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

Lifeng An,Quan Zou,Yanshu Wang,Lin Li,Xiangyin Kong,Tao Huang

doi:10.1371/journal.pone.0182592

Abstract

As a chronic illness derived from hair cells of the inner ear, Menière’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.

Highlights

Menière’s disease (MD) is a disorder that involves the inner ear with various episodic symptoms, including vertigo, hearing loss, tinnitus and ear fullness, and it is a frustrating condition with a sensation of pressure in the middle ears [1, 2]
The random walk with restart (RWR) algorithm was applied on the protein-protein interaction (PPI) network constructed in Section 2.2 by setting the 106 Ensembl IDs of MD-related genes as seed nodes
Each node in the network was assigned a probability of it being a novel MD-related gene. 1E-05 was set as the threshold of probability, resulting in 4,514 RWR genes

Summary

Introduction

Menière’s disease (MD) is a disorder that involves the inner ear with various episodic symptoms, including vertigo, hearing loss, tinnitus and ear fullness, and it is a frustrating condition with a sensation of pressure in the middle ears [1, 2]. MD only affects one ear and may induce at least two to three of the symptoms mentioned above, in contrast to other problems in the ear [3]. Two tests have been widely applied in the diagnostic processes, involving two explicit symptoms of MD. A hearing test is one of the most significant diagnostic methods that has been widely applied for preliminary.

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Conclusion