Integrated Bioinformatics Analysis For Differentially Expressed Genes,Micrornas And Pathways Identification In Age-Related Macular Degeneration

Age Related Macular Degeneration is leading cause of irreversible visual loss in developed countries. Mechanisms of Age Related Macular Degeneration pathology include Aging of Retinal Pigment Epithelium cells, Oxidative Stress, increased levels of High-density lipoprotein cholesterol, Complement system activation, Neovascularization and other mechanisms.Purpose:In this study we aimed to identify genes and microRNAs important in pathogenesis of Age Related Macular Degeneration.Methods:Gene expression profile of GSE۱۷۱۹ was available from Gene Expression Omnibus database. ۱۸ samples of Dermal fibroblasts of healthy people and ۱۸ samples from patients were selected from database. Dataset was analyzed with GEO۲R tools to calculate Di↵erentially Expressed Genes. A defined formula [-log(p.value)×| log(fold change)| ] was applied to select top significant probs. After filtering and removing duplicates, Protein-Protein Interaction network of Di↵erentially Expressed Genes established through STRING database. Gephi software was used to select hub genes. Toppgene database was used for Gene Ontology and microRNA target prediction. Cytoscape software was used to identify hub microRNAs.Results:Total ۱۷۵۶ Differentially Expressed Genes were identified of which ۸۳۶ were upregulated and ۹۲۰ were downregulated. ۵ hub genes (TP۵۳, ACTB, HSP۹۰AA۱, HRAS, VEGFA), ۵ hub genes based on closeness centrality (ACTB, TP۵۳, HSP۹۰AA۱, HRAS, HSPA۴) and ۵ microRNA hubs (mir-۷, mir-۴۹۵, mir-۵۶۸۸, mir-۳۰۲b, mir-۲۵, mir-۲۲۲) based on degree were identified. Significant Gene Ontologies were extracellular matrix organization, focal adhesion and axon guidance.Conclusion:Our study investigated genes and microRNAs e↵ective in pathogenesis of Age Related Macular Degeneration that can help discovering new biomarkers for diagnosis and new treatment methods.

کلیدواژه ها:

Age Related Macular Degeneration ، Biomarkers ، Transcriptomics ، microRNA ، Hub Genes