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研究生: 田耘政
Yun-Cheng Tian
論文名稱: ChemiRs - 化學物質、微核糖核酸對人體健康影響之網路應用系統
ChemiRs - Web App for Chemicals, MicroRNAs and Human Health
指導教授: 沈林琥
Sher, Singh
學位類別: 碩士
Master
系所名稱: 生命科學系
Department of Life Science
論文出版年: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 48
中文關鍵詞: 網路應用資料庫化學物質微核糖核酸生物途徑疾病基因本體論
英文關鍵詞: web application, database, chemical, microRNA, pathway, disease, gene ontology
論文種類: 學術論文
相關次數: 點閱:158下載:3
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  •   微核糖核酸(microRNA, miRNA)是一種長度約22個核苷酸,具有高度保守性的單股非編碼RNA(non-coding RNA, ncRNA),其在生物體中扮演相當多樣且重要的基因調控角色。目前約有1500種不同的miRNA在人體內被發現並記錄,並且有多種預測miRNA目標基因的演算法,然而卻缺乏miRNA、環境化合物與人體健康關聯性的資料庫或演算法。環境中的多種化學物質對於我們的健康與生活產生很大的影響,部分化學物質會藉由參與生物體內的作用機制對疾病發生產生影響。為了發展一套關於miRNA與化學物質間關聯性的可信預測方法,此應用平臺會比較化學物質影響的基因與miRNA目標基因,並通過生物途徑,找出化學物質、miRNA與人體健康之間可能的關聯。此應用平臺的目標是預測化學物質、miRNA、生物途徑之間的交互作用或關聯性。藉由文獻探討,我們獲得關於miRNA、化學物質對人體基因的影響,並藉由miRNA目標基因(Target genes)預測方法找出miRNA與基因間可能的關聯性。這些基因會再進行生物途徑(pathway)分析,找出在人體中可能的影響範圍與作用機制。此平臺由三個部分構成:(1)關聯性資料庫:資料庫中將目前現已被確認出的基因、miRNA、疾病、基因本體論與生物途徑儲存並建立起關聯性。(2)通用網關介面(Common gateway interface, CGI):CGI處理使用者輸入的資訊,從資料庫中取得所需資料並處理以提供使用者所需的訊息(3)使用者介面:使用者介面提供使用者輸入搜尋條件並獲得所需資訊的管道。此平臺可以協助研究人員預測環境化學物質與microRNA對於人體健康的影響,進一步減少在尋找研究題材時耗費的時間、人力成本與資源。

      MicroRNAs (miRNAs) are about 22 nucleotides, non-coding RNAs that affect various cellular functions, and play a regulatory role in different organisms including human. Until now, about 1500 miRNAs in human have been discovered and registered, but still lack of information or algorithms to reveal the relationships among miRNAs, environmental chemicals and human health. Chemicals in environment affect our health and daily life; some of them lead to diseases by inferring biological pathways. To develop a creditable method for predicting relationships between miRNAs and chemicals, the database can not only compare the gene lists affected by chemicals and miRNAs, but also use curated pathway to find possibly interactions. The web server we describe here is an online system for evaluating the interactions/relationships between chemicals, miRNAs and pathways. Here, we manually retrieved the associations of miRNAs and chemicals from literatures. We built an online web server system, which contains miRNA IDs, disease names, MeSH IDs, chemical IDs, gene names, pathways, and the literature PubMed IDs. We connected each miRNA to miRBase and every current gene symbol to HUGO Gene Nomenclature Committee (HGNC) for detailed genome annotations. The pathway information in human are also provided from KEGG and Reactome database. The information about gene ontology is queried by SQL from GO Online SQL Environment (GOOSE) built by AmiGO lab. With a user-friendly interface, the web application is easy to use. Association analyses of miRNAs and chemicals will help us the understanding of the pathogenesis of such chemical components.

