Incorporating Differential Gene Expression Analysis with Predictive Biomarkers to Identify Novel Therapeutic Drugs for Fuchs Endothelial Corneal Dystrophy. (29th June 2021)

• Record Type: Journal Article
• Authors: Wen, Huaming; Gallo, Ryan A.; Huang, Xiaosheng; Cai, Jiamin; Mei, Shaoyi; Farooqi, Ammad Ahmad; Zhao, Jun; Tao, Wensi
• Other Names: Asiedu Kofi Academic Editor.
• Is Part Of: Journal of ophthalmology. Volume 2021(2021)
• Publication Date: 2021-06-29
• Subjects: Ophthalmology -- Periodicals; Eye Diseases; Ophthalmology; Ophthalmology; Electronic journals; Periodicals; Periodicals; Fulltext; Internet Resources; Periodicals; 617.7
• DOI: 10.1155/2021/5580595
• Languages: English
• ISSNs: 2090-004X

Abstract

Abstract : Purpose . Based on the differential gene expression analysis for predictive biomarkers with RNA-Sequencing data from Fuchs endothelial corneal dystrophy (FECD) patients, we are aiming to evaluate the efficacy of Library of Integrated Network-based Cellular Signatures (LINCS) perturbagen prediction software to identify novel pharmacotherapeutic targets that can revert the pathogenic gene expression signatures and reverse disease phenotype in FECD. Methods . A publicly available RNA-seq dataset was used to compare corneal endothelial specimens from controls and patients with FECD. Based on the differential gene expression analysis for predictive biomarkers, we evaluated the efficacy of LINCS perturbagen prediction software to identify novel therapeutic targets that can revert the pathogenic gene expression signatures and reverse disease phenotypes in FECD. Results . The RNA-seq dataset of the corneal endothelial cells from FECD patients revealed the differential gene expression signatures of FECD. Many of the differential expressed genes are related to canonical pathways of the FECD pathogenesis, such as extracellular matrix reorganization and immunological response. The expression levels of genes VSIG 2, IL 18, and ITGB 8 were significantly increased in FECD compared with control. Meanwhile, the expression levels of CNGA 3, SMOX, and CERS 1 were significantly lower in the FECD than in control. We employed LINCS L1000 Characteristic Direction Signature Search Engine (L1000-CDS2) to investigate pathway-based molecular treatment. L1000-CDS2 predicted that small molecule drugs such as histone deacetylase (HDAC) inhibitors might be a potential candidate to reverse the pathological gene expression signature in FECD. Conclusions . Based on differential gene expression signatures, several candidate drugs have been identified to reverse the disease phenotypes in FECD. Gene expression signature with LINCS small molecule prediction software can discover novel preclinical drug candidates for FECD.