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完整後設資料紀錄
DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 阮雪芬(Hsueh-Fen Juan) | |
dc.contributor.author | Cho-Yi Chen | en |
dc.contributor.author | 陳卓逸 | zh_TW |
dc.date.accessioned | 2021-06-15T01:33:11Z | - |
dc.date.available | 2009-07-29 | |
dc.date.copyright | 2009-07-29 | |
dc.date.issued | 2009 | |
dc.date.submitted | 2009-07-19 | |
dc.identifier.citation | 1. Shen-Orr SS, Milo R, Mangan S, Alon U: Network motifs in the transcriptional regulation network of Escherichia coli. Nat Genet 2002, 31(1):64-68.
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dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/43021 | - |
dc.description.abstract | 系統生物學已成為生物醫學研究中一個新興的領域,其著重於以系統的觀點來了解生物系統的運作。由於細胞內的各種生物反應過程,皆由許多基因與蛋白質共同參與,形成複雜的生物分子網路,因此,建構出完整基因調控網路的系統模型,對於了解細胞的生理,以及疾病的分子機制,更顯得重要。
近年來,微型核醣核酸(microRNA, 簡稱 miRNA)被發現普遍存在於動植物以及某些病毒之中,其長度約為 22 個鹼基,並不會轉譯為蛋白質,但是會和細胞內與其部份序列互補的 mRNA 結合,破壞 mRNA 的穩定性或抑制其轉譯為蛋白質,進而調控基因與蛋白質的表現。過去的研究指出,miRNA 參與許多生物的發育、分化、生長及代謝等過程,調控相關基因的表現;此外,已發現miRNA 與基因轉錄因子(transcription factor)之間存在一些特殊的相關性。雖然 miRNA 對於單一基因的調控機制,已經有相當多的研究,其分子反應路徑也漸趨明朗;然而,在各種不同的生物反應過程中,參與的 miRNA 與蛋白質數目眾多,究竟 miRNA 在這些複雜的生物反應過程中扮演何種角色,以及如何與轉錄因子合作調控,仍然不清楚,需要進一步的研究與探討。 本論文首先藉由整合大規模的實驗資料,建立出人類基因調控網路,以描述細胞內的各個基因間彼此互相增強或抑制基因表現的調控關係。我們進一步嘗試將 miRNA 所預測的調控目標加入此網路,並發展出新的計算模型,利用功能性基因註解資訊,預測出高生物意義的共調控關係。 結果顯示,利用我們的計算模型,可成功預測 miRNA 與轉錄因子共同調控機制下,所參與的生物過程,並證明此乃傳統研究單一調控的方法難以發現的。接著,基於所預測出的共調控關係與功能性鏈結,我們更一步建立出功能性共調控網路,並發現不同型式的共調控網路呈現了不同的拓樸性質。其後,為了探討各類共調控關係於基因調控網路上的訊息傳遞模式,我們採用重抽樣方法進行比較與分析驗證,結果顯示共調控關係採用了多樣化的前饋模式,並且在其調控路徑上游可發現密切的交互作用。最後,藉由分析基因表現圖譜,我們更進一步發現不同的共調控關係存在著不同的表現相關性分佈,這可能是與 miRNA 與轉錄因子各自不同的分子機制有關。更重要的是,比較人類正常組織與腫瘤組織之間的基因表現圖譜,顯示出明顯的表現相關性分佈差異,暗示了共調控關係的破壞可能與癌症有關。 | zh_TW |
dc.description.abstract | MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression at the post-transcriptional level. Recent studies have suggested that miRNAs and transcription factors are primary metazoan gene regulators, but the crosstalk between them still remains unclear.
