Information-theoretic evaluation of predicted ontological annotations

Motivation: The development of effective methods for the prediction of ontological annotations is an important goal in computational biology, with protein function prediction and disease gene prioritization gaining wide recognition. Although various algorithms have been proposed for these tasks, evaluating their performance is difficult owing to problems caused both by the structure of biomedical ontologies and biased or incomplete experimental annotations of genes and gene products. Results: We propose an information-theoretic framework to evaluate the performance of computational protein function prediction. We use a Bayesian network, structured according to the underlying ontology, to model the prior probability of a protein's function. We then define two concepts, misinformation and remaining uncertainty, that can be seen as information-theoretic analogs of precision and recall. Finally, we propose a single statistic, referred to as semantic distance, that can be used to rank classification models. We evaluate our approach by analyzing the performance of three protein function predictors of Gene Ontology terms and provide evidence that it addresses several weaknesses of currently used metrics. We believe this framework provides useful insights into the performance of protein function prediction tools.