.
View Article and Find Full Text PDFGenome Biol
December 2024
Group Genome Instability in Tumors, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Single-cell DNA sequencing (scDNA-seq) enables decoding somatic cancer variation. Existing methods are hampered by low throughput or cannot be combined with transcriptome sequencing in the same cell. We propose HIPSD&R-seq (HIgh-throughPut Single-cell Dna and Rna-seq), a scalable yet simple and accessible assay to profile low-coverage DNA and RNA in thousands of cells in parallel.
View Article and Find Full Text PDFSci Data
December 2024
Rothamsted Research, Protecting Crops and the Environment, Harpenden, UK.
Alopecurus aequalis is a winter annual or short-lived perennial bunchgrass which has in recent years emerged as the dominant agricultural weed of barley and wheat in certain regions of China and Japan, causing significant yield losses. Its robust tillering capacity and high fecundity, combined with the development of both target and non-target-site resistance to herbicides means it is a formidable challenge to food security. Here we report on a chromosome-scale assembly of A.
View Article and Find Full Text PDFHeart
December 2024
Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.
Background: Deterioration of the cardiac conduction system is an important manifestation of cardiac ageing. Cellular ageing is accompanied by telomere shortening and telomere length (TL) is often regarded as a marker of biological ageing, potentially adding information regarding conduction disease over and above chronological age. We therefore sought to evaluate the association between leucocyte telomere length (LTL) on two related, but distinct aspects of the cardiac conduction system: ECG measures of conduction (PR interval and QRS duration) and incident pacemaker implantation in a large population-based cohort.
View Article and Find Full Text PDFNat Rev Microbiol
December 2024
APC Microbiome Ireland, University College Cork, Cork, Ireland.
Nat Neurosci
December 2024
Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.
medRxiv
December 2024
Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA.
Genetic mutations that yield defective cystic fibrosis transmembrane regulator () protein cause cystic fibrosis, a life-limiting autosomal recessive Mendelian disorder. A protective role of loss-of-function mutations in inflammatory bowel disease (IBD) has been suggested, but its evidence has been inconclusive and contradictory. Here, leveraging the largest IBD exome sequencing dataset to date, comprising 38,558 cases and 66,945 controls in the discovery stage, and 35,797 cases and 179,942 controls in the replication stage, we established a protective role of CF-risk variants against IBD based on evidence from the association test of delF508 (p-value=8.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Institute of Parasitology, Justus Liebig University, Schubertstrasse 81, 35392 Giessen, Germany.
Studies on transcription regulation in platyhelminth development are scarce, especially for parasitic flatworms. Here, we employed single-cell transcriptomics to identify genes involved in reproductive development in the trematode model Schistosoma mansoni. This parasite causes schistosomiasis, a major neglected infectious disease affecting >240 million people worldwide.
View Article and Find Full Text PDFLancet Oncol
December 2024
Department of Haematology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK; Faculty of Health, Medicine, and Social Care, Anglia Ruskin University, Cambridge, UK; Department of Haematology, University of Cambridge, Cambridge, UK. Electronic address:
Background: Procarbazine-containing chemotherapy regimens are associated with cytopenias and infertility, suggesting stem-cell toxicity. When treating Hodgkin lymphoma, procarbazine in escalated-dose bleomycin-etoposide-doxorubicin-cyclophosphamide-vincristine-procarbazine-prednisolone (eBEACOPP) is increasingly replaced with dacarbazine (eBEACOPDac) to reduce toxicity. We aimed to investigate the impact of this drug substitution on the mutation burden in stem cells, patient survival, and toxicity.
View Article and Find Full Text PDFNucleic Acids Res
December 2024
Open Targets, Wellcome Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UK.
The Open Targets Platform (https://platform.opentargets.org) is a unique, open-source, publicly-available knowledge base providing data and tooling for systematic drug target identification, annotation, and prioritisation.
View Article and Find Full Text PDFMol Biol Evol
December 2024
Institut des Sciences de l'Evolution de Montpellier, ISEM, Univ Montpellier, CNRS, IRD, EPHE, Montpellier, France.
