A5035568718- Molecular Biology Techniques and Applications
- Gene expression and cancer classification
- Evolution and Genetic Dynamics
- Chronic Disease Management Strategies
- Cancer Genomics and Diagnostics
- Crystallography and molecular interactions
- Cancer, Hypoxia, and Metabolism
- Epilepsy research and treatment
- Genomics and Phylogenetic Studies
- RNA modifications and cancer
- X-ray Diffraction in Crystallography
- Mathematical and Theoretical Epidemiology and Ecology Models
- Crystallization and Solubility Studies
- Genetic factors in colorectal cancer
- Pharmaceutical Practices and Patient Outcomes
- Epigenetics and DNA Methylation
- Evolutionary Game Theory and Cooperation
- Pharmacological Effects and Toxicity Studies
- Genomics and Chromatin Dynamics
- Prostate Cancer Treatment and Research
- Environmental DNA in Biodiversity Studies
- Plant and animal studies
- Adolescent and Pediatric Healthcare
- Chromosomal and Genetic Variations
- DNA Repair Mechanisms
University of Manchester
2019-2024
University of Liverpool
1997-2024
Cancer Research UK Manchester Institute
2017-2024
University of Dundee
2006-2019
Wellcome Trust
2011
RNA-seq is now the technology of choice for genome-wide differential gene expression experiments, but it not clear how many biological replicates are needed to ensure valid interpretation results or which statistical tools best analyzing data. An experiment with 48 in each two conditions was performed answer these questions and provide guidelines experimental design. With three replicates, nine 11 evaluated found only 20%-40% significantly differentially expressed (SDE) genes identified full...
Oxygen sensing revisited The cellular response to hypoxia (oxygen deficiency) is a contributing factor in many human diseases. Previous studies examining the way which alters gene expression have focused on oxygen-sensing enzymes that regulate activity of transcription called hypoxia-inducible (see Perspective by Gallipoli and Huntly). Chakraborty et al. Batie now show can also affect through direct effects chromatin regulators. Certain histone demethylases, such as KDM6A KDM5A, were found...
The nuclear space is mostly occupied by chromosome territories and bodies. Although this organization of chromosomes affects gene function, relatively little known about the role bodies in chromosomal regions. nucleolus best-studied subnuclear structure forms around rRNA repeat clusters on acrocentric chromosomes. In addition to rDNA, other chromatin sequences also surround nucleolar surface may even loop into nucleolus. These additional nucleolar-associated domains (NADs) have not been well...
The positioning of nucleosomes within the coding regions eukaryotic genes is aligned with respect to transcriptional start sites. This organization likely influence many genetic processes, requiring access underlying DNA. Here, we show that combined action Isw1 and Chd1 nucleosome-spacing enzymes required maintain this organization. In absence these enzymes, regular majority lost. Exceptions include region upstream promoter, +1 nucleosome, a subset locations distributed throughout where...
Throughout their lifetime, cells are subject to extrinsic and intrinsic mutational processes leaving behind characteristic signatures in the genome. DNA mismatch repair (MMR) deficiency leads hypermutation is found different cancer types. Although it possible associate extracted from human cancers with processes, exact causation often unknown. Here, we use
Within the genomes of metazoans, nucleosomes are highly organised adjacent to binding sites for a subset transcription factors. Here we have sought investigate which chromatin remodelling enzymes responsible this. We find that ATP-dependent enzyme SNF2H plays major role organising arrays architectural factor CTCF and acts promote binding. At many other related SNF2L contribute nucleosome organisation. The action at is functionally important as depletion or affects common group genes. This...
The increasing burden of multimorbidity and its socioeconomic gradient poses unique challenges to the provision structure health care. We aimed describe inequalities trends over time in prevalence, incidence, case fatality among adults all ages England using primary care electronic records.We used a random sample 991 243 individuals from Clinical Practice Research Datalink Aurum database registered at participating general practices within between Jan 1, 2004, Dec 31, 2019, linked 2015...
The small ubiquitin-like modifier 2 (SUMO-2) is required for survival when cells are exposed to treatments that induce proteotoxic stress by causing the accumulation of misfolded proteins. Exposure heat shock or other forms induces conjugation SUMO-2 proteins in nucleus. We investigated chromatin landscape modifications response stress. Through immunoprecipitation assays coupled high-throughput DNA sequencing and mRNA sequencing, we showed shock, accumulated at nucleosome-depleted, active...
