A5088091812- Epigenetics and DNA Methylation
- Birth, Development, and Health
- Neonatal Respiratory Health Research
- RNA Research and Splicing
- Childhood Cancer Survivors' Quality of Life
- Growth Hormone and Insulin-like Growth Factors
- Gestational Diabetes Research and Management
- Genetic Syndromes and Imprinting
- Single-cell and spatial transcriptomics
- Asthma and respiratory diseases
- Genomics and Chromatin Dynamics
- Bioinformatics and Genomic Networks
- Immune responses and vaccinations
- Cardiovascular Conditions and Treatments
- RNA and protein synthesis mechanisms
- Prenatal Screening and Diagnostics
- Air Quality and Health Impacts
- Prenatal Substance Exposure Effects
- Health, Environment, Cognitive Aging
- Alcohol Consumption and Health Effects
- Congenital Diaphragmatic Hernia Studies
- Cellular Mechanics and Interactions
- Gut microbiota and health
- Gene Regulatory Network Analysis
- Maternal Mental Health During Pregnancy and Postpartum
University of British Columbia
2015-2025
British Columbia Children's Hospital
2017-2025
Canada's Michael Smith Genome Sciences Centre
2021-2023
University of British Columbia Hospital
2019
Child and Family Research Institute
2015-2017
Family Research Institute
2015
DNA methylation is an epigenetic mark thought to be robust environmental perturbations on a short time scale. Here, we challenge that view by demonstrating the infection of human dendritic cells (DCs) with live pathogenic bacteria associated rapid and active demethylation at thousands loci, independent cell division. We performed integrated analysis data genome-wide methylation, histone patterns, chromatin accessibility, gene expression, before after infection. found infection-induced rarely...
The development of biological markers aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring age that show impressive accuracy across most tissues and ranges. In adults, deviations from the DNA methylation (DNAm) prediction correlated with several age-related phenotypes, such as mortality frailty. children, however, fewer associations have been made, possibly because DNAm changes more dynamic in pediatric populations compared to adults. To address...
Significance Environments in infancy and childhood influence levels of inflammation adulthood—an important risk factor for multiple diseases aging—but the underlying biological mechanisms remain uncertain. Using data from a unique cohort study Philippines with lifetime information on each participant, we provide evidence that nutritional, microbial, psychosocial exposures predict adult DNA methylation—biochemical marks genome affect gene expression—in genes regulate inflammation. We also...
The capacity of technologies measuring DNA methylation (DNAm) is rapidly evolving, as are the options for applicable bioinformatics methods. most commonly used DNAm microarray, Illumina Infinium HumanMethylation450 (450K array), has recently been replaced by HumanMethylationEPIC (EPIC nearly doubling number targeted CpG sites. Given that a subset 450K sites absent on EPIC array and several tools both data normalization analyses were developed array, it important to assess their utility when...
Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There growing evidence that suboptimal intrauterine environment can perturb metabolic programing fetus, thereby increasing risk developing obesity in later life. However, link between early exposures womb, genetic susceptibility, perturbed epigenome on not well understood. In this study, we shed more light aspect by performing a comprehensive analysis...
Fetal alcohol spectrum disorder (FASD) is a developmental that manifests through range of cognitive, adaptive, physiological, and neurobiological deficits resulting from prenatal exposure. Although the North American prevalence currently estimated at 2–5%, FASD has proven difficult to identify in absence overt physical features characteristic fetal syndrome. As interventions may have greatest impact an early age, accurate biomarkers are needed children risk for FASD. Building on our previous...
Aim: Determine if the association of HIF3A DNA methylation with weight and adiposity is detectable early in life. Material & methods: We determined genotype patterns (on hybridization arrays) extracted from umbilical cords 991 infants. Methylation levels at three CpGs first intron were related to neonatal infant anthropometry nearby polymorphic sites. Results conclusion: Higher previously described associated greater adiposity. The effect sizes slightly smaller than those reported for adult...
Cord blood is a commonly used tissue in environmental, genetic, and epigenetic population studies due to its ready availability potential inform on sensitive period of human development. However, the introduction maternal during labor or cross-contamination sample collection may complicate downstream analyses. After discovering contamination cord cohort study 150 neonates using Illumina 450K DNA methylation (DNAm) data, we combination linear regression random forest machine learning create...
Abstract Background Epigenetic alterations may represent new therapeutic targets and/or biomarkers of allergic rhinitis ( AR ). Our aim was to examine genome‐wide epigenetic changes induced by controlled pollen exposure in the environmental unit EEU Methods 38 sufferers and eight nonallergic controls were exposed grass for 3 hours on two consecutive days. We interrogated DNA methylation at baseline peripheral blood mononuclear cells PBMC s) using Infinium Methylation 450K array. corrected...
Epigenetic modifications such as DNA methylation are both cell type and developmental age specific. Here, we show that the immunological maturation of blood types influences changes from naive cord to fully functional adult blood. Lymphoid cells in showed more variability than suggesting an antigen-dependent lymphoid throughout lifespan. Fewer between were observed myeloid cells, particularly monocytes, which demonstrated least number We also noted differences epigenetic ages by immune...
Persons living with human immunodeficiency virus (HIV) harbor an increased risk of age-related conditions.We measured changes in telomere length and DNA methylation the peripheral blood 31 intravenous drug users, who were followed longitudinally samples pre-HIV (T1), immediately post-HIV (T2; 1.9±1 year from T1), at a later follow-up time (T3; 2.2±1 T2). Absolute measurements performed using polymerase chain reaction methods.Methylation profiles obtained Illumina Human Methylation450...
