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研究生: 莊明達
Chuang, Ming-Ta
論文名稱: 利用白色念珠菌宿主與斑馬魚寄主之間的整合性動態網路預測細胞內與物種之間的蛋白質交互作用
Prediction of intra-cellular and inter-species protein interactions by integrated dynamic host-pathogen network between Candida albicans and zebrafish
指導教授: 陳博現
Chen, Bor-Sen
口試委員: 曾慶平
Tseng, Ching-Ping
藍忠昱
Lan, Chung-Yu
莊永仁
Chuang, Yung-Jen
李曉青
Lee, Hsiao-Ching
陳博現
Chen, Bor-Sen
學位類別: 碩士
Master
系所名稱: 電機資訊學院 - 電機工程學系
Department of Electrical Engineering
論文出版年: 2011
畢業學年度: 99
語文別: 中文
論文頁數: 55
中文關鍵詞: 白色念珠菌微陣列晶片斑馬魚系統生物學
外文關鍵詞: Candida, Microarray, zebrafish, Systems biology
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  • 至今,感染疾病仍然是健康的首要問題,通常在藥物治療上有很大的挑戰。隨著快速發展的高通量為陣列晶片(high-through microarray)以及蛋白質交互作用資料庫的興起對系統性的研究有很大的幫助。為了預測物種之間的蛋白質交互作用,我們使用直向同源物種當基底(ortholog-based)的方法來得到粗略的蛋白質交互作用候選人。根據實驗資料以及組織切片,我們同時使用宿主以及寄主的微陣列晶片資料、隨機的系統模型以及同源物種資訊來建構三個階段細胞內以及物種間蛋白質交互作用網路。透過GO這個資料庫以及整合蛋白質交互作用的網路資料庫和直系物種的相關性,我們也使用功能性集合的方法(functional clustering)來研究白色念珠菌細胞壁相關物種間蛋白質交互作用。透過不同階段的互動變化來建立宿主寄主的蛋白質動態網路之後,許多白色念珠菌黏附以及菌絲生長功能的中樞蛋白質在早期階段被發現。許多宿主免疫反應以及細胞凋零相關的蛋白質也用來研究宿主的防禦機制。利用動態系統生物學的觀點,不同階段,我們也預測了白色念珠菌感染過重中,與宿主相關的免疫反應,以及細胞凋亡的機制,以及寄主菌絲生長以及黏附的蛋白質調控網路和可能的蛋白質交互作用。透過感染過程中動態的宿主寄主蛋白質互動,將來可以設計根白色念珠菌相關的感染藥物,以及詳細的了解致病的機制,對未來宿主寄主之間的蛋白質互動有進一步貢獻。


    So far, infectious diseases are still the top global healthcare problem, usually causing serious challenge in medical therapy. The rapid growth of high-throughput microarray and protein-protein interaction PPI data has led to emergence of system mechanism investigation. In order to predict the inter-species protein interactions, we used ortholog-based approach to obtain the rough protein-protein interaction candidates. Based on experimental histological section, simultaneous host and pathogen microarray data, orthologous information and stochastic system model, we have constructed the three stages inter-species and intra-cellular protein interaction network under the infection. Through GO database, we also focus on C. albicans cell-wall-related proteins to investigate the specific inter-species protein interactions by functional clustering method. After constructing the host and pathogen dynamic protein interaction network through protein interaction changes between different infection stages, several C. albicans adhesion hub proteins are found at early stage and hyphal growth-related hub proteins are also obtained for pathogenicity of morphology of pathogen at early and late stages. Several host immune response and several apoptosis-related proteins of infectious process are also investigated for host defense mechanisms. We also predicted some potential inter-species protein interactions in the infectious process. Through this integrated dynamic host-pathogen interaction network, the potential drug target and the C. albicans related pathogenesis could be understood in more detail.

