Finding underlying molecular mechanisms of diseases is one of the important issues in biomedical research. In which, prediction of novel disease-associated genes is mostly focused. Many methods have been proposed based on biological networks and shown effectively for the problem. These network-based methods are usually relied on a "disease module" principle that functionally similar genes are associated with similar phenotypes or diseases. Among them, methods solely based on gene/protein networks only exploit that principle by structural modules in the gene/protein networks. Meanwhile, others based on integration of these networks with a disease similarity network better exploit the principle and consequently result in higher prediction performance. In these studies, the disease similarity network is extracted from a disease similarity matrix which was calculated using text mining techniques on OMIM records. Considering that diseases have been recently well annotated by human phenotype ontology (i.e., a controlled vocabulary database) and semantic similarity measures can be used to calculate similarities among them. Therefore, it would be more accurate to construct disease similarity network based on semantic similarity measures on phenotype ontol- Experiment results show that the ontology-based disease similarity network much improves the prediction performance compared to the one based on OMIM records, irrespective of gene/protein networks. In addition, we show ability of our method in predicting novel Alzheimer's disease-associated genes, in which 19 out of top 100 ranked candidate genes are supported with evidences from literature.
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