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研究生： 方昱慶
Yu-Ching Fang
論文名稱： G-蛋白偶合接受體與G-蛋白訊號調控蛋白之整合型資料庫
An Integrated Database for G-Protein Coupled Receptors and Regulators of G-Protein Signaling
指導教授： 洪炯宗
Jorng-Tzong Horng
孫維欣
Wei-Hsin Sun
口試委員:
學位類別： 碩士
Master
系所名稱： 生醫理工學院 - 生命科學系
Department of Life Science
畢業學年度： 93
語文別： 英文
論文頁數： 51
中文關鍵詞： G-蛋白訊號調控蛋白 、G-蛋白偶合接受體
外文關鍵詞： Regulators of G-Protein Signaling, G-Protein Coupled Receptor, RGS, GPCR
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    • 許多市面上的醫療用藥已經被開發來針對G-蛋白偶合接受體 (GPCRs) 的功能來做調控。為了便利醫學和製藥的研究，我們開發了一個命名為RINGdb的新整合型生物資料庫來提供廣泛和組織過的G-蛋白偶合接受體與G-蛋白訊號調控蛋白 (RGS) 的資訊。在這個資料庫中，特定關於突變 (Mutation) 、組織分佈 (Tissue Distribution) 、蛋白質間的交互作用 (Protein-Protein Interaction) 、疾病/失調 (Diseases/Disorders) 、G-蛋白偶合接受體與G-蛋白訊號調控蛋白之間的關係等等的資訊是從許多文獻收集而來，而這些資訊和其他資料庫相比是獨一無二的。除此之外，RINGdb提供各式各樣對使用者友善的查詢功能來回答許多關於G-蛋白偶合接受體與G-蛋白訊號調控蛋白的問題，例如：他門促成某些疾病發生的可能性、他們在哪些組織共同表現、在G-蛋白訊號調控蛋白上除了最主要的功能區域 (Domain) 外，其他非G-蛋白訊號調控蛋白功能區域的潛在功能、哪些蛋白質可能會和G-蛋白訊號調控蛋白結合等等，並提供相關的統計數值來協助過濾出比較可能的結合蛋白。此資料庫也整合了組織好的資料庫交叉參考(Database Cross-Reference)，讓使用者可以直接獲得細部的資訊。這個知識庫將會有益於醫學研究、藥物開發、G-蛋白訊號調控蛋白和其它蛋白資交互作用的研究以及未來G-蛋白偶合接受體訊號傳遞路徑(GPCR Signaling Pathway)的模擬。

    Many marketed therapeutic agents have been developed to modulate the function of G-protein coupled receptors. To facilitate clinical and pharmacological research, we develop a novel integrated biological database called RINGdb to provide comprehensive and organized RGS/GPCR information. In RINGdb, information with respect to mutation, tissue distribution, protein-protein interaction, diseases/disorders, and the RGS/GPCR relationship are collected from various literature surveys and the result is unique by comparing other databases. In addition, RINGdb offers various user-friendly query functions to answer different questions about RGS/GPCR such as their possible contribution to disease processes, in which tissue they are expressed together, the potential function of the non-RGS domain, putative RGS binding partners and so on and provides statistical values to filter putative RGS binding partners. It also integrates organized database cross-referencing to allow users direct access to detailed information. This knowledge base will be very useful for clinical research, drug discovery, the study of RGS/other binding partner interactions and for future GPCR signaling pathway modeling.

