scholarly journals Differences in DNA methylation of white blood cell types at birth and in adulthood reflect postnatal immune maturation and influence accuracy of cell type prediction

2018 ◽  
Author(s):  
Meaghan J Jones ◽  
Louie Dinh ◽  
Hamid Reza Razzaghian ◽  
Olivia de Goede ◽  
Julia L MacIsaac ◽  
...  

AbstractBackgroundDNA methylation profiling of peripheral blood leukocytes has many research applications, and characterizing the changes in DNA methylation of specific white blood cell types between newborn and adult could add insight into the maturation of the immune system. As a consequence of developmental changes, DNA methylation profiles derived from adult white blood cells are poor references for prediction of cord blood cell types from DNA methylation data. We thus examined cell-type specific differences in DNA methylation in leukocyte subsets between cord and adult blood, and assessed the impact of these differences on prediction of cell types in cord blood.ResultsThough all cell types showed differences between cord and adult blood, some specific patterns stood out that reflected how the immune system changes after birth. In cord blood, lymphoid cells showed less variability than in adult, potentially demonstrating their naïve status. In fact, cord CD4 and CD8 T cells were so similar that genetic effects on DNA methylation were greater than cell type effects in our analysis, and CD8 T cell frequencies remained difficult to predict, even after optimizing the library used for cord blood composition estimation. Myeloid cells showed fewer changes between cord and adult and also less variability, with monocytes showing the fewest sites of DNA methylation change between cord and adult. Finally, including nucleated red blood cells in the reference library was necessary for accurate cell type predictions in cord blood.ConclusionChanges in DNA methylation with age were highly cell type specific, and those differences paralleled what is known about the maturation of the postnatal immune system.

Epigenetics ◽  
2018 ◽  
Vol 13 (9) ◽  
pp. 941-958 ◽  
Author(s):  
Xinyi Lin ◽  
Jane Yi Lin Tan ◽  
Ai Ling Teh ◽  
Ives Yubin Lim ◽  
Samantha J Liew ◽  
...  

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qian Chen ◽  
Yanhong Ming ◽  
Yuexin Gan ◽  
Lisu Huang ◽  
Yanjun Zhao ◽  
...  

Abstract Background Mounting evidence suggests that cesarean delivery may have a long-lasting effect on infant health. But the underlying mechanisms remain unclear. This study aims to examine whether cesarean delivery on maternal request without any medical indications (CDMR) impacts DNA methylation status in the umbilical cord blood of the infant. Methods A cross-sectional study was conducted in Shanghai, China. A total of 70 CDMR and 70 vaginal deliveries (VD) were recruited in 2012. The cord blood DNA methylation status was measured in 30 CDMR and 30 VD newborns using Illumina Infinium Human Methylation 450 K BeadChip. To validate the results, the cord blood DNA methylation status was measured in another 40 CDMR and 40 VD newborns using targeted bisulfite sequencing assay. A total of 497 CpG sites from 40 genes were included in the analysis. Results A total of 165 differentially methylated positions (DMPs) exhibited differences in DNA methylation by 10% or more between the CDMR and VD groups, many of which were related to the development of the immune system. Based on the targeted bisulfite sequencing assay, 16 genes (16/22, 72.7%) had higher methylation level in the CDMR group than the VD group. Among them, 5 genes were related to the immune system. After considering the estimation of cell type proportions, there was few significant differences in DNA methylation between CDMR and VD groups. Conclusions The DMPs identified between CDMR and VD groups might be largely explained by the cell type proportions. Further studies are needed to examine DNA methylation in each cell type separately.


2017 ◽  
Author(s):  
John Dou ◽  
Rebecca J. Schmidt ◽  
Kelly S. Benke ◽  
Craig Newschaffer ◽  
Irva Hertz-Picciotto ◽  
...  

AbstractBackgroundCord blood DNA methylation is associated with numerous health outcomes and environmental exposures. Whole cord blood DNA reflects all nucleated blood cell types, while centrifuging whole blood separates red blood cells by generating a white blood cell buffy coat. Both sample types are used in DNA methylation studies. Cell types have unique methylation patterns and processing can impact cell distributions, which may influence comparability.ObjectivesTo evaluate differences in cell composition and DNA methylation between buffy coat and whole cord blood samples.MethodsCord blood DNA methylation was measured with the Infinium EPIC BeadChip (Illumina) in 8 individuals, each contributing buffy coat and whole blood samples. We analyzed principal components (PC) of methylation, performed hierarchical clustering, and computed correlations of mean-centered methylation between pairs. We conducted moderated t-tests on single sites and estimated cell composition.ResultsDNA methylation PCs were associated with individual (PPC1=1.4x10-9; PPC2=2.9x10-5; PPC3=3.8x10-5; PPC4=4.2x10-6; PPC5=9.9x10-13), and not with sample type (PPC1-5>0.7). Samples hierarchically clustered by individual. Pearson correlations of mean-centered methylation between paired individual samples ranged from r=0.66 to r=0.87. No individual site significantly differed between buffy coat and whole cord blood when adjusting for multiple comparisons (5 sites had unadjusted P<10-5). Estimated cell type proportions did not differ by sample type (P=0.86), and estimated cell counts were highly correlated between paired samples (r=0.99).ConclusionsDifferences in methylation and cell composition between buffy coat and whole cord blood are much lower than inter-individual variation, demonstrating that both sample preparation types can be analytically combined and compared.


