Integration of DNA methylation patterns and genetic variation in human pediatric tissues help inform EWAS design and interpretation
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA511861 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Background: The widespread use of accessible peripheral tissues for epigenetic analyses has prompted increasing interest in the study of tissue-specific DNA methylation (DNAm) variation in human populations. To date, characterizations of inter-individual DNAm variability and DNAm concordance across tissues have been largely performed in adult tissues and therefore are limited in their relevance to DNAm profiles from pediatric samples. Given that DNAm patterns in early life undergo rapid changes and have been linked to a wide range of health outcomes and environmental exposures, direct investigations of tissue-specific DNAm variation in pediatric samples may help inform the design and interpretation of DNAm analyses from early life cohorts. In this study, we present a systematic comparison of genome-wide DNAm patterns between matched pediatric buccal epithelial cells (BECs) and peripheral blood mononuclear cells (PBMCs), two of the most widely used peripheral tissues in human epigenetic studies. Specifically, we assessed DNAm variability, cross-tissue DNAm concordance and genetic determinants of DNAm across two independent early life cohorts encompassing different ages. Results: BECs had greater inter-individual DNAm variability compared to PBMCs and highly variable CpGs were more likely to be positively correlated between the matched tissues compared to less variable CpGs. These sites were enriched for CpGs under genetic influence, suggesting that a substantial proportion of DNAm co-variation between tissues can be attributed to genetic variation. Finally, we demonstrated the relevance of our findings to human epigenetic studies by categorizing CpGs from published DNAm association studies of pediatric BECs and peripheral blood. Conclusions: Taken together, our results highlight a number of important considerations and practical implications in the design and interpretation of EWAS analyses performed in pediatric peripheral tissues.
2018-12-27 | GSE124366 | GEO
Project description:BACKGROUND:The widespread use of accessible peripheral tissues for epigenetic analyses has prompted increasing interest in the study of tissue-specific DNA methylation (DNAm) variation in human populations. To date, characterizations of inter-individual DNAm variability and DNAm concordance across tissues have been largely performed in adult tissues and therefore are limited in their relevance to DNAm profiles from pediatric samples. Given that DNAm patterns in early life undergo rapid changes and have been linked to a wide range of health outcomes and environmental exposures, direct investigations of tissue-specific DNAm variation in pediatric samples may help inform the design and interpretation of DNAm analyses from early life cohorts. In this study, we present a systematic comparison of genome-wide DNAm patterns between matched pediatric buccal epithelial cells (BECs) and peripheral blood mononuclear cells (PBMCs), two of the most widely used peripheral tissues in human epigenetic studies. Specifically, we assessed DNAm variability, cross-tissue DNAm concordance and genetic determinants of DNAm across two independent early life cohorts encompassing different ages. RESULTS:BECs had greater inter-individual DNAm variability compared to PBMCs and highly the variable CpGs are more likely to be positively correlated between the matched tissues compared to less variable CpGs. These sites were enriched for CpGs under genetic influence, suggesting that a substantial proportion of DNAm covariation between tissues can be attributed to genetic variation. Finally, we demonstrated the relevance of our findings to human epigenetic studies by categorizing CpGs from published DNAm association studies of pediatric BECs and peripheral blood. CONCLUSIONS:Taken together, our results highlight a number of important considerations and practical implications in the design and interpretation of EWAS analyses performed in pediatric peripheral tissues.
| S-EPMC6314079 | biostudies-literature
Project description:Using HELP-Tagging, we defined the cytosine methylation profiles of hematopoietic stem/progenitor cells (CD34+) from umbilical cord blood in 29 healthy newborns. We found substantial variation of DNA methylation to occur in human CD34+ hematopoietic stem and progenitor cells from different individuals. Empirical annotation of the genome of this cell type reveals the variability to be targeted to candidate promoters and to candidate enhancer sequences of genes expressed at lower levels. The variability of DNA methylation at candidate enhancers was low for housekeeping genes but high for genes associated with leukocyte differentiation. The enrichment of DNA methylation variability at loci with intermediate methylation values, occurring at apparently “poised” enhancers, suggests cell subpopulation heterogeneity between individuals as the basis for the epigenomic variability observed. The “meta-epigenome” present even in purified cells complicates the design and interpretation of epigenome-wide association studies, but also allows insights into the gene expression characteristics and the number of cell types comprising the cell population analyzed. One Sentence Summary: Variability in epigenomic patterns between different individuals occurs predominantly at promoters and enhancers, reflecting cell subpopulation heterogeneity.
