六種複雜疾病：第二型糖尿病，慢性腎臟病，阿茲海默症，甲狀腺癌，高雪氏症以及多發性硬化症之 共同與獨特的功能基因組和分子特徵

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姓名

田雅馨(Ya-Hsin Tien) 查詢紙本館藏

畢業系所

系統生物與生物資訊研究所

論文名稱

六種複雜疾病：第二型糖尿病，慢性腎臟病，阿茲海默症，甲狀腺癌，高雪氏症以及多發性硬化症之共同與獨特的功能基因組和分子特徵
(Common and unique functional genomic and molecular features of six complex diseases: type 2 diabetes, chronic kidney disorder, Alzheimer’s disease, thyroid cancer, Gaucher disease, and multiple sclerosis)

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摘要(中)

複雜疾病，如癌症、神經退化性疾病、糖尿病以及心血管疾病等都和數千個基因間的相互作用改變有著很密切的關係。雖然許多遺傳和環境因素上的變異都跟複雜疾病有關，但與這些疾病有關的遺傳病因仍然是很大的未知。在此，我們收集19組基因表現量數據集包含了6種複雜疾病(第二型糖尿病、慢性腎臟病、阿茲海默症、甲狀腺癌、高雪氏症以及多發性硬化症)進行功能基因組分析，探索疾病功能的相似性與差異性，並鑑定跟功能相關的基因型獨特重要基因。我們的研究結果提出了許多實驗驗證文獻，並為六種複雜疾病的預防、診斷和治療提供了有用的信息。

摘要(英)

Complex diseases such as cancer, neurodegenerative disorders, diabetes mellitus, and cardiovascular disease are associated with altered interactions between thousands of genes. Although variants in many genetic and environmental factors have been associated with complex diseases, inter-disease relations remains largely unexplored. Here, based on nineteen gene expression datasets on six complex diseases – type 2 diabetes, chronic kidney disorder, Alzheimer’s disease, thyroid cancer, Gaucher disease, and multiple sclerosis – we construct functional genomic analysis of the diseases, explore functional similarity/dissimilarity among the diseases, and identify function-associated genotype-unique significant genes for the diseases. Our results suggest many validating experiments and provide useful information for the prevention, diagnostic, and treatment of the six complex diseases.

關鍵字(中)

★ 複雜疾病
★ 基因表達微陣列分析
★ 功能基因組學
★ 疾病-疾病比較
★ 基因型獨特顯著基因

關鍵字(英)

★ Complex diseases
★ gene expression microarray analysis
★ functional genomics
★ disease-disease comparison
★ genotype-unique significant genes

論文目次

中文摘要 i
Abstract ii
誌謝 iii
目錄 iv
圖目錄 vi
表目錄 vii
第一章、緒論 1
1.1 複雜疾病 1
1.2 基因表達與調控 4
1.3 微陣列分析 6
1.4 功能基因組學與複雜疾病 8
1.5 研究目標 9
第二章、材料與方法 13
2.1 複雜疾病數據組與前處理 13
2.2 分子標籤資料庫 15
2.3 基因集富集分析 16
2.3.1 ES值 16
2.3.2 NES值 17
2.3.3 名義p值 18
2.3.4 前緣子集 18
2.4 KEGG生物路徑的富集分析 19
2.5 挑選分子標籤的門檻與篩選顯著分子標籤 19
2.6 疾病與顯著分子標籤的雙向集群分析 19
2.7 疾病特異性集群基因集的建立 20
2.8 相似係數 20
第三章、研究結果 21
3.1 19組數據集與191個顯著分子標籤的雙向集群 21
3.2 篩選四大集群前緣子集基因 22
3.3 各集群前緣子集基因的KEGG術語富集強度趨勢 23
3.4 篩選基因型獨特的分子標籤 25
3.5 八種基因型獨特分子標籤集群與191個顯著分子標籤集群的結果相似 27
3.6 八種基因型前緣子集基因的交集 28
3.7 篩選基因型特異性高頻前緣子集基因進行KEGG分析 30
3.8 基因型特異性高頻前緣子集基因在KEGG術語中的富集強度 31
3.9 篩選基因型獨特顯著基因 34
3.10 七大基因型獨特顯著基因與KEGG術語網路圖譜 37
第四章、討論 40
第五章、總結 46
參考文獻 47
附錄 53

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指導教授

李弘謙(Hoong-Chien Lee)

審核日期

2018-7-27

推文