    Contents 1. Introduction................................................................................................................ 1 2. Materials and Methods............................................................................................... 6 2.1 Overview of the proposed method................................................................... 6 2.2 Data selection................................................................................................... 6 2.3 Inference of putative intra-cellular and inter-species protein interaction candidates............................................................................................................... 7 2.4 Integrating putative intra-cellular dynamic protein interaction network with putative inter-species protein interaction network in infectious process............... 9 2.5 Identification of the integrated host-pathogen interaction network parameters through dynamic protein interaction model by microarray data.......................... 11 2.6 Determination of significant protein interactions by pruning insignificant protein-protein interactions.................................................................................. 14 2.7 The dynamic protein interaction network between differentstages...............15 3. Results and Discussion............................................................................................ 17 3.1 Construction of dynamic intra-cellular protein interaction network and inter-species protein interaction network............................................................. 17 3.2 Highly connected hub proteins in intra-cellular host-pathogen protein interaction network.............................................................................................. 19 3.3 The dynamic protein interaction network between C. albicans cell wall and zebrafish............................................................................................................... 20 3.4 Inter-species dynamic protein interaction network between adhesion stage and invasion stage in infectious process.............................................................. 21 3.5 Inter-species dynamic protein interaction network between invasion stage and damage stage in infectious process............................................................... 24 3.6 Host immune and defense response in infectious process............................. 25 3.7 Host apoptosis response in infectious process............................................... 27 4. Conclusion............................................................................................................... 29 5. Reference................................................................................................................. 31

    [1] M. C. Arendrup, et al., "Invasive fungal infections in the paediatric and neonatal population: diagnostics and management issues," Clin Microbiol Infect, vol. 15, pp. 613-24, Jul 2009.
    [2] A. Gullo, "Invasive fungal infections: the challenge continues," Drugs, vol. 69 Suppl 1, pp. 65-73, 2009.
    [3] A. F. Shorr, et al., "Candidemia on presentation to the hospital: development and validation of a risk score," Crit Care, vol. 13, p. R156, 2009.
    [4] B. Wachtler, et al., "From attachment to damage: defined genes of Candida albicans mediate adhesion, invasion and damage during interaction with oral epithelial cells," PLoS One, vol. 6, p. e17046, 2011.
    [5] M. Duo, et al., "Inhibition of Candida albicans growth by brominated furanones," Appl Microbiol Biotechnol, vol. 85, pp. 1551-63, Feb 2010.
    [6] A. Bishop, et al., "Hyphal growth in Candida albicans requires the phosphorylation of Sec2 by the Cdc28-Ccn1/Hgc1 kinase," EMBO J, vol. 29, pp. 2930-42, Sep 1 2010.
    [7] M. Carmon, et al., "Candida sepsis during total parenteral nutrition: An endogenous infection indicating the severity of patients' disease state," Clin Nutr, vol. 11, pp. 240-3, Aug 1992.
    [8] B. Hube, "From commensal to pathogen: stage- and tissue-specific gene expression of Candida albicans," Curr Opin Microbiol, vol. 7, pp. 336-41, Aug 2004.
    [9] G. Tronchin, et al., "Adherence mechanisms in human pathogenic fungi," Med Mycol, vol. 46, pp. 749-72, Dec 2008.
    [10] W. L. Chaffin, "Candida albicans cell wall proteins," Microbiol Mol Biol Rev, vol. 72, pp. 495-544, Sep 2008.
    [11] P. Sundstrom, "Adhesion in Candida spp," Cell Microbiol, vol. 4, pp. 461-9, Aug 2002.
    [12] S. G. Filler and D. C. Sheppard, "Fungal invasion of normally non-phagocytic host cells," PLoS Pathog, vol. 2, p. e129, Dec 2006.
    [13] F. Dalle, et al., "Cellular interactions of Candida albicans with human oral epithelial cells and enterocytes," Cell Microbiol, vol. 12, pp. 248-71, Feb 2010.
    [14] C. A. Kumamoto and M. D. Vinces, "Contributions of hyphae and hypha-co-regulated genes to Candida albicans virulence," Cell Microbiol, vol. 7, pp. 1546-54, Nov 2005.
    [15] M. Whiteway and C. Bachewich, "Morphogenesis in Candida albicans," Annu Rev Microbiol, vol. 61, pp. 529-53, 2007.
