The relationship between protein sequences and their gene ontology functions

One main research challenge in the post-genomic era is to understand the relationship between protein sequences and their biological functions. In recent years, several automated annotation systems have been developed for the functional assignment of uncharacterized proteins. The underlying assumption of these systems is that similar sequences imply similar biological functions. However, it has been noted that matching sequences do not always infer similar functions.

In this paper, we present the correlation between protein sequences and protein functions for the yeast proteome in the context of gene ontology. A novel measure is introduced to define the overall similarity between two protein sequences. The effects of the level as well as the size of a gene ontology group on the degree of similarity were studied. The similarity distributions at different levels of gene ontology trees are presented. To evaluate the theoretical prediction power of similar sequences, we computed the posterior probability of correct predictions.

The results indicate that protein pairs of similar biological functions tend to have higher sequence similarity, although the similarity distribution in each functional group is heterogeneous and varies from group to group. We conclude that sequence similarity can serve as a key measure in protein function prediction. However, the resulting annotations must be verified through other means. A method that combines a broader range of measures is more likely to provide more accurate prediction. Our study indicates that the posterior probability of a correct prediction could serve as one of the key measures.