A5023984745- Tuberculosis Research and Epidemiology
- Mycobacterium research and diagnosis
- Single-cell and spatial transcriptomics
- Gene expression and cancer classification
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- Bioinformatics and Genomic Networks
- Scientific Computing and Data Management
- interferon and immune responses
- RNA and protein synthesis mechanisms
- Semantic Web and Ontologies
- vaccines and immunoinformatics approaches
- Distributed and Parallel Computing Systems
- Genomics and Rare Diseases
- Epigenetics and DNA Methylation
- Immune cells in cancer
- Cell Image Analysis Techniques
- Inflammatory Bowel Disease
- Retinal Development and Disorders
- Monoclonal and Polyclonal Antibodies Research
- Genomics and Phylogenetic Studies
- Pulmonary Hypertension Research and Treatments
- Genetics, Bioinformatics, and Biomedical Research
- Telomeres, Telomerase, and Senescence
- Molecular Biology Techniques and Applications
MRC Weatherall Institute of Molecular Medicine
2020-2025
University of Oxford
2017-2025
University College Dublin
2011-2021
Nuffield Orthopaedic Centre
2021
Imperial College London
2016-2020
Hammersmith Hospital
2016-2018
Forum of European National Highway Research Laboratories
2017
The Royal Free Hospital
2016
Newcastle University
2016
University College London
2016
Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to two major domestic extant cattle taxa, B. taurus and indicus. While previous genetic studies have shed some light on evolutionary relationships between European aurochs modern cattle, important questions remain unanswered, including phylogenetic status whether gene flow from into early populations occurred, which genomic regions were subject selection processes during after domestication. Here, we address these...
Abstract Current inflammatory bowel disease (IBD) therapies are ineffective in a high proportion of patients. Combining bulk and single-cell transcriptomics, quantitative histopathology situ localization across three cohorts patients with IBD (total n = 376), we identify coexpressed gene modules within the heterogeneous tissular response that map to distinct histopathological cellular features (pathotypes). One these pathotypes is defined by neutrophil infiltration, activation fibroblasts...
Background: Pulmonary arterial hypertension (PAH) is a heterogeneous disorder with high mortality. Methods: We conducted comprehensive study of plasma metabolites using ultraperformance liquid chromatography mass spectrometry to identify patients at risk early death, who respond well treatment, and provide novel molecular insights into disease pathogenesis. Results: Fifty-three circulating distinguished well-phenotyped idiopathic or heritable PAH (n=365) from healthy control subjects (n=121)...
Data exploration is critical to the comprehension of large biological data sets generated by high-throughput assays such as sequencing. However, most existing tools for interactive visualisation are limited specific or analyses. Here, we present iSEE (Interactive SummarizedExperiment Explorer) software package, which provides a general visual interface exploring in object. directly compatible with many R/Bioconductor packages analysing data, and useful features simultaneous examination...
Members of the Mycobacterium tuberculosis complex (MTBC) are causative agents in a range mammals, including humans. A key feature MTBC pathogens is their high degree genetic identity yet distinct host tropism. Notably, while bovis highly virulent and pathogenic for cattle, human pathogen M. attenuated cattle. Previous research also suggests that preference amongst members has basis innate immune responses. To explore tropism, we present in-depth profiling reference strains AF2122/97 H37Rv at...
The Mycobacterium tuberculosis complex (MTBC) is the collective term given to group of bacteria that cause (TB) in mammals. It has been reported M. H37Rv, a standard reference MTBC strain, attenuated cattle compared bovis. However, as H37Rv was isolated early 1930s, and genetic variants are known exist, we sought revisit this question attenuation for by performing bovine experimental infection with recent isolate. Here report using bovis AF2122/97, BTB1558, latter 2008 during TB surveillance...
Abstract Single-cell multiomic analysis of the epigenome, transcriptome, and proteome allows for comprehensive characterization molecular circuitry that underpins cell identity state. However, holistic interpretation such datasets presents a challenge given paucity approaches systematic, joint evaluation different modalities. Here, we present Panpipes, set computational workflows designed to automate multimodal single-cell spatial transcriptomic analyses by incorporating widely-used...
Bovine tuberculosis (BTB), caused by infection with Mycobacterium bovis, is a major endemic disease affecting cattle populations worldwide, despite the implementation of stringent surveillance and control programs in many countries. The development high-throughput functional genomics technologies, including gene expression microarrays RNA sequencing (RNA-seq), has enabled detailed analysis host transcriptome to M. bovis infection, particularly at macrophage peripheral blood level. In present...
