Network-based hub biomarker discovery for glaucoma

Abstract

Abstract Purpose Glaucoma is an optic neuropathy, and the leading cause of irreversible blindness worldwide. However, the early detection of glaucoma remains challenging as chronic forms of glaucoma remain largely asymptomatic until considerable irreversible visual field deficits have ensued. Thus, biomarkers that facilitate early diagnosis and treatment for glaucoma patients with a high risk of progression are pressing. Methods Human disease-biomarker interactions network (HDBIN) and Human disease-target-drug interactions network (HDTDIN) were first constructed based on multi-omics data. The greedy search algorithm was utilized to search for the hub biomarkers and drug targets for glaucoma. Genome-wide association studies (GWAS) and epidemiological data from the UK Biobank (UKB) were used to verify our results. Biological network and function analysis was conducted to find common network features and pathways for hub biomarkers and drug targets for glaucoma. Results We identified 10 hub biomarkers/drug targets for the diagnosis, treatment and prognosis for glaucoma. These results were verified by text-mining and genomic/epidemiology data. We also predicted the new application of BMP1 and MMP9 to diagnose glaucoma and confirm the theory of hub biomarkers with multiple clinical applications. Further, relevant pivotal pathways for these hub biomolecules were discovered, which may be foundations for future biomarker and drug target prediction for glaucoma. Conclusions Based on complex networks, hub biomolecules, essential pathways, and close diseases were identified for glaucoma in diagnosis, treatment and prognosis. Translational Relevance Our network approach could be a new way to identify important biomarkers and drug targets for glaucoma or other complex eye diseases.