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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游志誠(Chih-Cheng Yu) 查詢紙本館藏

畢業系所

資訊工程學系

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)

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摘要(中)

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。

摘要(英)

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

關鍵字(中)

★ 替代性剪接
★ 同形體

關鍵字(英)

★ splice sites
★ alternative splicing
★ isoform

論文目次

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

參考文獻

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.
4. HD Huang, JT Horng, CC Lee, BJ Liu: ProSplicer: a database of putative alternative splicing information derived from protein, mRNA and expressed sequence tag sequence data. Genome Biol 2003, 4:R29.
5. SA Haas, T Beissbarth, E Rivals, A Krause, M Vingron: GeneNest: automated generation and visualization of gene indices. Trends Genet 2000, 16:521-3.
6. A Krause, SA Haas, E Coward, M Vingron: SYSTERS, GeneNest, SpliceNest: exploring sequence space from genome to protein. Nucleic Acids Res 2002, 30:299-300.
7. H Ji, Q Zhou, F Wen, H Xia, X Lu, Y Li: AsMamDB: an alternative splice database of mammals. Nucleic Acids Res 2001, 29:260-3.
8. WJ Kent: BLAT--the BLAST-like alignment tool. Genome Res 2002, 12:656-64.
9. M Burset, IA Seledtsov, VV Solovyev: SpliceDB: database of canonical and non-canonical mammalian splice sites. Nucleic Acids Res 2001, 29:255-9.
10. YH Huang, YT Chen, JJ Lai, ST Yang, UC Yang: PALS db: Putative Alternative Splicing database. Nucleic Acids Res 2002, 30:186-90.
11. I Dralyuk, M Brudno, MS Gelfand, M Zorn, I Dubchak: ASDB: database of alternatively spliced genes. Nucleic Acids Res 2000, 28:296-7.
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13. LD Hillier, G Lennon, M Becker, MF Bonaldo, B Chiapelli, S Chissoe, N Dietrich, T DuBuque, A Favello, W Gish, et al: Generation and analysis of 280,000 human expressed sequence tags. Genome Res 1996, 6:807-28.
14. MS Gelfand, I Dubchak, I Dralyuk, M Zorn: ASDB: database of alternatively spliced genes. Nucleic Acids Res 1999, 27:301-2.
15. A Bairoch, R Apweiler: The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res 2000, 28:45-8.
16. DA Benson, I Karsch-Mizrachi, DJ Lipman, J Ostell, DL Wheeler: GenBank. Nucleic Acids Res 2003, 31:23-7.
17. GD Schuler, MS Boguski, EA Stewart, LD Stein, G Gyapay, K Rice, RE White, P Rodriguez-Tome, A Aggarwal, E Bajorek, et al: A gene map of the human genome. Science 1996, 274:540-6.
18. B Modrek, A Resch, C Grasso, C Lee: Genome-wide detection of alternative splicing in expressed sequences of human genes. Nucleic Acids Res 2001, 29:2850-9.
19. C Burge, S Karlin: Prediction of complete gene structures in human genomic DNA. J Mol Biol 1997, 268:78-94.

指導教授

洪炯宗、張猷忠
(Jorng-Tzong Horng、Yu-Chung Chang)

審核日期

2003-7-3

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