利用兩階段群集方法以微陣列辨識轉錄調控點

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莊淳翔(Chun-Hsiang Chuang) 查詢紙本館藏

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資訊工程學系

論文名稱

利用兩階段群集方法以微陣列辨識轉錄調控點
(Two-stage clustering method for identifying transcriptional regulatory sites based on gene expression profiles)

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摘要(中)

瞭解基因調控機制在研究分子生物學上是非常重要的議題，辨識轉錄調控點對於瞭解基因調控機制扮演了極為重要的角色。透過實驗的方式來尋找轉錄調控點是準確的，但是也相當費時的。微陣列晶片技術可以同時顯現數以千計的基因表現，透過分析基因表現的狀況可以找出有相似表現結果的群組。大範圍的基因表現研究與基因體定序計畫提供了大量的資訊可供辨識或預測轉錄調控點。在本研究中，我們提出一個兩階段的群集方法透過微陣列晶片資料與基因序列上游區特定片段出現次數的資訊以辨識轉錄調控點。利用已知公開的酵母菌細胞週期基因表現資料加以檢驗微陣列晶片資料與基因序列上游區特定片段出現次數的相互關係。最後實際分析結果呈現本方法的確能夠找出更緊密、被共同調控的基因群組，並有助於辨識轉錄調控點。

摘要(英)

The research of gene regulation mechanisms is an important issue of studying molecular biology. The identification of transcriptional regulatory sites plays an important role of understanding gene expression regulation mechanism. It is precise but time-consuming by using the experimental approach to discover the transcriptional regulatory sites. The microarray technology can reveal expression profiles of several thousands of genes in parallel. By analyzing gene expression profiles, gene groups with the similar expression pattern can be found. Large-scale gene expression studies and genomic sequencing projects are providing numerous amounts of information that can be used to identify or predict transcriptional regulatory sites. In this study, we describe a two-stage clustering method for identifying transcriptional regulatory sites from both gene expression and promoter sequence data. The correlation between time-series gene expression patterns and the occurrence frequency of several motifs in their upstream sequences is examined by using publicly available yeast cell-cycle data. The results show that the two-stage clustering method taken here conducts dense co-regulated gene group and identifies transcriptional regulatory sites usefully.

關鍵字(中)

★ 微陣列
★ 轉錄
★ 調控

關鍵字(英)

★ transcrption
★ gene expression
★ microarray
★ regulatory

論文目次

Chapter 1 Introduction....................................................1
1.1 Background............................................................1
1.1.1 Gene Expression.....................................................1
1.1.2 Microarray..........................................................2
1.1.3 Regulation of gene expression.......................................3
1.1.4 Gene Ontology.......................................................3
1.2 Motivation............................................................5
1.3 Goal..................................................................6
Chapter 2 Related Works...................................................7
2.1 Clustering methods....................................................7
2.1.1 K-means clustering..................................................7
2.1.2 Hierarchical clustering.............................................8
2.1.3 Self-organizing map.................................................8
2.2 Motif discovery.......................................................9
2.2.1 MEME................................................................9
2.2.2 Gibbs sampler......................................................10
2.2.3 Consensus..........................................................10
2.3 Integrate system for gene expression analysis........................11
Chapter 3 Materials and Methods..........................................13
3.1 Materials............................................................13
3.2 Overview of our methodology..........................................13
3.3 Similarity measurement for gene expression data......................14
3.4 Clustering method....................................................15
3.5 Motif discovery......................................................16
3.6 Eliminate redundant motifs...........................................17
3.7 Extract motif occurrence frequency...................................18
Chapter 4 Results........................................................19
4.1 First stage clustering...............................................19
4.2 Second stage clustering..............................................21
4.3 Case study...........................................................25
Chapter 5 Discussion.....................................................30
Appendix.................................................................34

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指導教授

洪炯宗(Jorng-Tzong Horng)

審核日期

2006-7-20

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