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Domain ontologies are formal descriptions of the classes of concepts and the relationships among those concepts that describe an application area. The Protege software-engineering methodology provides a clear division between domain ontologies and domain-independent problemsolvers that, when mapped to domain ontologies, can solve application tasks. The Protege approach allows domain ontologies to inform the total software-engineering process, and for ontologies to be shared among a variety of problem-solving components. We illustrate the approach by describing the development of EON, a set of middleware components that automate various aspects of protocol-directed therapy. Our work illustrates the organizing effect that domain ontologies can have on the software-development process. Ontologies, like all formal representations, have limitations in their ability to capture the semantics of …