A5005082169- Single-cell and spatial transcriptomics
- Gene Regulatory Network Analysis
- Epigenetics and DNA Methylation
- Statistical Methods and Inference
- Gene expression and cancer classification
- Cell Image Analysis Techniques
- Chronic Disease Management Strategies
- Acute Myocardial Infarction Research
- Statistical Methods and Bayesian Inference
- Cardiac Imaging and Diagnostics
- Higher Education Research Studies
- Inflammatory Bowel Disease
- Bayesian Methods and Mixture Models
- Advanced Biosensing Techniques and Applications
- Bioinformatics and Genomic Networks
- Machine Learning in Healthcare
- Intergenerational Family Dynamics and Caregiving
- Birth, Development, and Health
- Cancer Genomics and Diagnostics
- Health disparities and outcomes
- Genetic Associations and Epidemiology
- Healthcare Policy and Management
- Liver Disease Diagnosis and Treatment
- Health Systems, Economic Evaluations, Quality of Life
- RNA Research and Splicing
Institute of Genetics and Cancer
2018-2025
University of Edinburgh
2018-2025
The Alan Turing Institute
2017-2025
Medical Research Council
2017-2025
Turing Institute
2017-2024
Western General Hospital
2018-2023
British Library
2017-2023
Christchurch Hospital
2022
British Heart Foundation
2022
National Institute for Health Research
2022
High-sensitivity cardiac troponin assays permit use of lower thresholds for the diagnosis myocardial infarction, but whether this improves clinical outcomes is unknown. We aimed to determine introduction a high-sensitivity I (hs-cTnI) assay with sex-specific 99th centile diagnostic threshold would reduce subsequent infarction or cardiovascular death in patients suspected acute coronary syndrome.In stepped-wedge, cluster-randomised controlled trial across ten secondary tertiary care hospitals...
Single-cell sequencing of mouse immune cells reveals how aging destabilizes a conserved transcriptional activation program.
Single-cell mRNA sequencing can uncover novel cell-to-cell heterogeneity in gene expression levels seemingly homogeneous populations of cells. However, these experiments are prone to high unexplained technical noise, creating new challenges for identifying genes that show genuine heterogeneous within the population cells under study. BASiCS (Bayesian Analysis Single-Cell Sequencing data) is an integrated Bayesian hierarchical model where: (i) cell-specific normalisation constants estimated...
Background: The introduction of more sensitive cardiac troponin assays has led to increased recognition myocardial injury in acute illnesses other than coronary syndrome. Universal Definition Myocardial Infarction recommends high-sensitivity testing and classification patients with based on pathogenesis, but the clinical implications implementing this guideline are not well understood. Methods: In a stepped-wedge cluster randomized, controlled trial, we implemented assay recommendations 48...
Abstract Background Epigenetic clocks can track both chronological age (cAge) and biological (bAge). The latter is typically defined by physiological biomarkers risk of adverse health outcomes, including all-cause mortality. As cohort sample sizes increase, estimates cAge bAge become more precise. Here, we aim to develop accurate epigenetic predictors bAge, whilst improving our understanding their epigenomic architecture. Methods First, perform large-scale ( N = 18,413) epigenome-wide...
Abstract The liver has a unique ability to regenerate 1,2 ; however, in the setting of acute failure (ALF), this regenerative capacity is often overwhelmed, leaving emergency transplantation as only curative option 3–5 . Here, advance understanding human regeneration, we use paired single-nucleus RNA sequencing combined with spatial profiling healthy and ALF explant livers generate single-cell, pan-lineage atlas regeneration. We uncover novel ANXA2 + migratory hepatocyte subpopulation, which...
Traditional differential expression tools are limited to detecting changes in overall expression, and fail uncover the rich information provided by single-cell level data sets. We present a Bayesian hierarchical model that builds upon BASiCS study lie beyond comparisons of means, incorporating built-in normalization quantifying technical artifacts borrowing from spike-in genes. Using probabilistic approach, we highlight genes undergoing cell-to-cell heterogeneity but whose remains unchanged....
Cell-to-cell transcriptional variability in otherwise homogeneous cell populations plays an important role tissue function and development. Single-cell RNA sequencing can characterize this a transcriptome-wide manner. However, technical variation the confounding between mean expression estimates hinder meaningful comparison of populations. To address problem, we introduce analysis approach that extends BASiCS statistical framework to derive residual measure is not confounded by expression....
