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研究生: 周彥如
Chou, Yen-Ju
論文名稱: 以疾病相關之蛋白激酶為核心化簡蛋白質交互作用網路工具
DKNY: A Disease Associated Kinase PPI Network Refinement Tool Combining Microarray Data
指導教授: 蔣榮先
Chiang, Jung-Hsien
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 資訊工程學系
Department of Computer Science and Information Engineering
論文出版年: 2007
畢業學年度: 95
語文別: 中文
論文頁數: 46
中文關鍵詞: 激酶疾病蛋白質交互作用網路交互作用網路信號傳導相關性反應路徑
外文關鍵詞: pathway, ppi, kinase, disease, signal transduction, interaction
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  • 生物反應路徑為目前相當重要的研究,而在生物反應路徑中,信號傳導扮演著極重要的角色,磷酸化反應為主要的信傳導方式,因此探討磷酸化反應直接或間接對其他蛋白質的影響,可對生物反應路徑有更進一步的瞭解。然而,現今天研究中,尚未提供一個工具建立與疾病相關之信號傳導蛋白質交互作用網路,因此在本論文中,我們提出以疾病相關之蛋白激酶為核心化簡蛋白質交互作用網路之工具。本論文先建立與疾病相關聯之蛋白激酶交互作用網路,並將此交互作用網路擴張以得到蛋白激酶直接或間接對其他蛋白質的影響之資訊,接著我們採用「六度分離」理論化簡此網路中的雜訊,並且整合疾病之微陣列實驗資料,利用視覺化呈現給使用者。
    本論文提供查詢以疾病相關之蛋白激酶為核心化簡蛋白質交互作用網路之工具,利用此工具,生醫研究者可經由視覺化呈現之蛋白質交互作用網路中,得到可能之調控路徑,並根據分析過之微陣列實驗的結果表現值,得到可能與此疾病相關之異常表現基因。

    Studies have shown that signal transduction pathways play key roles in most biological process pathway. Phosphorylation is the critical way of signal transduction. Study the regulation of protein kinase on other proteins can help us to realize biological process pathway further. Besides, we can get more information of disease by combining the protein kinase-related network and disease-related gene expression data. However, the general PPI networks are too complex to see the information in it. In this study, we use statistical method to find disease-related protein kinase and construct protein kinase-related network. In order to decrease the network complexity, we apply Six Degrees of Separation theory to refine the network. Finally, we combined this network with microarray data of the disease.
    We present a tool to visualize a disease associated kinase PPI network which is called DKNY. Users can see the possibly regulated path with analyzed express data by using DKNY.

    第一章 導論 1 1.1 前言 1 1.2 研究動機 1 1.3 解決方法 2 1.4 論文架構 2 第二章 文獻探討與相關研究 3 2.1 生物資訊學 3 2.2 激?與磷酸化 4 2.3 基因與疾病 6 2.4 蛋白質間交互作用網路建構與視覺化 7 2.5 網路化簡 8 2.6 六度分隔 8 第三章 疾病與蛋白激?相關蛋白質交互作用網路 10 3.1 方法概述 10 3.2 系統流程架構 11 3.3 特定疾病之蛋白激?相關蛋白質交互作用網路之建立 13 3.4 蛋白質交互作用網路化簡 16 3.5 生物實驗數據結果分析 24 3.6 系統流程與使用簡介 25 第四章 實驗設計與結果分析 27 4.1 資料收集與處理 27 4.1.1 磷酸化相關資料收集與處理 27 4.1.2 蛋白質交互作用資料收集 28 4.2 實驗設計與結果分析 29 4.2.1 蛋白質與疾病關聯性計算之參數調整 29 4.2.2 網路化簡前後複雜度比較 30 4.2.3 信號傳導相關顯著性分析 33 4.2.4 交互作用網路路徑驗證 35 第五章 結論與未來展望 38 5.1 結論 38 5.2 未來展望 38 參考文獻 39 附錄A 各疾病參數及排名比例之F-MEASURE實驗結果 43

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