Gene Ontology term overlap as a measure of gene functional similarity

Background: The availability of various high-throughput experimental and computational methods allows biologists to rapidly infer functional relationships between genes. It is often necessary to evaluate these predictions computationally, a task that requires a reference database for functional relatedness. One such reference is the Gene Ontology ( GO). A number of groups have suggested that the semantic similarity of the GO annotations of genes can serve as a proxy for functional relatedness. Here we evaluate a simple measure of semantic similarity, term overlap (TO). Results: We computed the TO for randomly selected gene pairs from the mouse genome. For comparison, we implemented six previously reported semantic similarity measures that share the feature of using computation of probabilities of terms to infer information content, in addition to three vector based approaches and a normalized version of the TO measure. We find that the overlap measure is highly correlated with the others but differs in detail. TO is at least as good a predictor of sequence similarity as the other measures. We further show that term overlap may avoid some problems that affect the probability-based measures. Term overlap is also much faster to compute than the information content-based measures. Conclusion: Our experiments suggest that term overlap can serve as a simple and fast alternative to other approaches which use explicit information content estimation or require complex precalculations, while also avoiding problems that some other measures may encounter.