開發整合知識庫與資料建構基因集網路之方法

Development of a knowledge-based and data-driven network construction method for gene sets

張宏卿(Hung-Ching Chang)

指導教授 ： 蕭朱杏

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/碩士(2019年)

https://doi.org/10.6342/NTU201901037

摘要

網路模型建構已經被廣泛的應用在各個領域中，像是社群網路、生物傳導
路徑、神經網路等，其主要目的在於建構不同物件之間的關係。近年來，在生物醫學領域中，生物途徑分析的應用有越來越廣的趨勢，但是可能受限於目前已知的生物途徑數量，此趨勢逐漸趨於平緩。由於一個新的生物途徑必須經由許多實驗驗證，往往要耗費許多時間；若是能藉由網路模型建構方法來預測基因網路，並提供實驗端進行驗證，就可以加速研究的進程。然而，現有的網路模型建構方法是以資料驅動方法為主，所預測的結果並不一定都有高度的可信度。因此本研究提出「開發整合知識庫與資料建構基因集網路」的想法，試圖提高基因網路模型的可信度。方法的第一階段為網路結構之建構，著重於網路結構的分析，強調所預測的基因網路必須具備相關領域的網路特性，並透過知識庫所提供的資訊評估生成的網路結構的表現；而第二階段則是網路節點名稱之指定，藉由實際資料並透過互動式操作模式讓使用者能更加靈活的完成基因網路的建立。最後，我們將乳癌及卵巢癌的基因表達量資料應用在本研究之方法上，並預測兩種癌症的基因網路。

關鍵字

生物資料庫 ； 網路模型建構 ； 生物途徑 ； 基因網路 ； 節點度分佈

並列摘要

Network modeling aiming to discover the relationship among individual entities has been an active research topic in social network, biochemical reaction network and neural network. In biomedical area, pathway analysis of gene expression levels can be handled in the context of network as well. The pathway analysis has become a popular approach to analyzing gene expression profile, as it can summarize the complexity of gene relationship, reduce the number of genes and increase the explanatory power. However, this disease-pathway association analysis depends strongly on the accuracy of pathway structure and the availability of pathways, not to mention the challenging task in verifying a new pathway. It involves time-consuming laboratory work conducted in multiple research groups. Here, we propose a knowledge-based and data-driven approach to efficiently construct potential networks for a given set of genes, so that time and cost can be saved in discovering the pathway structure. A reference library of validated networks will be considered first and used to evaluate several network properties. This resulting information will next be utilized when developing the unknown network structure for a set of genes. Two cancer studies are considered to illustrate the proposed approach and to provide visualized results in predicting network structures and discovering relationship among genes.

並列關鍵字

knowledge-based ； network construction ； biological pathway ； gene network ； degree distribution

參考文獻

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