Abstract
Bioinformatics is the rational study at an abstract level that can influence the way we understand biomedical facts and the way we apply the biomedical knowledge. Bioinformatics is facing challenges in helping with finding the relationships between genetic structures and functions, analyzing genotype–phenotype associations, and understanding gene–environment interactions at the systems level. One of the most important issues in bioinformatics is data integration. The data integration methods introduced here can be used to organize and integrate both public and in-house data. With the volume of data and the high complexity, computational decision support is essential for integrative transporter studies in pharmacogenomics, nutrigenomics, epigenetics, and systems biology. For the development of such a decision support system, object-oriented (OO) models can be constructed using the Unified Modeling Language (UML). A methodology is developed to build biomedical models at different system levels and construct corresponding UML diagrams, including use case diagrams, class diagrams, and sequence diagrams. By OO modeling using UML, the problems of transporter pharmacogenomics and systems biology can be approached from different angles with a more complete view, which may greatly enhance the efforts in effective drug discovery and development. Bioinformatics resources of membrane transporters and general bioinformatics databases and tools that are frequently used in transporter studies are also collected here. An informatics decision support system based on the models presented here is available at http://www.pharmtao.com/transporter. The methodology developed here can also be used for other biomedical fields.
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References
Pipas, J.M. and McMahon, J.E. (1975) Method for predicting RNA secondary structure. Proc. Natl. Acad. Sci. USA 72, 2017–2021.
Studnicka, G.M., Rahn, G.M., Cummings, I.W., Salser, W.A. (1978) Computer method for predicting the secondary structure of single-stranded RNA. Nucleic Acids Res. 5, 3365–3387.
Erdmann, V.A. (1978) Collection of published 5S and 5.8S ribosomal RNA sequences. Nucleic Acids Res. 5, r1–r13.
Dayhoff, M.O., Schwartz, R.M., Chen, H.R., Hunt, L.T., Barker, W.C., Orcutt, B.C. (1980) Nucleic acid sequence bank. Science 209, 1182.
Korn, L.J., Queen, C.L., Wegman, M.N. (1977) Computer analysis of nucleic acid regulatory sequences. Proc. Natl. Acad. Sci. USA 74, 4401–4405.
McCallum, D. and Smith, M. (1977) Computer processing of DNA sequence data. J. Mol. Biol. 116, 29–30.
Fuchs,C., Rosenvold,E.C., Honigman,A., Szybalski, W. (1978) A simple method for identifying the palindromic sequences recognized by restriction endonucleases: the nucleotide sequence of the AvaII site. Gene 4, 1–23.
Gingeras, T.R., Milazzo, J.P., Roberts, R.J. (1978) A computer assisted method for the determination of restriction enzyme recognition sites. Nucleic Acids Res. 5, 4105–4127.
Paulsen IT, Nguyen L, Sliwinski MK, Rabus R, Saier MH Jr. (2000) Microbial genome analyses: comparative transport capabilities in eighteen prokaryotes. J. Mol. Biol. 4, 75–100.
Chen, L., Ortiz-Lopez A., Jung A., Bush D.R. (2001) ANT1, an aromatic and neutral amino acid transporter in Arabidopsis. Plant Physiol. 125, 1813–1820.
Dawson, P.A., Mychaleckyj, J.C., Fossey, S.C., Mihic, S.J., Craddock, A.L., Bowden, D.W. (2001) Sequence and functional analysis of GLUT10: a glucose transporter in the Type 2 diabetes-linked region of chromosome 20q12-13.1. Mol. Genet. Metab. 74, 186–199.
Kihara, D. and Kanehisa, M. (2000) Tandem clusters of membrane proteins in complete genome sequences. Genome Res. 10, 731–743.
Yan, Q. (2001) Informatics Support for Human Membrane Transporter Pharmacogenomics Studies. ProQuest, Ann Arbor, MI, pp. 1–138.
http://tcdb.ucsd.edu/index.php (accessed in May 2009).
Nebert, D.W. (1999) Pharmacogenetics and pharmacogenomics: why is this relevant to the clinical geneticist? Clin. Genet. 56, 247–258.
