利用蛋白質交互作用及生物資訊資料庫重建訊號網路與定性模式分析

Reconstruction Qf Signaling Transduction Pathway Via Protein-protein-interaction And Bioinformatical Database And Pathway Analysis Of Qualitative Model

吳佩容(Wu, Pei Jung)

指導教授 ： 王逢盛

國立中正大學/工學院/化學工程學系/碩士(2012年)

摘要

此研究以Hela cell蛋白質交互作用為研究標的重建蛋白質網路，首先從鄰位蛋白質原位表現技術(in situ proximity ligation assay)取得Hela cell 557筆蛋白質交互作用對(positive protein protein interaction pair)。根據557筆交互作用，挑出其中108個與七個主要與癌症相關之信號路徑(EGF、PDGF、FGF、IGF、p38MAPK、Wnt/B-catenin、Sonic Hedgehog) 對應的物質，藉由Ingenuity Pathway Analysis 資料庫重建出包含此7個訊號路徑的蛋白質訊號傳遞網路，共包含70個節點及113條反應。將重建過後的訊號網路，比對557筆蛋白質交互作用，共有95筆交互作用對與重建出的訊號路徑重疊，其中46筆為直接作用對，22筆為間接作用，27筆為蛋白質模組中的作用對。
接著我們使用系統生物學軟體CellNetAnalyzer 來做細胞內模擬和分析訊號路徑。利用基本網路分析原理進行訊號傳遞路徑定性上分析，例如蛋白質間的相依矩陣、訊號途徑；再運用布林(boolean)邏輯網路運算，設定與細胞凋亡和增生的目標函數來計算最小干擾集合(minimal intervention set)，並計算邏輯穩態(logical steady state)下的分析結果，進行生物意義上的討論，以提供生物學家設計疾病標靶的實驗方向。

關鍵字

訊號傳遞網路 ； 蛋白質交互作用 ； 最小干擾集合

並列摘要

In this search, we reconstruct protein signaling network to study the subject of Hela cell. First, we obtain 557 positive protein protein interactions(PPIs) pair of Hela cell from in situ proximity ligation assay. We select 108 proteins, belonging to 557 positive PPIs, corresponds with seven cancer-relating signaling pathway, such as EGF, PDGF, FGF, IGF, p38MAPK, Wnt/B-catenin and Sonic Hedgehog, which are searched by
IPA database, then we rebuild a signaling transduction network containing total of 70 protein nodes and 113 interaction edges. According to overlapping between 557 PPIs and signaling pathway, there are 95 PPIs overlapping interactions in the network, 46 for direct relationship, 22 for indirect relationship, 27 for PPI in protein module.

並列關鍵字

signal transduction network ； protein protein interaction ； minimal intervention sets

參考文獻

[1] H. Kitano, "Computational systems biology," Nature, vol. 420, pp. 206-210, Nov 14 2002.

[2] M. W. Covert, et al., "Integrating metabolic, transcriptional regulatory and signal transduction models in Escherichia coli," Bioinformatics, vol. 24, pp. 2044-2050, Sep 15 2008.

[3] T. Pfeiffer, et al., "METATOOL: for studying metabolic networks," Bioinformatics, vol. 15, pp. 251-257, Mar 1999.

[4] D. R. Hyduke and B. O. Palsson, "Towards genome-scale signalling-network reconstructions," Nature Reviews Genetics, vol. 11, pp. 297-307, Apr 2010.

[6] K. Oda, et al., "A comprehensive pathway map of epidermal growth factor receptor signaling," Molecular Systems Biology, vol. 1, 2005.