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研究生:邱于榮
研究生(外文):Yu-Jung Chiu
論文名稱:利用雙分群演算法研究環狀RNA的生成
論文名稱(外文):Study biogenesis of circular RNAs using biclustering algorithms
指導教授:劉俊吉
口試委員:謝立青黃耀廷
口試日期:2016-06-23
學位類別:碩士
校院名稱:國立中興大學
系所名稱:基因體暨生物資訊學研究所
學門:生命科學學門
學類:生物訊息學類
論文種類:學術論文
論文出版年:2016
畢業學年度:104
語文別:中文
論文頁數:37
中文關鍵詞:環狀RNARNA-seqRNA結合蛋白雙分群演算法
外文關鍵詞:Circular RNAsRNA-seqRNA binding proteinsbiclustering
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環狀RNA (Circular RNA,簡稱CircRNA)是一種環型的 noncoding RNA,這種特殊的RNA與一般常見的Linear RNA不同,因為其環狀的外型不會受到RNA外切酶影響,使它不易降解,在細胞中也顯得比一般線性RNA來的穩定。由於有前人研究指出有一種RNA binding protein “QKI” 會結合在pre-mRNA的頭尾兩端,使其剪切並形成頭尾相接, 所以在本篇論文中,我們想要利用環狀RNA的junction site資料以及RNA結合蛋白的binding site資料來討論環狀RNA的生成以及功能。這些資料被用來建構出一個觀察RNA結合蛋白是否位於環狀RNA junction site上下游的矩陣,使我們可以利用雙分群演算法的套件:ISA來進行分析。用ISA分析所得到的module會被我們使用Gene Ontology和KEGG pathway 富集分析。在Gene Ontology富集分析方面,我們發現RNA processing 相關的機制對於RNA結合蛋白是有潛在力的,這跟QKI研究相符。然後再KEGG pathway 富集分析方面,我們找到了fatty acid degradation、ABC transporter以及TCA cycle等機制,而阿茲海默症的形成會與脂肪酸的降解相關,且在一篇論文中有提到阿茲海默症的形成會與環狀RNA有關聯性。

Circular RNAs (circRNAs) are types of noncoding RNAs, which are different from linear RNAs. Since the circular structure makes circRNAs are not be influenced by Exoribonucleases, they do not degrade by removing terminal nucleotide from either the 5’ end or 3’ end of the RNA molecules. Previous studies reported that an RNA binding protein, quaking (QKI), can bind on the two sides of pre-mRNA and then generate circRNAs. In this study, we investigated biogenesis of circRNAs using the circRNAs junction sites and protein binding sites in RNAs. These data used to build a binding site matrix, and then we performed bicluster algorithm using ISA package for identifying potential RNA binding proteins (RBPs) which may participate the biogenesis of circRNAs. For each bicluster module, we used circRNAs to perform Gene Ontology and KEGG pathway enrichment analysis. From Gene Ontology enrichment analysis, we discovered that RNA processing associated mechanisms are enriched in potential RNA binding proteins. Furthermore, some mechanisms also found in KEGG enrichment analysis, such as fatty acid degradation, ABC transporters, and TCA cycle. The Alzheimer’s disease formation associated with fatty acid degradation is known mechanism.

中文摘要………………………………………………………………………………i
Abstract……………………………………………………………………………ii
目錄…………………………………………………………………………………iii
表目錄………………………………………………………………………………iv
圖目錄…………………………………………………………………………………v
第一章 前言………………………………………………………………………1
第一節 研究背景………………………………………………………………1
一、CircRNA概述…………………………………………………………1
二、CircRNA資料庫………………………………………………………3
第二章 研究材料與方法……………………………………………………………4
第一節 材料來源………………………………………………………………4
一、CircNet資料庫………………………………………………………4
第二節 分析工具………………………………………………………………6
一、Cluster algorithm分群演算法…………………………………………6
二、Bicluster algorithm 雙分群演算法……………………………………7
三、ISA……………………………………………………………………10
四、Enrichment analysis 富集分析……………………………………….12
第三節 分析方法……………………………………………………………13
一、biogenesis……………………………………………………………13
二、function study…………………………………………………………17
第三章 研究結果………………………………………………………………20
第四章 討論………………………………………………………………22
第五章 結論與未來展望………………………………………………………………23
第六章 附表………………………………………………………………24
第七章 參考文獻………………………………………………………………35


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