藉由隨機系統模型辨識轉錄因子中的協同作用

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研究生：	張昱翔 Yu-Hsiang Chang
論文名稱：	藉由隨機系統模型辨識轉錄因子中的協同作用 Identification of Cooperativity among Transcription Factors via Stochastic System Model
指導教授：	陳博現 Bor-Sen Chen
口試委員:
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：	2005
畢業學年度：	93
語文別：	英文
論文頁數：	40
中文關鍵詞：	轉錄因子間的協同作用、動態模型、基因調控網路、細胞週期
外文關鍵詞：	cooperativity among TFs, dynamic model, gene regulatory network, cell cycle
相關次數：	點閱：1 下載：0
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現在已經知道轉錄因子(transcription factor)之間會產生協同作用來調控基因。對全基因的免疫蛋白沈澱反應實驗 (genome-wide location data) 可以幫助我們瞭解個別的轉錄因子如何去其標的基因(target gene)。但是，轉錄因子之間的協調作用如何去調控其標的基因卻需要更進一步的研究。在本篇論文中，為了探索基因表現出來的動態特性，我們使用隨機系統模型和最大相似度方法來整合全基因免疫蛋白沈澱反應實驗資料和基因表現資料，並藉由生物系統的角度來發現在細胞週期時轉錄因子之間的協同作用是如何去調控其標的基因。
隨著隨機動態模型的建立，根據轉錄因子間協同作用的調控能力大小以及其出現的次數，我們定義一種新的協同作用量測方式。將我們的方法應用在酵母菌的細胞週期上時，我們成功地發現許多所預測的協同作用已被之前實驗所驗證，而其他吾人所預測的協同作用可以作為未來生物實驗的研究方向。除此之外，我們的方法也提供數化轉錄因子對其標的基因的調控能力的能力。最後我們可以藉由吾人所列出轉錄因子之中協同作用的關係來建立出一個轉錄因子的協同作用網路圖。

Transcription factors (TFs) are known to co-occur with cooperativity to regulate genes. Genome-wide location data can help us understand how an individual TF regulates its target gene, but how TFs cooperate to regulate their target genes still needs further study. In this study, to explore dynamic property of gene expression profiles, an approach based on the stochastic system model and the maximum likelihood estimation method is proposed to integrate genome-wide location data and expression profiles to reveal how TFs cooperate to regulate their target genes from the systems biological perspective in the yeast cell cycle.
Based on a stochastic dynamic model, a new measurement of cooperativity among TFs is developed according to the regulatory abilities of cooperative TF pairs and the number of their occurrences. Our method is applied to the yeast cell cycle to successfully reveal many cooperative TF pairs confirmed by previous experiments, and other TF pairs mentioned potentially with cooperativity in our results can provide a direction for future experiments. Furthermore, our method also provides quantitative regulatory ability of the individual TF and the cooperativity of TFs to their target genes. Finally, a cooperative TF network of cell cycle is constructed based on significant cooperative TF pairs.

Contents

Abstract ................................................ i
Acknowledgements ....................................... ii
Contents .............................................. iii
List of Figures ......................................... v
List of Table .......................................... vi
1. Introduction ......................................... 1
2. Materials and Methods ................................ 6
  2.1 Selecting and Processing Experimental Data ........ 6
  2.2 Dynamic Model of Gene Regulatory Networks ......... 7
  2.3 Identifying Gene Regulatory Networks ............. 10
  2.4 Measurement of Cooperativity among TFs ........... 14
3. Results ............................................. 18
  3.1 Analysis of the Cooperativity among TFs .......... 18
  3.2 Cell Cycle ....................................... 19
     3.2.1 G1/S Phase .................................. 19
     3.2.2 G2/M Phase .................................. 20
     3.2.3 M/G1 Phase .................................. 21
  3.3 Mating ........................................... 22
  3.4 Comparison with the Results of Banerjee and Zhang's Method ..................... ........................... 23
  3.5 Regulatory Ability of Transcription Factors for Target Genes ........................................... 24
4. Discussion .......................................... 26
Bibliography ........................................... 29
Abbreviation ........................................... 40


List of Figures

Figure 1. Examples of dynamic transcriptional regulatory models of target genes CLB5 and HO ..................... 35
Figure 2. Probability Density Function ................. 36
Figure 3. The significant cooperative TF pair network of cell cycle target genes ................................ 37
Figure 4. Overlap of our results, Banerjee and Zhang’s results, and cooperative TF pairs by literature evidences .............................................. 38


List of Table

Table 1. Significant cooperative TF pairs of cell cycle target genes ........................................... 39

                                

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