    致謝 I 中文摘要 III 英文摘要 V 目錄 VII 壹、前言 1 1-1. 研究動機 1 1-2. 研究目的 2 貳、文獻回顧 3 2-1. 表觀基因體學 3 2-2. 微核糖核酸 5 2-3. 微核糖核酸相關資料庫 6 2-4. 環境化學物質 9 2-5. 生物途徑 11 2-6. 基因本體論 13 2-7. R語言 15 參、研究方法 16 3-1. 系統架構 16 3-2. 資料來源 18 3-3. 設計資料庫框架 20 3-4. 設計使用者介面及編寫介面控制器 22 3-5. 編寫統計方法 23 肆、結果與討論 26 4-1. 系統簡述 26 4-2. 操作流程簡介 27 4-3. 利用miRNA搜尋相關生物途徑或基因本體論 33 4-4. 案例分析─以戴奧辛 (Dioxins)為例 37 伍、結論 43 陸、未來研究方向 44 柒、參考文獻 45

    Anglicheau, D., T. Muthukumar, et al. (2010). "MicroRNAs: small RNAs with big effects." Transplantation 90(2): 105-112.
    Ashburner, M., C. A. Ball, et al. (2000). "Gene ontology: tool for the unification of biology. The Gene Ontology Consortium." Nat Genet 25(1): 25-29.
    Carbon, S., A. Ireland, et al. (2009). "AmiGO: online access to ontology and annotation data." Bioinformatics 25(2): 288-289.
    Chen, D., M. A. Farwell, et al. (2010). "MicroRNA as a new player in the cell cycle." J Cell Physiol 225(2): 296-301.
    Chen, T. (2010). "The role of MicroRNA in chemical carcinogenesis." J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 28(2): 89-124.
    Cole, P., D. Trichopoulos, et al. (2003). "Dioxin and cancer: a critical review." Regul Toxicol Pharmacol 38(3): 378-388.
    Davis, A. P., B. L. King, et al. (2011). "The Comparative Toxicogenomics Database: update 2011." Nucleic Acids Res 39(Database issue): D1067-1072.
    Draghici, S., P. Khatri, et al. (2003). "Global functional profiling of gene expression." Genomics 81(2): 98-104.
    Dweep, H., C. Sticht, et al. (2011). "miRWalk--database: prediction of possible miRNA binding sites by "walking" the genes of three genomes." J Biomed Inform 44(5): 839-847.
    Elyakim, E., E. Sitbon, et al. (2010). "hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy." Cancer Res 70(20): 8077-8087.
    Fukata, H. and C. Mori (2004). "Epigenetic alteration by the chemical substances, food and environmental factors." Reproductive Medicine and Biology 3(3): 115-121.
    Fukushima, T., Y. Hamada, et al. (2007). "Changes of micro-RNA expression in rat liver treated by acetaminophen or carbon tetrachloride--regulating role of micro-RNA for RNA expression." J Toxicol Sci 32(4): 401-409.
    Gentleman, R. C., V. J. Carey, et al. (2004). "Bioconductor: open software development for computational biology and bioinformatics." Genome Biol 5(10): R80.
    Gomase, V. S. and S. Tagore (2008). "Epigenomics." Curr Drug Metab 9(3): 232-237.
    Jiang, Q., Y. Wang, et al. (2009). "miR2Disease: a manually curated database for microRNA deregulation in human disease." Nucleic Acids Res 37(Database issue): D98-104.
    John, B., A. J. Enright, et al. (2004). "Human MicroRNA targets." PLoS Biol 2(11): e363.
    Joshi-Tope, G., M. Gillespie, et al. (2005). "Reactome: a knowledgebase of biological pathways." Nucleic Acids Res 33(Database issue): D428-432.
    Kanehisa, M., M. Araki, et al. (2008). "KEGG for linking genomes to life and the environment." Nucleic Acids Res 36(Database issue): D480-484.
    Kelder, T., M. P. van Iersel, et al. (2012). "WikiPathways: building research communities on biological pathways." Nucleic Acids Res 40(Database issue): D1301-1307.
    Kozomara, A. and S. Griffiths-Jones (2011). "miRBase: integrating microRNA annotation and deep-sequencing data." Nucleic Acids Res 39(Database issue): D152-157.
    Krek, A., D. Grun, et al. (2005). "Combinatorial microRNA target predictions." Nat Genet 37(5): 495-500.
    Lewis, B. P., C. B. Burge, et al. (2005). "Conserved seed pairing, often flanked by adenosines, indicates that thousands of human genes are microRNA targets." Cell 120(1): 15-20.