Abstract Recent developments in experimental technologies such as single-cell RNA sequencing have enabled the profiling a high-dimensional number of genome-wide features individual cells, inspiring formation large-scale data generation projects quantifying unprecedented levels biological variation at level. The generated exhibits unique characteristics, including increased sparsity and scale, terms both samples. Due to these specialized statistical methods are required along with fast...
Mycobacterium bovis, the causative agent of bovine tuberculosis, is an intracellular pathogen that can persist inside host macrophages during infection via a diverse range mechanisms subvert immune response. In current study, we have analysed and compared transcriptomes M. bovis-infected monocyte-derived (MDM) purified from six Holstein-Friesian females with non-infected control MDM same animals over 24 h period using strand-specific RNA sequencing (RNA-seq). addition, compare gene...
Abstract Mycobacterium bovis , the agent of bovine tuberculosis, causes an estimated $3 billion annual losses to global agriculture due, in part, limitations current diagnostics. Development next-generation diagnostics requires a greater understanding interaction between pathogen and host. Therefore, explore early response alveolar macrophage infection, we report first application RNA-sequencing define, exquisite detail, transcriptomes M. -infected non-infected macrophages from ten calves at...
<ns3:p>Data organized into hierarchical structures (e.g., phylogenies or cell types) arises in several biological fields. It is therefore of interest to have data containers that store the structure together with profile data, and provide functions easily access manipulate at different resolutions. Here, we present TreeSummarizedExperiment, a R/S4 class extends commonly used SingleCellExperiment by incorporating tree representations rows and/or columns (represented objects phylo class)....
Modern biological research is increasingly data-intensive, leading to a growing demand for effective training in data science. In this article, we provide an overview of key resources and best practices available within the Bioconductor project - open-source software community focused on omics analysis. This guide serves as valuable reference both learners educators field.
<ns3:p>Data organized into hierarchical structures (e.g., phylogenies or cell types) arises in several biological fields. It is therefore of interest to have data containers that store the structure together with profile data, and provide functions easily access manipulate at different resolutions. Here, we present TreeSummarizedExperiment, a R/S4 class extends commonly used SingleCellExperiment by incorporating tree representations rows and/or columns (represented objects phylo class)....
Abstract Background Identification of gene expression profiles that differentiate experimental groups is critical for discovery and analysis key molecular pathways also selection robust diagnostic or prognostic biomarkers. While integration differential statistics has been used to refine set enrichment analyses, such approaches are typically limited single lists resulting from simple two-group comparisons time-series analyses. In contrast, functional class scoring machine learning provide...
Non-typhoidal Salmonella (NTS) are highly prevalent food-borne pathogens. Recently, a invasive, multi-drug resistant S. Typhimurium, ST313, emerged as major cause of bacteraemia in children and immunosuppressed adults, however the pathogenic mechanisms remain unclear. Here, we utilize invasive non-invasive strains combined with single-cell RNA-sequencing to study transcriptome individual infected bystander monocyte-derived dendritic cells (MoDCs) implicated disseminating ST313. Compared...
The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use control programmes against human tuberculosis (TB) and bovine (bTB). Identification potential epitopes recognised by CD4 + T cells requires prediction peptide binding to MHC class-II, obligatory prerequisite cell recognition. To comprehensively prioritise MHC-II-binding from Mycobacterium bovis , the agent bTB zoonotic TB humans, we integrated three methods with M. proteome using a...
Bovine tuberculosis, caused by infection with members of the Mycobacterium tuberculosis complex, particularly bovis , is a major endemic disease affecting cattle populations worldwide, despite implementation stringent surveillance and control programs in many countries. The development high-throughput functional genomics technologies, including RNA sequencing, has enabled detailed analysis host transcriptome to M. infection, at macrophage peripheral blood level. In present study, we have...
Mycobacterium abscessus (MAB) is an emerging pathogen causing pulmonary infections in those with inflammatory lung disorders, such as Cystic Fibrosis (CF), and associated the highest fatality rate among rapidly growing mycobacteria (RGM). Phenotypically, MAB manifests either a Smooth (MAB-S) or Rough (MAB-R) morphotype, which differ their levels of cell wall glycopeptidolipids (GPLs) pathogenicity vivo. As one primary immune cells encountered by MAB, we sought to examine early...