A5047139968- Epigenetics and DNA Methylation
- Health, Environment, Cognitive Aging
- Genomics and Chromatin Dynamics
- Birth, Development, and Health
- Machine Learning in Healthcare
- Alzheimer's disease research and treatments
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Artificial Intelligence in Healthcare and Education
- Genetic Syndromes and Imprinting
- Nuclear Receptors and Signaling
- Dementia and Cognitive Impairment Research
- Cancer-related gene regulation
- Diet and metabolism studies
- Genetic Associations and Epidemiology
- Bioinformatics and Genomic Networks
- Prenatal Screening and Diagnostics
- Biomedical Text Mining and Ontologies
- Child Welfare and Adoption
- RNA Research and Splicing
- Hematopoietic Stem Cell Transplantation
- Child Development and Digital Technology
- Eating Disorders and Behaviors
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
UK Dementia Research Institute
2020-2024
Imperial College London
2020-2024
King's College London
2016-2024
Neuroscience Institute
2024
Queen Mary University of London
2018-2022
South London and Maudsley NHS Foundation Trust
2018
Objective: DNA methylation has been proposed as an epigenetic mechanism by which early-life experiences become “embedded” in the genome and alter transcriptional processes to compromise health. The authors sought investigate whether victimization stress is associated with genome-wide methylation. Method: tested hypothesis that Environmental Risk (E-Risk) Longitudinal Study, a nationally representative 1994–1995 birth cohort of 2,232 twins born England Wales assessed at ages 5, 7, 10, 12, 18...
Abstract Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental physical health problems across the lifespan. Although mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied impact of early-life adversity on variation a sample adolescents adopted from severely depriving orphanages Romanian communist era 1980s....
Abstract Background Ribosomal DNA (rDNA) displays substantial inter-individual genetic variation in human and mouse. A systematic analysis of how this impacts epigenetic states expression the rDNA has thus far not been performed. Results Using a combination long- short-read sequencing, we establish that 45S units C57BL/6J mouse strain exist as distinct haplotypes influence state transcriptional output any given unit. methylation dynamics at these are dichotomous life-stage specific: one...
An inversion polymorphism at the 17q21.31 locus defines H1 and H2 haplotypes, with former linked to multiple neurodegenerative disorders, including an increased risk of Parkinson's disease (PD). Although high linkage disequilibrium this has made it difficult decipher which gene(s) drive PD association, there is increasing evidence support role KANSL1 as a gene. been shown regulate expression some PD-associated genes pathways, likely part histone acetylating non-specific lethal (NSL) complex....
Abstract DNA-protein interactions have traditionally been profiled via chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq). Cleavage Under Targets & Tagmentation (CUT&Tag) is a rapidly expanding technique that enables the profiling of such in situ at high sensitivity. However, thorough evaluation and benchmarking against established ChIP-seq datasets are lacking. Here, we comprehensively benchmarked CUT&Tag for H3K27ac H3K27me3 published profiles from...
While DNA methylation is usually thought to be symmetrical across both alleles, there are some notable exceptions. Genomic imprinting and X chromosome inactivation two well-studied sources of allele-specific (ASM), but recent research has indicated a more complex pattern in which genotypic variation can associated with allelically-skewed cis. Given the known heterogeneity tissues cell types we explored inter- intra-individual ASM several regions human brain whole blood from multiple...
Most variants associated with complex phenotypes in genome-wide association studies (GWAS) do not directly index coding changes affecting protein structure. Instead they are hypothesized to influence gene regulation, common disease being enriched regulatory domains including enhancers and regions of open chromatin. There is interest, therefore, using epigenomic annotation data identify the specific mechanisms involved prioritize risk variants. We quantified lysine H3K27 acetylation (H3K27ac)...
Several epigenome-wide association studies of DNA methylation have highlighted altered in the ANK1 gene Alzheimer's disease (AD) brain samples. However, no study has specifically examined histone modifications disease. We use chromatin immunoprecipitation-qPCR to quantify tri-methylation at 3 lysine 4 (H3K4me3) and 27 (H3K27me3) entorhinal cortex from donors with high (n = 59) or low 29) pathology. demonstrate decreased levels H3K4me3, a marker active transcription, change H3K27me3, inactive...
Allogeneic hematopoietic cell transplantation (HCT) is used to treat many blood-based disorders and malignancies, however it can also result in serious adverse events, such as the development of acute graft-versus-host disease (aGVHD). This study aimed develop a donor-specific epigenetic classifier reduce incidence aGVHD by improving donor selection. Genome-wide DNA methylation was assessed discovery cohort 288 HCT donors selected based on recipient outcome; this consisted 144 cases with...
Abstract Female mammals achieve dosage compensation by inactivating one of their two X chromosomes during development, a process entirely dependent on Xist , an X-linked long non-coding RNA (lncRNA). At the onset chromosome inactivation (XCI), is up-regulated and spreads along future inactive chromosome. Contextually, it recruits repressive histone DNA modifiers that transcriptionally silence regulation tightly coupled to differentiation its expression under control both pluripotency...
Epidemiological research suggests that paternal obesity may increase the risk of fathering small for gestational age offspring. Studies in non-human mammals indicate such associations could be mediated by DNA methylation changes spermatozoa influence offspring development utero. Human is associated with differential peripheral blood. It unclear, however, whether this reflected spermatozoa. We profiled genome-wide using Illumina MethylationEPIC array a cross-sectional study matched human...
Abstract Techniques for genome-wide epigenetic profiling have been undergoing rapid development toward recovery of high quality data from bulk and single cell samples. DNA-protein interactions traditionally profiled via chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq), which has become the current standard studying histone modifications or transcription factor binding. Cleavage Under Targets & Tagmentation (CUT&Tag) is a promising new technique, enables...
Abstract To understand the complex relationship between histone mark activity and gene expression, recent advances have used in silico predictions based on large-scale machine learning models. However, these approaches omitted key contributing factors like cell state, function or distal effects, that impact relationship, limiting their findings. Moreover, downstream use of models for new biological insight is lacking. Here, we present most comprehensive study this to date - investigating...
Abstract Astrocyte morphology in vivo is heterogeneous across different subtypes and dynamically changes response to various stimuli. However, several questions on the mechanistic links between shape function remain unanswered. Here, we developed an efficient protocol generate pure populations of morphologically distinct human astrocytes vitro , which used for a systematic analysis shape-function relationships. We performed structural, molecular, functional characterization these highlighted...
Environmental influences fluctuate throughout the life course of an organism. It is therefore important to understand how timing exposure impacts molecular responses. Herein, we examine responses two key markers dietary stress, namely variant-specific methylation at ribosomal DNA (rDNA) and small RNA distribution, including tRNA fragments, in a mouse model protein restriction (PR) with pre- and/or post-weaning. We first confirm that pre-weaning PR modulates state rDNA genotype-dependent...
Abstract Acetylation of histone H3 lysine 27 (H3K27ac) has emerged as an informative disease-associated epigenetic mark. However, cell type-specific contributions to dysregulation in disease are unclear studies have often used bulk brain tissue. Therefore, methods for the deconvolution H3K27ac profiles critical. Here we developed Cell Histone Score (CHAS), a computational tool inferring signatures profiles. We applied CHAS > 300 ChIP-seq samples from Alzheimer’s disease, Parkinson’s...