    Chapter 1 Introduction 1 1.1 Background 1 1.2 Motivation 3 1.3 Goal 4 Chapter 2 Related Works 5 2.1 GPCRDB 5 2.2 ORDB 5 2.3 gpDB 6 Chapter 3 Materials and Methods 7 3.1 Materials 7 3.1.1 Protein Sequences Database 7 3.1.2 PubMed 7 3.1.3 Gene Expression Database 7 3.1.4 Protein-Protein Interaction Database 9 3.1.5 Protein Domain Database 10 3.1.6 The Pharmacogenetics and Pharmacogenomics Knowledge Base 11 3.1.7 Ligand-Receptor Interaction 12 3.2 Methods 15 3.2.1 System Flow 15 3.2.2 Organization of the Database 16 3.2.3 Data Collection, Preprocessing and Integration 18 3.2.4 Database Cross-Reference 20 3.2.5 Query Design 21 3.2.6 Analysis of Co-expression 21 Chapter 4 Implementation and Results 23 4.1 Data Storage 23 4.2 The Web Interfaces 24 4.2.1 RGS Search Page 25 4.2.2 GPCR Search Page 27 4.2.3 General Information 29 4.2.4 Diseases/Disorders 30 4.2.5 Mutation 31 4.2.6 Tissue specificity/distribution/expression 32 4.2.7 Protein-Protein Interaction 34 4.2.8 Ligand-Receptor and Orphan GPCR Information 38 4.3 RGS, GPCR and Disease Relationship Inference 40 4.4 Disease and Drug Relationship Inferences 42 Chapter 5 Discussion 45 5.1 Comparison 45 5.2 Future Works 46 Chapter 6 Conclusion 48 References 49

    1. Zhong, H. and Neubig, R.R. (2001) Regulator of G protein signaling proteins: novel multifunctional drug targets. J Pharmacol Exp Ther, 297, 837-845.
    2. Bockaert, J. and Pin, J.P. (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. Embo J, 18, 1723-1729.
    3. Hollinger, S. and Hepler, J.R. (2002) Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev, 54, 527-559.
    4. Chasse, S.A. and Dohlman, H.G. (2003) RGS proteins: G protein-coupled receptors meet their match. Assay Drug Dev Technol, 1, 357-364.
    5. Horn, F., Bettler, E., Oliveira, L., Campagne, F., Cohen, F.E. and Vriend, G. (2003) GPCRDB information system for G protein-coupled receptors. Nucleic Acids Res, 31, 294-297.
    6. Elefsinioti, A.L., Bagos, P.G., Spyropoulos, I.C. and Hamodrakas, S.J. (2004) A database for G proteins and their interaction with GPCRs. BMC Bioinformatics, 5, 208.
    7. Crasto, C., Marenco, L., Miller, P. and Shepherd, G. (2002) Olfactory Receptor Database: a metadata-driven automated population from sources of gene and protein sequences. Nucleic Acids Res, 30, 354-360.
    8. Bairoch, A. and Apweiler, R. (2000) The SWISS-PROT protein sequence database and its supplement TrEMBL in 2000. Nucleic Acids Res, 28, 45-48.
    9. Diehn, M., Sherlock, G., Binkley, G., Jin, H., Matese, J.C., Hernandez-Boussard, T., Rees, C.A., Cherry, J.M., Botstein, D., Brown, P.O. et al. (2003) SOURCE: a unified genomic resource of functional annotations, ontologies, and gene expression data. Nucleic Acids Res, 31, 219-223.
    10. Ringwald, M., Mangan, M.E., Eppig, J.T., Kadin, J.A. and Richardson, J.E. (1999) GXD: a gene expression database for the laboratory mouse. The Gene Expression Database Group. Nucleic Acids Res, 27, 106-112.
    11. Edgar, R., Domrachev, M. and Lash, A.E. (2002) Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res, 30, 207-210.
    12. Bader, G.D., Betel, D. and Hogue, C.W. (2003) BIND: the Biomolecular Interaction Network Database. Nucleic Acids Res, 31, 248-250.
    13. Zanzoni, A., Montecchi-Palazzi, L., Quondam, M., Ausiello, G., Helmer-Citterich, M. and Cesareni, G. (2002) MINT: a Molecular INTeraction database. FEBS Lett, 513, 135-140.
    14. Xenarios, I., Salwinski, L., Duan, X.J., Higney, P., Kim, S.M. and Eisenberg, D. (2002) DIP, the Database of Interacting Proteins: a research tool for studying cellular networks of protein interactions. Nucleic Acids Res, 30, 303-305.
