Dataset Information

Integrated Analysis of DNA Methylation and Biochemical/Metabolic Parameter During the Long-Term Isolation Environment.

ABSTRACT: Numerous studies have shown that changes in the epigenome are an important cause of human biochemical or metabolic parameter changes. Biochemical/metabolic parameter disorders of the human body are usually closely related to the occurrence of disease. Therefore, constructing credible DNA methylation site-biochemical/metabolic parameter associations are key in interpreting the pathogenesis of diseases. However, there is a lack of research on systematic integration analysis of DNA methylation with biochemical/metabolic parameter and diseases. In this study, we attempted to use the four-people, multiple time point detected data from the long-term isolation experiment to conduct a correlation analysis. We used the biclustering algorithm FABIA to cluster the DNA methylation site-parameter correlation matrixes into 28 biclusters. The results of the biological function analysis for these biclusters were consistent with the biochemical/metabolic parameter change characteristics of the human body during long-term isolation, demonstrating the reliability of the biclusters identified by our method. In addition, from these biclusters, we obtained highly credible biochemical/metabolic parameter-disease associations, which is supported by several studies. Our results indicate that there is an overlap of biochemical/metabolic parameter-disease associations derived from a small sample, multiple time point data in healthy populations and the associations obtained from a large sample data in patients during disease development. These findings provide insights into understanding the role of the epigenome in biochemical/metabolic parameter change and disease development and has potential applications in biology and medicine research.

SUBMITTER: Quan Y

PROVIDER: S-EPMC6676193 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Integrated Analysis of DNA Methylation and Biochemical/Metabolic Parameter During the Long-Term Isolation Environment.

Quan Yuan Y Liang Fengji F Zhu Yuexing Y Chen Ying Y Xu Zi Z Du Fang F Lv Ke K Chen Hailong H Qu Lina L Xu Ruifeng R Zhang Hong-Yu HY Xiong Jianghui J Li Yinghui Y

Frontiers in physiology 20190724

Numerous studies have shown that changes in the epigenome are an important cause of human biochemical or metabolic parameter changes. Biochemical/metabolic parameter disorders of the human body are usually closely related to the occurrence of disease. Therefore, constructing credible DNA methylation site-biochemical/metabolic parameter associations are key in interpreting the pathogenesis of diseases. However, there is a lack of research on systematic integration analysis of DNA methylation with ...[more]

PMID: 31402871

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Project description:It has been reported that several aspects of human health could be disturbed during a long-term isolated environment (for instance, the Mars-500 mission), including psychiatric disorders, circadian disruption, temporal dynamics of gut microbiota, immune responses, and physical-activity-related neuromuscular performance. Nevertheless, the mechanisms underlying these disturbances and the interactions among different aspects of human adaptation to extreme environments remain to be elucidated. Epigenetic features, like DNA methylation, might be a linking mechanism that explains the involvement of environmental factors between the human genome and the outcome of health. We conducted an exploration of personalized longitudinal DNA methylation patterns of the peripheral whole blood cells, profiling six subjects across six sampling points in the Mars-500 mission. Specifically, we developed a Personalized Epigenetic-Phenotype Synchronization Analysis (PeSa) algorithm to explore glucose- and mood-state-synchronized DNA methylation sites, focusing on finding the dynamic associations between epigenetic patterns and phenotypes in each individual, and exploring the underling epigenetic connections between glucose and mood-state disturbance. Results showed that DMPs (differentially methylated-probes) were significantly enriched in pathways related to glucose metabolism (Type II diabetes mellitus pathway), mood state (Long-term depression) and circadian rhythm (Circadian entrainment pathway) during the mission. Furthermore, our data revealed individualized glucose-synchronized and mood-state-synchronized DNA methylation sites, and PTPRN2 was found to be associated with both glucose and mood state disturbances across all six subjects. Our findings suggest that personalized phenotype-synchronized epigenetic features could reflect the effects on the human body, including the disturbances of glucose and mood-states. The association analysis of DNA methylation and phenotypes, like the PeSa analysis, could provide new possibilities in understanding the intrinsic relationship between phenotypic changes of the human body adapting to long-term isolation environmental factors.

