Epigenome analysis of whole-blood samples of septic and healthy preterm neonates
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE155952 | GEO | 2020/08/11
REPOSITORIES: GEO
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Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context. DNA methylation analysis of three septic newborns and three non-septic newborns were performed with Illumina Infinium HumanMethylation450 BeadChip. Peripheral venous blood sample was collected from the babies during the third day of birth while taking blood for routine investigations. Non-septic babies are babies admitted to NICU and sampled for other minor ailments. Genomic DNA was extracted using QIAmp DNA Blood Mini kit (Qiagen, Hilden, Germany) and bisulfite treated using EZ DNA methylation kit (Zymoresearch, USA).
2014-06-20 | E-GEOD-58651 | biostudies-arrayexpress
Project description:DNA methylation is the current strategy in the field of biomarker discovery due to its prognostic efficiency. Its role in prognosis and early diagnosis has been recognized in various types of cancer. Sepsis still remains one of the major causes of neonatal mortality due to the lack of sensitive diagnostic and prognostic biomarkers. Delay in sepsis diagnosis leads to treatment difficulties and poor outcomes. In this study, we have done an epigenome wide search to identify potential markers for prognosis of neonatal sepsis which may improve the treatment strategies. Illumina 450K methylation microarray revealed that the genes involved in transendothelial leukocyte migration were differentially methylated in septic newborns compared to non-septic newborns, especially the Protocadherin Beta group. Genes like ITGB2-AS1, CCS were found to be differentially methylated significantly, which gives the hope of developing novel, potential epigenetic markers for neonatal sepsis. From this study, we conclude that DNA methylation might play crucial functions in the pathophysiology of neonatal sepsis which was obvious from the difference in methylation level among septic and non-septic babies. In future, the potentiality of these epigenetic biomarkers can be studied in large scale with appropriate techniques which will give further in depth knowledge in this context.
2014-06-20 | GSE58651 | GEO
Project description:Preterm birth is the major cause of newborn and infant mortality affecting nearly one in every ten live births. This study was designed to develop an epigenetic biomarker for susceptibility of preterm birth using buccal cells from the mother, father, and child (triads). MeDIP-seq was used to identify differential DNA methylation regions (DMRs) using a comparison of control term birth versus preterm birth triads. Epigenetic DMR associations with preterm birth were identified for both the mother and father that were distinct and suggest potential epigenetic contributions from both parents. The mother (165 DMRs) and female child (136 DMRs) at p<1e-04 had the highest number of DMRs and were highly similar suggesting potential epigenetic inheritance of the epimutations. The male child had negligible DMR associations. The DMR associated genes for each group involve previously identified preterm birth associated genes.
2022-03-09 | GSE194227 | GEO
Project description:We hypothesized that the immature pig intestine would be highly sensitive to gene methylation changes in the immediate prenatal and neonatal periods. We performed a Reduced Representation Bisulfite Sequencing (RRBS) to assess the DNA methylation differences occurring during the last 10 days prenatally (PN, 0d-term vs. 0d-preterm), neonatally after 4 days (NN, 4d-preterm vs. 0d-preterm) and after NEC development (4d-preterm-NEC vs. 4d-preterm) in pigs (each group n=2-3). Differentially methylated gene regions (DMRs) between the groups were identified, subjected to KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis and selected genes were chosen for further validation of gene expression levels by RT-PCR (n= 6 for each group). Consistent with the need to increase expression of many intestinal genes in the perinatal period, methylation levels of most genes decreased during the prenatal and neonatal periods. We identified four intestinal genes (CYP2W1, GPR146, TOP1MT, CEND1), related to intestinal metabolism, that were significantly hyper-methylated in their promoter CGIs, and transcriptionally down-regulated in the 4 d-old preterm pigs. This down-regulation of intestinal metabolism may predispose to intestinal dysfunction and NEC. The first enteral feeds and bacterial colonization are critical factors for NEC sensitivity and it remains to be investigated whether these factors affect intestinal gene methylation and thereby predispose to, or prevent from, disease more long term.
2014-12-31 | GSE53747 | GEO
Project description:Autism spectrum disorder (ASD) is a neurodevelopmental disorder with complex heritability and higher prevalence in males. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development and influence future health outcomes. We performed whole-genome bisulfite sequencing of 152 umbilical cord blood samples from the MARBLES and EARLI high-familial risk prospective cohorts to identify an epigenomic signature of ASD at birth. Samples were split into discovery and replication sets and stratified by sex, and their DNA methylation profiles were tested for differentially methylated regions (DMRs) between ASD and typically developing control cord blood samples. DMRs were mapped to genes and assessed for enrichment in gene function, tissue expression, chromosome location, and overlap with prior ASD studies. DMR coordinates were tested for enrichment in chromatin states and transcription factor binding motifs. Results were compared between discovery and replication sets and between males and females. We identified DMRs stratified by sex that discriminated ASD from control cord blood samples in discovery and replication sets. At a region level, 7 DMRs in males and 31 DMRs in females replicated across two independent groups of subjects, while 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMR genes were significantly enriched for brain and embryonic expression, X chromosome location, and identification in prior epigenetic studies of ASD in post-mortem brain. In males and females, autosomal ASD DMRs were significantly enriched for promoter and bivalent chromatin states across most cell types, while sex differences were observed for X-linked ASD DMRs. Lastly, these DMRs identified in cord blood were significantly enriched for binding sites of methyl-sensitive transcription factors relevant to fetal brain development. At birth, prior to the diagnosis of ASD, a distinct DNA methylation signature was detected in cord blood over regulatory regions and genes relevant to early fetal neurodevelopment. Differential cord methylation in ASD supports the developmental and sex-biased etiology of ASD and provides novel insights for early diagnosis and therapy.
