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研究生:謝允中
研究生(外文):Yun-Chung Heish
論文名稱:利用時間相關性磷酸化蛋白體資料建構B細胞訊息傳遞路徑
論文名稱(外文):Reconstruct the B Cell Signaling Network Using Time-dependent Phospho-proteomic Data
指導教授:李宗夷
指導教授(外文):Tzong-Yi Lee
口試委員:翁資雅吳欣怡
口試委員(外文):Tzu-Ya WengHsin-Yi Wu
口試日期:2014-07-17
學位類別:碩士
校院名稱:元智大學
系所名稱:資訊工程學系
學門:工程學門
學類:電資工程學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:58
中文關鍵詞:蛋白質磷酸化訊息傳遞網路
外文關鍵詞:PhosphorylationSignaling pathway
相關次數:
  • 被引用被引用:0
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在免疫系統當中,B細胞會透過其表面的免疫球蛋白接收器來辨認外在的抗原進而產生適應性的變化,B細胞傳遞路徑根據不同的成熟時期、訊息傳遞的強弱和持續時間影響著B細胞產生細胞凋亡、分化和增殖等不同結果B細胞訊息傳遞路徑,目前已知磷酸化對細胞內傳遞訊息與B細胞訊息傳遞路徑傳導需要仰賴磷酸化的蛋白激脢(kinase)來做訊息傳遞與放大的功能,表示磷酸化對於訊息傳遞路徑是不可或缺的。B細胞訊息傳遞路徑其中仍含有未知的機制與成員,由於生物實驗成本考量所以生物資訊的方法來解決問題,本次研究以時序性蛋白質磷酸化實驗資料為主,結合了蛋白質交互作用,磷酸化蛋白激脢與基質蛋白關係與蛋白質屬性相關註解提出一個計分方式來有效的計算出蛋白質與B細胞訊息傳遞路徑的相關程度,由計分方式與磷酸化時序性資料所分析與已知的文獻記載遴選出Nck、Lpxn與Sin1等蛋白質可能涉及在B細胞訊息傳遞路徑當中卻未被標示出的成員;本次研究所提出分析方法也能推及應用到其他或多個訊息傳遞路徑的應用上,來揭開聯繫兩個訊息傳遞路徑之間機制的重要因子。
In immune System, the B cell would respond to the environment by identifying the antigen with the antibody receptor on cell membrane and this signaling path of B cell is celled B cell receptor(BCR) signaling pathway. The different situation of signaling transduction could carry out the transferring of B cell in different state. The protein phosphorylation is an indispensable mechanism in signal transduction and the protein kinase also play an important role in protein phosphorylation.
MS/MS technology development has controbuted to many time-series phosphoproteomic research about trying to reveal the unknown mechanism and member in cell transduction. So this study proposes a method calculating the protein-pathway association of phospho-proteomic data and investigating the known BCR signaling pathway, kinase-substrate relation of phosphorylation, protein-protein interaction and protein attribute annotation to choose the novel candidate that may be involved in BCR pathway. After that the BCR network can be reconstructed by time-series phosphor-proteomic data. By this approach, we revealed the novel candidates Nck1, Lpxn and Sin1 with high probability taking part in BCR signaling transduction. This analysis method also could find the key connecting molecules between two signaling transduction by observing the multi-pathway combined from two or more signaling pathways.
目錄
書名頁 i
摘要 ii
英文摘要 iii
致謝 iv
目錄 v
圖目錄 vii
表目錄 viii
附件目錄 ix
第一章 簡介 1
1.1 背景知識 1
1.2 研究動機與目的 5
1.2.1 研究動機 5
1.2.2 研究目的 5
1.3 相關研究 6
第二章 研究資料 7
2.1 磷酸化蛋白質資料 9
2.2 蛋白質相關資訊 10
2.3 蛋白質交互作用資料 10
2.4 蛋白質磷酸化關係料 11
2.5 已知的訊息傳遞路徑 11
2.6 蛋白質功能特性註解 12
2.7 網路圖形化工具 12
第三章 研究方法 13
3.1 研究流程 13
3.2 建構BCR訊息傳遞網路 15
3.3 蛋白質與訊息路徑相關性計算 18
3.3.1 蛋白質於訊息傳遞路徑之連結數量 18
3.3.2 蛋白質於訊息路徑中關聯蛋白質特性統計 19
3.3.3 蛋白質於訊息傳遞路徑中相關蛋白質磷酸化表現量相關性 21
第四章 研究初步結果 22
4.1 蛋白質與訊息路徑相關性計分排名 22
4.2 訊息路徑視覺化分析 23
第五章 議題討論 21
5.1 可能包含在BCR訊息路徑的蛋白質 25
5.1.1 Nck1在BCR訊息傳遞路徑中的機制 26
5.1.2 Lpxn在BCR訊息傳遞路徑中的機制 27
5.1.3 Sin1在BCR訊息傳遞路徑中的機制 29
5.2 應用蛋白質與訊息路徑相關性運算於多元訊息路徑 31
第六章 總結
6.1 結論 36
6.2 未來研究工作 36
参考文獻 37
附件 38
參考文獻
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21. Makino, C., et al., Sin1 binds to both ATF-2 and p38 and enhances ATF-2-dependent transcription in an SAPK signaling pathway. Genes Cells, 2006. 11(11): p. 1239-51.
22. Tracy, S., P. van der Geer, and T. Hunter, The receptor-like protein-tyrosine phosphatase, RPTP alpha, is phosphorylated by protein kinase C on two serines close to the inner face of the plasma membrane. J Biol Chem, 1995. 270(18): p. 10587-94.
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