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研究生: 鄭成偉
Cheng-Wei Cheng
論文名稱: Predicting RNA-binding sites of proteins using support vector machines and evolutionary information
使用支援向量機與演化資訊預測蛋白質核醣核酸結合位
指導教授: 許聞廉
Wen-Lian Hsu
口試委員:
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 資訊系統與應用研究所
Institute of Information Systems and Applications
論文出版年: 2008
畢業學年度: 96
語文別: 英文
論文頁數: 62
中文關鍵詞: 核醣核酸蛋白質交互作用平滑化特定位置計分矩陣生物資訊計算生物
外文關鍵詞: RNA-protein interaction, RNA-binding sites, Smoothed PSSM, Bioinformatics, Computational biology
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  • RNA-protein interaction plays an essential role in several biological processes, such as protein synthesis, gene expression, post-transcriptional regulation, and antiviral drug discovery. Identification of RNA-binding sites in proteins can provide valuable insights for biologists. However, experimental determination RNA-protein interaction remains time-consuming and labor-intensive. Thus, computational approaches for the prediction of RNA-binding sites from protein sequences have become highly desirable. In this paper, we propose a method, RNAProB, to predict RNA-binding sites based on support vector machines and a new encoding scheme for smoothed position-specific scoring matrix. Evaluated by five-fold cross-validation, our method achieves Matthew’s correlation coefficient (MCC) values of 0.68, 0.58, and 0.42 compared to 0.45, 0.35, and 0.32 by the state-of-the-art systems for three benchmark data sets, respectively. Moreover, to avoid data overfitting, we use a three-way data split procedure to estimate our predictive performance, and our approach obtains MCC values of 0.67, 0.56, and 0.40, respectively. In conclusion, our method significantly improves the predictive performance of RNA-binding site prediction. The proposed encoding scheme for smoothed PSSM can be used in other research problems, such as DNA-protein interaction, protein-protein interaction, and prediction of post-translational modification, etc.


    核醣核酸與蛋白質交互作用在生物體內扮演者重要的角色,像是蛋白質的生成、基因表現、後轉錄調控以及抗病毒藥物的開發皆和此有密切的相關。鑑別蛋白質序列中的核醣核酸結合胺基酸可以幫助生物學家進一步了解蛋白質與核醣核酸交互作用時的機制。然而以傳統生物實驗方法來決定核醣核酸與蛋白質交互作用時的結構非常耗費時間與人力成本。因此最近許多科學家們以計算方法和蛋白質序列來預測蛋白質中的核醣核酸結合位。在這篇論文中我們使用支援向量機(Support Vector Machine)與平滑化特定位置計分矩陣(Smoothed PSSM, Smoothed Position-Specific Scoring Matrix)來預測此問題,並且使用五重交叉驗證(Five-Fold Cross-Validation)來訓練和測驗所提出方法的表現。在結果部分顯示我們的方法在三個不同的資料集(Data Sets)中有馬修相關係數(MCC, Matthew’ s Correlation Coefficient)0.68、0.58和0.42的成果,相較於之前在三個不同的資料集中的研究,馬修相關係數分別只有0.45、0.35和 0.32。此外為防止過度配適(data overfitting)的評量結果,我們使用三重資料分割法(Three-way data split)來評估我們所提出的方法,而結果顯示在三個不同的資料集中,馬修相關係數也分別達到了0.67、0.56和 0.40。綜上言之,我們所提出的方法改進了現有方法的預測結果,且這種編碼方式可以應用在許多其他的生物預測問題中,像是去氧核醣核酸與蛋白質交互作用、蛋白質與蛋白質交互作用、後轉錄調控修飾預測…等。

    摘要 I Abstract II 致謝詞 III Table of Contents IV List of Figures VI List of Tables VII Chapter 1. INTRODUCTION 1 1.1. Central dogma of molecular biology 1 1.2. Background 2 1.3. Previous works 3 1.4. Challenges 4 1.5. Our method and future applications 4 Chapter 2. METHOD 6 2.1. Data sets 6 2.2. Support vector machines (SVM) 7 2.3. Feature extraction and representation 8 2.4. Window size and parameter optimization 10 2.5. System architecture 12 2.6. Performance evaluation 13 2.7. Training and testing 14 Chapter 3. RESULTS 16 3.1. Effect of smoothed PSSM 16 3.2. Performance of five-fold cross-validation and three-way data split 18 3.3. Comparison with other approaches 23 Chapter 4. DISCUSSION 25 4.1. Amino acid composition of data sets 25 4.2. Comparisons of the effects of smoothed PSSM and standard PSSM 27 Chapter 5. CONCLUSION 30 REFERENCES 31 APPENDIX A. Experiment results of the RBP86 33 APPENDIX B. Experiment results of the RBP109 43 APPENDIX C. Experiment results of the RBP107 53

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