| 研究生: |
曾怡靜 Tzseng, Yi-Jing |
|---|---|
| 論文名稱: |
卡路里限制下的基因表現及其代謝路徑的探討 Gene Expression in Caloric Restriction and Pathway Analysis |
| 指導教授: |
詹世煌
Chan, Shih-Huang |
| 學位類別: |
碩士 Master |
| 系所名稱: |
管理學院 - 統計學系 Department of Statistics |
| 論文出版年: | 2010 |
| 畢業學年度: | 98 |
| 語文別: | 中文 |
| 論文頁數: | 23 |
| 中文關鍵詞: | 多時期互補核酸微陣列晶片 、蛋白激酶 、卡路里限制法 、轉折時間點 、代謝路徑 |
| 外文關鍵詞: | time-course cDNA microarray data, protein kinase, gene expression, calorie restriction, change time point, pathway |
| 相關次數: | 點閱:94 下載:1 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
大部分的生物現象或疾病表現通常都是由許多基因一起發揮作用產生的結果。近年來,科學家發現卡路里限制法(Caloric restriction)可使生物延長壽命,且與蛋白激酶的調控機制有關。 王佩力(2009)分析多時期互補核酸微陣列晶片(cDNA microarray),篩選出210條蛋白激酶。本文進一步分析此210條蛋白激酶之表現行為。以無母數迴歸之lowess法概估基因表現,之後就此lowess估計值利用piecewise線性模型來估計轉折時間點和基因表現速率後分群,挑選出32個感興趣的基因。進一步分析,發現其中有4個基因,其Locus分別為TVAG_089630、TVAG_339340、 TVAG_089630與 TVAG_339340,並經實驗驗證其表現(王儷霖,2010),此4個基因經統計方法驗證其顯著性。由於此等基因和MAPK family pathway及AMPK Enzyme Complex pathway有關,對基因間互動行為的探討或許有助於我們對長壽基因的了解。
Most of the biological phenomena or disease is the result of the interactions of multiple genes. Extensive studies on the restriction of caloric (CR) intake showed that CR can extend the longevity in many organisms. Wang (2009) examined the expression level of 210 T.vaginals protein kinase genes under CR by using time-course cDNA microarray. In this thesis, we smoothed the gene expression of the 210 protein kinase, then used piecewise linear model to estimate the changing time that gene expression is dramatically different from the previous behavior, and the rate of gene expression. Applying complete linkage clustering method, thirty-two genes are found to have large changing point or with increasing pattern in gene expression after changing point. Statistical analysis shows that those patterns are highly significant, and four out of these thirty-two genes, TVAG_089630, TVAG_339340,TVAG_123500 and TVAG_456650,have been verified (Wang, 2010). The association of the found 32 genes is to be studied further, hoping that the interaction behaviors of these significant genes can be understood.
1. Ballman, K.V. et al. (2004), Faster cyclic loess: normalizing RNA arrays via
linear models, Bioinformatics, 20, 2778-2786.
2.Clancy, D. et al. (2001), Extension of lifespan to CR in these mice as a first approximation of span by loss of Chico, a Drosophila insulin receptor substrate protein, Science ,292, 104-106.
3. Dummler, B. and Hammings, B. (2007), Physiological roles of PKB/Akt isoforms development
and disease , Bio. S. Trans, 35,231-235.
4. Draghici. S. et al. (2003), Global functional profiling of gene expression, Genomics, 81, 98-104.
5. Efron, B. and Tibshirani, R. (2002), Empirical Bayes methods and false discovery rates for microarrays, Genetic Epidemiology, 23, 70-86.
6. Efron, B. et al. (2001), Empirical Bayes analysis of a microarray experiment, Journal of the American Statistical Association, 96, 1151-1160.
7. Feder, Paul. (1975), On Asymptotic Distribution Theory in Segmented Regression Problems-Identified Case, Annals of Statistics, 3, 49-83.
8. Lee, C. et al. (2000), Gene expression profiling of the aging brain in mice. Nat. Genet. 25, 294-297.
9. Jiang, Z. et al.(2007), Extensions to gene set enrichment, Bioinformatics, 23, 306-313.
10. Masaro, E. et al. (1982), Action of food restriction in delaying the aging process. Proc. Natl.
Acad. Sci, 79, 4239-4241.
11. McCay, C. et al. (1935), The effect of retarded growth upon the length of life span and ultimate body size, J. Nutr,10, 63-79.
12. Ricki, J. et al. (2009) Caloric restriction delays disease onset and mortality in Rhesus monkeys. Science , 325, 201-204.
13. Schena, M. et al. (1995), Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science , 270,467-470.
14. Subramanian, A. et al. (2005), Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles, Proceedings National Academy of Science, 102, 15545–15550.
15. Tian, L. et al. (2005), Discovering statistically significant pathways in expression profiling studies, Proceedings National Academy of Science, 102, 13544–13549.
16. Vergenes, B. et al. (2002), Cytoplasmic SIR2 jomologue overexpression promotes survival of Leishmania parasites by preventing programmed cell death. Gene, 296, 139-150.
17. 王姵力(2009),多時期微陣列資料的基因集分析,國立成功大學,碩士
論文。
18. 林若慈(2006),以連續互補微陣列晶片分析陰道鞭毛蟲卡路里限制相關基因
表達,台北醫學大學,碩士論文。
19. 王儷霖(2010),探討陰道鞭毛蟲蛋白激酶調控延長壽命的機轉,長庚大學,碩
士論文。