2020-03-24 | GSE140730 | GEO
Project description:Differentially-methylated-regions (DMRs), pivotal to the diagnosis/pathogenesis of imprinting disorders, control imprinted gene expression with histone modifications; however, their establishment, numbers, boundaries, and crosstalk with chromatin remain elusive. Herein our global profiling reveals that although de novo methyltransferases DNMT3a/3b are required for locus-specific DMR maintenance, DNMT1 is required for all known DMRs. Based on the latter and the DMR concept, we have developed two novel approaches, “no restored DMRs (NORED)” and “Tag-mosaicity,” to identify/demarcate 31 known and 7 novel DMRs from 21 known loci, and 20 novel DMRs from novel loci. Tag-mosaicity analyses reveal the expected bimodal patterns of hypo/hypermethylated tags of known and new DMRs. Using Gtl2 locus, we demonstrate that methylation of DMRs controls H3K9me3 distribution to a long- range ”DMR-territory” that extends beyond our defined DMR boundary. These findings contrast that H3K9me3 controls CG methylation in Arabidopsis and Neurospora. Our analyses reveal that promoters of imprinted genes within a DMR-territory tend to have H3K4me2 and H3K9me3 with/without H3K27me3, whereas promoters outside have H3K27me3 and H3K4me2. Lastly, we confirmed that the transient DMR of Hcn2/Polrmt locus is conserved in the human genome. Our data link transient DMRs to epilepsy and chronic pain, Parkinson’s disease, Charcot-Marie-Tooth disease, and type 2 diabetes.
2016-09-15 | GSE61648 | GEO
Project description:We previously reported a child with transient neonatal diabetes mellitus (TNDM), who upon molecular diagnosis was homozygous for a one base-pair deletion in ZFP57, inheriting the mutations from both heterozygous parents. Methylation profiling at diagnosis revealed severe hypomethylation at PLAGL1 and mosaic loss-of-methylation (LOM) at GRB10, NAP1L5 and GNAS-XL DMRs. Some years after the first child, a second sibling was born with a comparable clinical presentation. Upon molecular investigation this child was shown to have the same homozygous deletion. Using Illumina Infinium BeadChip arrays, we confirmed similar hypomethylated signatures at ubiquitous imprinted DMRs. To further characterize the stability of the imprinting defects and understand the role of this mutation in tissue-specific mosaicism, we hybridised buccal-derived DNA and a second leukocyte sample from first child to the HumanMethylationEPIC arrays. When comparing the two blood-derived samples, we observed that the hypomethylation signature is stable over time with the PLAGL1 DMR being the most severely affected, consistent with this being the disease-causing locus. Furthermore, when comparing the leukocyte and buccal samples, the same imprinted DMRs were affected to a similar extent.
2020-11-27 | GSE149568 | GEO
Project description:Tissue and their component cells have unique DNA methylation profiles comprising DNA methylation patterns of tissue-dependent and differentially methylated regions (T-DMRs). T-DMRs are found throughout the genome and influence tissue-specific gene expression. DNA methylation profile of T-DMRs underlies the network of tissue- and developmental stage-specific transcription factors and their targets. The adult brain consists of various kinds of cells that sequentially appear as neurons, astrocytes, and oligodendrocytes from late gestation through the neonatal period. Distinctive neural progenitor cells (NPCs) that exhibit different differentiation poteintials to neurons to glial cells are generated during mid-to-late gestation. To explore DNA methylation profiles of mouse NPCs, we compared neurospheres derived from telencephalons at embryonic day 11.5 (E11.5NSph) and 14.5 (E14.5NSph) by T-DMR profiling with restriction tag-mediated amplification (D-REAM) combined with Affymetrix GeneChip Mouse Promoter 1.0R Array. We used HpyCH4IV, a methylation-sensitive restriction enzyme that recognizes ACGT residues. Because these are uniformly distributed across the genome, it enables less biased analysis. By comparing D-REAM data between E11.5NSph and E14.5NSph, we identified genes with T-DMRs including those involved in neural develpment and/or associated with neurological disorders in humans. The present study elucidates the underlying dynamics of the DNA methylation profile of T-DMRs during neural development, including insights into developmental stage-specific hypomethylation of T-DMRs around TSSs.
2012-12-01 | E-MTAB-1150 | biostudies-arrayexpress
Project description:To investigate if appropriately adjusted parenteral glucose supply may help to shift liver metabolism profiling to further prevent sepsis or improve sepsis outcomes of preterm newborns, we using a preterm pig model inoculated with Staphylococcus epidermidis to mimic the inflammation condition of preterm newborns at birth and treated them with different parenteral nutrition glucose supplyment. We then performed gene expression profiling analysis using data obtained from RNA-seq of preterm pigs` liver tissue, which collected at 22 hours after SE infection, treated with different parenteral glucose supply.
2022-06-29 | GSE201550 | GEO
Project description:To investigate if appropriately adjusted parenteral glucose supply and/or temporary glycolysis inhibition by administration may help to prevent sepsis or improve sepsis outcomes of preterm newborns, we using a preterm pig model inoculated with Staphylococcus epidermidis to mimic the inflammation condition of preterm newborns at birth and treated them with different parenteral nutrition glucose supplyment and glycolysis inhibitor administration. We then performed gene expression profiling analysis using data obtained from RNA-seq of preterm pigs` whole blood, which collected at 12 hours after SE infection, treated with different parenteral glucose supply and glycolysis inhibitor administration.
2022-06-29 | GSE201552 | GEO