Project description:BackgroundPatients suffering from acute myocardial infarction (AMI) are at risk of secondary outcomes including major adverse cardiovascular events (MACE) and heart failure (HF). Comprehensive molecular phenotyping and cardiac imaging during the post-discharge time window may provide cues for risk stratification for the outcomes.Materials and methodsIn a prospective AMI cohort in New Zealand (N = 464), we measured plasma proteins and lipids 30 days after hospital discharge and inferred a unified partial correlation network with echocardiographic variables and established clinical biomarkers (creatinine, c-reactive protein, cardiac troponin I and natriuretic peptides). Using a network-based data integration approach (iOmicsPASS+), we identified predictive signatures of long-term secondary outcomes based on plasma protein, lipid, imaging markers and clinical biomarkers and assessed the prognostic potential in an independent cohort from Singapore (N = 190).ResultsThe post-discharge levels of plasma proteins and lipids showed strong correlations within each molecular type, reflecting concerted homeostatic regulation after primary MI events. However, the two molecular types were largely independent with distinct correlation structures with established prognostic imaging parameters and clinical biomarkers. To deal with massively correlated predictive features, we used iOmicsPASS + to identify subnetwork signatures of 211 and 189 data features (nodes) predictive of MACE and HF events, respectively (160 overlapping). The predictive features were primarily imaging parameters, including left ventricular and atrial parameters, tissue Doppler parameters, and proteins involved in extracellular matrix (ECM) organization, cell differentiation, chemotaxis, and inflammation. The network signatures contained plasma protein pairs with area-under-the-curve (AUC) values up to 0.74 for HF prediction in the validation cohort, but the pair of NT-proBNP and fibulin-3 (EFEMP1) was the best predictor (AUC = 0.80). This suggests that there were a handful of plasma proteins with mechanistic and functional roles in predisposing patients to the secondary outcomes, although they may be weaker prognostic markers than natriuretic peptides individually. Among those, the diastolic function parameter (E/e' - an indicator of left ventricular filling pressure) and two ECM proteins, EFEMP1 and follistatin-like 3 (FSTL3) showed comparable performance to NT-proBNP and outperformed left ventricular measures as benchmark prognostic factors for post-MI HF.ConclusionPost-discharge levels of E/e', EFEMP1 and FSTL3 are promising complementary markers of secondary adverse outcomes in AMI patients.

Project description:Periodontitis, the leading cause of adult tooth loss, has been identified as an independent risk factor for cardiovascular disease (CVD). Studies suggest that periodontitis, like other CVD risk factors, shows the persistence of increased CVD risk even after mitigation. We hypothesized that periodontitis induces epigenetic changes in hematopoietic stem cells in the bone marrow (BM), and such changes persist after the clinical elimination of the disease and underlie the increased CVD risk. We used a BM transplant approach to simulate the clinical elimination of periodontitis and the persistence of the hypothesized epigenetic reprogramming. Using the low-density lipoprotein receptor knockout (LDLRo ) atherosclerosis mouse model, BM donor mice were fed a high-fat diet to induce atherosclerosis and orally inoculated with Porphyromonas gingivalis (Pg), a keystone periodontal pathogen; the second group was sham-inoculated. Naïve LDLR o mice were irradiated and transplanted with BM from one of the two donor groups. Recipients of BM from Pg-inoculated donors developed significantly more atherosclerosis, accompanied by cytokine/chemokines that suggested BM progenitor cell mobilization and were associated with atherosclerosis and/or PD. Using whole-genome bisulfite sequencing, 375 differentially methylated regions (DMRs) and global hypomethylation in recipients of BM from Pg-inoculated donors were observed. Some DMRs pointed to the involvement of enzymes with major roles in DNA methylation and demethylation. In validation assays, we found a significant increase in the activity of ten-eleven translocase-2 and a decrease in the activity of DNA methyltransferases. Plasma S-adenosylhomocysteine levels were significantly higher, and the S-adenosylmethionine to S-adenosylhomocysteine ratio was decreased, both of which have been associated with CVD. These changes may be related to increased oxidative stress as a result of Pg infection. These data suggest a novel and paradigm-shifting mechanism in the long-term association between periodontitis and atherosclerotic CVD.

Dataset Information

Integrated Analysis of DNA Methylation and Biochemical/Metabolic Parameter During the Long-Term Isolation Environment.

Publications

Integrated Analysis of DNA Methylation and Biochemical/Metabolic Parameter During the Long-Term Isolation Environment.

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