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研究生: 葉嘉銘
Yeh, Chia-Ming
論文名稱: 發展以轉錄調控因子結合序列為基礎的調控相似測度
A regulatory similarity measure between two genes using only transcription factor binding site data
指導教授: 吳謂勝
Wu, Wei-Sheng
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2013
畢業學年度: 101
語文別: 中文
論文頁數: 37
中文關鍵詞: 調控相似轉錄因子轉錄因子結合序列共同調控基因
外文關鍵詞: regulatory similarity, transcription factors, transcription factors binding sites, co-regulated genes
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  • 定義兩個基因之間調控相似(regulatory similarity)的測度,為定義共同調控基因的第一步。基因調控是一個包含各種機制且複雜的過程。在啟動子中,轉錄因子結合到轉錄因子結合序列,在控制基因表現是最關鍵且被充分理解的步驟。迄今為止,轉錄因子結合位已經被廣泛的運用在兩個基因的調控相似的測度上。然而,現存且建立在轉錄因子結合序列基礎上的調控相似測度,只將轉錄因子結合序列和基因的關係考慮為布林值(1:存在或 0:不存在),並沒有應用轉錄因子結合序列在啟動子中位置的資訊。這個研究的目的主要在研究,將轉錄因子結合序列考慮到調控相似計算的影響。在酵母菌和人類中已經知道,許多具功能性的轉錄因子的轉錄因子結合序列,常在啟動子中的某一特定區域出現。在此研究中,我們提出了一個單純以轉錄因子結合序列為基礎,且引入轉錄因子結合序列位置資訊的新測度。在後續識別生物顯著性的驗證裡,顯示結合在啟動子中轉錄因子結合位的位置資訊,有助於識別共同調控基因。我們所提出的調控相似測度在使用三種不同的統計分析下,於識別共同調控基因的生物顯著性,更優於七種現存的調控相似測度。這顯示我們所提出的調控相似測度所識別出的共同調控基因更加趨於執行相似生物學功能、擁有蛋白質交互作用、和(或)有 mRNA 共同表現的趨勢。這也表示我們所提出的調控相似測度,能更準確的識別共同調控基因,有助於了解基因的轉錄調控機制。

    Defining a measure of regulatory similarity (RS) of two genes is the first step toward identifying co-regulated genes. Gene regulation is a complex process involving various mechanisms, in which transcription factors (TFs) binding to TF binding sites (TFBSs) in promoters is the most crucial and well understood step. To date, TFBSs have been widely used to measure the regularity similarity (RS) of two genes. However, existing TFBS-based RS measures consider the relation of a TFBS to a gene as a Boolean (either ‘presence’ or ‘absence’) without utilizing the information of TFBS locations in promoters. This study aims to figure out the effect of considering the TFBS locations to the calculation of RS, since the activity of TFBSs is highly related to their locations in promoters. The functional TFBSs of many TFs in yeast and human are known to have a strong positional preference to occur in a small region in the promoters. By proposing a new TFBS location-dependent RS measure, this study shows that the information of TFBS locations in promoters helps to identify genes that perform similar biological functions, have physical protein-protein interactions and/or are co-expressed.Using three different statistical analyses, the proposed RS measure has been shown better than seven existing RS measures in identifying biologically significant co-regulated genes. The proposed RS measure will be useful for studying the underlying molecular mechanisms of specific cellular functions.

    英文摘要 i 中文摘要 iii 誌謝 v 表目錄 vii 圖目錄 viii 第一章、緒論 1 第二章、研究方法 3 2.1 現有的七種調控相似測度 3 2.2 我們所提出的調控相似測度 5 第三章、統計分析與分析結果 8 3.1 評估調控相似測度的三個性能指標 8 3.1.1 功能豐富度分數 8 3.1.2 交互作用豐富度分數 9 3.1.3 mRNA 共同表現量豐富度分數 10 3.2 提出的調控相似測度與七種現有測度的性能比較 11 第四章、結果討論 14 4.1 轉錄因子結合序列數據品質對調控相似測度的影響 14 4.2 轉錄因子結合序列數據資料對調控相似測度的影響 28 第五章、生物資訊分析應用 30 第六章、結論 32 參考文獻 33

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