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  • 學位論文

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
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摘要


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。

並列摘要


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.

並列關鍵字

web application database chemical microRNA pathway disease gene ontology

參考文獻


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.

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