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A Pathway Analysis Based on Genome-Wide DNA Methylation of Chinese Patients with Graves' Orbitopathy

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机构: [1]Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China [2]Department of Mathematics, School of Biomedical Engineering, Capital Medical University, Beijing, China [3]Physical Examination Department, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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Background. The pathogenesis Graves' Orbitopathy (GO) is not yet fully understood. Here, we conducted a pathway analysis based on genome-wide DNA methylation data of Chinese GO patients to explore GO-related pathways and potential feature genes. Methods. Six GO patients and 6 age-matched control individuals were recruited, and a genome-scale screen of DNA methylation was measured using their peripheral blood sample. After extracting the differentially methylated regions (DMRs), we classified DMRs into three clusters with respect to median absolute deviation (MAD) for GO and control group, respectively. Then the extract tests were performed to identify significant pathways by comparing the counts of genes in each cluster between GO and control group in a pathway. For each significant pathway, we calculated the Methylation-based Inference of Regulatory Activity (MIRA) score to infer the regulatory activity of genes involved in the pathway. Furthermore, we took the significant pathways as the subsets and applied Random forests (RF) method to extract GO-related feature genes. Results. We identified four potential significant pathways associated with the occurrence and development of GO disease. There were Toxoplasmosis, Axon guidance, Focal adhesion, and Proteoglycans in cancer (p<0.001 or p=0.007). The identified genes involved in the significant pathways, such as LDLR (p=0.019), CDK5 (p=0.036), and PIK3CB (p=0.020), were found to be correlated with GO phenotype. Conclusion. Our study suggested pathway analyses can help understand the potential relationships between the DNA methylation level of some certain genes and their regulation in Chinese GO patients.

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出版当年[2018]版:
大类 | 3 区 生物
小类 | 3 区 生物工程与应用微生物 4 区 医学:研究与实验
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出版当年[2017]版:
Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 MEDICINE, RESEARCH & EXPERIMENTAL
最新[2023]版:
Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Q3 MEDICINE, RESEARCH & EXPERIMENTAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2017版] 出版当年五年平均 出版前一年[2016版] 出版后一年[2018版]

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第一作者机构: [1]Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, China
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