Cartilaginous fishes (chondrichthyans: chimaeras and elasmobranchs -sharks, skates and rays) hold a key phylogenetic position to explore the origin and diversifications of jawed vertebrates. Here, we report and integrate reference genomic, transcriptomic and morphological data in the small-spotted catshark Scyliorhinus canicula to shed light on the evolution of sensory organs. We first characterise general aspects of the catshark genome, confirming the high conservation of genome organisation across cartilaginous fishes, and investigate population genomic signatures.
View Article and Find Full Text PDFNucleic Acids Res
November 2024
The Arctic University Museum of Norway, UiT - The Arctic University of Norway, Lars Thørings veg 10, 9006 Tromsø, Norway.
We present a major update of MirGeneDB (3.0), the manually curated animal microRNA gene database. Beyond moving to a new server and the creation of a computational mirror, we have expanded the database with the addition of 33 invertebrate species, including representatives of 5 previously unsampled phyla, and 6 mammal species.
View Article and Find Full Text PDFNat Methods
December 2024
Department of Computational Health, Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.
The rapid adoption of single-cell technologies has created an opportunity to build single-cell 'atlases' integrating diverse datasets across many laboratories. Such atlases can serve as a reference for analyzing and interpreting current and future data. However, it has become apparent that atlasing approaches differ, and the impact of these differences are often unclear.
View Article and Find Full Text PDFNat Neurosci
December 2024
F.M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA.
Genet Med Open
January 2024
Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom.
Purpose: Structural variants such as multiexon deletions and duplications are an important cause of disease but are often overlooked in standard exome/genome sequencing analysis. We aimed to evaluate the detection of copy-number variants (CNVs) from exome sequencing (ES) in comparison with genome-wide low-resolution and exon-resolution chromosomal microarrays (CMAs) and to characterize the properties of de novo CNVs in a large clinical cohort.
Methods: We performed CNV detection using ES of 9859 parent-offspring trios in the Deciphering Developmental Disorders (DDD) study and compared them with CNVs detected from exon-resolution array comparative genomic hybridization in 5197 probands from the DDD study.
Cancer Discov
December 2024
Wellcome Trust Sanger Institute, Cambridgeshire, United Kingdom.
Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumourigenesis.
View Article and Find Full Text PDFWellcome Open Res
October 2024
Tree of Life, Wellcome Sanger Institute, Hinxton, England, UK.
Wellcome Open Res
November 2024
University of Ghent, Ghent, Belgium.
We present a genome assembly from an individual male ichneumonid wasp, (Arthropoda; Insecta; Hymenoptera; Ichneumonidae). The genome sequence has a total length of 270.30 megabases.
View Article and Find Full Text PDFNat Biomed Eng
December 2024
Translational Pancreatic Cancer Research Center, Klinik und Poliklinik für Innere Medizin II, Klinikum rechts der Isar, Technical University of Munich, München, Germany.
In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.
View Article and Find Full Text PDFWellcome Open Res
November 2024
Butterfly Conservation Scotland, Stirling, Scotland, UK.
We present a genome assembly from an individual female (the Scalloped Hook-tip; Arthropoda; Insecta; Lepidoptera; Drepanidae). The genome sequence has a total length of 300.20 megabases.
View Article and Find Full Text PDFLancet Microbe
November 2024
Department of Mathematics and Statistics University of Helsinki, Helsinki, Finland; Department of Biostatistics, University of Oslo, Oslo, Norway; Wellcome Sanger Institute, Hinxton, UK; Department of Genetics, University of Cambridge, Cambridge, UK. Electronic address:
Biomedical research has implicated the bacterial metabolite colibactin as a causal risk factor for several cancer types, in particular, colorectal cancer. Colibactin has been known to drive tumorigenesis by inducing double-strand breaks in the DNA of epithelial cells exposed to colibactin-producing bacteria. Some phylogroup B2 Escherichia coli secrete colibactin during interbacterial warfare, concomitantly exposing the host to an increasing risk of DNA damage.
View Article and Find Full Text PDFCommun Biol
December 2024
BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Iron homoeostasis is tightly regulated, with hepcidin and soluble transferrin receptor (sTfR) playing significant roles. However, the genetic determinants of these traits and the biomedical consequences of iron homoeostasis variation are unclear. In a meta-analysis of 12 cohorts involving 91,675 participants, we found 43 genomic loci associated with either hepcidin or sTfR concentration, of which 15 previously unreported.
View Article and Find Full Text PDFWellcome Open Res
November 2024
University of Oxford, Oxford, England, UK.