A Pilot Study on DNA Methylation in Pediatric HAdV-7-induced Sepsis

2021 ◽  
Author(s):  
Bolun Huang ◽  
Feiyan Chen ◽  
Run Dang ◽  
Wenmin Yang ◽  
Hongyan Peng ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Peripheral Blood ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Differential Methylation ◽  
Functional Enrichment ◽  
High Morbidity ◽  
Respiratory Pathogens ◽  
Healthy Children

Abstract Human adenovirus (HAdV) is one of the most common respiratory pathogens affecting children. HAdV infection has high morbidity and mortality, and it may lead to severe complications and long-term pulmonary sequelae. However, the pathogenesis of pediatric HAdV-7-induced sepsis remains unclear. The analysis of DNA methylation profiles in peripheral blood is attracting increasing attention as an effective method for investigating the pathogenesis of various diseases and identifying biomarkers of disease progression. Here, we performed reduced representation bisulfite sequencing to analyze DNA methylation in peripheral blood samples collected from 11 children with HAdV-7-induced sepsis and 5 healthy children. The Metilene software was used to analyze differential methylation in the two groups. We also performed functional enrichment analysis of the genes with differentially methylated regions (DMRs). We detected 1,138 DMRs between the two groups. Additionally, 122 DMRs were detected between the HAdV-7-induced sepsis survivor and non-survivor groups. After screening based on biological and clinical significance, we found that a group of genes (KCNQ1OT1, KPNB1, GRB10, HOXA5, HOXA4, and BCL9L) with differential methylation played an essential role in Wnt signaling. Additionally, genes related to the Wnt/β-catenin signaling pathway, such as MEG3, GNAS-AS1, and GNAS, exhibited differential methylation in the survivor and non-survivor groups. Our data suggest that specific patterns of DNA methylation are associated with the occurrence and progression of HAdV-7-induced sepsis. Wnt signaling was also affected by the changes in methylation. Thus, we identified potential biomarkers and therapeutic targets for pediatric HAdV-7-induced sepsis.

scholarly journals Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma

2021 ◽  
Vol 28 (1) ◽  
pp. 20-33
Author(s):  
Lydia-Eirini Giannakou ◽  
Athanasios-Stefanos Giannopoulos ◽  
Chrissi Hatzoglou ◽  
Konstantinos I. Gourgoulianis ◽  
Erasmia Rouka ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Cell Junctions ◽  
Respiratory Pathogens ◽  
Gram Negative ◽  
Human Proteins ◽  
Apoptotic Pathways

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.

scholarly journals Identification of Potential Biomarkers and Related Transcription Factors in Peripheral Blood of Tuberculosis Patients

2020 ◽  
Vol 17 (19) ◽  
pp. 6993
Author(s):  
Longxiang Xie ◽  
Xiaoyu Chao ◽  
Tieshan Teng ◽  
Qiming Li ◽  
Jianping Xie
Keyword(s):  
Transcription Factors ◽  
T Cell Activation ◽  
Peripheral Blood ◽  
Cell Activation ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Ppi Network ◽  
Peripheral Blood Mononuclear ◽  
Potential Biomarkers

Tuberculosis (TB), one major threat to humans, can infect one third of the worldwide population, and cause more than one million deaths each year. This study aimed to identify the effective diagnosis and therapy biomarkers of TB. Hence, we analyzed two microarray datasets (GSE54992 and GSE62525) derived from the Gene Expression Omnibus (GEO) database to find the differentially expressed genes (DEGs) of peripheral blood mononuclear cell (PBMC) between TB patients and healthy specimens. Functional and pathway enrichment of the DEGs were analyzed by Metascape database. Protein-protein interaction (PPI) network among the DEGs were constructed by STRING databases and visualized in Cytoscape software. The related transcription factors regulatory network of the DEGs was also constructed. A total of 190 DEGs including 36 up-regulated genes and 154 down-regulated genes were obtained in TB samples. Gene functional enrichment analysis showed that these DEGs were enriched in T cell activation, chemotaxis, leukocyte activation involved in immune response, cytokine secretion, head development, etc. The top six hub genes (namely, LRRK2, FYN, GART, CCR7, CXCR5, and FASLG) and two significant modules were got from PPI network of DEGs. Vital transcriptional factors, such as FoxC1 and GATA2, were discovered with close interaction with these six hub DEGs. By systemic bioinformatic analysis, many DEGs associated with TB were screened, and these identified hub DEGs may be potential biomarkers for diagnosis and treatment of TB in the future.

scholarly journals Comparative transcriptomic analysis of porcine peripheral blood reveals differentially expressed genes from the cytokine–cytokine receptor interaction pathway related to health status

Genome ◽  
2017 ◽  
Vol 60 (12) ◽  
pp. 1021-1028 ◽  
Author(s):  
M.H. Ye ◽  
H. Bao ◽  
Y. Meng ◽  
L.L. Guan ◽  
P. Stothard ◽  
...  
Keyword(s):  
Health Status ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Cytokine Receptor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Marker Genes

