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研究生:何其偉
研究生(外文):Chi-wei Ho
論文名稱:人類肝臟組織特定基因啟動子之研究與辨識
論文名稱(外文):Investigation and identification of liver-specific gene promoters in humans
指導教授:李宗夷
指導教授(外文):Tzong-Yi Lee
學位類別:碩士
校院名稱:元智大學
系所名稱:生物與醫學資訊碩士學位學程
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:38
中文關鍵詞:肝臟組織特定基因啟動子
外文關鍵詞:liver-specific gene promoters
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啟動子在基因轉錄的調控中是一個很重要的調控元件,分析啟動子能幫助生物學家更加了解整個基因調控網路。根據文獻,一群基因會受到特定轉錄因子(transcription factor)的共同調控,因而在特定組織內共同表現(co-expression),人類肝臟(liver)是常被用來研究基因之組織特定性(Tissue specificity)的標的。根據基因表現的資料(gene expression data)並結合生物資訊的方法去研究肝臟組織特定基因內調控區域的短片段序列(oligo-nucleotide)之表現程度,接著利用統計方法取得重要之短片段序列並用來辨識人類所有基因啟動子(promoter)中屬於肝臟組織特定基因的啟動子,在這裡也加入已知的轉錄因子接合位置(transcription factor binding site)資料去做預測。在22,000多條人類基因啟動子序列內,對於肝臟組織特定基因的預測可以達到70%以上的效能,接著使用這些資料集做跨物種(老鼠)的分析與預測,並且利用同源基因的特性,對於跨物種做更進一步的分析,經過分析之後,還加入UniProtKB/SwissProt的資料當作獨立資料去測試我們的方法並分析結果,希望藉由我們的分析能對了解基因調控的機制有所幫助。

Promoters play the important roles in gene transcriptional regulation. Promoter investigation is the way to help biologists to understand the gene regulatory networks. A group of co-expressed genes might be regulated by a set of transcription factors (TFs), especially for tissue-specific genes. With regard to the tissue specificity of genes, human liver is one of the tissues that are usually used in the study of tissue-specific regulation of transcription. Based on gene expression data and bioinformatics method, we investigate the oligo-nucleotides in liver-specific gene promoter sequences and use the statistically significant oligo-nucleotides to identify liver-specific gene promoters against all human promoters. Additionally, the transcription factor binding sites with the annotation of liver specificity were taken into account. The investigation indicates that the proposed method can perform better than 70% accuracy in the dataset of 22,000 human promoters. Moreover, the cross-species analysis between human and mouse genes is investigated to try the improvement of predictive performance. Finally, the independent testing data from UniProtKB/SwissProt were used to test the proposed method. After the investigation of human liver-specific gene promoters, the significant sequence features can help biologists studying the liver specificity of gene regulation

書名頁 i
審定書 ii
授權書 iii
中文摘要 iv
英文摘要 v
誌謝 vi
目錄 vii
表目錄 ix
圖目錄 x
第一章、簡介 1
1.1 背景知識 2
1.1.1 基因的轉錄 2
1.1.2 基因的表現 3
1.1.3 轉錄起始位置、轉錄因子和轉錄因子結合位置 3
1.1.4 肝臟組織 4
1.2 動機 4
1.3 目標 4
第二章、相關研究 5
2.1 組織特定基因 5
2.2 TRANSFAC資料庫 6
第三章、資料與方法 7
3.1 資料 7
3.1.1 人類(human)和老鼠(mouse)基因序列 7
3.1.2 基因表現資料(Gene Expression Data) 8
3.1.3 已知的TFBS資料庫 9
3.1.4 人類(human)與老鼠(mouse)的同源基因 9
3.1.5 獨立資料(Independent data) 9
3.2 方法 10
3.2.1 系統流程 10
3.2.2 重複序列之處理(Repeat Mask) 11
3.2.3 組織特定基因的篩選 12
3.2.4 Z分數(Z-score) 12
3.2.5 基因晶片分析工具(TreeView) 13
3.2.6 序列片段選取 16
3.2.7 超幾何測試(Hypergeometric Test) 17
3.2.8 同源基因片段的選取 18
3.2.9 資料的格式轉換 19
3.2.10 分類器(Support Vector Machine) 20
3.2.11 效能評估方式 21
3.2.12 Five-fold cross-validation 21
3.3 各組織之基因數量 22
3.4 肝臟組織特定基因的高度表現片段資料集 23
3.5 TRANSFAC屬性資料集 24
3.6 同源基因資料集 25
第四章、結果 26
4.1 肝臟組織特定基因預測 26
4.2 肝臟組織與其他組織之預測(人類組織) 27
4.3 TRANSFAC資料集預測肝臟組織特定基因 28
4.4 跨物種的分析預測 29
4.5 組織與組織的分析預測(老鼠組織) 30
4.6 同源基因的預測分析 30
4.7 獨立資料的測試 31
第五章、討論 32
5.1 同源基因分析 32
5.2 獨立資料分析 32
第六章、總結 33
6.1 結論 33
6.1.1 8-mer短片段與已知的TFBS 33
6.2 未來研究 34
6.2.1 基因抑制(Gene Silencing) 34
6.2.2 加強TFBS的挑選 35
參考文獻 36


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