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Innovations in computational biology such as high throughput genomic technologies have resulted in numerous large databases containing genomic information which are being annotated with terms from the gene ontology to ensure consistency of the referenced biological concepts. These annotations are being used in determining the similarity between genes and gene products, an important task in post-genomics study. This paper presents an investigation of similarity measures between annotated objects with a focus on the domain of computational biology and the gene ontology. A framework for experimenting with and developing new similarity measures between annotated objects in other domains is discussed in the context of the querying with ontological terminologies and their annotations (QUOTA) system currently being developed.