While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs that may be infected with multiple pathogens on farms. In this study, the architecture of the peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology. In total, 246 differentially expressed genes were identified to be specific to the sick animals. Functional enrichment analysis for those genes revealed that the over-represented gene ontology terms for the biological processes category were exclusively immune activity related. The cytokine–cytokine receptor interaction pathway was significantly enriched. Nine functional genes from this pathway encoding members (as well as their receptors) of the interleukins, chemokines, tumor necrosis factors, colony stimulating factors, activins, and interferons exhibited significant transcriptional alteration in sick animals. Our results suggest a subset of novel marker genes that may be useful candidate genes in the evaluation and prediction of health status in pigs under commercial production conditions.

scholarly journals Integrated DNA Methylation and Gene Expression Analysis Identified S100A8 and S100A9 in the Pathogenesis of Obesity

2021 ◽  
Vol 8 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Donghua Zou ◽  
Ling Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Regulatory Networks ◽  
Enrichment Analysis ◽  
Microarray Dataset ◽  
Functional Enrichment Analysis ◽  
Normal Subjects ◽  
Functional Enrichment ◽  
Differentially Methylated Genes

Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects. (2) Functional enrichment analysis and construction of differential methylation gene regulatory networks were performed. (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray dataset. (4) Correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNAs matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes—s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interesting different expression positions [differentially methylated positions (DMPs)] and their corresponding gene expression, we found that methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expressions in obese subjects were validated in a separate microarray dataset.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.

Identification of Specific Modules and Hub microRNAs Related to Osteosarcoma by Weighted microRNA Co-Expression Network Analysis

2021 ◽  
Vol 11 (4) ◽  
pp. 619-670
Author(s):  
Mei Hanying ◽  
Yueling Zhao ◽  
Na Suo
Keyword(s):  
Network Analysis ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
High Morbidity ◽  
Clear Understanding ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
New Biomarkers

Osteosarcoma (OS) is a malignant tumor with high morbidity and poor prognosis, especially for patients with metastasis. New therapeutic approaches are extremely needed. MicroRNAs can affect manykey biological processes, including the development and progression of complex diseases, such as OS. Here we identified specific modules and hub microRNAs related to OS through weighted gene co-expression network analysis (WGCNA). A module consisting of 72 microRNAs were found to be highly related to OS and 22 of them have been reported as deregulatedmicroRNAs in OS patients which play a role in OS tumorigenesis, development or prognosis. Then the target genes of the microRNAs were predicted and the functional enrichment analysis was performed on these genes. This study will provide a more clear understanding for facilitating the characterization and identification of new biomarkers and treatment for patients with OS by targeted miRNA.

DNA methylation profile of liver of mice conceived by in vitro fertilization

2021 ◽  
pp. 1-9
Author(s):  
Saúl Lira-Albarrán ◽  
Xiaowei Liu ◽  
Seok Hee Lee ◽  
Paolo Rinaudo
Keyword(s):  
Dna Methylation ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Global Dna Methylation ◽  
Analysis Tool ◽  
Gene Promoters ◽  
Vitro Fertilization ◽  
Natural Mating

Abstract Offspring generated by in vitro fertilization (IVF) are believed to be healthy but display a possible predisposition to chronic diseases, like hypertension and glucose intolerance. Since epigenetic changes are believed to underlie such phenotype, this study aimed at describing global DNA methylation changes in the liver of adult mice generated by natural mating (FB group) or by IVF. Embryos were generated by IVF or natural mating. At 30 weeks of age, mice were sacrificed. The liver was removed, and global DNA methylation was assessed using whole-genome bisulfite sequencing (WGBS). Genomic Regions for Enrichment Analysis Tool (GREAT) and G:Profilerβ were used to identify differentially methylated regions (DMRs) and for functional enrichment analysis. Overrepresented gene ontology terms were summarized with REVIGO, while canonical pathways (CPs) were identified with Ingenuity® Pathway Analysis. Overall, 2692 DMRs (4.91%) were different between the groups. The majority of DMRs (84.92%) were hypomethylated in the IVF group. Surprisingly, only 0.16% of CpG islands were differentially methylated and only a few DMRs were located on known gene promoters (n = 283) or enhancers (n = 190). Notably, the long-interspersed element (LINE), short-interspersed element (SINE), and long terminal repeat (LTR1) transposable elements showed reduced methylation (P < 0.05) in IVF livers. Cellular metabolic process, hepatic fibrosis, and insulin receptor signaling were some of the principal biological processes and CPs modified by IVF. In summary, IVF modifies the DNA methylation signature in the adult liver, resulting in hypomethylation of genes involved in metabolism and gene transcription regulation. These findings may shed light on the mechanisms underlying the developmental origin of health and disease.

scholarly journals Identification of LINC01503 as Biomarker Regulated by CTBP1 with Prognostic and Diagnostic Role in Epithelial Ovarian Cancer

2021 ◽  
Author(s):  
Yanchun Wang ◽  
Zheng Wei ◽  
Junping Zhang ◽  
Xuemei Wang ◽  
Xiaohua Li
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Underlying Mechanism ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
High Morbidity ◽  
Promote Cell Proliferation ◽  
Important Relationship

