尼曼匹克症轉錄體學研究

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姓名

劉明翰(Ming-Han Liu) 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

尼曼匹克症轉錄體學研究
(Transcriptomics research of Niemann-Pick disease)

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摘要(中)

尼曼匹克症C型是基因突變所導致的罕見疾病，它會使次級內體及溶酶體中的膽固醇及鞘糖脂過度累積，導致患者引發神經或精神上的症狀。尼曼匹克症C型與其他疾病相比，尼曼匹克症C型的研究相對少很多，而運用轉錄組來瞭解這種疾病的研究更是屈指可數。在這份研究中，我們從患者的周邊血液中取得轉錄組需要的樣本，透過次世代定序取得RNA的表現量，這些基因表現量透過顯著檢定與差異倍數篩選出顯著的基因，我們使用這些基因進行後續的生物途徑分析。我們也將這些尼曼匹克症C型的患者進行不同表徵的分組，並在分析後進行討論。透過生物途徑的分析，我們從尼曼匹克症C型的患者的差異表達基因中發現了與神經退化疾病相關的生物途徑，也找出與尼曼匹克症C型相關的PIK3CG及PIK3CD兩個基因和磷酸肌醇的代謝路徑。

摘要(英)

Niemann-Pick disease type C is a rare disease caused by gene mutations that cause excessive accumulation of cholesterol and glycosphingolipids in late endosomes and lysosomes, resulting in neurological or psychiatric symptoms. The research of Niemann-Pick disease type C is relatively understudied compared to other diseases, and it is rare that use transcriptomes to understand this disease. In this study, we obtained the samples needed for the transcriptome from the peripheral blood of patients, and we got RNA expressions through next-generation sequencing. The expressions of these genes were filtered by significance testing and foldchange. After the analysis, we also grouped these Niemann-Pick disease type C patients with different characteristics and discussed them. Through the analysis of biological pathways, we found some pathways related to neurodegenerative diseases from the differentially expressed genes of patients with Niemann-Pick disease type C. We also identified that PIK3CG, PIK3CD, and the inositol phosphate metabolism pathway are associated with Niemann-Pick disease type C.

關鍵字(中)

★ 尼曼匹克症C型
★ 罕見疾病
★ 次世代定序
★ 轉錄組

關鍵字(英)

★ Niemann-Pick disease type C
★ rare disease
★ next generation sequence
★ transcriptome

論文目次

中文摘要 i
Abstract ii
目錄 iii
圖目錄 vi
表目錄 vii
一、緒論 1
1-1尼曼匹克症C型 1
1-2尼曼匹克症C型治療方法 2
1-3 尼曼匹克症C型的淋巴細胞 2
1-4次世代定序 3
1-5基因表現量、差異表達基因 3
1-6研究動機與目的 4
二、材料與方法 5
2-1資料來源 5
2-2研究方法 7
2-2-1開發環境 7
2-2-2 RNA-Sequencing 8
2-2-3資料預處理 8
2-2-4基因集富集分析 9
2-2-5 Ingenuity Pathways Analysis 9
2-2-6 CIBERSORT 10
2-2-7 Kyoto Encyclopedia of Genes and Genomes 10
2-2-8 Gene Ontology 11
三、實驗流程 12
四、結果 13
4-1 NPC患者與一般人的RNA表達差異 13
4-1-1 CIBERSORT分析 13
4-1-2主成分分析 14
4-1-3基因集富集分析 16
4-1-4基因篩選 17
4-1-5 IPA 18
4-1-6 KEGG 途徑分析 20
4-1-7 GO功能分析 21
4-2在NPC患者之間分組的RNA表達差異 23
4-2-1使用HPβCD治療的NPC患者與使用Miglustat治療的NPC患者 24
4-2-1-1基因集富集分析 24
4-2-1-2基因篩選 25
4-2-1-3 IPA 27
4-2-1-4 KEGG 途徑分析 29
4-2-1-5 GO功能分析 30
4-2-2 NPC1基因有兩個突變點的NPC患者與單一突變點的NPC患者 32
4-2-2-1基因篩選 32
4-2-2-2 IPA 34
4-2-2-3 KEGG 途徑分析 36
4-2-2-4 GO功能分析 37
4-2-3發病年齡小於6歲的NPC患者與大於6歲的NPC患者 39
4-2-3-1基因篩選 39
4-2-3-2 IPA 41
4-2-3-3 KEGG 途徑分析 43
4-2-4男性NPC患者與女性NPC患者 44
4-2-4-1基因篩選 44
4-2-4-2 IPA 46
4-2-4-3 KEGG 途徑分析 48
4-3 各組別分析結果當中的重要基因 49
五、討論與結論 51
5-1 NPC患者與一般人的差異表達基因分析 51
5-2 PI3K/AKT與mTOR訊號通路 52
5-3 NPC患者之間分組的差異表達基因分析 53
5-4 NPC患者的免疫系統 54
5-5結論 55
參考文獻 56

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指導教授

許藝瓊(Yi-Chiung Hsu)

審核日期

2022-9-16

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