Identifying Hub Genes for Glaucoma based on Bulk RNA Sequencing Data and Multi-machine Learning Models.

Aims: The aims of this study were to determine hub genes in glaucoma through multiple machine learning algorithms.

Background: Glaucoma has afflicted many patients for many years, with excessive pressure in the eye continuously damaging the nervous system and leading to severe blindness. An effective molecular diagnostic method is currently lacking.

Objective: The present study attempted to reveal the molecular mechanism and gene regulatory network of hub genes in glaucoma, followed by an attempt to reveal the drug-gene-disease network regulated by hub genes.

Methods: A microarray sequencing dataset (GSE9944) was obtained through the Gene Expression Omnibus database. The differentially expressed genes in Glaucoma were identified. Based on these genes, we constructed three machine learning models for feature training, Random Forest model (RF), Least absolute shrinkage and selection operator regression model (LASSO), and Support Vector Machines model (SVM). Meanwhile, Weighted Gene Co-Expression Network Analysis (WGCNA) was performed for GSE9944 expression profiles to identify Glaucoma-related genes. The overlapping genes in the four groups were considered as hub genes of Glaucoma. Based on these genes, we also constructed a molecular diagnostic model of Glaucoma. In this study, we also performed molecular docking analysis to explore the gene-drug network targeting hub genes. In addition, we evaluated the immune cell infiltration landscape in Glaucoma samples and normal samples by applying CIBERSORT method.

Results: 8 hub genes were determined: ATP6V0D1, PLEC, SLC25A1, HRSP12, PKN1, RHOD, TMEM158 and GSN. The diagnostic model showed excellent diagnostic performance (area under the curve=1). GSN might positively regulate T cell CD4 naïve as well as negatively regulate T cell regulation (Tregs). In addition, we constructed gene-drug networks in an attempt to explore novel therapeutic agents for Glaucoma.

Conclusion: Our results systematically determined 8 hub genes and established a molecular diagnostic model that allowed the diagnosis of Glaucoma. Our study provided a basis for future systematic studies of Glaucoma pathogenesis.