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系統識別號 U0026-2507201110365400
論文名稱(中文) 以文獻實證及特定組織生物晶片為基礎之癌症微核糖核酸調控元件建構與分析
論文名稱(英文) Identification of cancer-related miRNA regulatory components from evidence-supported literatures and specific tissue expression profiles
校院名稱 成功大學
系所名稱(中) 醫學資訊研究所
系所名稱(英) Institute of Medical Informatics
學年度 99
學期 2
出版年 100
研究生(中文) 陳建銘
研究生(英文) Jian-Ming Chen
學號 q56981012
學位類別 碩士
語文別 中文
論文頁數 77頁
口試委員 指導教授-蔣榮先
口試委員-曾大千
口試委員-劉校生
中文關鍵字 文獻探勘  資訊擷取  微核糖核酸  調控模組  微陣列分析 
英文關鍵字 Text Mining  Information Extraction  miRNA  Regulatory Module  Microarray analysis 
學科別分類
中文摘要 分子醫學研究在近十年的變化與進展非常快速。隨著生物實驗及相關研究資源與日俱增下,如何透過高效能的實驗設計分析與計算方法來有效且快速地找出研究者感興趣的資訊是一件相當重要的研究議題。過去在微核糖核酸的研究中,主要以微核糖核酸之發掘及其調控標的基因之預測為主。對於了解微核糖核酸在複雜的後轉錄調控作用機制中所扮演的角色及其功能並無太大的助益。基於欲解開小分子在生物體內的完整作用機制之需求。本研究將透過高效能的計算方法與分析技術並整合多項異質微陣列生物晶片等資訊,在特定的生物條件實驗設計下,於多個微核糖核酸及基因資料中找出一群具有共同表現的微核糖核酸及其調控標的基因。進而建構出以特定功能為基礎之整合式微核糖核酸調控元件。本研究亦結合文獻探勘技術的設計以協助找出與微陣列分析結果相關的文獻資訊,及探討透過顯著性功能分析與註解及階層式功能分群法所建構的癌症微核糖核酸調控模組。並設計若干組實驗如交互作用關聯擷取實驗與評估、微核糖核酸功能性驗證與評估、標的基因功能性驗證與評估、跨組織癌症調控模組之比較及調控元件模型之合理性驗證等來說明本研究的發現與價值。故本研究的主要貢獻將協助生物學家由複雜的後轉錄調控機制中,快速且正確地取得影響生物功能或疾病產生時的重要調控資訊。
英文摘要 In last decade, research issues for the area of molecular medicine have been constantly changing and rapidly progressing. However, discovering interesting biological information efficiently and accurately from a great deal of increasing biological experiments and related resources from high throughput experiments and computational analysis is a critical job. In previous miRNA studies, the main researches were focused on identification of miRNAs and prediction of its target genes. Nevertheless, there are quite few studies for understanding the roles and functions which miRNA plays in the complicated post-transcription level. To identify the complete molecule regulatory mechanisms within biological entities, this study will focus on identification of a group of co-expressed miRNAs and their target genes from multiple datasets for further constructing function-specific integrated miRNA regulatory components by combining with techniques of throughput experimental design and computational analysis, and integrating/analyzing multiple heterogeneous microarray gene expression profiles. This study also combines with the techniques of text mining approach for discovering literature information which are related to the results of microarray analyses, and discusses the cancer miRNA regulatory modules which are constructed by functional annotation and hierarchical functional clustering. Several experimental designs and analyses such as text mining evaluation, miRNA/gene functional validation, cross-tissue comparisons and validation on the model of regulatory components will also be proposed for elucidating our discoveries and values. So the main contribution of this study is to help biologists receive the important miRNA regulatory information which are related to biological functions or diseases from complicated regulatory mechanisms under post-transcription level.
論文目次 中文摘要 III
Abstract IV
誌 謝 VI
章節目次 VII
表 目 錄 IX
圖 目 錄 X
第一章 緒論 1
1.1 研究背景 1
1.2 研究動機與目的 3
1.3 研究方法 4
1.4 章節架構 6
第二章 文獻探討及相關研究 7
2.1 微陣列基因表現樣式 7
2.2 微核糖核酸之生成及其調控作用機制 8
2.3 微核糖核酸調控模組 10
2.4 文獻探勘技術 11
2.5 文字分析工具 12
2.5.1 LingPipe 12
2.5.2 Stanford POS Tagger 13
2.5.3 Stanford Parser 14
2.5.4 HTML Parser 15
2.5.5 Porter Stemmer 16
2.6 生物醫學資料庫 16
2.6.1 PubMed 16
2.6.2 Entrez Gene 17
2.6.3 miRBase 18
2.6.4 Gene Ontology 19
2.6.5 Ingenuity Pathway Analysis 21
第三章 微核糖核酸調控元件之建構與文獻探勘 23
3.1 整合式微核糖核酸調控元件之建構 23
3.1.1 微陣列基因表現資料之校正與篩選 24
3.1.2 候選微核糖核酸之挑選 25
3.1.3 候選基因之挑選 26
3.1.4 微核糖核酸與基因之關聯過濾 27
3.1.5 微核糖核酸調控元件之整合與建構 28
3.2 文獻探勘與實作 29
3.2.1 文字前置處理 29
3.2.2 名稱詞組識別 33
3.2.3 交互作用關聯擷取樣板之建構 36
3.2.4 交互作用關聯擷取 38
3.3 顯著性功能分析與註解 42
3.4 階層式功能分群演算法 42
第四章 實驗設計與驗證 47
4.1 交互作用關聯擷取實驗與評估 47
4.2 微核糖核酸功能驗證與評估 50
4.3 標的基因功能驗證與評估 55
4.4 跨組織癌症調控模組之比較 63
4.5 調控元件模型之合理性驗證 68
第五章 結論與展望 70
5.1 結論 70
5.2 未來展望 71
參考文獻 72
附錄A 詞性標記列表 75
附錄B 交互作用關聯詞彙 77
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