    [16] R. Martin, et al., "Host-pathogen interactions and virulence-associated genes during Candida albicans oral infections," Int J Med Microbiol, vol. 301, pp. 417-22, Jun 2011.
    [17] L. I. Zon and R. T. Peterson, "In vivo drug discovery in the zebrafish," Nat Rev Drug Discov, vol. 4, pp. 35-44, Jan 2005.
    [18] N. D. Meeker and N. S. Trede, "Immunology and zebrafish: spawning new models of human disease," Dev Comp Immunol, vol. 32, pp. 745-57, 2008.
    [19] A. M. van der Sar, et al., "A star with stripes: zebrafish as an infection model," Trends Microbiol, vol. 12, pp. 451-7, Oct 2004.
    [20] H. A. Phelps and M. N. Neely, "Evolution of the zebrafish model: from development to immunity and infectious disease," Zebrafish, vol. 2, pp. 87-103, 2005.
    [21] M. Kanther and J. F. Rawls, "Host-microbe interactions in the developing zebrafish," Curr Opin Immunol, vol. 22, pp. 10-9, Feb 2010.
    [22] N. Trede, et al., "Model systems for infectious disease and cancer in zebrafish: a report on an EMBO workshop held at the Lorentz Center, Leiden, The Netherlands, July 16-18, 2007," Zebrafish, vol. 4, pp. 287-92, Winter 2007.
    [23] M. Mione, et al., "Disease modeling in zebrafish: cancer and immune responses--a report on a workshop held in Spoleto, Italy, July 20-22, 2009," Zebrafish, vol. 6, pp. 445-51, Dec 2009.
    [24] D. Traver, et al., "The zebrafish as a model organism to study development of the immune system," Adv Immunol, vol. 81, pp. 253-330, 2003.
    [25] N. S. Trede, et al., "The use of zebrafish to understand immunity," Immunity, vol. 20, pp. 367-79, Apr 2004.
    [26] G. J. Lieschke and N. S. Trede, "Fish immunology," Curr Biol, vol. 19, pp. R678-82, Aug 25 2009.
    [27] C. C. Chao, et al., "Zebrafish as a model host for Candida albicans infection," Infect Immun, vol. 78, pp. 2512-21, Jun 2010.
    [28] S. A. Lee, et al., "Ortholog-based protein-protein interaction prediction and its application to inter-species interactions," BMC Bioinformatics, vol. 9 Suppl 12, p. S11, 2008.
    [29] J. M. Doolittle and S. M. Gomez, "Structural similarity-based predictions of protein interactions between HIV-1 and Homo sapiens," Virol J, vol. 7, p. 82, 2010.
    [30] C. Stark, et al., "BioGRID: a general repository for interaction datasets," Nucleic Acids Res, vol. 34, pp. D535-9, Jan 1 2006.
    [31] G. Ostlund, et al., "InParanoid 7: new algorithms and tools for eukaryotic orthology analysis," Nucleic Acids Res, vol. 38, pp. D196-203, Jan 2010.
    [32] Y. Bradford, et al., "ZFIN: enhancements and updates to the Zebrafish Model Organism Database," Nucleic Acids Res, vol. 39, pp. D822-9, Jan 2011.
    [33] M. S. Skrzypek, et al., "New tools at the Candida Genome Database: biochemical pathways and full-text literature search," Nucleic Acids Res, vol. 38, pp. D428-32, Jan 2010.
    [34] M. Ashburner, et al., "Gene ontology: tool for the unification of biology. The Gene Ontology Consortium," Nat Genet, vol. 25, pp. 25-9, May 2000.
    [35] K. H. Young, "Yeast two-hybrid: so many interactions, (in) so little time," Biol Reprod, vol. 58, pp. 302-11, Feb 1998.
    [36] Y. C. Wang and B. S. Chen, "Integrated cellular network of transcription regulations and protein-protein interactions," BMC Syst Biol, vol. 4, p. 20, 2010.
    [37] U. Alon, "An introduction to systems biology: design principles of biological circuits Boca Raton," Boca Raton, FL: Chapman & Hall/CRC, 2007.
