以生物資訊方法探討致癌蛋白質及抑癌蛋白質之蛋白質功能域相互作用

In silico study of oncoproteins and tumor suppressor protein Domain-Domain interactions

李育良(Yu-Liang Lee)

指導教授 ： 吳家樂

亞洲大學/資訊學院/生物資訊學系碩士班/碩士(2009年)

摘要

蛋白質與蛋白質之相互作用(protein-protein interaction 簡稱PPI)於癌症生成扮演重要的角色。在本研究裡面主要是探討致癌蛋白(onco-proteins簡稱OCP)和抑癌蛋白(tumor suppressor proteins簡稱TSP)的domain-domain interactions(簡稱DDI)。
研究中主要使用三種資料，蛋白質相互作用、癌症蛋白質及蛋白質的Domain資料，分別來自資料庫Biogrid、Tumor Associated Gene (簡稱TAG)與Interpro。
為了找出致癌蛋白及抑癌蛋白特異性的DDI，分別以兩種模型，一對一模型及多對多模型來做來研究。得知結果後分別測試OCP-OCP、TSP-TSP 和 OCP-TSP的靈敏度，靈敏度測試中以OCP-OCP結果最佳，靈敏度達到79.9%，TSP-TSP的靈敏度測試最低為54.8%。研究中也對誤判率進行測試，誤判率最低的結果為使用TSP-TSP資料做Training，OCP-OCP資料做Test，誤判率為11.6%。
在多對多模型中，也許多對多模型結果會因DDI組合影響計分排名，故研究取OCP-OCP前二十名DDI，與一對一模型DDI做比對。結果顯示多對多模型中與一對一組合的DDI 有60% 吻合。經過比較後，了解多對多模型可增加DDI的組合，在DDI排名上並不會造成太大更動。
研究結果建置成網頁，供使用者查詢，網址為：http://210.70.83.81/TsgOcg-ppi/

關鍵字

蛋白質相互作用 ； 蛋白質功能域相互作用 ； 癌症蛋白質

並列摘要

Cancer diseases could possibly induced by abnormal protein-protein interactions (PPIs). Given the PPIs (Biogrid), cancer genes (Tumor Associate Gene, TAG) and domain annotation (InterPro) information, we derived the onco-proteins (OCP) and tumor suppressor proteins (TSP) domain-domain interactions (DDIs).
Two interaction models are introduced to describe cancerous proteins domain-domain interactions (DDI), that is the single domain interaction model and the multi-domain interaction model. The cancer-specific DDIs scoring information are employed to valid the single domain interaction model for the OCP-OCP, TSP-TSP and OCP-TSP dataset. It is found that the OCP-OCP DDIs score achieved the best sensitivity test result, which is 79.9%. The TSP-TSP DDIs score obtained the lowest sensitivity result, which is 54.8%. Furthermore, the lowest false positive is obtained by training the TSP-TSP DDIs score against the OCP-OCP test set, which has a 11.6% false positive rate.
On the other hand, we also compared the top 20 OCP-OCP DDIs for both the single domain interaction model and multi-domain interaction model, it is found that 60% of the DDIs overlapped, hence, the multi-domain interaction model could provide much more DDIs pairs information, but it does not incur much effects on their ranking.
A web-based interface has been set up to report our results, which is available at http://210.70.83.81/tsgocg-ppi/.

並列關鍵字

protein-protein interactions ； domain-domain interactions ； cancerous proteins

參考文獻

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