    Maragkakis, M., M. Reczko, et al. (2009). "DIANA-microT web server: elucidating microRNA functions through target prediction." Nucleic Acids Res 37(Web Server issue): W273-276.
    Maragkakis, M., T. Vergoulis, et al. (2011). "DIANA-microT Web server upgrade supports Fly and Worm miRNA target prediction and bibliographic miRNA to disease association." Nucleic Acids Res 39(Web Server issue): W145-148.
    Mattingly, C. J., G. T. Colby, et al. (2003). "The Comparative Toxicogenomics Database (CTD)." Environ Health Perspect 111(6): 793-795.
    Megraw, M., P. Sethupathy, et al. (2007). "miRGen: a database for the study of animal microRNA genomic organization and function." Nucleic Acids Res 35(Database issue): D149-155.
    Min, H. and S. Yoon (2010). "Got target? Computational methods for microRNA target prediction and their extension." Exp Mol Med 42(4): 233-244.
    Ogata, H., S. Goto, et al. (1999). "KEGG: Kyoto Encyclopedia of Genes and Genomes." Nucleic Acids Res 27(1): 29-34.
    Pico, A. R., T. Kelder, et al. (2008). "WikiPathways: pathway editing for the people." PLoS Biol 6(7): e184.
    Povey, S., R. Lovering, et al. (2001). "The HUGO Gene Nomenclature Committee (HGNC)." Hum Genet 109(6): 678-680.
    Reamon-Buettner, S. M. and J. Borlak (2007). "A new paradigm in toxicology and teratology: altering gene activity in the absence of DNA sequence variation." Reprod Toxicol 24(1): 20-30.
    Reimers, M. and V. J. Carey (2006). "Bioconductor: an open source framework for bioinformatics and computational biology." Methods Enzymol 411: 119-134.
    Rogers, F. B. (1963). "Medical subject headings." Bull Med Libr Assoc 51: 114-116.
    Seal, R. L., S. M. Gordon, et al. (2011). "genenames.org: the HGNC resources in 2011." Nucleic Acids Res 39(Database issue): D514-519.
    Sewell, W. (1964). "Medical Subject Headings in Medlars." Bull Med Libr Assoc 52: 164-170.
    Singh, S. and S. S. Li (2011). "Phthalates: toxicogenomics and inferred human diseases." Genomics 97(3): 148-157.
    Stein, R. A. (2012). "Epigenetics and environmental exposures." J Epidemiol Community Health 66(1): 8-13.
    Tilghman, S. L., E. N. Nierth-Simpson, et al. (2010). "Environmental hormones: Multiple pathways for response may lead to multiple disease outcomes." Steroids 75(8-9): 520-523.
    Uemura, H., K. Arisawa, et al. (2009). "Prevalence of metabolic syndrome associated with body burden levels of dioxin and related compounds among Japan's general population." Environ Health Perspect 117(4): 568-573.
    Vecchione, A. and C. M. Croce (2010). "Apoptomirs: small molecules have gained the license to kill." Endocr Relat Cancer 17(1): F37-50.
    Vergoulis, T., I. S. Vlachos, et al. (2012). "TarBase 6.0: capturing the exponential growth of miRNA targets with experimental support." Nucleic Acids Res 40(Database issue): D222-229.
    Wang, X. (2008). "miRDB: a microRNA target prediction and functional annotation database with a wiki interface." RNA 14(6): 1012-1017.
    Weinberg, M. S. and M. J. Wood (2009). "Short non-coding RNA biology and neurodegenerative disorders: novel disease targets and therapeutics." Hum Mol Genet 18(R1): R27-39.
    Xiao, F., Z. Zuo, et al. (2009). "miRecords: an integrated resource for microRNA-target interactions." Nucleic Acids Res 37(Database issue): D105-110.
    Yang, J. H., J. H. Li, et al. (2011). "starBase: a database for exploring microRNA-mRNA interaction maps from Argonaute CLIP-Seq and Degradome-Seq data." Nucleic Acids Res 39(Database issue): D202-209.
    Yu, Z., R. Baserga, et al. (2010). "microRNA, cell cycle, and human breast cancer." Am J Pathol 176(3): 1058-1064.
    Zimmerman, A. L. and S. Wu (2011). "MicroRNAs, cancer and cancer stem cells." Cancer Lett 300(1): 10-19.

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