Abstract Motivation: High-throughput RNA sequencing (RNA-seq) is now the standard method to determine differential gene expression. Identifying differentially expressed genes crucially depends on estimates of read-count variability. These are typically based statistical models such as negative binomial distribution, which employed by tools edgeR, DESeq and cuffdiff. Until now, validity these has usually been tested either low-replicate RNA-seq data or simulations. Results: A 48-replicate...
SCLC accounts for approximately 250,000 deaths worldwide each year. Acquisition of adequate tumor biopsy samples is challenging, and liquid biopsies present an alternative option patient stratification response monitoring.
The emergence of castration-resistant prostate cancer remains an area unmet clinical need. We recently identified a subpopulation normal progenitor cells, characterized by intrinsic resistance to androgen deprivation and expression LY6D. here demonstrate that conditional deletion PTEN in the murine epithelium causes expansion transformed LY6D+ cells without impairing stem cell properties. Transcriptomic analyses luminal autocrine positive feedback loop, based on secretion amphiregulin...
Abstract Background Polycystic ovary syndrome (PCOS) is associated with adverse clinical outcomes that may differ according to PCOS phenotype. Methods Using UK Biobank data, we compared the incidence of type 2 diabetes (T2D), metabolic dysfunction steatotic liver disease, cardiovascular disease (CVD), hormone-dependent cancers, and dementia between participants age- body mass index-matched controls. We also multiorgan (liver, cardiac, brain) magnetic resonance imaging (MRI) data examined...
Structured medication reviews (SMRs), introduced in the United Kingdom (UK) 2020, aim to enhance shared decision-making optimisation, particularly for patients with multimorbidity and polypharmacy. Despite its potential, there is limited empirical evidence on implementation of SMRs, challenges faced process. This study part a larger DynAIRx (Artificial Intelligence dynamic prescribing optimisation care integration multimorbidity) project which aims introduce Artificial (AI) SMRs develop...
All animals and plants are, to some extent, susceptible disease caused by varying combinations of parasites, viruses bacteria. In this paper, we present a mathematical model interactions between host, two parasitoids pathogen which shows that the presence an infection can preserve promote diversity in such multi-species systems. Initially, use system ordinary differential equations investigate species parasitoids, host infection. We show all four is necessary for as whole persist,...
We present a novel hybrid modelling framework that takes into account two aspects which have been largely neglected in previous models of spatial evolutionary games: random motion and chemotaxis. A stochastic individual-based model is used to describe the player dynamics, whereas evolution chemoattractant governed by reaction-diffusion equation. The are coupled deriving individual movement rules via discretisa- tion taxis-diffusion equation describes local number players. In this framework,...
Abstract Introduction Structured medication reviews (SMRs), introduced in the United Kingdom (UK) 2020, aim to enhance shared decision-making optimisation, particularly for patients with multimorbidity and polypharmacy. Despite its potential, there is limited empirical evidence on implementation of SMRs, challenges faced process. This study part a larger DynAIRx (Artificial Intelligence dynamic prescribing optimisation care integration multimorbidity) project which aims introduce Artificial...
Valproate is the most effective treatment for idiopathic generalised epilepsy. Currently, its use restricted in women of childbearing potential owing to high teratogenicity. Recent evidence extended this risk men's offspring, prompting recommendations restrict everybody aged <55 years. This study will evaluate mortality and morbidity risks associated with valproate withdrawal by emulating a hypothetical randomised-controlled trial (called "target trial") using retrospective observational...
Abstract The title of a journal paper offers crucial portal into any scientific field. It determines whether interested readers locate the and others have enough interest sparked to lead them read abstract. This article looks at authored titles in Medical Education over its first 50 years ( n = 6357) publication Teacher 35 publication, revealing both trends areas how those interests are worded. Word clouds per decade showed shift from teaching learning examination assessment, new foci on...
Summary 1. T‐RFLP is an established tool for high‐throughput studies of microbial communities, which can, with care and practical validation, be enhanced to aid identification specific organisms in a community by associating T‐RFs from experimental runs predicted set existing sequences. A barrier this approach the laborious process selecting diagnostic restriction enzyme(s) further validation. 2. Here, we describe directed terminal analysis (DRAT), software that aids design...