以共調控人類基因的上游調控區預測轉錄調控模組之系統

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姓名

孫怡明(Yi-Ming Sun) 查詢紙本館藏

畢業系所

資訊工程學系

論文名稱

以共調控人類基因的上游調控區預測轉錄調控模組之系統
(A System for Prediction of Transcriptional Regulatory Modules in Human Upstream Control Regions of Coregulated Genes)

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摘要(中)

基因晶片技術提供了大量顯現基因表現的方法，針對基因表現的狀況可以找出有相同表現結果的群組，基因調控機制在研究分子生物運作上是非常重要的議題，而找出基因調控點則是全面了解基因調控機制的重點之一。本研究之貢獻在於提出一個整合各種方法並能自動化進行調控點分析的系統。
本研究發展了一個調控點預測系統，由使用者提供在調控機制上有相關性的基因群組，系統提供多種己被實際運用的預測程式(如Meme、gibbs、..)以及特殊序列(過度出現的重複序列、己知調控點)找尋各種可能的調控點，並提供相關的統計數值來協助過濾出比較重要的結果，接著利用找出的調控點資訊進行相關性分析來找出調控模組。經由整合在此系統的各個資料庫(TRANSFAC、HomoloDB、…)所提供的資訊，還可以提供使用者在進行分析時，能很方便地取得相關資訊來調整分析參數，來得到較佳的結果。系統同時提供個幾個不同的方法來呈現預測的結果，可以讓使用者更容易理解與決策。最後提供了實際分析的案例，來說明本系統的成效。

摘要(英)

The microarray technology provides a method to reveal expression profiles of huge number genes. By using gene expression profiles, gene groups with the same expression pattern can be found. The mechanisms to regulate gene expression are an important subject in studying molecular biology. Finding transcriptional regulatory binding sites is one key point to totally understand gene expression regulation mechanisms. Therefore, an automatic system integrates various methods to analyze regulatory sites is the contribution of this study.
In this study we develop a system to predict transcriptional regulatory binding sites. Using the gene group, which is correlated in regulatory mechanisms, is submitted by users. The system provides the followings to discover every possible regulatory site. 1. Various prediction programs (e.g. Meme, Gibbs, etc.) that are applied in many real cases. 2. Special sequences (e.g. over-represented repeat and known-site). It also provides useful statistical values to filter significant results. Then, by analyzing the association, we can use the information of candidate sites to find regulatory modules. The information in each databases integrated in this system can provide users to get some related information. This helps to adjust parameters efficiently in analyzing process for better results. The system also provides a lot of methods to represent prediction results. We will get more understanding and assistance to make decisions. At the end, we propose an analyzed real cases to describe the result of this system.

關鍵字(中)

★ 共調控
★ 調控區
★ 調控模組

關鍵字(英)

★ regulatory module
★ coregulate
★ regulation

論文目次

Chapter 1 Introduction 1
1.1 Backgrounds 1
The Central Dogma 2
Gene Expression 3
Regulation of gene expression 3
Regulation of gene expression 4
1.2 Motivation 5
1.3 Goals 5
Chapter 2 Related Works 7
2.1 Gene Expression Clustering 7
2.2 Regulatory Site Prediction 7
2.3 Consensus pattern and Motifs 8
2.4 Regulatory Site Co-occurrence 9
Chapter 3 Materials and Methods 10
3.1 Materials 10
3.1.1 Human Genome Sequence 10
3.1.2 Known TF Binding Site 11
3.2 Methods 11
3.2.1 DNA Motif Discovery 12
MEME 12
Gibbs Sampler. 13
AlignACE 14
3.2.2 Eliminate Redundant Motifs 15
3.2.3 Over-Represented Repeats Discovery 15
Z-Score 16
Whole genome index 17
3.2.4 Association Rule 17
X2 Test 18
P-Value 19
Chapter 4 Implementation 20
4.1 System Flow 20
4.2 Data Preprocessing 22
4.3 Data Storage 23
4.4 Web Interface 25
Chapter 5 Case Study 28
5.1 Predicted Candidate Sites 29
5.2 Significant co-occurrence combinations 30
Chapter 6 Summary 35
6.1 Discussion 35
6.2 Future Work 37
Referrences 39
Appendix 42

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指導教授

洪炯宗(Jorng-Tzong Hong)

審核日期

2003-7-7

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