以资料探勘方式探究启动子的共通特色Characterizationofthe.pptVIP

以資料探勘方式探究啟動子的共通特色Characterization of the hallmarks of a promoter by data-mining techniques(NSC89-2316-B-029-001) 羅能文 博士 東海大學畜產學研究所 細胞與分子生物學研究室 Overview 啟動區或是啟動子 (promoter) 是一個基因轉訊開端的訊息提供者，通常位於轉訊起始 (transcriptional initiation) 的上游。 對一些蛋白質基因而言，pol-II在合成訊息RNA之初，會認識轉訊起始點上游約25個bps的共通序列－TATAAA或稱TATA BOX，以及轉訊起始點上游約75個bps的共通序列CAAT BOX。 人類基因體計劃（human genome project）DNA解序完成後，如何由基因資料庫裡辨識出功能基因(function gene)的完整序列，已成為一項重要工作。 解決途徑 EST database 尋找轉譯的起點與終點，決定ORF 尋找轉訊的起始與啟動區、 決定exon/intron boundries 、轉訊的終點 計畫完成工作項目 由NCBI 資料庫查詢基因啟動區序列，摘取並儲存DNA序列， 重新以電腦軟體過濾、處理建檔 建立國際網頁方式，對外公開，提供各類相關資訊 以統計與資料探勘方式，搜尋潛在具有turn on基因表現的啟動區序列或轉訊因子 生物驗證─ 利用in vitro mutagenesis方式進行reporter analysis Predicting Pol II Promoter Sequences (Prestridge, 1995) Predicting Pol II Promoter Sequences Using Transcription Factor Binding Sites (Prestridge, 1995) Promoter 2.0: for the Recognition of Pol II Promoter Sequences (Knudsen, 1999) Promoter 2.0: for the Recognition of Pol II Promoter Sequences (Knudsen, 1999) Neural network 1: TATA box weights set to give maximum response for sequence TATAAA Neural network 2: cap site weights set to TCA Neural network 3: CCAAT box weights set to CCAATC Neural network 4: GC box weights set to GGGCGG PromoterInspector: A Novel Context Analysis Approach (Scherf et al., 2000) PromoterInspector focuses on genetic context rather than their exact location Context feature: based on an approach using oligonucleotides with one variable mismatch. IUPAC group is uniquely defined by a set of oligonucleotides and a number of undefined basepairs (wildcards, “N”). Example : two wildcards and the oligonucleotide set E.g., (AGC, GCA) ? (AGCGCA, AGCNGCA, AGCNNGCA) PromoterInspector: A Novel Context Analysis Approach (Scherf et al., 2000) (cont.) A classifier is defined by two disjunct sets of IUPAC groups: Promoter-related IUPAC groups ? “promoter” Non-promoter-related IUPAC groups ? “non-promoter” Classification is based on IUPAC group matches. AGCTG: (AGCT, AGNCT, AGNNCT),