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UM E-Theses Collection (澳門大學電子學位論文庫)

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Title

利用生物網絡和基因表達譜分析評價阿爾茲海默症和二型糖尿病的關聯性研究

English Abstract

Objective: This study aimed to identify common genes and biological pathways between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) based on the analyses of biological networks and gene expression profiles, and evaluate the association between AD and T2DM. Methods: The susceptibility genes of AD and T2DM were retrieved from Online Mendelian Inheritance in Man database (OMIM). Molecule interactions of the disease genes and their neighbors were extracted from Human Protein Reference Database (HPRD), IntAct molecular interaction database (IntAct) and Kyoto Encyclopedia of Genes and Genomes database (KEGG) to construct the networks of AD and T2DM with Cytoscape, respectively. Eligible gene expression profiles of AD and T2DM were retrived from Gene Expression Omnibus database (GEO), which were analyzed with affy and limma packages in R software to identify differentially expressed genes (DEGs) of AD and T2DM. Active modules of AD and T2DM were identified through combining the biological networks with differentially expressed genes of AD and T2DM by jActiveModules app of Cytoscape, respectively. Active networks of AD and T2DM were constructed by combining the active modules. Molecular complex detection method (MCODE) was used to decompose the active networks into AD and T2DM clusters to retrieve DEGs. Gene pathway enrichment analysis of AD and T2DM DEGs retrieved from clusters was performed with DAVID. Results: Sixteen AD and 39 T2DM susceptibility genes were retrieved form OMIM, and none of them was shared by AD and T2DM. AD and T2DM had 75 and 125 DEGs retrieved from clusters and these DEGs enriched in 15 and 34 biological pathways, respectively. AD and T2DM shared 20 DEGs and 13 biological pathways. None of the DEGs and biological pathways was specific for AD and T2DM by checking the available data. Conclusion: The study identified 20 DEGs and 13 biological pathways shared by AD and T2DM, which genes and pathways were not specific for the two diseases. The current findings from genes and biological pathways were inadequate to support the hypothesis of any specific association between the two diseases.

Chinese Abstract

目的:利用生物網絡和基因表達譜尋找阿爾茲海默症 (AD) 和二型糖尿病 (T2DM) 共有的基因和生物路徑,並分析評價兩者的關聯性。 方法:從在線人類孟德爾遺傳數據庫(OMIM)中提取 AD 和 T2DM 的易感基 因。從人類蛋白質相互作用數據庫(HPRD)、IntAct 分子間相互作用數據庫 (IntAct) 和京都基因和基因組百科數據庫 (KEGG) 提取和易感基因及其相鄰分 子相互作用的數據。使用 Cytoscape 軟件分別構建 AD 和 T2DM 的生物網絡圖。 從基因表達綜合數據庫 (GEO) 中提取符合標準的 AD 和 T2DM 的基因表達譜。 使用 R 軟件的 affy 和 limma 包計算得到 AD 和 T2DM 的差異表達基因。使用 Cytoscape 軟件的插件 jActiveModules 分別將 AD 和 T2DM 的生物網絡圖和差異 表達基因結合,分別得到 AD 和 T2DM 活躍模塊。將活躍模塊合併構建活躍網 絡圖,然後使用分子複合物檢測方法 (MCODE) 從活躍網絡圖中分別得到 AD 和 T2DM 的集群提取差異表達基因。使用 DAVID 在線工具分別對從 AD 和 T2DM 集群中提取的差異表達基因進行基因路徑富集分析。 結果:從 OMIM 數據庫得到 16 個 AD 和 39 個 T2DM 的易感基因,兩者沒有相 同的易感基因。分別從 AD 和 T2DM 活躍網絡圖中得到 AD 和 T2DM 的集群, 從集群中分別提取 75 個 AD 和 125 個 T2DM 差異表達基因,兩者共有 20 個差 異表達基因。AD 和 T2DM 的差異表達基因分別富集在 15 個和 34 個生物路徑, 兩者共有 13 個生物路徑。檢查現有數據發現 AD 和 T2DM 共有的 20 個差異表 達基因和 13 個生物路徑都不是兩者所特有。 結論:本研究找到 AD 和 T2DM 共有 20 個差異表達基因和 13 個生物路徑,並 不是兩者所特有。本研究發現從目前個別基因與生物路徑研究結果尚不能支持 AD 和 T2DM 有特異關聯性。

Issue date

2016

Author

靳單蘋

Faculty

Institute of Chinese Medical Sciences

Degree

M.Sc.

Subject

Alzheimer's disease

阿茲海默症

Non-insulin-dependent diabetes

二型糖尿病

Medicinal Administration -- Institute of Chinese Medical Sciences

醫藥管理 -- 中華醫藥研究院

Supervisor

梁少偉

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1/F Zone C
Library URL
991001881939706306