Network-Based Approaches for Disease-Gene Association Prediction Using Protein-Protein Interaction Networks

Genome-wide association studies (GWAS) can be used to infer genome intervals that are involved in genetic diseases. However, investigating a large number of putative mutations for GWAS is resource- and time-intensive. Network-based computational approaches are being used for efficient disease-gene association prediction. Network-based methods are based on the underlying assumption that the genes causing the same diseases are located close to each other in a molecular network, such as a protein-protein interaction (PPI) network. In this survey, we provide an overview of network-based disease-gene association prediction methods based on three categories: graph-theoretic algorithms, machine learning algorithms, and an integration of these two. We experimented with six selected methods to compare their prediction performance using a heterogeneous network constructed by combining a genome-wide weighted PPI network, an ontology-based disease network, and disease-gene associations. The experiment was conducted in two different settings according to the presence and absence of known disease-associated genes. The results revealed that HerGePred, an integrative method, outperformed in the presence of known disease-associated genes, whereas PRINCE, which adopted a network propagation algorithm, was the most competitive in the absence of known disease-associated genes. Overall, the results demonstrated that the integrative methods performed better than the methods using graph-theory only, and the methods using a heterogeneous network performed better than those using a homogeneous PPI network only.