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    National Tsing Hua University Institutional Repository > 生命科學院  > 生命科學系 > 期刊論文 >  A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining

    Please use this identifier to cite or link to this item: http://nthur.lib.nthu.edu.tw/dspace/handle/987654321/49072

    Title: A systems biology approach to construct the gene regulatory network of systemic inflammation via microarray and databases mining
    Authors: Chen BS;Yang SK;Lan CY;Chuang YJ
    教師: 莊永仁
    Date: 2008
    Publisher: BioMed Central
    Relation: BMC MEDICAL GENOMICS, BioMed Central, Volume 1, SEP 30 2008
    Keywords: NF-KAPPA-B
    Abstract: ©2008 BioMed Central - Background: Inflammation is a hallmark of many human diseases. Elucidating the mechanisms underlying systemic inflammation has long been an important topic in basic and clinical research. When primary pathogenetic events remains unclear due to its immense complexity, construction and analysis of the gene regulatory network of inflammation at times becomes the best way to understand the detrimental effects of disease. However, it is difficult to recognize and evaluate relevant biological processes from the huge quantities of experimental data. It is hence appealing to find an algorithm which can generate a gene regulatory network of systemic inflammation from high-throughput genomic studies of human diseases. Such network will be essential for us to extract valuable information from the complex and chaotic network under diseased conditions.
    Results: In this study, we construct a gene regulatory network of inflammation using data extracted from the Ensembl and JASPAR databases. We also integrate and apply a number of systematic algorithms like cross correlation threshold, maximum likelihood estimation method and Akaike Information Criterion (AIC) on time-lapsed microarray data to refine the genome-wide transcriptional regulatory network in response to bacterial endotoxins in the context of dynamic activated genes, which are regulated by transcription factors (TFs) such as NF-kappa B. This systematic approach is used to investigate the stochastic interaction represented by the dynamic leukocyte gene expression profiles of human subject exposed to an inflammatory stimulus (bacterial endotoxin). Based on the kinetic parameters of the dynamic gene regulatory network, we identify important properties (such as susceptibility to infection) of the immune system, which may be useful for translational research. Finally, robustness of the inflammatory gene network is also inferred by analyzing the hubs and "weak ties" structures of the gene network.

    Conclusion: In this study, Data mining and dynamic network analyses were integrated to examine the gene regulatory network in the inflammatory response system. Compared with previous methodologies reported in the literatures, the proposed gene network perturbation method has shown a great improvement in analyzing the systemic inflammation.
    URI: http://www.biomedcentral.com/
    Appears in Collections:[生命科學系] 期刊論文

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