The Nicoya Peninsula in Costa Rica has one of the highest old-age life expectancies world, but underlying biological mechanisms this longevity are not well understood. As DNA methylation is hypothesized to be a component aging, we focused on malleable epigenetic mark determine its association with current residence versus elsewhere Rica. Examining population's unique pattern allows us differentiate hallmarks from individual stochastic variation. These differences may characteristic...
Epigenomes are tissue specific and thus the choice of surrogate can play a critical role in interpreting neonatal epigenome-wide association studies (EWAS) their extrapolation to target tissue. To develop better understanding link between specificity EWAS, contributions genotype prenatal factors, we compared genome-wide DNA methylation cord blood, two most accessible tissues at birth. In 295 neonates, was profiled using Infinium HumanMethylation450 beadchip arrays. Sites inter-individual...
Abstract Motivation: DNA methylation patterns are well known to vary substantially across cell types or tissues. Hence, existing normalization methods may not be optimal if they do take this into account. We therefore present a new R package for of data from the Illumina Infinium Human Methylation450 BeadChip (Illumina 450 K) built on concepts in recently published funNorm method, and introducing cell-type tissue-type flexibility. Results: funtooNorm is relevant sets containing samples two...
Epigenetics links perinatal influences with later obesity. We identifed differentially methylated CpG (dmCpG) loci measured at 17 years associated concurrent adiposity measures and examined whether these were hsCRP, adipokines, early life environmental factors. Genome-wide DNA methylation from 1192 Raine Study participants years, identified 29 dmCpGs (Bonferroni corrected p < 1.06E-07) body mass index (BMI), 10 waist circumference (WC) 9 subcutaneous fat thickness. DmCpGs within Ras...
Abstract Accelerated epigenetic aging relative to chronological age has been found be associated with higher risk of mortality in adults. However, little is known about whether and how utero exposures might shape child gestational (EA) at birth. We aimed explore associations between maternal psychosocial factors deviation EA birth (i.e., greater or lower age) a South African cohort study—the Drakenstein Child Health Study. Maternal included trauma/stressor exposure; posttraumatic stress...
Abstract Several studies have shown an association of alcohol dependence with DNA methylation (DNAm), suggesting that environmentally-induced changes on epigenomic variation may play important role in dependence. In the present study, we analysed genome-wide DNAm profiles purified CD3 + T-cells from pre- and post-treatment dependent patients, as well closely matched healthy controls. We identified 59 differentially methylated CpG sites comparing patients prior to treatment controls were able...
Abstract Motivation Thousands of studies have used co-expression analysis bulk tissue samples to probe gene regulation. However, the extent that intracellular regulatory signals are present in these data is unclear. Specifically, we lack clarity factors promote or impede propagation from single cell level level. To bring issues into focus, developed a novel computational simulator, grounded real data, explore theoretical relationship between events cells and expression profiles, clarify...
Public health and pediatric nurses typically focus on supporting parenting to reduce the likelihood of children's behavioral problems. Studies have identified interactions between early exposures stress in caregiving child genotype predicting problems, such that certain genotypes connote greater differential susceptibility or plasticity environmental stressors. We sought uncover interaction observational measures parent-child relationship quality early-onset problems 24-month-olds, using...
Mapping the gene targets of chromatin-associated transcription regulators (TRs) is a major goal genomics research. ChIP-seq TRs and experiments that perturb TR measure differential abundance transcripts are primary means by which direct relationships tested on genomic scale. It has been reported there poor overlap in evidence across regulation strategies, emphasizing need for integrating results from multiple experiments. Although research consortia interested have produced valuable trove...
Air pollution is associated with early declines in lung function and increased levels of asthma-related cysteinyl leukotrienes (CysLT) but a biological pathway linking this rapid response has not been delineated. In randomized controlled diesel exhaust (DE) challenge study 16 adult asthmatics, exposure-attributable urinary leukotriene E4 (uLTE4, biomarker production) was correlated (p = 0.04) forced expiratory volume 1-second (FEV1) within 6 hours exposure. Exposure-attributable uLTE4...
Rationale: Acute exposure to ambient particle matter is associated with increased levels of the cysteinyl leukotriene (CysLT) biomarker, urinary E4 (uLTE4), in subjects asthma.Objectives: The role CysLTs mediating asthma worsening after particulate exposures was explored.Methods: Daily concentrations 2.5 μm and smaller diameter (PM2.5) repeated measurements albuterol use over a 5-month period were collected 44 urban school children persistent asthma. DNA analyzed for gene polymorphisms on...
To facilitate the development of large-scale transcriptional regulatory networks (TRNs) that may enable in-silico analyses disease mechanisms, a reliable catalogue experimentally verified direct interactions (DTRIs) is needed for training and validation. There has been long history using low-throughput experiments to validate single DTRIs. Therefore, we reason set DTRIs could be produced by curating published literature such evidence. In our survey previous curation efforts, identified lack...
Abstract Background DNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in specific white cell types between newborn adult could add insight into maturation immune system. As a consequence developmental changes, profiles derived from cells are poor references for prediction cord data. We thus examined cell-type differences leukocyte subsets blood, assessed impact these on blood. Results Though all showed some patterns stood...