博碩士論文 972211010 詳細資訊




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姓名 戴貝蓁(Pei-Chen Tai)  查詢紙本館藏   畢業系所 系統生物與生物資訊研究所
論文名稱 啟動子甲基化與對應之基因表現微陣列資訊整合分析
(The integrative analysis of promoter methylation & gene expression patterns in chip data)
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摘要(中) 微晶片被廣泛應用於各方研究,無論是整個基因體表現模式或是其中特定區塊的探討,皆深受研究者的喜愛。我們從國防醫學中心微生物及免疫所取得肝癌組織的甲基化晶片,並由美國國家衛生研究院生物資訊中心 (National Center for Biotechnology Information; NCBI) 提供的資料庫 Gene Expression Omnibus (GEO) 取得相對應C型肝癌的基因表現晶片,分別藉由基因的挑選建立許多基因表單,交叉比對相關性。由結果顯示,從腫瘤周圍的正常組織到腫瘤組織甲基化程度的改變是非常劇烈的,當基因上游發生甲基化,基因下游可能受其他狀況影響,導致甲基化與基因表現沒有一定的結果,從中對照一些已發表的基因甲基化與表現情況加以探討。
摘要(英) There is a tendency towards high throughput technology in many aspects. A large number of researches utilize microarray to study the whole genome or the majority of specific sites that would be concerned. We use the HCC methylation beadchip obtained from the Department of Microbiology and Immunology at National Defense Medical Center, and download the raw data of HCV relative expression array from The Gene Expression Omnibus (GEO) database was established by National Center for Biotechnology Information (NCBI) to compare with methylation array data. Construct gene lists by cross mapping gene selection. We show the evidence that the variation of gene methylation level is obvious between the tumor tissues and peripheral tissues. When the methylation occurs at the upstream of a gene, its downstream may be affected by other factors at the same time. To have a comparison with the condition of some genes were proved by others, this study may provide a point of view to combine epigenetic knowledge and expression data, therefore make if helpful for our further research.
關鍵字(中) ★ 微陣列晶片
★ 晶片
★ 基因表現
★ 甲基化
★ 啟動子甲基化
★ 整合分析
關鍵字(英) ★ gene expression
★ methylation
★ integration
★ promoter
★ promoter methylation
★ integrative analysis
★ array
★ chip
論文目次 Chinese Abstract i
English Abstract ii
List of figures iv
List of tables v
Chapter 1 Introduction 1
1-1 Background 1
1-1-1 Summary of promoter 3
1-1-2 Illumina's HumanMethylation27 DNA Analysis BeadChip 4
1-1-3 Affymetrix Oligonucleotide Expression array 6
1-2 Motivation 8
Chapter 2 Material and methods 9
2-1 Material 10
2-1-1 Illumina Methylation Array 10
2-1-2 Gene Expression Omnibus and Affymetrix Expression Array 11
2-2 Methods 12
2-2-1 Affymetrix array’s multiple probe sets problem 12
2-2-2 Quantile normalization 14
2-2-3 DAVID 16
Chapter 3 Result 17
3-1 Gene selection 17
3-1-1 Methylation Array 17
3-1-2 Cross Gene Mapping 20
3-2 Gene Ontology (GO) Clustering Analysis 28
3-3 Case study 32
Chapter 4 Discussion 34
References 35
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9. Beck, S. and V.K. Rakyan, The methylome: approaches for global DNA methylation profiling. Trends Genet, 2008. 24(5): p. 231-7.
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11. Fuks, F., DNA methylation and histone modifications: teaming up to silence genes. Curr Opin Genet Dev, 2005. 15(5): p. 490-5.
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17. Mas, V.R., et al., Genes involved in viral carcinogenesis and tumor initiation in hepatitis C virus-induced hepatocellular carcinoma. Mol Med, 2009. 15(3-4): p. 85-94.
18. AFFYMETRIX, Design and Performance of the GeneChip® Human Genome U133 Plus 2.0 and Human Genome U133A 2.0 Arrays.
19. Bolstad, B.M., et al., A comparison of normalization methods for high density oligonucleotide array data based on variance and bias. Bioinformatics, 2003. 19(2): p. 185-93.
20. Dennis, G., Jr., et al., DAVID: Database for Annotation, Visualization, and Integrated Discovery. Genome Biol, 2003. 4(5): p. P3.
21. Huang da, W., B.T. Sherman, and R.A. Lempicki, Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc, 2009. 4(1): p. 44-57.
22. Yang, B., et al., Aberrant promoter methylation profiles of tumor suppressor genes in hepatocellular carcinoma. Am J Pathol, 2003. 163(3): p. 1101-7.
23. Wang, S.N., et al., Potential role of leptin expression in hepatocellular carcinoma. J Clin Pathol, 2006. 59(9): p. 930-4.
指導教授 吳立青(Li-Ching Wu) 審核日期 2010-7-29
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