    15. Bateman, A., Coin, L., Durbin, R., Finn, R.D., Hollich, V., Griffiths-Jones, S., Khanna, A., Marshall, M., Moxon, S., Sonnhammer, E.L. et al. (2004) The Pfam protein families database. Nucleic Acids Res, 32, D138-141.
    16. Mulder, N.J., Apweiler, R., Attwood, T.K., Bairoch, A., Bateman, A., Binns, D., Biswas, M., Bradley, P., Bork, P., Bucher, P. et al. (2002) InterPro: an integrated documentation resource for protein families, domains and functional sites. Brief Bioinform, 3, 225-235.
    17. Ng, S.K., Zhang, Z., Tan, S.H. and Lin, K. (2003) InterDom: a database of putative interacting protein domains for validating predicted protein interactions and complexes. Nucleic Acids Res, 31, 251-254.
    18. Klein, T.E. and Altman, R.B. (2004) PharmGKB: the pharmacogenetics and pharmacogenomics knowledge base. Pharmacogenomics J, 4, 1.
    19. Kanehisa, M. and Goto, S. (2000) KEGG: kyoto encyclopedia of genes and genomes. Nucleic Acids Res, 28, 27-30.
    20. Hamosh, A., Scott, A.F., Amberger, J., Bocchini, C., Valle, D. and McKusick, V.A. (2002) Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res, 30, 52-55.
    21. Benson, D.A., Karsch-Mizrachi, I., Lipman, D.J., Ostell, J. and Wheeler, D.L. (2003) GenBank. Nucleic Acids Res, 31, 23-27.
    22. Rebhan, M., Chalifa-Caspi, V., Prilusky, J. and Lancet, D. (1997) GeneCards: integrating information about genes, proteins and diseases. Trends Genet, 13, 163.
    23. Lenhard, B., Hayes, W.S. and Wasserman, W.W. (2001) GeneLynx: a gene-centric portal to the human genome. Genome Res, 11, 2151-2157.
    24. Frezal, J. (1998) Genatlas database, genes and development defects. C R Acad Sci III, 321, 805-817.
    25. Birney, E. (2003) Ensembl: a genome infrastructure. Cold Spring Harb Symp Quant Biol, 68, 213-215.
    26. Maglott, D., Ostell, J., Pruitt, K.D. and Tatusova, T. (2005) Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res, 33 Database Issue, D54-58.
    27. Apweiler, R., Attwood, T.K., Bairoch, A., Bateman, A., Birney, E., Biswas, M., Bucher, P., Cerutti, L., Corpet, F., Croning, M.D. et al. (2001) The InterPro database, an integrated documentation resource for protein families, domains and functional sites. Nucleic Acids Res, 29, 37-40.
    28. Marchler-Bauer, A., Anderson, J.B., Cherukuri, P.F., DeWeese-Scott, C., Geer, L.Y., Gwadz, M., He, S., Hurwitz, D.I., Jackson, J.D., Ke, Z. et al. (2005) CDD: a Conserved Domain Database for protein classification. Nucleic Acids Res, 33 Database Issue, D192-196.
    29. Corpet, F., Gouzy, J. and Kahn, D. (1998) The ProDom database of protein domain families. Nucleic Acids Res, 26, 323-326.
    30. Attwood, T.K. (2002) The PRINTS database: a resource for identification of protein families. Brief Bioinform, 3, 252-263.
    31. Bhasin, M. and Raghava, G.P. (2004) GPCRpred: an SVM-based method for prediction of families and subfamilies of G-protein coupled receptors. Nucleic Acids Res, 32, W383-389.
    32. Papasaikas, P.K., Bagos, P.G., Litou, Z.I., Promponas, V.J. and Hamodrakas, S.J. (2004) PRED-GPCR: GPCR recognition and family classification server. Nucleic Acids Res, 32, W380-382.
    33. Qin, Y. and Duquette, P. (2003) B-cell immunity in MS. Int MS J, 10, 110-120.

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