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Committee on a National Collaboratory:
Staff
A complete community information system to support research would encompass an electronic library containing all sources of data, software enabling interactive display and analysis of all data types, and an underlying information infrastructure that transparently supports extensive facilities for browsing, filtering, and sharing knowledge across the international Internet. Building working models of such a complete collaboration system is possible today and is actually being done in an ongoing research project, the Worm Community System. Basic Elements and Capabilities The first step in building a community information system is to decide the extent of the knowledge to be captured, which depends in turn on the needs of the particular community whose work is to be facilitated. Not all of the elements in the scientific process described in Chapter 1 are equally important in genome research. For example, investigators rarely wish to examine actual raw data and are satisfied if the maintainers of instruments, e.g., those in the large sequencing projects, keep the raw data streams and release only a final version to the archival databases. Because experiments in genome research typically involve only a few people or only loose cooperation between different laboratories, the need for realtime cooperative work tools is relatively small, and support for collaboration should focus on retrieval and analysis of the archival data and literature, and on extending the same facilities to more informal material that is critical to progress in science. In genome research, this informal material typically includes results that are not yet publishable in journal articles but may be discussed in newsletters (e.g., giving one- to two-page descriptions of current experiments) and in conference proceedings (e.g., giving abstracts of new results). It also typically includes data too specialized to be publishable in archival databases-such as strain lists (local sets of mutant organisms) and restriction maps (detailed locations of genes)-yet still extremely useful to other researchers working on similar problems. These informal results are usually stored in individual laboratories inside filing cabinets or taped to the backs of doors and are usually retrieved from the outside only by telephoning the laboratory. Electronic sharing of this knowledge would make it available to a much wider set of potential collaborators. To collect and check this informal knowledge, the appropriate biological community must be directly involved. The experience with GenBank demonstrates that biologists conducting genome research will electronically submit material that is deemed useful, as does the extensive experience of scientists with electronic bulletin boards such as Netnews. The experience with the Genome Data Base shows that electronic support for distributed editors (human editors to check the quality of materials) is workable with community-chosen curators of the individual data sources. A complete electronic publishing environment will support entry of all the specific types of knowledge and publishing in all the different styles. With such a system, for example, an investigator will be able to run a program that enables interactive specification of a restriction map or preparation of a newsletter article and then automatically submits it to a central archive, which then automatically distributes it to the community. Local maps might be unchecked and newsletter articles might be moderated (checked for topic), as opposed to centrally archived data or literature that must be checked for quality and consistency. The process of associating and relating items from myriad formal and informal sources involves major technological and sociological complications. Interconnection of informal sources of information depends on implicit associations being made automatically, e.g., by parsing the text of newsletter articles to locate gene names with which to make associations. In a community information system, interconnection is facilitated by community members themselves, who may add most associations. That is, the users of the system can specify their own associations between items, including associations discovered while using the system itself. A distributed system is required to support sharing of information in a scientific community, since the users and the generators of knowledge are geographically distributed. National networks are expected to be a necessary component of a community information system or analysis environment, even if the total amount of knowledge is small. A community information system should present users with what appears to be a single logical "database" for retrieval and storage of data. A Model Collaboratory-Worm Community System A model of a complete community information system is under active development in the Community Systems Laboratory at the University of Arizona (Box 4.5). This system represents a substantial operational model of a collaboratory. The community is the collection of molecular biologists who study the nematode worm Caenorhabditis elegans; the system itself is called the Worm Community System. The size of the community and the amount of data are manageable-large enough to be interesting from the perspective of data organization and management yet small enough to be doable. The community's approximately 500 members are spread across the United States, Europe, and Japan. Significant sources of data already exist in electronic format, with a range of types and location. Community members have a long tradition of openness and sharing of data. The underlying technology of a community information system such as WCS is based on a representation called an information space (Schatz, 1987, 1989) that supports transparent manipulation of objects from multiple, heterogeneous, distributed sources and is thus a form of a federated object-oriented database. The goal is to enable users to manipulate data items from many sources of different types as though the items are uniform units of information. The information space consists of the set of associations among these information units. Thus, a single set of user commands suffices to browse, filter, and share all the different types of data. This is accomplished internally by packaging data from all external sources as uniform objects with a generic set of operations for publishing, searching, displaying, and associating the data. The system itself also handles retrieval of objects from remote sources across the network and provides the necessary caching policies to make this retrieval speed-transparent. For the types of data common in genome research, the existing Internet has sufficient bandwidth to support interactive retrieval across the country.
