競爭性內源核糖核酸(ceRNA) 假設最近已成為生物訊息學研究中最熱門的話題之一。Cell 是在生物科學界上經常被引用的學術期刊，早前亦有一班學者在Cell 2011年同一期成功發佈四篇關於ceRNA 假設的學術文章。跟據有關ceRNA 假設的學術文章，大部份學者均以不同的個別例子成功驗證假定，可是，欠缺一個大規模的及全面性的分析。 / 在我兩年碩士的研究中，我引入了一個新的概念微核糖核酸及其目標對向聚類(MTB) 運用了ceRNA 的假設，還提出算法，成功從微核糖核酸與信使核糖核酸的相互數據中找出一系列的MTB' 還利用GENCODE 項目上大量的微核糖核酸及信使核糖核酸的表達數據去驗証MTB 的概念。一方面，我從大量的表達數據中成功推斷出微核糖核酸與信使核糖核酸之間的相反關連、信使核糖核酸之間的正面關運和微核糖核酸之間的正面關連;另一方面，這些關連進一步肯定ceRNA 假設的真實性。此外，我提出一個從大量基因組中找出基因功能分析的方法，並在大量的MTB 的基因組中找出重要的基因註解。最後，我提出另一個MTB 概念的應用一新算法來預測微核糖核酸與信使核糖核酸的相互影響。總括而吉， MTB 概念從複雜且混亂的微核糖核酸與信使核糖核酸網絡中定義簡單且穩固的模姐，提供一個系統生物學分析微核糖核酸調節能力的方法。 / The competing Endogenous RNA (ceRNA) hypothesis has become one of the hottest topics in bioinformatics research recently. Four papers related to the ceRNA hypothesis were published simultaneously in Cell in 2011, a top journal in life sciences. For most papers related to the ceRNA hypothesis, the corresponding studies have successfully validated the hypothesis with different individual examples, without a large-scale and comprehensive analysis. / In my Master of Philosophy study, a novel concept, called mi-RNA Target Bicluster (MTB), is introduced to model the ceRNA hypothesis. The MTBs are identified computationally from validated and/or predicted miRNA-mRNA interaction pairs. The MTB models were tested with the mRNAs and miRNAs expression data from the GENCODE Project. Statistically significant miRNA-mRNA anti-correlation, mRNA-mRNA correlation and miRNA-miRNA correlation in expression data are found, verifying the correlation relations among mRNAs and miRNAs stated in the ceRNA hypothesis with large-scale data support. Moreover, a novel large-scale functional enrichment analysis is performed, and the mRNAs selected by the MTBs are found to be biologically relevant. Besides, some new target prediction algorithms are suggested, as another application of the MTBs, are suggested. Overall, the concept of MTB defines simple and robust modules from the complex and noisy miRNA-mRNA network, suggesting ways for system biology analyses in miRNA-mediated regulations. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Yip, Kit Sang Danny. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves [117]-126). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts also in Chinese. / Abstract --- p.i / Acknowledgement --- p.iv / Chapter 1 --- Introduction --- p.1 / Chapter 1.1 --- Contributions --- p.1 / Chapter 1.2 --- Thesis Outline --- p.2 / Chapter 2 --- Background --- p.3 / Chapter 2.1 --- Bioinformatics --- p.3 / Chapter 2.2 --- Biological Background --- p.7 / Chapter 2.2.1 --- The Central Dogma of Molecular Biology . --- p.7 / Chapter 2.2.2 --- RNAs --- p.8 / Chapter 2.2.3 --- Competing Endogenous RNA (ceRNA) hypothesis --- p.9 / Chapter 2.2.4 --- Biological Considerations in Functional Enrichment Analysis --- p.11 / Chapter 2.3 --- Computational Background --- p.12 / Chapter 2.3.1 --- miRNA Genomic Annotation Prediction --- p.13 / Chapter 2.3.2 --- miRNA Target Interaction Prediction --- p.14 / Chapter 2.3.3 --- Applying Computational Algorithms on Related Problems --- p.16 / Chapter 2.3.4 --- Algorithms in Functional Enrichment Analysis --- p.16 / Chapter 2.4 --- Experiments and Data --- p.17 / Chapter 2.4.1 --- miRNA Target Interactions --- p.17 / Chapter 2.4.2 --- Expression Data --- p.18 / Chapter 2.4.3 --- Annotation Datasets --- p.19 / Chapter 2.5 --- Research Motivations --- p.20 / Chapter 3 --- Definitions of miRNA Target Biclusters (MTB) --- p.22 / Chapter 3.1 --- Representations --- p.22 / Chapter 3.1.1 --- Binary Association Matrix Representation --- p.23 / Chapter 3.1.2 --- Bipartite Graph Representation --- p.23 / Chapter 3.1.3 --- Mathematical Representation --- p.24 / Chapter 3.2 --- Concept of MTB --- p.24 / Chapter 3.2.1 --- MTB Restrictive Type (Type R) --- p.27 / Chapter 3.2.2 --- MTB Restrictive Type on miRNA (Type Rmi) --- p.31 / Chapter 3.2.3 --- MTB