研究生: |
陳芝妤 Chih-Yu Chen |
---|---|
論文名稱: |
從基因微陣列作轉錄因子與基因調控之計算分析: 前列腺癌之案例研究 Computational Analysis of Transcription Factors and Gene Regulation from cDNA Microarray Expression – a Case Study on Prostate Cancer |
指導教授: |
蘇豐文
Von-Wun Soo |
口試委員: | |
學位類別: |
碩士 Master |
系所名稱: |
電機資訊學院 - 資訊系統與應用研究所 Institute of Information Systems and Applications |
論文出版年: | 2005 |
畢業學年度: | 93 |
語文別: | 英文 |
論文頁數: | 84 |
中文關鍵詞: | 基因微陣列 、基因調控 、轉錄因子 、DNA結合位置 |
外文關鍵詞: | Microarray, Gene Regulation, Trancription Factor, Composite Element, Binding Position |
相關次數: | 點閱:3 下載:0 |
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 |
基因微陣列的出現使得上萬的基因表現得以同時被測量,此科技幫助達成生物計算分析:轉錄因子與表現變動的基因之互動關係。由於實驗證明許多不同轉錄因子會產生互動,且對基因調控有相輔相成之作用,而過去從微陣列數據裡只找單個首要轉錄因子的方法,很明顯地不足以解釋錯綜複雜之基因調控。
所以本論文中運用轉錄因子相對的DNA結合區之位置與轉錄因子兩兩相互關係作更深入的分析,進而對基因表現之變動達到更深層的理解。換言之,在表現變動的基因群裡,試圖找出較能解釋所控制的基因表現之轉錄因子、轉錄因子之相互關係或特定DNA結合區之位置。
Emerging of microarray experiments have rendered simultaneous screenings of thousands of gene expressions possible, and subsequent analyses of transcription factors that highly correlate with differentially expressed genes can be conducted to determine the likely mechanism of gene regulation. Since transcription factors have been proven to work cooperatively with one another as composite elements by a growing body of evidence, previous efforts in identifying only one transcription factor for each experiment are clearly insufficient to decipher the complex underlying mechanism of expression changes.
Therefore, the attempt here incorporates the analysis of TF binding positions and focuses on detecting TF pairs from genes with altered expressions. In combination of microarray and promoter binding site analysis, we predict pairs of transcription factors that mostly likely contribute to the regulated transcription of differentially expressed genes. The Expectation Maximization clustering of the TF binding positions is made available in order to detect a pattern in specific TF binding and predict the role it might play in regulation.
[1] Ogata, K., Sato, K., and Tahirov, T.H, “Eukaryotic transcriptional regulatory complexes: cooperativity from near and afar,” Curr Opin Struct Biol. 2003 Feb;13(1):40-8. Review.
[2] Ball, C.A., Awad, I.A., Demeter, J., Gollub, J., Hebert, J.M., Hernandez-Boussard, T., Jin, H., Matese, J.C., Nitzberg, M., Wymore, F., Zachariah, Z.K., Brown, P.O., and Sherlock, G., “The Stanford Microarray Database accommodates additional microarray platforms and data formats,” Nucleic Acids Res. 2005 Jan 1;33(Database issue):D580-2.
[3] Maglott, D., Ostell, J., Pruitt, K.D., and Tatusova, T., ”Entrez Gene: gene-centered information at NCBI,” Nucleic Acids Res. 2005 Jan 1;33(Database issue):D54-8.
[4] Zhang, H., Ramanathan, Y., Soteropoulos, P., Recce, M.L., and Tolias, P.P., “EZ-Retrieve: a web-server for batch retrieval of coordinate-specified human DNA sequences and underscoring putative transcription factor-binding sites,” Nucleic Acids Res. 2002 Nov 1;30(21):e121.
[5] Suzuki, Y., Yamashita, R., Sugano, S., and Nakai, K., “DBTSS, DataBase of Transcriptional Start Sites: progress report 2004,” Nucleic Acids Res. 2004 Jan 1;32(Database issue):D78-81.
[6] Wingender, E., Chen, X., Fricke, E., Geffers, R., Hehl, R., Liebich, I., Krull, M., Matys, V., Michael, H., Ohnhauser, R., Pruss, M., Schacherer, F., Thiele, S., and Urbach, S., “The TRANSFAC system on gene expression regulation.” Nucleic Acids Res. 2001 Jan 1;29(1):281-3.
[7] Sandelin, A., Alkema, W., Engstrom, P., Wasserman, W.W., and Lenhard, B., “JASPAR: an open-access database for eukaryotic transcription factor binding profiles,” Nucleic Acids Res. 2004 Jan 1;32(Database issue):D91-4.
[8] http://www.cbrc.jp/research/db/TFSEARCH.html
[9] Chekmenev, D.S., Haid, C., and Kel, A.E., “P-Match: transcription factor binding site search by combining patterns and weight matrices,” Nucleic Acids Res. 2005 Jul 1;33(Web Server issue):W432-7.
[10] Haverty, P.M., Hansen, U., and Weng, Z., “Computational inference of transcriptional regulatory networks from expression profiling and transcription factor binding site identification,” Nucleic Acids Res. 2004 Jan 2;32(1):179-88.
