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研究生:陳柏志
研究生(外文):Chen, Bojhih
論文名稱:利用蛋白質交互作用與生物資訊資料庫重建與分析癌症路徑
論文名稱(外文):Reconstruction and analysis of cancer pathway via PPI database and bioinformatical database
指導教授:王逢盛
指導教授(外文):Wang, Fengsheng
口試委員:黃光策黃奇英周宜雄王逢盛
口試委員(外文):Huang ,KuangtseHuang ,ChiyingChou ,YishyongWang, Fengsheng
口試日期:2011-07-05
學位類別:碩士
校院名稱:國立中正大學
系所名稱:化學工程研究所
學門:工程學門
學類:化學工程學類
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:116
中文關鍵詞:網路重建癌症路徑布林邏輯
外文關鍵詞:reconstructioncancer pathwayboolean logic
相關次數:
  • 被引用被引用:0
  • 點閱點閱:258
  • 評分評分:
  • 下載下載:11
  • 收藏至我的研究室書目清單書目收藏:0
本研究以HeLa cell為研究的標的重建蛋白質網路,首先,我們從POINeT資料庫選取經過HeLa cell實驗驗證的蛋白質交互作用對(protein interaction pair),並由商用IPA資料庫中篩選出五項癌症相關的訊號路徑(EGF、PDGF、FGF、IGF、p38 MAPK),以及兩項目前較少研究的Wnt/B-catenin與Sonic Hedgehog途徑,接著將資料庫與實驗數據的蛋白質交互作用(proein-protein interaction)做比對,經由比對這兩種不同的資料後重建出一個包含48個蛋白質節點以及80條交互作用邊的訊號傳遞網路。
接著我們使用系統生物學的軟體來模擬和分析訊號路徑,分析分為兩部分,第一部分我們利用網路分析原理得到此訊號路徑定性上的特性,例如兩個蛋白質的相依路徑、回饋迴路和訊號路徑,第二部份將訊號網路轉換成布林邏輯網路,然後設定目標函數來計算最小干擾集合,最後,將計算的結果進行統計與篩選以提供給生物學家設計實驗的方向和治療癌症的標靶藥物。

In this research, we reconstruct the protein network in HeLa cell. First, we selected the protein interaction pair, which was validated via HeLa cell experiment by using protein-protein interaction database: POINeT. Then, five cancer related signaling pathways (EGF, PDGF, FGF, IGF and p38 MAPK) and two signaling pathways (Wnt/B-catenin and Sonic Hedgehog), which are seldom studied by researcher from IPA commercial software, were extracted. By comparing those two different data, we could reconstruct a signaling transduction pathway including the 48 protein nodes and 80 interaction edges.
Next step, we use systems biological software to analyze and model our signaling pathway. Analysis can be separate in two parts. First part, using network analyzing principle we could obtain qualitative property of signaling pathway, e.g. the dependency path between proteins, feedback loops and signal paths. Second part, the signaling network converted into Boolean logical model. And then, we set object function to compute the minimal intervention set. Finally, statistics and selecting our computing result may help biological researcher to design the direction of experiment and cancer targeted drugs.

摘要 I
Abstract II
圖目錄 VI
表目錄 IX
第一章 緒論 1
1.1前言 1
1.2文獻回顧 4
1.3研究動機 7
1.4 組織章節 7
第二章 資料庫簡介與分析原理 9
2.1資料庫簡介 9
2.1.1 PID (Pathway Interaction Database) 9
2.1.2 KEGG (Kyoto Encyclopedia of Genes and Genomes) 11
2.1.3 IPA (Ingenuity Pathway Analysis) 12
2.1.4資料庫間的比較 14
2.2 分析原理 14
2.2.1訊號網路分析 15
2.2.2布林邏輯網路 19
2.2.3 最小干擾集合 21
2.2.4 範例:Toymodel 23
第三章 重建訊號網路 34
3.1 資料來源 34
3.2 訊號路徑的選取與生物意義 34
3.2.1 EGF訊號路徑 35
3.2.2 PDGF訊號路徑 37
3.2.3 FGF訊號路徑 39
3.2.4 IGF訊號路徑 40
3.2.5 p38 MAPK訊號路徑 41
3.2.6 Wnt/B-catenin訊號路徑 43
3.2.7 Sonic Hedgehog訊號路徑 45
3.3 蛋白質交互作用數據分析 46
3.4 整合個別訊號路徑 47
3.5 路徑圖與數據疊合 49
3.6 決定未知方向 52
第四章 網路模式分析 56
4.1 分析軟體簡介 56
4.1.1 ProMoT 56
4.1.2 CellNetAnalyzer 58
4.2 癌細胞的生理機制 59
4.3 訊號網路中的crosstalk 61
4.4 訊號路徑分析 63
4.4.1 交互作用矩陣 63
4.4.2 最短距離矩陣 64
4.4.3 相依矩陣 67
4.4.4 強連結成分 68
4.4.5 回饋迴路 69
4.4.6 訊號路徑 70
4.4.7 物質參與度統計 71
4.4 邏輯網路分析 75
4.4.1 同等階層物質 75
4.4.2 邏輯穩定狀態 77
4.4.3 最小干擾集合 80
參考文獻 88
附錄A 96
附錄B 98
附錄C 102
附錄D 105
附錄E 106
附錄F 115

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