Abstract Single-cell RNA-seq reveals the role of pathogenic cell populations in development and progression chronic diseases. In order to expand our knowledge on cellular heterogeneity, we have developed a single-nucleus RNA-seq2 method tailored for comprehensive analysis nuclear transcriptome from frozen tissues, allowing dissection all types present liver, regardless size or fragility. We use this approach characterize transcriptional profile individual hepatocytes with different levels...
Abstract Alcohol consumption is an important risk factor for multiple diseases. It typically assessed via self-report, which open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used derive a more objective measure of alcohol by incorporating information from cytosine-phosphate-guanine (CpG) sites known linked the trait. Here, we explore epigenetic architecture self-reported weekly units in Generation Scotland study. We...
Abstract The myelinated white matter tracts of the central nervous system (CNS) are essential for fast transmission electrical impulses and often differentially affected in human neurodegenerative diseases across CNS region, age sex. We hypothesize that this selective vulnerability is underpinned by physiological variation glia. Using single nucleus RNA sequencing post-mortem samples from brain, cerebellum spinal cord subsequent tissue-based validation we found substantial glial...
Type 2 diabetes mellitus (T2D) presents a major health and economic burden that could be alleviated with improved early prediction intervention. While standard risk factors have shown good predictive performance, we show the use of blood-based DNA methylation information leads to significant improvement in 10-year T2D incidence risk. Previous studies been largely constrained by linear assumptions, cytosine–guanine pairs one-at-a-time binary outcomes. We present flexible approach (via an R...
Despite poor cardiovascular outcomes, there are no dedicated, validated risk stratification tools to guide investigation or treatment in type 2 myocardial infarction. The goal of this study was derive and validate a tool for the prediction death future infarction patients with T2-risk score developed prospective multicenter cohort consecutive Cox proportional hazards models were constructed primary outcome at 1 year using variables selected priori based on clinical importance. Discrimination...
The benefit and utility of high-sensitivity cardiac troponin (hs-cTn) in the diagnosis myocardial infarction patients with kidney impairment is unclear. Here, we describe implementation hs-cTnI testing on diagnosis, management, outcomes without impairment. Consecutive suspected acute coronary syndrome enrolled a stepped-wedge, cluster-randomized controlled trial were included this pre-specified secondary analysis. Kidney was defined as an eGFR under 60mL/min/1.73m
Abstract Background Despite major advances in our understanding of the molecular underpinning IBD, we remain challenged deciphering observed disease heterogeneity. Attempts to characterise longitudinal behaviour have either been restricted symptom-based profiling - as exemplified IBSEN cohorts or reliance on stochastic endpoints “progression” such hospitalisation, surgery and fibrosis. Here present a novel method examine IBD by modelling inflammatory patterns two large, well-characterised...
High-throughput single-cell measurements of DNA methylomes can quantify methylation heterogeneity and uncover its role in gene regulation. However, technical limitations sparse coverage preclude this task. scMET is a hierarchical Bayesian model which overcomes sparsity, sharing information across cells genomic features to robustly genuine biological heterogeneity. identify highly variable that drive epigenetic heterogeneity, perform differential variability analyses. We illustrate how...
Summary Dropouts and delayed graduations are critical issues in higher education systems world wide. A key task this context is to identify risk factors associated with these events, providing potential targets for mitigating policies. For this, we employ a discrete time competing risks survival model, dealing simultaneously university outcomes its temporal component. We define times as the duration of student's enrolment at possible graduation or two types dropout (voluntary involuntary),...
Survival models such as the Weibull or log-normal lead to inference that is not robust presence of outliers. They also assume all heterogeneity between individuals can be modeled through covariates. This article considers use infinite mixtures lifetime distributions a solution for these two issues. interpreted introduction random effect in survival distribution. We introduce family shape distributions, which covers wide range density and hazard functions. Bayesian under nonsubjective priors...
The progressive nature of Crohn's disease is highly variable and hard to predict. In addition, symptoms correlate poorly with mucosal inflammation. There therefore an urgent need better characterize the heterogeneity trajectories in by utilizing objective markers We aimed understand this clustering patients similar longitudinal fecal calprotectin profiles.We performed a retrospective cohort study at Edinburgh IBD Unit, tertiary referral center, used latent class mixed models cluster subjects...