A network-based method using a random walk with restart algorithm and screening tests to identify novel genes associated with Meniere's disease

As a chronic illness derived from hair cells of the inner ear, Meniere's disease (MD) negatively influences the quality of life of individuals and leads to a number of symptoms, such as dizziness, temporary hearing loss, and tinnitus. The complete identification of novel genes related to MD would help elucidate its underlying pathological mechanisms and improve its diagnosis and treatment. In this study, a network-based method was developed to identify novel MD-related genes based on known MD-related genes. A human protein-protein interaction (PPI) network was constructed using the PPI information reported in the STRING database. A classic ranking algorithm, the random walk with restart (RWR) algorithm, was employed to search for novel genes using known genes as seed nodes. To make the identified genes more reliable, a series of screening tests, including a permutation test, an interaction test and an enrichment test, were designed to select essential genes from those obtained by the RWR algorithm. As a result, several inferred genes, such as CD4, NOTCH2 and IL6, were discovered. Finally, a detailed biological analysis was performed on fifteen of the important inferred genes, which indicated their strong associations with MD.