Systematic mining of gene co-expression network suggests a new drug repositioning for the effective treatment of Duchenne Muscular Dystrophy

Document Type : Research Paper

Authors

1 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.

2 Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran

3 Department. of Molecular Medicine, Cardiovascular Research Centre, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran

4 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran, Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran; Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

10.22034/ijps.2020.119862.1630

Abstract

DMD is the prototype of muscular dystrophy in childhood. As there is currently no absolute treatment, the present study aimed to propose a new drug repositioning for DMD therapy. A microarray dataset of 16 DMD and 6 control samples were analyzed and 208 differentially expressed genes were screened. Weighted gene co-expression network analysis (WGCNA) algorithm, applied to obtain co-expressed gene networks for the establishment of transcriptional modules related to clinical and demographic data of DMD patients. Results indicated that a maximum of 11 co-expression modules is present in datasets with a varying number of genes. Turquoise module with 3334 genes was strongly correlated with collagen fibril organization as a positive regulator in DMD pathogenesis (r=0.98, p-value=2/00E-15) through which other DMD related hub-genes were identified as COL1A1, FZD10, COL1A2, CRISPLD1, FMO1, COL5A1, COL3A1, COL5A2, TP53I3, PLAGL1, RIPK2, SBF1, MLXIP, CFAP46, and TYRP1. Drug repositioning of the turquoise module identified some candidate drugs which are not presently approved for the treatment of DMD. The targets in the turquoise module indicate some drugs can greatly affect DMD's structure and function as COL1A1 with 42 fold changes was the most up-regulated gene. Furthermore, drug repositioning introduced Zoledronic acid as a potent antagonist for COL1A1.

Keywords