Abstract Background: Epithelial ovarian cancer (EOC) is a disease with high morbidity and mortality worldwide, which is seriously harmful to female health. LncRNA has an important relationship with the occurrence and development of tumors. Hence, the investigation of the underlying mechanism between LncRNA and EOC is of great importance.Results: In this study, we found that LINC01503 was highly expressed in EOC with a poor prognosis based on microarray datasets GSE119056 and GSE135886 obtained from Gene Expression Omnibus (GEO) database, and this result was verified by RT-qPCR. The database lncBase Predicted v.2 and starBase v2.0 were used to predict the targeted relationship of lncRNA-miRNA-mRNA, then the ceRNA network was established by Cytoscape software. Following, the expression and overall survival (OS) analysis of key lncRNAs were analyzed by GEPIA and Kaplan-Meier plotter database. Gene Ontology (GO) functional enrichment analysis was performed by DAVID database and enriched two cancer related biological processes (BP) that response to endoplasmic reticulum stress and IRE1-mediated unfolded protein. Moreover, we verified that LINC01503 was an oncogene regulated by C-terminal binding protein 1 (CTBP1) to promote cell proliferation, migration and inhibited cell apoptosis in ovarian cancer. Conclusion: In conclusion, these results identified LINC01503 as a potential gene for EOC diagnosis and prognosis.

scholarly journals Integrated DNA Methylation and Gene Expression Analysis Identified S100A8 and S100A9 in the Pathogenesis of Obesity

2020 ◽  
Author(s):  
Ningyuan Chen ◽  
Liu Miao ◽  
Wei Lin ◽  
Dong-Hua Zhou ◽  
Ling Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Microarray Data ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Normal Subjects ◽  
Functional Enrichment ◽  
Data Set ◽  
Differentially Methylated Genes

Abstract Background: To explore the association of DNA methylation and gene expression in the pathology of obesity.Methods: (1) Genomic DNA methylation and mRNA expression profile of visceral adipose tissue (VAT) were performed in a comprehensive database of gene expression in obese and normal subjects; (2) functional enrichment analysis and construction of differential methylation gene regulatory network were performed; (3) Validation of the two different methylation sites and corresponding gene expression was done in a separate microarray data set; and (4) correlation analysis was performed on DNA methylation and mRNA expression data.Results: A total of 77 differentially expressed mRNA matched with differentially methylated genes. Analysis revealed two different methylation sites corresponding to two unique genes-s100a8-cg09174555 and s100a9-cg03165378. Through the verification test of two interested different expression positions (DMPS) and their corresponding gene expression, we found that the methylation in these genes was negatively correlated to gene expression in the obesity group. Higher S100A8 and S100A9 expression in obese subjects were validated in a separate microarray data set.Conclusion: This study confirmed the relationship between DNA methylation and gene expression and emphasized the important role of S100A8 and S100A9 in the pathogenesis of obesity.

scholarly journals Transcriptome profiling of human thymic CD4+ and CD8+ T cells compared to primary peripheral T cells

2019 ◽  
Author(s):  
Hanna Helgeland ◽  
Ingvild Gabrielsen ◽  
Helle Akselsen ◽  
Arvind Y.M. Sundaram ◽  
Siri Tennebø Flåm ◽  
...  
Keyword(s):  
Cell Cycle ◽  
T Cells ◽  
Cd8 T Cells ◽  
Peripheral Blood ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Functional Enrichment ◽  
Valuable Insight ◽  
Thymic Tissue ◽  
Peripheral T Cells

Abstract Background: The thymus is a highly specialized organ of the immune system where T cell precursors develop and differentiate into self-tolerant CD4+ or CD8+ T cells. No studies to date have investigated how the human transcriptome profiles differ, between T cells still residing in the thymus and T cells in the periphery.Results: We have performed high-throughput RNA sequencing to characterize the transcriptomes of primary single positive (SP) CD4+ and CD8+ T cells from infant thymic tissue, as well as primary CD4+ and CD8+ T cells from infant and adult peripheral blood, to enable the comparisons across tissues and ages. In addition, we have assessed the expression of candidate genes related to autoimmune diseases in thymic CD4+ and CD8+ T cells. Thymic SP T cells displayed a broader transcriptome than peripheral T cells, indicated by a higher number of uniquely expressed genes. Comparing T cells of thymic and blood origin, revealed more differentially expressed genes, than between infant and adult blood. Functional enrichment analysis revealed an over-representation of genes involved in cell cycle and replication in thymic T cells, whereas infant blood T cells were dominated by immune related terms. Comparing adult and infant blood T cells, the former was enriched for inflammatory response, cytokine production and biological adhesion, while upregulated genes in infant blood T cells were associated with cell cycle, cell death and gene expression.Conclusion: This study provides valuable insight into the transcriptomes of the human primary SP T cells still residing within the thymus, and offers a unique comparison to the more frequently studied primary blood derived T cells. We discovered that genes involved in migration, homing and recirculation, between peripheral blood and lymphatic tissue, were particularly active in infant blood T cells, suggesting active migration and recirculation in young children.

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