Combing all the potential targets of miRNAs and transcription factors from several published databases and miRNA gene locus information, we first built up an integrative human transcriptional regulation network involving both kinds of regulators and investigated the characterization of miRNA regulation in the integrative network. Secondly, we proposed a novel model utilizing functional annotation information to identify significant co-regulation between transcriptional and post-transcriptional layers. Based on this model, function-enriched co-regulation pairs were discovered, and the paired regulators were linked by enriched functions. We further constructed functional co-regulation networks between regulators and investigated their characteristics. Next, we searched for the network motifs consisting of those function-enriched co-regulation pairs and found that an abundance of pairs were closely linked in upstream. Finally, the expression patterns of function-enriched co-regulation pairs were explored. Different co-regulation types showed distinct expression correlation trends. More importantly, we found that the disruption of co-regulation may be closely related to cancers. To conclude, this work uncovers the co-regulation principles between microRNAs and transcription factors, and proposes that coordinated regulation may significantly regulate many biological processes. These findings together elucidated the combinatorial and cooperative properties of TFs and miRNAs co-regulation. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T01:33:11Z (GMT). No. of bitstreams: 1 ntu-98-R96945018-1.pdf: 4616437 bytes, checksum: d4e69a58fd8676f1a75518101037b070 (MD5) Previous issue date: 2009 | en |
dc.description.tableofcontents | 口試委員會審定書 i
Acknowledgments ii 中文摘要 iii Abstract v Contents vii List of Figures x 1 Introduction 1 1.1 Transcriptional Regulation Networks 1 1.2 MicroRNA Regulation 1 1.3 Coordinated Regulation 2 2 Materials and Methods 5 2.1 Transcriptional Regulation Relationships 5 2.2 MicroRNA Targets 6 2.3 MicroRNA Host Genes 6 2.4 Gene Ontology Annotations 8 2.5 Gene Symbols 8 2.6 Identification of Significant Co-regulation Relationship 9 2.6.1 Adjacency Matrixes 9 2.6.2 Functional Profiles 10 2.6.3 The Permutation Test 11 2.7 Functional Linkages and Networks 12 2.8 Enriched Network Motifs 13 2.9 Expression Profiles 15 3 Results 16 3.1 MicroRNA Regulation in the Transcriptional Regulation Network 16 3.2 Functional Co-regulation Pairs 19 3.3 Functional Co-regulation Networks 24 3.4 Network Motifs for Co-regulation Pairs 28 3.5 Expression Analysis of Co-regulation 30 4 Discussion and Conclusion 35 5 Bibliography 39 Appendixes 43 A. List of Gene Ontology in Biological Process Level 2 43 B. List of Transcription Factors 45 C. Function-enriched Co-regulation Pairs 49 C.1 TF-TF Co-regulation 49 C.2 TF-miRNA Co-regulation 58 C.3 miRNA-miRNA Co-regulation 60 D. Enriched Motifs in TF-TF co-regulation 70 D.1 Bidirectional Feed-Forward Loop 70 D.2 Unidirectional Feed-Forward Loop 71 D.3 Common Upstream TF 73 D.4 Common Upstream TF & miRNA 77 D.5 Upstream Crosstalk 78 E. Enriched Motifs in TF-miRNA co-regulation 85 E.1 Feed-Forward Loop 85 E.2 Common Upstream TF 85 E.3 Upstream Crosstalk 86 F. Oral Presentation at the 24th Joint Annual Conference of Biomedical Science (JACBS) 88 | |
dc.language.iso | en | |
dc.title | 微型核醣核酸與轉錄因子對於轉錄調控網路之共同調控機制 | zh_TW |
dc.title | Co-regulation of microRNAs and Transcription Factors in Transcriptional Regulation Network | en |
dc.type | Thesis | |
dc.date.schoolyear | 97-2 | |
dc.description.degree | 碩士 | |
dc.contributor.coadvisor | 黃宣誠(Hsuan-Cheng Huang),傅楸善(Chiou-Shann Fuh) | |
dc.contributor.oralexamcommittee | 李文雄(Wen-Hsiung Li),施純傑(Chun-Chieh Arthur Shih) | |
dc.subject.keyword | 系統生物學,生物資訊,微型核醣核酸,基因轉錄因子,基因調控網路, | zh_TW |
dc.subject.keyword | systems biology,bioinformatics,microRNAs,transcription factors,transcriptional regulation network, | en |
dc.relation.page | 89 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2009-07-20 | |
dc.contributor.author-college | 電機資訊學院 | zh_TW |
dc.contributor.author-dept | 生醫電子與資訊學研究所 | zh_TW |
顯示於系所單位: | 生醫電子與資訊學研究所 |
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