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研究生:包盛盈
研究生(外文):Sheng-Ying Pao
論文名稱:人類與小鼠組織特異表現基因之鑑別及其比較分析
論文名稱(外文):In Silico Identification and Comparative Analysis of Tissue-Specific Genes in Human and Mouse
指導教授:林文澧林文澧引用關係
指導教授(外文):Win-Li Lin
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:醫學工程學研究所
學門:工程學門
學類:綜合工程學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:英文
論文頁數:61
中文關鍵詞:功能基因體學組織特異表現基因比較基因體學表現序列標誌
外文關鍵詞:tissue-specific geneexpression profileESTfunctional genomicsUniGenecomparative genomics
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在不同組織中基因表現程度之差異對於維持以及調控細胞功能扮演十分重要的角色,而這些組織特異表現基因可以藉由比較各組織基因表現量之顯著差異來加以判斷。人類與小家鼠具有演化上相近之親緣關係,同時小家鼠亦廣為應用於當代生醫研究與臨床實驗之模式系統,本研究係由比較基因體學以及功能基因體學的角度來分析人類與小家鼠各組織具有顯著表現之基因。本計畫之方法為發展生物資訊學的程序根據表現序列標誌(EST)及其相應的標誌群集(EST cluster of UniGene)鑑別出組織特異表現之基因。目前本研究已鑑別出157種人類組織及108種小家鼠組織當中具有顯著表現的基因。其中我們將人類胎盤顯著表現基因之文獻與我們的結果比較顯示其97.2%的高度顯著基因與我們的預測(p<10-6)吻合,另外在人類大腦顯著表現基因之文獻與我們的結果比較顯示其100%的高度顯著基因與我們的預測(p<10-6)吻合。我們鑑定出的小家鼠腦內紋狀核(striatum)的基因中有86%的結果是與目前微陣列(microarray)的已知結果相符。我們並將人類與小家鼠組織特異表現之同源基因比較分析,整體而言其組織特異基因(p<10-6)之平均相關係數為0.6。另外,同源基因的個別相關係數分析則顯示人類與小家鼠表現組織之異同。這些結果已建立在一名為HMDEG之資料庫中,並提供圖形介面供使用者透過網路查詢。分析這些組織中特異表現的基因將有助於功能基因體學以及系統生物學的研究,這些基因不論在臨床研究或診斷上亦是理想的標的基因。
At the transcriptome level, differential expression of genes is important to maintain and regulate cellular functions. Tissue specific patterns of mRNA expression can provide important information about gene function. Genes expressed with tissue specificity can be characterized by their significantly different amount of transcripts found in different tissues. In this study, we have organized the EST libraries into hierarchical tissue classes and identified preferentially expressed genes in 157 human tissues and 108 mouse tissues by analyzing the EST database along with their clusters as collected in UniGene (build #161 for human and build #128 for mouse). In validation, we compared our results with tissue-specific genes reported in literature and microarray data. Our results yielded a prediction that covered 97.2% of placenta-specific genes and 100% of brain-specific genes reported in recent studies for human, and 86% of mouse striatum-specific genes identified in our results coincided with current findings of microarray data. We have comparatively analyzed 7854 homologous gene pairs. The average correlation coefficient of homologous tissue specific genes with statistical significance (p value < 10-6) reaches 0.6. Detailed analysis of homologous gene pairs reveals similarity and disparity in their expression pattern in human and mouse. We have created a database, named HMDEG (Human and Mouse Differentially Expressed Genes), and a user-friendly website for easy query of tissue-specific genes. The tissue-specific genes identified in this study may serve as targets for seeking candidate markers for genomic research and for investigating gene expression profiles in the scope of comparative genomics.
CONTENTS

中文摘要 I
ABSTRACT II
INTRODUCTION 1
BACKGROUND AND LITERATURE REVIEWS 5
A BRIEF REVIEW OF DBEST 5
A BRIEF REVIEW OF UNIGENE 6
A BRIEF REVIEW OF HOMOLOGENE 7
TOOLS FOR DETECTION OF DIFFERENTIALLY EXPRESSED GENES FROM ESTS 7
PREVIOUS STUDIES OF TISSUE-SPECIFIC GENES IDENTIFICATION FROM ESTS 9
MATERIALS AND METHODS 11
UNIGENE DATA RETRIEVING 11
EST DATA RETRIEVING 11
TISSUE HIERARCHY AND LIBRARY CLASSIFICATION 12
DIFFERENTIALLY EXPRESSED GENES IDENTIFICATION 13
TISSUE DENDROGRAM 14
HOMOLOGOUS GENE DATA PROCESSING 14
CORRELATION ANALYSIS 15
RESULTS 16
HUMAN EST DATA PROCESSING 16
MOUSE EST DATA PROCESSING 16
HUMAN LIBRARY CLASSIFICATION 17
MOUSE LIBRARY CLASSIFICATION 17
TISSUE SPECIFIC GENES IDENTIFICATION 17
VALIDATION 19
HOMOLOGOUS TISSUE SPECIFIC GENE 20
DATABASE AND USER INTERFACE 23
DISCUSSION 26
REFERENCES 29






