Information Content-Based Gene Ontology Semantic Similarity Approaches: Toward a Unified Framework Theory

Several approaches have been proposed for computing term information content (IC) and semantic similarity scores within the gene ontology (GO) directed acyclic graph (DAG). These approaches contributed to improving protein analyses at the functional level. Considering the recent proliferation of these approaches, a unified theory in a well-defined mathematical framework is necessary in order to provide a theoretical basis for validating these approaches. We review the existing IC-based ontological similarity approaches developed in the context of biomedical and bioinformatics fields to propose a general framework and unified description of all these measures. We have conducted an experimental evaluation to assess the impact of IC approaches, different normalization models, and correction factors on the performance of a functional similarity metric. Results reveal that considering only parents or only children of terms when assessing information content or semantic similarity scores negatively impacts the approach under consideration. This study produces a unified framework for current and future GO semantic similarity measures and provides theoretical basics for comparing different approaches. The experimental evaluation of different approaches based on different term information content models paves the way towards a solution to the issue of scoring a term's specificity in the GO DAG.