Cited references and notes

1. M. Shaw and D. Garlan, Software Architecture: Perspectives on an Emerging Discipline, Prentice Hall, Upper Saddle River, NJ (1996).
2. “Comparative genomics” is a broad term used here in reference to various techniques for learning about one organism's genome through comparison to a better-studied relative.
3. K. Sirotkin, “NCBI: Integrated Data for Molecular Biology Research,” Bioinformatics: Databases and Systems, S. Letovsky, Editor, Kluwer Academic Publishers, Norwell, MA (1999), pp. 11–19.
4. R. Unwin, J. Fenton, M. Whitsitt, C. Jamison, M. Stupar, E. Jakobsson, and S. Subramaniam, “Biology Workbench: A Computing and Analysis Environment for the Biological Sciences,” Bioinformatics: Databases and Systems, S. Letovsky, Editor, Kluwer Academic Publishers, Norwell, MA (1999), pp. 233–244.
5. T. Etzold, A. Ulyanov, and P. Argos, “SRS: Information Retrieval System for Molecular Biology Data Banks,” Methods in Enzymology 266, 114–128 (1996).
6. R. F. Smith, B. A. Wiese, M. K. Wojzynski, D. B. Davison, and K. C. Worley, “BCM Search Launcher—An Integrated Interface to Molecular Biology Data Base Search and Analysis Services,” Genome Research 6, No. 5, 454–462 (1996).
7. Entigen Corporation (formerly eBioinformatics, Inc., and Empatheon, Inc.), http://www.bionavigator.com.
8. DoubleTwist, Inc., http://www.doubletwist.com.
9. V. M. Markowitz, I. M. A. Chen, A. Kosky, and E. Szeto, “OPM: Object-Protocol Model Data Management Tools '97,” Bioinformatics: Databases and Systems, S. Letovsky, Editor, Kluwer Academic Publishers, Norwell, MA (1999), pp. 187–199.
10. S. B. Davidson, O. P. Buneman, J. Crabtree, V. Tannen, G. C. Overton, and L. Wong, “BioKleisli: Integrating Biomedical Data and Analysis Packages,” Bioinformatics: Databases and Systems, S. Letovsky, Editor, Kluwer Academic Publishers, Norwell, MA (1999), pp. 201–211.
11. P. G. Baker, A. Brass, S. Bechhofer, C. Goble, N. Paton, and R. Stevens, “TAMBIS: Transparent Access to Multiple Bioinformatics Information Sources,” Proceedings, Sixth International Conference on Intelligent Systems for Molecular Biology, Montreal, Canada (June 28–July 1, 1998), pp. 25–34.
12. Mapping one database schema to another, even with the aid of human-defined meta-data, is an extremely difficult problem, unless the semantics and syntactic conventions of both schemas are formally defined and rigidly obeyed (which is generally not true of bioinformatics databases). This is one of the main motivations for the “looser” data model we have used.
13. We elaborate on this claim in: A. Siepel, A. Farmer, A. Tolopko, M. Zhuang, P. Mendes, W. Beavis, and B. Sobral, “ISYS: A Decentralized, Component-Based Approach to the Integration of Heterogeneous Bioinformatics Resources,” Bioinformatics 17, No. 1, 83–94 (2001). Note, however, that some query systems for heterogeneous databases have created advanced graphical user interfaces that do support exploratory querying to a degree. Examples are GeneLogic, Inc.'s Object-Protocol Model (see Reference 9) and IBM's PESTO (M. J. Carey, L. M. Haas, V. Maganty, and J. H. Williams, “PESTO: An Integrated Query/Browser for Object Databases,” Proceedings 22nd International Conference on Very Large Databases (VLDB), Bombay, India (September 3–6, 1996), pp. 203–214.
14. Life Sciences Research Task Force of the Object Management Group, http://www.omg.org/homepages/lsr.
15. C. Szyperski, Component Software: Beyond Object-Oriented Programming, Addison-Wesley Longman Limited, Essex, England (1998).
16. K. Jungfer, G. Cameron, and T. Flores, “EBI: CORBA and the EBI Databases,” Bioinformatics: Databases and Systems, S. Letovsky, Editor, Kluwer Academic Publishers, Norwell, MA (1999), pp. 245–254.
