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The gene ontology and annotations derived from the S.cerivisiae genome database were analyzed to calculate functional similarity of gene products. Three methods for measuring similarity (including a distance-based approach) were implemented. Significant, quantitative relationships between similarity and expression correlation of pairs of genes were detected. Using a known gene expression dataset in yeast, this study compared more than three million pairs of gene products on the basis of these functional properties. Highly correlated genes exhibit strong similarity based on information originating from the gene ontology taxonomies. Such a similarity is significantly stronger than that observed between weakly correlated genes. This study supports the feasibility of applying gene ontology-driven similarity methods to functional prediction tasks, such as the validation of gene expression analyses and the identification of false positives in protein interaction studies.