    [38] P. Lu, et al., "Absolute protein expression profiling estimates the relative contributions of transcriptional and translational regulation," Nat Biotechnol, vol. 25, pp. 117-24, Jan 2007.
    [39] H. Akaike, "A new look at the statistical model identification.," IEEE Transactions on Automatic Control, vol. 19, pp. 716-723, 1974.
    [40] R. Johansson, "System modeling and identification," Englewood Cliffs, N.J.:Prentice Hall 1993.
    [41] S. T. Mendenhall W, "Statistics for engineering and the sciences," Englewood Cliffs, N.J.: Prentice-Hall, 1995.
    [42] R. Hocking, "A Biometrics invited paper. The analysis and selection of variables in linear regression.," Biometrics, vol. 32, pp. 1-49, 1976.
    [43] G. Seber, "Linear regression analysis," Hoboken, N.J.: Wiley-Interscience, 2003.
    [44] A. L. Barabasi and Z. N. Oltvai, "Network biology: understanding the cell's functional organization," Nat Rev Genet, vol. 5, pp. 101-13, Feb 2004.
    [45] T. Jouault, et al., "Specific recognition of Candida albicans by macrophages requires galectin-3 to discriminate Saccharomyces cerevisiae and needs association with TLR2 for signaling," J Immunol, vol. 177, pp. 4679-87, Oct 1 2006.
    [46] R. S. Almeida, et al., "Candida albicans iron acquisition within the host," FEMS Yeast Res, vol. 9, pp. 1000-12, Oct 2009.
    [47] L. Wang and B. J. Cherayil, "Ironing out the wrinkles in host defense: interactions between iron homeostasis and innate immunity," J Innate Immun, vol. 1, pp. 455-64, Aug 2009.
    [48] D. Gozalbo, et al., "The cell wall-associated glyceraldehyde-3-phosphate dehydrogenase of Candida albicans is also a fibronectin and laminin binding protein," Infect Immun, vol. 66, pp. 2052-9, May 1998.
    [49] C. F. Flach, et al., "Differential expression of intestinal membrane transporters in cholera patients," FEBS Lett, vol. 581, pp. 3183-8, Jul 10 2007.
    [50] B. J. DiDomenico, et al., "Homologs of the yeast neck filament associated genes: isolation and sequence analysis of Candida albicans CDC3 and CDC10," Mol Gen Genet, vol. 242, pp. 689-98, Mar 1994.
    [51] A. J. Warenda, et al., "Candida albicans septin mutants are defective for invasive growth and virulence," Infect Immun, vol. 71, pp. 4045-51, Jul 2003.
    [52] G. Pardini, et al., "The CRH family coding for cell wall glycosylphosphatidylinositol proteins with a predicted transglycosidase domain affects cell wall organization and virulence of Candida albicans," J Biol Chem, vol. 281, pp. 40399-411, Dec 29 2006.
    [53] C. Alberti-Segui, et al., "Identification of potential cell-surface proteins in Candida albicans and investigation of the role of a putative cell-surface glycosidase in adhesion and virulence," Yeast, vol. 21, pp. 285-302, Mar 2004.
    [54] F. Mirbod, et al., "Molecular cloning of a Rho family, CDC42Ca gene from Candida albicans and its mRNA expression changes during morphogenesis," J Med Vet Mycol, vol. 35, pp. 173-9, May-Jun 1997.
    [55] M. Bassilana, et al., "Cdc24, the GDP-GTP exchange factor for Cdc42, is required for invasive hyphal growth of Candida albicans," Eukaryot Cell, vol. 2, pp. 9-18, Feb 2003.
    [56] S. E. Smith, et al., "Candida albicans RHO1 is required for cell viability in vitro and in vivo," Fems Yeast Research, vol. 2, pp. 103-111, May 2002.
    [57] F. J. Alvarez and J. B. Konopka, "Identification of an N-acetylglucosamine transporter that mediates hyphal induction in Candida albicans," Molecular Biology of the Cell, vol. 18, Mar 2007.