The first release of the Worm Community System is now running in worm laboratories across the country and supports a sample range of the necessary knowledge and functionality (Figure 4.1). The second release will be available in 1993 and will support a sample range of publishing mechanisms. As the publishing system and the electronic community evolve, subsequent releases will support deeper knowledge semantics and begin to move toward a generic information infrastructure. OPPORTUNITIES TO ENHANCE RESEARCH Genome research in molecular biology has undergone a significant revolution owing to the existence of archival databases such as MedLine, GenBank, and the Genome Data Base. All practicing genome researchers consider it essential to cross-compare their experimental results with existing results by running similarity searches on these databases. Next-generation central archives, now in use in research prototypes, promise even greater utility and opportunities for collaboration. Remote analysis servers (e.g., Blast) will enable rapid, daily comparisons of sequences. Systems for interconnecting multiple archives (e.g., Entrez) will enable rapid comparison across different sources. The fact that such prototypes are being implemented with a standard data exchange format by the National Center for Biotechnology Information at the National Library of Medicine promises that integrated analysis environments for standard archives will become a reality in the foreseeable future. At the same time, models for a complete collaboratory are also being developed. The Worm Community System illustrates what a complete collaboratory in genome research could become in the foreseeable future. It provides analysis of both formal and informal knowledge and electronic sharing of user-provided knowledge. As a distributed system utilizing the existing network communications infrastructure, it points the way toward a national information infrastructure that will enable scientists to manipulate sources of information transparently across the country. However, it is still a preliminary model and will have to be expanded considerably to demonstrate a functional community information infrastructure. For example, the sets of knowledge and analysis must be expanded, a true distributed system across platforms and networks must be developed, and a case-hardened implementation must be evolved before the technology is ready to support standard archives. But with sufficient resources, complete collaboratories for sharing, comparing, and analyzing data will be built for genome research since the need is there and the technology is available. The pattern discovery enabled by "dry-lab" analysis environments promises another significant revolution for the support of research in molecular biology.
1. Replication is the process in which existing DNA is used as a template for the synthesis of new DNA strands. Mutagenesis is the process by which DNA is mutated or modified. Transcription is the synthesis of RNA, a long-chain nucleic acid consisting of repeating nucleotide units, from a sequence of DNA. Translation is the process in which the genetic code directs the synthesis of proteins from amino acids. 2. Two examples of gene sequencing technology are Polymerase Chain Reaction (PCR) and gel electrophoresis. PCR is a method for increasing the number of copies of a specific DNA fragment to make the fragment easier to detect and identify. Gel electrophoresis is a method of separating large molecules in an electric field, allowing DNA fragments differing by single bases to be readily separated. Combined with methods such as Sanger's dideoxynucleotide chain termination procedure, gel electrophoresis can produce ladders of DNA molecules from which DNA sequences can be determined. 3. "A primary goal of the Human Genome Project is to make a series of descriptive diagrams--maps--of each human chromosome at increasingly finer resolutions. Mapping involves (1) dividing the chromosomes into smaller fragments that can be propagated and characterized and (2) ordering (mapping) them to correspond to their respective locations on the chromosomes. After mapping is completed, the next step is to determine the sequence of base pairs of the ordered DNA fragments. A genome map describes the order of genes or other markers and the spacing between them on each chromosome. If the full sequence of genes were known, research emphasis could shift to determining gene function." (Cantor and Spengler, 1992, p.198) 4. The common stages for publishing data in the electronic domain are similar to the steps in ordinary publishing. The raw data are recorded in laboratory notebooks that are kept private, or kept on archival disk if generated directly by a sequencing machine. A processed form of these data, such as a map location or a sequence, is submitted for inclusion into a database. This is edited for publication by a central editor; typically a single curator chooses what data in what form will be included. Finally, the edited database is distributed for use by other biologists. |
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