Improving the Prediction of Disease-associated Genes by Integrating Annotated Gene Sets

Identifying disease-associated genes is key to studying the pathogenic mechanism of complex diseases. Existing methods for predicting disease genes are dominantly based on molecular networks or omics data, including gene expression, protein expression, co-expression networks, protein-protein interaction, etc. The annotated gene sets such as Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes pathways represent knowledge about the functional association between genes, which may be of predictive value for disease gene identification. However, the knowledge is barely explored in existing approaches. In this study, we propose a new method for predicting disease-associated genes by integrating annotated gene sets. It first constructs a signal matrix by integrating annotated gene sets in the MSigDB data, a comprehensive database of curated gene sets. Then it uses the signal matrix as input features to build a prediction model with machine learning approaches. We compared our method with existing disease gene prediction methods on five complex diseases. The results showed that our method is superior to other methods.