17. NetGenics, Inc., http://www.netgenics.com.
18. Synomics, Ltd., http://www.synomics.com.
19. J. Hu, C. Mungall, D. Nicholson, and A. L. Archibald, “Design and Implementation of a CORBA-Based Genome Mapping System Prototype,” Bioinformatics 14, No. 2, 112–120 (1998).
20. H. R. Pagels, Dreams of Reason: The Computer and the Rise of the Sciences of Complexity, Simon and Schuster, New York (1988).
21. S. Levy, Artificial Life: A Report from the Frontier Where Computers Meet Biology, Random House, New York (1992).
22. In contrast to the elements of cellular automata and Boolean networks, the components in ISYS are not necessarily simple; but they encapsulate their complexity and interact with one another in simple ways.
23. S. F. Altschul, W. Gish, W. Miller, E. W. Myers, and D. L. Lipman, “Basic Local Alignment Search Tool,” Journal of Molecular Biology 215, No. 3, 403–410 (1990).
24. J. D. Thompson, D. G. Higgins, and T. J. Gibson, “CLUSTAL W: Improving the Sensitivity of Progressive Multiple Sequence Alignment through Sequence Weighting, Position-Specific Gap Penalties and Weight Matrix Choice,” Nucleic Acids Research 22, 4673–4680 (1994).
25. JalView, http://www2.ebi.ac.uk/~michele/jalview/.
26. M. P. Skupski, M. Booker, A. Farmer, M. Harpold, W. Huang, J. Inman, D. Kiphart, C. Kodira, S. Root, F. Schilkey, J. Schwertfeger, A. Siepel, D. Stamper, N. Thayer, R. Thompson, J. Wortman, M. Zhuang, and C. Harger, “The Genome Sequence DataBase: Toward an Integrated Functional Genomics Resource,” Nucleic Acids Research 27, 35–38 (1999).
27. This capability is perhaps more powerful than the example here suggests. A slightly better illustration appears in Reference 13.
28. The EventChannel and ServiceBroker components represent a division into two parts of the component called the ClientBus in Reference 13, Siepel et al. (2000).
29. E. Gamma, R. Helm, R. Johnson, and J. Vlissides, Design Patterns: Elements of Reusable Object-Oriented Software, Addison-Wesley Publishing Co., Reading, MA (1995).
30. F. Buschmann, R. Meunier, H. Rohnert, P. Sommerlad, and M. Stal, A System of Patterns: Pattern-Oriented Software Architecture, John Wiley & Sons Ltd., Chichester, England (1996).
31. CORBA: Common Request Broker Architecture and Specification, available from the Object Management Group (1996). See http://www.omg.org/ for contact information.
32. The latter is called dynamic discovery in Reference 13.
33. Clement Szyperski defines components as “XXX.” We have taken the liberty of allowing that while they may be independently executable, they need not be independently executing. In fact, ISYS components are JAR files that may have, but are not required to have, classes with main methods that allow execution with or without the ISYS platform.
34. P. Karp, “A Strategy for Database Interoperation,” Journal of Computational Biology 2, No. 4, 573–586 (1995).
35. V. M. Markowitz and O. Ritter, “Characterizing Heterogeneous Molecular Biology Database Systems,” Journal of Computational Biology 2, No. 4, 547–556 (1995).
36. S. B. Davidson, C. Overton, and P. Buneman, “Challenges in Integrating Biological Data Sources,” Journal of Computational Biology 2, No. 4, 557–572 (1995).
37. See Reference 13, Siepel et al.
38. Although the IsysObject interface does not explicitly support this capability, it is possible to implement an IsysObject such that new attributes can be added later in its life. In this way, an object can gain attributes as new data are produced by the system.
39. Space does not allow a full discussion of attribute “groups.” Essentially, they are necessary to maintain a sense of which attributes describe the same entities when networks of objects are “flattened” (as discussed later in the text). See the ISYS Web site for additional information.
40. A full treatment of the issue of the data model is not possible here. As they create their components, developers will be able to contribute attributes to the data model, if it does not meet their needs. Thus, the model for object attributes and relationships will evolve according to the needs of individual component developers.