Sissung, T. M., Gardner, E. R., et al. (2008) Pharmacogenetics of membrane transporters: a review of current approaches. Methods Mol. Biol. 448, 41–62.
Frishman, D., Heumann, K., Lesk, A., Mewes, H.W. (1998) Comprehensive, comprehensible, distributed and intelligent databases: current status. Bioinformatics 14, 551–561.
Rechenmann, F. (2000) From data to knowledge. Bioinformatics 16, 411.
Rumbaugh, J., Blaha, M., Premerlani, W., Eddy, F., Rumbaugh, J., Lorenson, W. (1991) Object-Oriented Modeling and Design. Prentice Hall, pp. 1–500.
Korson, T. and McGregor, J. (1990) Understanding Object-Oriented: A Unifying Paradigm. CACM 9, 40–60.
Object Management Group. (1999) OMG Unified Modeling Language Specification. Object Management Group, Inc., pp. 1–808.
Martinez, R., Rozenblit, J., Cook, J.F., Chacko, A.K., and Timboe, H.L. (1999) Virtual management of radiology examinations in the virtual radiology environment using common object request broker architecture services. J. Digit. Imaging 12, 181–185.
Quitadamo, L. R., Marciani, M. G., et al. (2008) Describing different brain computer interface systems through a unique model: a UML implementation. Neuroinformatics 6, 81–96.
Fridsma, D. B., Evans, J., et al. (2008) The BRIDG project: a technical report. J. Am. Med. Inform. Assoc. 15, 130–137.
Webb, K. and White, T. (2005) UML as a cell and biochemistry modeling language. Biosystems 80, 283–302.
Taylor, C. F., Paton, N. W., et al. (2003) A systematic approach to modeling, capturing, and disseminating proteomics experimental data. Nat. Biotechnol. 21, 247–254.
Xirasagar, S., Gustafson, S., et al. (2004) CEBS object model for systems biology data, SysBio-OM. Bioinformatics 20, 2004–2015.
Jedlitschky, G., Leier, I., Buchholz, U., Barnouin, K., Kurz, G., and Keppler, D. (1996) Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res. 56, 988–994.
Hipfner, D.R., Deeley, R.G., and Cole, S.P. (1999) Structural, mechanistic and clinical aspects of MRP1. Biochim. Biophys. Acta. 1461, 359–376.
Hyde, S.C., Emsley, P., Hartshorn, M.J., et al. (1990) Structural model of ATP-binding proteins associated with cystic fibrosis, multidrug resistance and bacterial transport. Nature 346, 362–365.
Cui, Y., Konig, J., Buchholz, J.K., et al. (1999) Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Mol. Pharmacol. 55, 929–937.
Keppler, D., Leier, I., Jedlitschky, G., and Konig, J. (1998) ATP-dependent transport of glutathione S-conjugates by the multidrug resistance protein MRP1 and its apical isoform MRP2. Chem. Biol. Interact. 111–112, 153–161.
Harmon, P. and Watson, M. (1997) Understanding Uml: The Developer's Guide: With a Web-Based Application in Java. Morgan Kaufmann Publishers, pp. 1–340.
http://pharmtao.com/transporter (accessed in May 2009).
Ross, D.D., Yang, W., Abruzzo, L.V., et al. (1999) Atypical multidrug resistance: breast cancer resistance protein messenger RNA expression in mitoxantrone-selected cell lines. J. Natl. Cancer Inst. 91, 429–433.
Yan, Q., and Sadée, W. (2000) Human membrane transporter database: a Web-accessible relational database for drug transport studies and pharmacogenomics. AAPS PharmSci 2, E20.
Marshall, A. (1997) Laying the foundations for personalized medicines. Nat. Biotechnol. 15, 954–957.
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Yan, Q. (2010). Bioinformatics for Transporter Pharmacogenomics and Systems Biology: Data Integration and Modeling with UML. In: Yan, Q. (eds) Membrane Transporters in Drug Discovery and Development. Methods in Molecular Biology, vol 637. Humana Press. https://doi.org/10.1007/978-1-60761-700-6_2
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DOI: https://doi.org/10.1007/978-1-60761-700-6_2
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