[11] Kel-Margoulis, O.V., Kel, A.E., Reuter, I., Deineko, I.V., and Wingender, E., “TRANSCompel: a database on composite regulatory elements in eukaryotic genes,” Nucleic Acids Res. 2002 Jan 1;30(1):332-4.
[12] Kanehisa, M., and Goto, S., "KEGG: kyoto encyclopedia of genes and genomes," Nucleic Acids Res. 2000 Jan 1;28(1):27-30.
[13] Pilpel, Y., Sudarsanam, P., and Church, G.M., “Identifying regulatory networks by combinatorial analysis of promoter elements,” Nat Genet. 2001 Oct;29(2):153-9.
[14] Zhao, H., Whitfield, M.L., Xu, T., Botstein, D., and Brooks, JD., “Diverse effects of methylseleninic acid on the transcriptional program of human prostate cancer cells,” Mol Biol Cell. 2004 Feb;15(2):506-19.
[15] Jones, S.B., DePrimo, S.E., Whitfield, M.L., and Brooks, J.D., “Resveratrol-induced gene expression profiles in human prostate cancer cells,” Cancer Epidemiol Biomarkers Prev. 2005 Mar;14(3):596-604.
[16] Witten, I.H., and Frank, E., “Data Mining: Practical machine learning tools with Java implementations,” Morgan Kaufmann, San Francisco, 2000.
[17] Bradley, P., Fayyad, U., and Reina, C., “Scaling EM (Expectation Maximization) clustering to large databases,” Technical Report MSR-TR-98-35, Microsoft Research, 1998.
[18] Dempster, A.P., Laird, N.M., and Rubin, D.B., “Maximum Likelihood from Incomplete Data via the EM algorithm,” Journal of the Royal statistical Society, Series B. 1997 39(1): 1-38.
[19] Dong, Y., Zhang, H., Hawthorn, L., Ganther, H.E., and Ip, C., “Delineation of the molecular basis for selenium-induced growth arrest in human prostate cancer cells by oligonucleotide array,” Cancer Res. 2003 Jan 1;63(1):52-9.
[20] Makropoulos, V., Bruning, T., and Schulze-Osthoff, K., “Selenium-mediated inhibition of transcription factor NF-kappa B and HIV-1 LTR promoter activity,” Arch.Toxicol. 70. 1996 277-283.
[21] Gasparian, A.V., Yao, Y.J., Lu, J., Yemelyanov, A.Y., Lyakh, L.A., Slaga, T.J., and Budunova, I.V., “Selenium compounds inhibit I kappa B kinase (IKK) and nuclear factor-kappa B (NF-kappa B) in prostate cancer cells,” Mol Cancer Ther. 2002 Oct;1(12):1079-87.
[22] Wang, H., Iakova, P., Wilde, M., Welm, A., Goode, T., Roesler, W.J., and Timchenko, N.A., “C/EBPalpha arrests cell proliferation through direct inhibition of Cdk2 and Cdk4,” Mol Cell. 2001 Oct;8(4):817-28.
[23] Wang, G.L., and Timchenko, N.A., “Dephosphorylated C/EBPalpha accelerates cell proliferation through sequestering retinoblastoma protein,” Mol Cell Biol. 2005 Feb;25(4):1325-38.
[24] Shim, M., Powers, K.L., Ewing, S.J., Zhu, S., and Smart, R.C., “Diminished expression of C/EBPalpha in skin carcinomas is linked to oncogenic Ras and reexpression of C/EBPalpha in carcinoma cells inhibits proliferation,” Cancer Res. 2005 Feb 1;65(3):861-7.
[25] Kim, Y.A., Rhee, S.H., Park, K.Y., and Choi, Y.H., “Antiproliferative effect of resveratrol in human prostate carcinoma cells,” J Med Food. 2003 Winter;6(4):273-80.
[26] Laux, M.T., Aregullin, M., Berry, J.P., Flanders, J.A., and Rodriguez, E., “Identification of a p53-dependent pathway in the induction of apoptosis of human breast cancer cells by the natural product, resveratrol,” J Altern Complement Med. 2004 Apr;10(2):235-9.
[27] Liontas, A., and Yeger, H., “Curcumin and resveratrol induce apoptosis and nuclear translocation and activation of p53 in human neuroblastoma,” Anticancer Res. 2004 Mar-Apr;24(2B):987-98.
[28] She, Q.B., Bode, A.M., Ma, W.Y., Chen, N.Y., and Dong, Z., “Resveratrol-induced activation of p53 and apoptosis is mediated by extracellular-signal-regulated protein kinases and p38 kinase,” Cancer Res. 2001 Feb 15;61(4):1604-10.
[29] Yang, T.T., and Chow, C.W., “Transcription cooperation by NFAT.C/EBP composite enhancer complex,” J Biol Chem. 2003 May 2;278(18):15874-85.
[30] Ge, Y., Jensen, T.L., Matherly, L.H., and Taub, J.W., “Physical and functional interactions between USF and Sp1 proteins regulate human deoxycytidine kinase promoter activity,” J Biol Chem. 2003 Dec 12;278(50):49901-10.