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研究生: 盧信智
Shin-Jr Lu
論文名稱: 應用卵巢癌之微陣列晶片分析基因表現量及調控路徑
Gene Expression Analysis and Regulator Pathway Exploration with the Use of Microarray data for Ovarian Cancer
指導教授: 蔡孟勳
Meng-Hsiun Tsai
蘇順豐
Shun-Feng Su
口試委員: 鍾聖倫
Sheng-Luen Chung
鄭錦聰
Jin-Tsong Jeng
莊鎮嘉
Chen-Chia Chuang
學位類別: 碩士
Master
系所名稱: 電資學院 - 電機工程系
Department of Electrical Engineering
論文出版年: 2006
畢業學年度: 94
語文別: 英文
論文頁數: 70
中文關鍵詞: 微陣列晶片非監督式分群調控基因卵巢癌化調控路徑疾病基因標記
外文關鍵詞: disease linked gene markers, ovarian cancer, microarray, regulator gene, unsupervised classification, biochemical pathways
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  • 微陣列晶片是發展及應用較為成熟的生物晶片技術,通常用來做為大量篩檢及平行分析的工具,可以應用在基因表現比較、基因序列分析、及新藥物開發等領域。本論文使用卵巢癌的微陣列樣本做為分析對象,提出適用於探索疾病基因表現量之流程,首先利用回歸分析粗略地挑出200個基因,再利用變異數分析檢定個別基因在不同樣本之表現差異,得到12個疾病基因標記,利用此12個基因表現量當作非監督式分群的輸入變數,比較哪種分群方法效果最好,並提供視覺化的圖形介面系統,可讓生醫學者更直觀且迅速的觀察基因表現之型態。
    一個生物體的表現型態是經由一群特定基因或蛋白質透過複雜交互作用,結合時序及空間的變化共同完成的,而形成生物學家所熟悉生化調控路徑。本論文建立了一搜尋機制,從龐大的網路資訊中找出和輸入基因相關的調控資訊和基因,並建立由輸入基因為起始的調控路徑,配合微陣列的基因表現量資料庫找出各調控基因和各期癌症的相關性,可以找出形成腫瘤或是造成腫瘤惡化的關鍵調控基因。


    Microarray is a mature technology of gene chip. It is a common tool for biological detection and parallel analysis and can be employed in comparison of gene expression, sequence analysis and development of new medicine etc. In this study, we consider ovarian cancer as the target for analysis and propose a procedure for analyzing gene expression in microarray data. At first, regression analysis is used to pick out 200 genes, and then ANOVA is employed to detect difference of gene expression in each sample to get 12 disease linked gene markers. These 12 gene expressions are considered as input variables of unsupervised classification methods to find the best effect of all methods. This paper also provides a graphic interface system for visualization. It can provide useful biological, diagnostic, and prognostic information for mechanistic studies. Specific genes or proteins are combined under mutual influence along time and space to archive the phenotype of an organism. Such a process is usually referred to as the biochemical pathways. In this paper, we construct a scheme of finding the related regulator gene and information with initial gene from Internet database to generate possible pathways. It can find the relations between regulator genes with each stage of cancer, and then get the critical regulator gene of causing tumor. Hopefully, such a scheme can provide researchers to use worldwide biological database to have clues on the research on microarray analysis.

    Contents 摘要..…………………………………………………………………………………..I Abstract………………………………………………………………………………II 誌謝……………………………….…………………………………………………III Contents……………………………………………………………………………..IV List of Tables………………………………………………………………………...VI List of Figures……………………………………………………………………..VIII Chapter 1 Introduction 1.1 Background…………………………………………………………...1 1.2 Gene chip……………………………………………………………...1 1.3 Motivation…………………………………………………………….2 Chapter 2 Literature Review 2.1 Linear regression……………………………………………………..3 2.2 ANOVA………………………………………………………………..3 2.3 Unsupervised clustering methods…………………………………...4 2.3.1 SOM……………………………………………………...4 2.3.2 FCM……………………………………………………...6 2.3.3 Hierarchical Clustering………………………………...8 2.4 Oncogene…………………………………………………………….10 2.5 Gene Regulatory Networks………………………………………...11 Chapter 3 Analysis procedure and interface Structure introduction 3.1 Scheme……………………………………………………………….14 3.2 The details of the procedure………………………………………..15 3.2.1 Data loading……………………………………………15 3.2.2 Regression Analysis……………………………………16 3.2.3 ANOVA………………………………………………...18 3.3 Clustering……………………………………………………………19 3.3.1 SOM……………………………………………….……19 3.3.2 FCM……………………………………………….……20 3.3.3 Hierarchical Clustering…………………………….…21 3.4 Up regulation and down regulation genes…………………………22 3.5 Pathway……………………………………………………………...23 Chapter 4 Experiment Results 4.1 Data pre-process- Regression Analysis…………………………….28 4.2 ANOVA……………………………………………………………....32 4.3 PCA……………………………………………………………..........36 4.4 Gene expression visualization………………………………............37 4.4.1 The Trend Graphs of Individual Sample…….............37 4.4.2 Individual Gene Trend Graphs……………….............38 4.4.3 3D Trend Graph……………………………….............40 4.5 Unsupervised Classification………………………………..............41 4.5.1 SOM………………………………………………….....41 4.5.2 FCM………………………………………………….....45 4.5.3 Hierarchical Clustering…………………………….....47 4.6 The comparison of each method…………………………………...50 4.7 Pathway………………………………………………………….......51 Chapter 5 Conclusions and Future Work 5.1 Conclusions………………………………………………………….58 5.2 Feature work………………………………………………………...59 Reference……………………………………………………….................................60 Appendix……………………………………………………….................................63 作者簡介………………………………………………………..................................69 授權書………………………………………………………......................................70

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