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研究生: 陳伯涵
Chen, Po-Han
論文名稱: 透過動態蛋白質交互作用網路研究斑馬魚心臟創傷恢復過程中再生機制的重要訊息路徑
Searching for significant pathways for regeneration mechanism in zebrafish heart wound healing process via dynamic protein-protein interaction network
指導教授: 陳博現
Chen, Bor-Sen
口試委員: 陳博現
林俊良
莊永仁
吳謂勝
林澤
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2012
畢業學年度: 100
語文別: 英文
論文頁數: 59
中文關鍵詞: 斑馬魚心臟再生系統生物學發炎反應
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  • 心血管疾病威脅著人類的健康且至今仍是全球人類最大的死因之一。這些威脅對人類的影響特別大,因為哺乳類心臟在心肌梗塞(MI)後並不能夠再生。不同於哺乳類,斑馬魚受傷後的心臟則是能夠完整再生的。因此研究斑馬魚創傷恢復及再生程序,對於人類疾病的療法發展是很重要的。基於直向同源資訊和時間序列微陣列資訊,我們利用動態交互作用模型建構出斑馬魚心臟再生過程中三個生理恢復階段的蛋白質交互作用網路。我們也建構出了創傷恢復過程中三個生理階段之間的蛋白質交互作用差異性網路來調查心臟創傷恢復中有意義的機制。使用現有的信號途徑分析工具,我們辨別出了蛋白質交互作用差異性網路中在第一階段到第二階段以及第二階段到第三階段裡有高度連接的軸心蛋白質所牽動的重要信號途徑。我們也更深入的辨別出,經由兩倍倍數變化挑選後的蛋白質池扮演的重要訊息途徑,並對照整個創傷恢復過程將其重要的訊息途徑串聯起來。最後,我們探究了蛋白質交互作用差異性網路中一些和發炎相關的軸心蛋白質並且透過信號途徑分析來探索其潛藏的功能模組。我們相信這些潛藏的功能模組對於心臟創傷恢復過程是至關重要的。藉由動態交互作用網路的建構和重要訊息途徑的確立,我們希望能夠釐清創傷恢復過程中發炎機制還不明確的作用,並且從系統生物學的觀點來提供心血管疾病治療方法之中可能的藥物目標。


    摘要 i Abstract iii 誌謝 v Content vi List of tables viii List of Figures ix Introduction 1 Materials and Methods 5 2.1 Overview of the process 5 2.2 Data selection and preprocessing 6 2.3 Selecting protein pool 8 2.4 Constructing PPI networks at three physiological stages of heart wound healing process 9 2.5 Network parameter identification by time series microarray 12 2.6 Determination of significant protein interaction by pruning insignificant PPIs 14 2.7 The network reconfiguration between different stages in heart wound healing process 16 2.8 Enriched functional modules and pathways in zebrafish wound healing process 19 Results 20 3.1 Construction of PPI networks at different time stages of heart wound healing process 20 3.1.1 Construction of general PPI networks by integrated omics databases 20 3.1.2 Profile of temporal gene expression in three stages of zebrafish heart wound healing process 22 3.2 Dynamic network analysis 23 3.2.1 Dynamic network transition between stages A, B and stages B,C in the heart wound healing process PPIs 23 3.2.2 Investigation of high transition hubs between different stages 25 3.3 Pathway analysis for three 2X-fold change protein pools 28 3.4 Inflammation related hubs to wound healing 32 Discussion & Conclusion 34 Reference 37

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