Restrictive Type on mRNA (Type Rm) --- p.34 / Chapter 3.2.4 --- MTB Restrictive and General Type (Type Rgen) --- p.37 / Chapter 3.2.5 --- MTB Loose Type (Type L) --- p.44 / Chapter 3.2.6 --- MTB Loose Type but restricts on miRNA (Type Lmi) --- p.47 / Chapter 3.2.7 --- MTB Loose Type but restricts on mRNA (Type Lm) --- p.50 / Chapter 3.2.8 --- MTB Loose and General Type (Type Lgen) --- p.53 / Chapter 3.2.9 --- A General Definition on all Eight Types --- p.58 / Chapter 3.2.10 --- Discussions --- p.60 / Chapter 4 --- MTB Workflow in Checking Correlation Relations --- p.61 / Chapter 4.1 --- MTB Workflow in Checking Correlation Relations --- p.61 / Chapter 4.1.1 --- MTB Identification --- p.62 / Chapter 4.1.2 --- Correlation Coefficients --- p.63 / Chapter 4.1.3 --- Scoring Scheme --- p.64 / Chapter 4.1.4 --- Background Construction --- p.65 / Chapter 4.1.5 --- Wilcoxon Rank-sum Test --- p.66 / Chapter 4.1.6 --- Preliminary Studies --- p.67 / Chapter 4.2 --- miRNA-mRNA Anti-correlation in Expression Data --- p.68 / Chapter 4.2.1 --- Interaction Datasets --- p.69 / Chapter 4.2.2 --- Expression Datasets --- p.72 / Chapter 4.2.3 --- Independence of the Choices of Datasets --- p.73 / Chapter 4.2.4 --- Independence of the Types of MTBs --- p.76 / Chapter 4.2.5 --- Independence of the Choices of Correlation Coefficients --- p.78 / Chapter 4.2.6 --- Dependence on the Way to Score --- p.79 / Chapter 4.2.7 --- Independence of theWay to Construct Background --- p.81 / Chapter 4.2.8 --- Independence of Natural Bias in Datasets --- p.82 / Chapter 4.3 --- mRNA-mRNA Correlation in Expression Data --- p.84 / Chapter 4.3.1 --- Variations in the Analysis --- p.85 / Chapter 4.3.2 --- Discussions --- p.87 / Chapter 4.4 --- miRNA-miRNA Correlation in Expression Data --- p.88 / Chapter 4.4.1 --- Variations in the Analysis --- p.89 / Chapter 4.4.2 --- Discussions --- p.92 / Chapter 5 --- Target Prediction Aided by MTB --- p.94 / Chapter 5.1 --- Workflow in Target Prediction --- p.94 / Chapter 5.2 --- Contingency Table Approach --- p.96 / Chapter 5.2.1 --- One-tailed Hypothesis Testing --- p.97 / Chapter 5.3 --- Ranked List Approach --- p.98 / Chapter 5.3.1 --- Wilcoxon Signed Rank Test --- p.99 / Chapter 5.4 --- Results and Discussions --- p.99 / Chapter 6 --- Large-scale Functional Enrichment Analysis --- p.102 / Chapter 6.1 --- Principles in Functional Enrichment Analysis --- p.102 / Chapter 6.1.1 --- Annotation Files --- p.104 / Chapter 6.1.2 --- Functional Enrichment Analysis on a gene --- p.set105 / Chapter 6.1.3 --- Functional Enrichment Analysis on many gene sets --- p.106 / Chapter 6.2 --- Results and Discussions --- p.107 / Chapter 7 --- Future Perspectives and Conclusions --- p.112 / Chapter 7.1 --- Applying MTB definition on other problems --- p.112 / Chapter 7.2 --- Matrix Definitions and Optimization Problems --- p.113 / Chapter 7.3 --- Non-binary association matrix problem settings --- p.114 / Chapter 7.4 --- Limitations --- p.114 / Chapter 7.5 --- Conclusions --- p.116 / Bibliography --- p.117 / Chapter A --- Publications --- p.127 / Chapter A.1 --- Publications --- p.127
| Identifer | oai:union.ndltd.org:cuhk.edu.hk/oai:cuhk-dr:cuhk_328229 |
| Date | January 2013 |
| Contributors | Yip, Kit Sang Danny., Chinese University of Hong Kong Graduate School. Division of Computer Science and Engineering. |
| Source Sets | The Chinese University of Hong Kong |
| Language | English, Chinese |
| Detected Language | English |
| Type | Text, bibliography |
| Format | electronic resource, electronic resource, remote, 1 online resource (xi, 126, [1] leaves) : ill. (some col.) |
| Rights | Use of this resource is governed by the terms and conditions of the Creative Commons “Attribution-NonCommercial-NoDerivatives 4.0 International” License (http://creativecommons.org/licenses/by-nc-nd/4.0/) |
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