Network-based hub biomarker discovery for glaucoma.

Objective: 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 and analysis: Human disease-biomarker interactions network and human disease-target-drug interactions network were first constructed based on multiomics data. The greedy search algorithm was used to search for the hub biomarkers and drug targets for glaucoma. Genome-wide association studies and epidemiological data from the UK Biobank were used to verify our results. Biological network and functional analysis was conducted to find common network features and pathways.

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 serve as foundations for future biomarker and drug target prediction for glaucoma.

Conclusion: We have used a network-based approach to identify hub diagnostic and therapeutic biomarkers for glaucoma and detected relationships between glaucoma and associated diseases. Several hub biomarkers were identified and verified, which may play more important roles in the diagnosis and treatment of glaucoma.