The Washington University Center for Genetics in Medicine has an extensive yeast artificial chromosome (YAC) library, consisting of over 50,000 clones with large inserts of human genomic DNA. These clones are used by investigators both inside and outside the University to study the structure and function of genes contributing to a variety of generic disorders. The continued growth in the size and the use of the clone library threatens our ability to manage the library and to respond to new research opportunities. We propose to develop a comprehensive information management environment that will help us to exploit the full potential of the YAC library. In constructing this information management environment, we will address a number of key research issues of direct relevance to other biomedical research laboratories facing similar information management crises: 1. We will develop a detailed representation of YAC library screening experiments to be used as a conceptual model for a comprehensive YAC clone information system which represents the entire range of laboratory activities. 2. We will design a conceptual data model and a formal database schema for a YAC library information system so that technological and methodological changes in YAC cloning methods can readily be incorporated. This is a significant research issue in information systems development in that traditional data models assume that the """"""""world"""""""" represented in the database is relatively static. Because of the rapid improvements in genetics research methodology, our data models must be flexible enough to incorporate new developments. 3. We will implement a comprehensive database management system, derived from the formal data model, to support ongoing YAC research activities. This system will identify clones and primer pairs by """"""""sequence-tagged sites"""""""" (STS), and it will facilitate collaborative research arrangements by tracking clones which have been sent to or received from outside investigators and by recording YAC structural information provided by these investigators. 4. We will develop a robust data acquisition environment so that laboratory personnel can enter experimental results directly into the information system. The goal is to eliminate the need for error-prone transcriptions of experimental results. A research team composed of geneticists and medical computer scientists will achieve these goals by creating a state-of-art, comprehensive YAC information management environment that is accessible, useful, reliable, and responsive to technological change, and that may ultimately serve as a central component of a more comprehensive """"""""molecular genetics workstation.""""""""
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