以基因替代性剪接結構為基礎來建立基因同形體預測系統

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研究生：	游志誠 Chih-Cheng Yu
論文名稱：	以基因替代性剪接結構為基礎來建立基因同形體預測系統 A predictive system for gene isoforms based on alternative splicing variants and signals
指導教授：	洪炯宗 Jorng-Tzong Horng 張猷忠 Yu-Chung Chang
口試委員:
學位類別：	碩士 Master
系所名稱：	資訊電機學院 - 資訊工程學系 Department of Computer Science & Information Engineering
畢業學年度：	91
語文別：	英文
論文頁數：	32
中文關鍵詞：	替代性剪接、同形體
外文關鍵詞：	splice sites, alternative splicing, isoform
相關次數：	點閱：5 下載：0
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比對表現序列標幟序列(EST)、訊息核醣核酸(mRNA)、蛋白質(protein)序列與基因組 (genome) 序列之間的相似度，是偵測基因同形體(gene isoforms)的主要方法。但是當表現序列標幟序列不完整時，有些基因同形體就無法被偵測到，而運用預測工具卻可能預測出這類的基因同形體。因此，我們建立了一套系統來偵測在基因組序列中的剪接位址(splice site)並且產生一些預測的基因同形體。為了提供關於基因更詳細的資訊，我們整合”Prosplicer”這個資料庫，建立了一個名為”ISOdb”的資料庫並且提供網頁形式的使用者介面。使用者可以透過網際網路得到包含預測以及跟表現序列標幟序列比對得來的基因同形體的相關資訊。

Alignments among ESTs, mRNA, protein sequences, and genome sequences are major approaches to reveal the gene isoforms. However, some isoforms can not be revealed by the alignments, because the ESTs are incomplete. Fortunately, such isoforms may be obtained by a prediction tool. In this study, we built a system to detect splice sites in the genomic DNA and to generate all possible isoforms. To provide detailed view of the gene structures, we developed a database, namely ISOdb, which integrated the ProSplicer database to reveal the alternative splicing in human genome. By aligning ESTs, mRNA, and protein sequences to the genome sequences, we provide a web-based interface for users to retrieve all possible isoforms that include alignments of the ESTs and other information. http://140.115.50.96/isodb/
Keywords : isoform, alternative splicing(AS), splice sites

Contents
Chapter 1 Introduction	1
1.1	Motivation	2
1.2	Goal	2
1.3 Background	3
1.3.1 Splice site	3
1.3.2 Alternative splicing	4
Chapter 2 Related Work	7
2.1 ASDB	7
2.2 AsMamDB	8
2.3 HASDB	10
2.4 PALS	11
2.5 SpliceNest	12
2.6 SpliceDB	13
2.7 Prosplicer	14
2.8 Maximal Dependence Decomposition(MDD)	14
Chapter 3 Methods	16
3.1 Approach	16
3.2 Data Collection	18
3.2.1 Gene sequences set	18
3.2.2 CDS Features	18
3.2.3 Splicing site sequences set	20
3.3 Generating Isoform Candidates	22
Chapter 4 Results	25
Chapter 5 Discussion	27
Chapter 6 Future work	28
References	29
List of Figures
Figure 1. Conserved sequences in vertebrate introns.	4
Figure 2. X2 statistics.	15
Figure 3. system flow	17
Figure 4. Distribution of internal exons and length.	19
Figure 5. Distribution of initial exons and length.	20
Figure 6. Distribution of terminal exons and length.	22
Figure 7. Flow to generate all possible isoform candidates	24
Figure 8. Percentage of isoform covered by mRNA.	25
Figure 9. Percentage of isoform covered by protein.	26
Figure 10 Overview of isoform graphical view	27
List of Tables
Table 1. Number of test data set.	22
Table 2. True positive and false positive rates for acceptor and donor site detection on test set.	22
Table 3. The comparisons among alternative splicing databases.	28

                                

References
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2. EV Kriventseva, I Koch, R Apweiler, M Vingron, P Bork, MS Gelfand, S Sunyaev: Increase of functional diversity by alternative splicing. Trends Genet 2003, 19:124-8.
3. Q Xu, B Modrek, C Lee: Genome-wide detection of tissue-specific alternative splicing in the human transcriptome. Nucleic Acids Res 2002, 30:3754-66.
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