2014-07-01 | GSE49836 | GEO
Project description:CD4+ T-cell help creates effector memory CTLs with innate and help-independent recall capacities
| PRJNA484725 | ENA
Project description:MicroRNA Profiling to Inform Disease Classification, Severity, and Treatment Response in Pediatric Pulmonary Hypertension
| PRJNA1178543 | ENA
Project description:The design of surveillance strategies is often a compromise between science, feasibility, and available resources, especially when sampling is based at fixed locations, such as slaughter-houses. Advances in animal identification, movement recording and traceability should provide data that can facilitate the development, design and interpretation of surveillance activities. Here, for the first time since the introduction of electronic identification of sheep, the utility of a statutory sheep movement database to inform the design and interpretation of slaughter-house based surveillance activities has been investigated. Scottish sheep movement records for 2015-2018 were analyzed in combination with several other data sources. Patterns of off-farm movements of Scottish sheep to slaughter were described and the spatial distribution of several distinct slaughter populations, throughputs and catchment areas for Scottish slaughterhouses were determined. These were used to evaluate the coverage of a convenience-sample slaughter-house based survey for antimicrobial resistance (AMR). In addition, non-slaughter sheep movements within and between Scottish regions were described and inter-and intra-regional movement matrices were produced. There is potential at a number of levels for bias in spatially-associated factors for ovine surveillance activities based at Scottish slaughterhouses. The first is intrinsic because the slaughtered in Scotland population differs from the overall Scottish sheep slaughter population. Other levels will be survey-dependent and occur when the catchment area differs from the slaughtered in Scotland population and when the sampled sheep differ from the catchment area. These are both observed in the AMR survey. Furthermore, the Scottish non-slaughter sheep population is dynamic. Inter-regional movements vary seasonally, driven by the sheep calendar year, structure of the Scottish sheep industry and management practices. These sheep movement data provide a valuable resource for surveillance purposes, despite a number of challenges and limitations that were encountered. They can be used to identify and characterize the spatial origin of relevant populations and so inform the interpretation of existing slaughterhouse-based surveillance activities. They can be used to improve future design by exploring the feasibility and cost:benefit of alternative sampling strategies. Further development could also contribute to other surveillance activities, such as situational awareness and resource allocation, for the benefit of stakeholders.
| S-EPMC7193055 | biostudies-literature
Project description: Not available
| S-EPMC10193981 | biostudies-literature
Project description:This paper presents a computational model to address one prominent psychological behavior of human beings to recognize images. The basic pursuit of our method can be concluded as that differences among multiple images help visual recognition. Generally speaking, we propose a statistical framework to distinguish what kind of image features capture sufficient category information and what kind of image features are common ones shared in multiple classes. Mathematically, the whole formulation is subject to a generative probabilistic model. Meanwhile, a discriminative functionality is incorporated into the model to interpret the differences among all kinds of images. The whole Bayesian formulation is solved in an Expectation-Maximization paradigm. After finding those discriminative patterns among different images, we design an image categorization algorithm to interpret how these differences help visual recognition within the bag-of-feature framework. The proposed method is verified on a variety of image categorization tasks including outdoor scene images, indoor scene images as well as the airborne SAR images from different perspectives.
| S-EPMC3670869 | biostudies-literature
Project description:This article reviews dual X-ray absorptiometry (DXA) technique and interpretation with emphasis on the considerations unique to pediatrics. Specifically, the use of DXA in children requires the radiologist to be a "clinical pathologist" monitoring the technical aspects of the DXA acquisition, a "statistician" knowledgeable in the concepts of Z-scores and least significant changes, and a "bone specialist" providing the referring clinician a meaningful context for the numeric result generated by DXA. The patient factors that most significantly influence bone mineral density are discussed and are reviewed with respect to available normative databases. The effects the growing skeleton has on the DXA result are also presented. Most important, the need for the radiologist to be actively involved in the technical and interpretive aspects of DXA is stressed. Finally, the diagnosis of osteoporosis should not be made on DXA results alone but should take into account other patient factors.
| S-EPMC1764599 | biostudies-other