LIST OF FIGURES

FIG. 1. LIBRARY CLASSIFICATION PROCEDURE. 34
FIG. 2. THE NUMBER OF TISSUE SPECIFIC GENES IDENTIFIED UNDER DIFFERENT P VALUE THRESHOLDS FOR ALL TARGET TISSUES AND NORMAL TISSUES. 35
FIG. 3. TISSUE DENDROGRAM FOR 94 NORMAL HUMAN TISSUES. 36
FIG. 4. TISSUE DENDROGRAM FOR 99 MOUSE TISSUES. 37
FIG. 5. AVERAGE CORRELATION COEFFICIENTS (R) AND NUMBERS OF HOMOLOGOUS GENE PAIRS UNDER DIFFERENT P-VALUE THRESHOLDS 38
FIG. 6. –LOG(P VALUE) OF HUMAN GENE KIAA0748 AND ITS HOMOLOGOUS MOUSE GENE 5830405N20RIK IN TISSUES THEY BOTH EXPRESSED. 39
FIG. 7. REGRESSION OF –LOG (P VALUE) FOR HUMAN GENE KIAA0748 AND ITS HOMOLOGOUS MOUSE GENE 5830405N20RIK IN TISSUES THEY BOTH EXPRESSED. 40
FIG. 8. REGRESSION OF –LOG (P VALUE) FOR HUMAN GENE KIAA0748 AND ITS HOMOLOGOUS MOUSE GENE 5830405N20RIK TISSUES THEY BOTH EXPRESSED EXCLUDING THYMUS. 41
FIG. 9. –LOG(P VALUE) OF HUMAN GENE PCDH8 AND ITS HOMOLOGOUS MOUSE GENE PCDH8 IN TISSUES THEY BOTH EXPRESSED. 42
FIG. 10. REGRESSION OF –LOG (P VALUE) FOR HUMAN GENE PCDH8 AND ITS HOMOLOGOUS MOUSE GENE PCDH8 IN TISSUES THEY BOTH EXPRESSED. 43
FIG. 11. –LOG(P VALUE) OF HUMAN AND MOUSE HOMOLOGOUS GENES IL2RG IN TISSUES THEY BOTH EXPRESSED. 44

FIG. 12. REGRESSION OF –LOG (P VALUE) FOR OF HUMAN AND MOUSE HOMOLOGOUS GENES IL2RG IN TISSUES THEY BOTH EXPRESSED. 45
FIG. 13. A DATABASE AND USER-FRIENDLY WEBSITE FOR HUMAN AND MOUSE DIFFERENTIALLY EXPRESSED GENES (HMDEG). 46
FIG. 14. QUERY TISSUE-SPECIFIC GENE BY SELECTING TISSUE NAME FROM THE PULL-DOWN MENU. 47
FIG. 15. THE RESULT PAGE OF QUERY BY TISSUE NAME. 48
FIG. 16. QUERY TISSUE-SPECIFIC GENE BY ID OR GENE NAME. 49
FIG. 17. RESULT OF QUERY BY UNIGENE CLUSTER ID. 50
FIG. 18. RESULT OF QUERY BY GENE NAME 51
FIG. 19. RESULT OF QUERY BY EST GENE BANK ACCESSION NUMBER. 52
FIG. 20. RESULT OF QUERY BY EST LIBRARY ID. 53
FIG. 21. DETAILED LIBRARY QUERY RESULT. 54
FIG. 22. RESULT OF HOMOLOGOUS LUNG-SPECIFIC GENE QUERY. 55




LIST OF TABLES


TABLE. 1. PREDICTED HUMAN PLACENTA-SPECIFIC GENES IN ACCORD WITH LITERATURE24. 56
TABLE. 2. PREDICTED HUMAN –BRAIN SPECIFIC GENES IN ACCORD WITH LITERATURE52. 57
TABLE. 3. THE TOP 35 MOUSE STRIATUM-SPECIFIC GENES COINCIDED WITH MICROARRAY DATA13. 58
TABLE. 4.THE NUMBER OF HOMOLOGOUS GENE PAIRS IN NORMAL TISSUES UNDER P VALUE THRESHOLDS OF 5E-2, 5E-3, 5E-4, 5E-5, AND 1E-6. 59
TABLE. 5. THE NUMBER OF HOMOLOGOUS GENE PAIRS WITH P VALUE < 10-6 IN DIFFERENT STRENGTH OF ASSOCIATION 60
TABLE. 6. P VALUE OF HUMAN GENE PCDH8 AND ITS MOUSE HOMOLOG PCDH8 DETECTED IN DIFFERENT TISSUES. 61
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