臺灣博碩士論文加值系統

選擇性剪裁是真核細胞生物在基因表現上很重要的一個調控機制。由於選擇性剪裁的影響會導致同一個基因可能因不同的發展階段而產生不同的蛋白質產物，從而加大了產物的差異性。然而生物體的基因中的哪些地方會在什麼情況下發生選擇性剪裁，至今生物學家仍未歸納出完整的相關調控機制。因此，大量地鑑別出所有能鑑別的選擇性剪裁事件，便能提供生物學家更好的研究資料。因為現今大量的表現序列標籤的定序，使得利用電腦技術自動化地位各物種鑑別選擇性剪裁資訊成為可能。選擇性減裁資料庫便是用來整理、儲存並呈現這些鑑別出來的選擇性減裁資訊的一個強而有力的工具。A value added transcriptome database (AVATAR)便是這麼一個選擇性減裁資料庫。然而，AVATAR中鑑別出來的選擇性減裁事件，有部分事件的因為序列在alignment時所得的結果，相比於其他alignment工具來說，較不理想。因此，我們在此同時利用兩種alignment工具重新設計建立一資料庫以解決此一問題，並且整合提供其他在轉錄體階層上的相關研究成果資訊，例如跨物種保留的選擇性減裁事件，鑑別、註明並提供NMD相關的選擇性減裁事件，此外還設計一個便利使用的web介面，為各類選擇性減裁事件提供更完整的視覺化呈現方式。
關鍵詞：選擇性減裁，基因表現，轉錄體，選擇性減裁資料庫

Alternative splicing is an important regulatory mechanism of gene expression in eukaryotic cells. It can increase the diversity of the proteins from the same gene, and variant splice isoforms are often specific to different stages of development. However, we still know less about the complete mechanisms in the transcriptome level. But now, because of the fast increasing of the amount of ESTs, we can systematically identify the alternative splicing events to help the biologists to do more deeply researches. Alternative splicing databases are powerful tools to systematically collect, annotate, store and provide the alternative splicing information. However, each alternative splicing database almost has its own alignment methods and criteria to filter out the alignment results. This reason results into that the alternative splicing events among distinct databases are almost different. For the reason, we build a new alternative splicing database to address the problem by composing three different alignment tools. In the new database, we not only address the defect but also integrate some other research achievements (such as cross-species conservation) into the new database, offer more visualized display for six kinds of alternative splicing events and the annotation of the tissue annotated in the ESTs for each alternative splicing event, and detect the NMD-related alternative splicing events. The new alternative database was built upon the latest version genome and ESTs from the NCBI in May 2006 A.D...
Keywords: alternative splicing, gene expression, transcriptome.

Acknowledgements i
中文摘要 ii
Abstract iii
Chapter 1 Introduction 1
1.1 Motivation 2
1.2 Objective 3
Chapter 2 Related Works 4
2.1 Alternative splicing database 4
2.1.1 The Mechanism of Alternative Splicing 4
2.1.2 Alternative splicing databases 7
2.1.3 The methods to build A.S. databases 16
2.1.4 The characteristics of the development about A.S. databases 17
2.1.5 A Value Added TrAnscRiptome Database (AVATAR) 18
2.2 The mechanism of NMD 19
Chapter 3 Materials and Methods 20
3.1 Materials 20
3.2 Methods 20
3.2.1 AS detector 20
3.2.2 Cross-species information Integration 27
3.2.3 NMD identifier 28
Chapter 4 Experimental results 30
4.1 Hardware and Software 30
4.1.1 Hardware 30
4.1.2 Software 30
4.2 Experimental results 31
4.2.1 Time cost 31
4.2.2 Comparison 33
4.3 The analysis about NMD 33
4.4 The introduction of the website 35
Chapter 5 Conclusion 39
5.1 Discussion 39
5.2 Conclusion 39
5.3 The future works 40
Reference 41

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