Incorporating Differential Gene Expression Analysis with Predictive Biomarkers to Identify Novel Therapeutic Drugs for Fuchs Endothelial Corneal Dystrophy

Wen, Huaming1,2,3; Gallo, Ryan A.4; Huang, Xiaosheng5,6; Cai, Jiamin5; Mei, Shaoyi6; Farooqi, Ammad Ahmad7; Zhao, Jun1,2,6; Tao, Wensi4,8

2021-06-29

10.1155/2021/5580595

Journal of Ophthalmology   影响因子和分区

2090-004X

2090-0058

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 VSIG2, IL18, and ITGB8 were significantly increased in FECD compared with control. Meanwhile, the expression levels of CNGA3, SMOX, and CERS1 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.

SCI

英语

通讯

Science, Technology, and Innovation Commission of Shenzhen Municipality[GJHZ20180420180937076] ; Sanming Project of Medicine in Shenzhen[SZSM201812090]

Ophthalmology

Ophthalmology

WOS:000674653400001

HINDAWI LTD

Web of Science

1.Jinan Univ, Shenzhen Peoples Hosp, Dept Ophthalmol, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China
3.Shenzhen Univ, Baoan Cent Hosp Shenzhen, Dept Ophthalmol, Affiliated Hosp 5, Shenzhen 518102, Guangdong, Peoples R China
4.Univ Miami, Miller Sch Med, Dr Nasser AlRashid Orbital Vis Res Ctr, Bascom Palmer Eye Inst,Dept Ophthalmol, Miami, FL 33136 USA
5.Shenzhen Univ, Shenzhen Eye Hosp, Sch Ophthalmol Ef Optometry, Shenzhen 518040, Guangdong, Peoples R China
6.Jinan Univ, Shenzhen Eye Inst, Shenzhen Eye Hosp, Shenzhen 518040, Guangdong, Peoples R China
7.Inst Biomed & Genet Engn IBGE, Islamabad 44000, Pakistan
8.Univ Miami, Miller Sch Med, Dept Radiat Oncol, Miami, FL 33136 USA

Wen, Huaming,Gallo, Ryan A.,Huang, Xiaosheng,et al. Incorporating Differential Gene Expression Analysis with Predictive Biomarkers to Identify Novel Therapeutic Drugs for Fuchs Endothelial Corneal Dystrophy[J]. Journal of Ophthalmology,2021,2021.

Wen, Huaming.,Gallo, Ryan A..,Huang, Xiaosheng.,Cai, Jiamin.,Mei, Shaoyi.,...&Tao, Wensi.(2021).Incorporating Differential Gene Expression Analysis with Predictive Biomarkers to Identify Novel Therapeutic Drugs for Fuchs Endothelial Corneal Dystrophy.Journal of Ophthalmology,2021.

Wen, Huaming,et al."Incorporating Differential Gene Expression Analysis with Predictive Biomarkers to Identify Novel Therapeutic Drugs for Fuchs Endothelial Corneal Dystrophy".Journal of Ophthalmology 2021(2021).