Gene Ontology-based Semantic Similarity Measures

Quantitative measure of functional similarity between gene products is important for post-genomics study. The similarity measures may be used to validate high-throughput protein interaction data, help the development of new pathway modelling tools and clustering methods, and enable the identification of functionally related gene products independent of homology [Guo et al., 2006, Schlicker et al., 2006]. The functional relationship is usually estimated by shared annotation of gene products in a controlled vocabulary system, such as Gene Ontology (GO). GO terms and their relationships are represented in the form of directed acyclic graphs (DAG). It comprises of three categories: molecular function (MF), biological process (BP), and cellular component (CC). However, simply identifying shared GO annotations may not be adequate for the estimation of semantic similarity. Even if two annotations are different, they can be closely related via their common ancestors in DAG. On the other hand, the shared terms may be too general to be used as evidence for the functional association of annotated gene products. GO graph structure can be taken into account to improve semantic similarity measures. For example, two methods (simUI and simLP) have been implemented in GOstats package to estimate the similarity between induced graphs each of which includes the specific set of GO annotations for a gene product and all parents of these GO terms. Recently, a new set of measures have been used to calculate the GO-derived semantic similarity. They are based on the assumption that the more information two terms share, the more similar they are. The shared information is indicated by the information content of the terms that subsume them in DAG. The information content is defined as the frequency of each term, or any of its children, occurring in an annotated dataset. Given the information content of each term, there are several ways to calculate similarity scores between annotated gene products.