Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 19 5 2020 10 18 517 528 EN Afshin Derakhshani Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Homa Mollaei Department of Biology, Faculty of Sciences, University of Birjand, Birjand, Iran Negin Parsamanesh Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran Mohammad Fereidouni Cellular and Molecular Research center, Birjand University of Medical Sciences, Birjand, Iran Ebrahim Miri-Moghaddam Department of Molecular Medicine, Cardiovascular Diseases Research Center, School of Medicine, Birjand University of Medical Sciences, Birjand, Iran Saeed Nasseri Cellular and Molecular Research center, Birjand University of Medical Sciences, Birjand, Iran Yongwen Luo Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan, China Hossein Safarpour Cellular and Molecular Research center, Birjand University of Medical Sciences, Birjand, Iran Behzad Baradaran Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran AND Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 2020 01 20 2020 08 09 Vitiligo is the most common cause of skin, hair, and oral depigmentation which is known as an autoimmune disorder. Genetic and environmental factors have important roles in the progression of the disease. Dysregulation of gene expression, like microRNAs (miRNA), may serve as major relevant factors. Several biological processes are involved in vitiligo disease and developing a comprehensive approach helps us to better understand the molecular mechanisms of disease. In this research, we describe how a weighted gene co-expression network analysis as a systems biology approach assists to define the primary gene modules, hub genes, and messenger RNA (mRNA)-miRNA regulatory network in vitiligo disease as the novel biomarkers. The results demonstrated a module with a high correlation with vitiligo state. Moreover, gene enrichment analysis showed that this module's genes were mostly involved in some biological activities including G protein-coupled receptors signaling pathway, lymphocyte chemotaxis, chemokine activity, neutrophil migration, granulocyte chemotaxis, etc. The co-expression network was constructed using top hub genes of the correlated module which are named as CXCL10, ARL9, AKR1B10, COX7B, RPL26, SPA17, NDUFAF2, RPF2, DAPL1, RPL34, CWC15, NDUFB3, RPL26L1, ACOT13, HSPB11, and NSA2. MicroRNAs prediction tool (miRWalk) revealed top miRNAs correlated with the interested module. Finally, a drug-target network was constructed which indicated interactions of some food and drug administration (FDA) approved drugs with hub genes. Our findings specified one important module and main hub genes which can be considered as novel biomarkers for vitiligo therapeutic purposes. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/2686