    [58] M. Ramsdale, et al., "MNL1 regulates weak acid-induced stress responses of the fungal pathogen Candida albicans," Molecular Biology of the Cell, vol. 19, pp. 4393-403, Oct 2008.
    [59] H. Park, et al., "Transcriptional responses of candida albicans to epithelial and endothelial cells," Eukaryot Cell, vol. 8, pp. 1498-510, Oct 2009.
    [60] T. Mio, et al., "Role of three chitin synthase genes in the growth of Candida albicans," J Bacteriol, vol. 178, pp. 2416-9, Apr 1996.
    [61] M. Sudoh, et al., "Cloning of the chitin synthase 3 gene from Candida albicans and its expression during yeast-hyphal transition," Mol Gen Genet, vol. 241, pp. 351-8, Nov 1993.
    [62] E. T. Buurman, et al., "Molecular analysis of CaMnt1p, a mannosyl transferase important for adhesion and virulence of Candida albicans," Proc Natl Acad Sci U S A, vol. 95, pp. 7670-5, Jun 23 1998.
    [63] M. S. S. Felipe, et al., "Comparative genomics allowed the identification of drug targets against human fungal pathogens," BMC Genomics, vol. 12, Jan 27 2011.
    [64] M. Woo, et al., "MYO2 is not essential for viability, but is required for polarized growth and dimorphic switches in Candida albicans," FEMS Microbiol Lett, vol. 218, pp. 195-202, Jan 21 2003.
    [65] S. M. Saporito and P. S. Sypherd, "The isolation and characterization of a calmodulin-encoding gene (CMD1) from the dimorphic fungus Candida albicans," Gene, vol. 106, pp. 43-9, Sep 30 1991.
    [66] T. Sato, et al., "Role of Ca2+/calmodulin signaling pathway on morphological development of Candida albicans," Biol Pharm Bull, vol. 27, pp. 1281-4, Aug 2004.
    [67] T. Roemer, et al., "Genome-wide fitness test and mechanism-of-action studies of inhibitory compounds in Candida albicans," Plos Pathogens, vol. 3, pp. 835-848, Jun 2007.
    [68] M. Nonaka and A. Kimura, "Genomic view of the evolution of the complement system," Immunogenetics, vol. 58, pp. 701-13, Sep 2006.
    [69] A. H. Meijer, et al., "Expression analysis of the Toll-like receptor and TIR domain adaptor families of zebrafish," Mol Immunol, vol. 40, pp. 773-83, Jan 2004.
    [70] C. Jault, et al., "Toll-like receptor gene family and TIR-domain adapters in Danio rerio," Mol Immunol, vol. 40, pp. 759-71, Jan 2004.
    [71] M. Cote, et al., "Munc18-2 deficiency causes familial hemophagocytic lymphohistiocytosis type 5 and impairs cytotoxic granule exocytosis in patient NK cells," J Clin Invest, vol. 119, pp. 3765-73, Dec 2009.
    [72] J. F. Kerr, et al., "Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics," Br J Cancer, vol. 26, pp. 239-57, Aug 1972.
    [73] G. Devasahayam, et al., "The ess1 prolyl isomerase is required for growth and morphogenetic switching in Candida albicans," Genetics, vol. 160, pp. 37-48, Jan 2002.
    [74] Z. Li, et al., "The structure of the Candida albicans Ess1 prolyl isomerase reveals a well-ordered linker that restricts domain mobility," Biochemistry, vol. 44, pp. 6180-9, Apr 26 2005.
    [75] A. S. Hackam, et al., "Huntingtin interacting protein 1 induces apoptosis via a novel caspase-dependent death effector domain," J Biol Chem, vol. 275, pp. 41299-308, Dec 29 2000.
    [76] K. H. Vousden and X. Lu, "Live or let die: the cell's response to p53," Nat Rev Cancer, vol. 2, pp. 594-604, Aug 2002.
    [77] J. S. Fridman and S. W. Lowe, "Control of apoptosis by p53," Oncogene, vol. 22, pp. 9030-40, Dec 8 2003.

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