Author(s):  
Apri Nur Liyantoko ◽  
Ika Candradewi ◽  
Agus Harjoko

 Leukemia is a type of cancer that is on white blood cell. This disease are characterized by abundance of abnormal white blood cell called lymphoblast in the bone marrow. Classification of blood cell types, calculation of the ratio of cell types and comparison with normal blood cells can be the subject of diagnosing this disease. The diagnostic process is carried out manually by hematologists through microscopic image. This method is likely to provide a subjective result and time-consuming.The application of digital image processing techniques and machine learning in the process of classifying white blood cells can provide more objective results. This research used thresholding method as segmentation and  multilayer method of back propagation perceptron with variations in the extraction of textural features, geometry, and colors. The results of segmentation testing in this study amounted to 68.70%. Whereas the classification test shows that the combination of feature extraction of GLCM features, geometry features, and color features gives the best results. This test produces an accuration value 91.43%, precision value of 50.63%, sensitivity 56.67%, F1Score 51.95%, and specitifity 94.16%.


2021 ◽  
Author(s):  
Taylor M. Lagler ◽  
Yuchen Yang ◽  
Yuriko Harigaya ◽  
Vijay G. Sankaran ◽  
Ming Hu ◽  
...  

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.


2008 ◽  
Vol 53 (No. 5) ◽  
pp. 255-259 ◽  
Author(s):  
L. Pisek ◽  
J. Travnicek ◽  
J. Salat ◽  
V. Kroupova ◽  
M. Soch

The aim of the experiment was to evaluate the impact of selenium supplementation on white blood cell parameters in the blood of ewes. The total white blood cell (WBC) and differentiation of leukocytes in blood smear were detected by a microscopic analysis, and the CD4<sup>+</sup> and CD8<sup>+</sup> subsets were detected by flow cytometry. A decrease in the count of WBC was recorded during pregnancy; it was statistically significant only in the group supplemented with organic selenium. In the postpartal period there was a statistically significant increase in the percentages of CD4<sup>+</sup> and CD8<sup>+</sup> subsets but differences between the groups were not statistically significant. The results of the experiment documented that the supplementation of different forms of selenium did not markedly influence the dynamics of blood parameters in non-pregnant, pregnant and lactating ewes if the intake of vitamins and other essential microelements was adequate.


2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Cilla Söderhäll ◽  
Lovisa E. Reinius ◽  
Pertteli Salmenperä ◽  
Massimiliano Gentile ◽  
Nathalie Acevedo ◽  
...  

Abstract Background Methylation of DNA at CpG sites is an epigenetic modification and a potential modifier of disease risk, possibly mediating environmental effects. Currently, DNA methylation is commonly assessed using specific microarrays that sample methylation at a few % of all methylated sites. Methods To understand if significant information on methylation can be added by a more comprehensive analysis of methylation, we set up a quantitative method, bisulfite oligonucleotide-selective sequencing (Bs-OS-seq), and compared the data with microarray-derived methylation data. We assessed methylation at two asthma-associated genes, IL13 and ORMDL3, in blood samples collected from children with and without asthma and fractionated white blood cell types from healthy adult controls. Results Our results show that Bs-OS-seq can uncover vast amounts of methylation variation not detected by commonly used array methods. We found that high-density methylation information from even one gene can delineate the main white blood cell lineages. Conclusions We conclude that high-resolution methylation studies can yield clinically important information at selected specific loci missed by array-based methods, with potential implications for future studies of methylation-disease associations.


Author(s):  
T Sudarshan Rao ◽  
◽  
N Rohan Sai ◽  
D Koteswara Rao ◽  
◽  
...  

Modern-day computation has become indispensable in the healthcare industry. From medical image processing to cost reduction, Artificial Intelligence has proved its significance in solving complex healthcare problems. One of the primary areas in which it can be of greater use in hematology. Categorization of white-blood cells is imperative to pre-identify abnormalities. Through this paper, we collected image samples for 4 major White Blood cell groups, which are Neutrophils, Lymphocytes, Monocytes, and Eosinophils. The aim of this research is to put forward an intelligent system that efficiently alleviates the stringent requirement of a cytological study. The proposed system classifies 4 white-blood-cell types based on their morphological variation. With the experimental modulations that we chose to integrate, the presented model attained an accuracy of 97%.


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