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

Document Type : Research Paper


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



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.


[1] Marianne Lisby, Lars Peter Nielsen, and Jan Mainz, Errors in the medication process: frequency, type, and potential clinical consequences. Int. J. Qual. Health Care (2005) 17 (1): 15-22.
[2] About Medication Errors, What is a Medication Error? 2016; (Accessed December 2016).
[3] Xavier Bohand, Laurent Simon, Eric Perrier, Hélène Mullot, Leslie Lefeuvre, and Christian Plotton, Frequency, types, and potential clinical significance of medication-dispensing errors. Clinics (2009) 64 (1): 11-16.
[4] Tehran Population 2016. 2016; (Accessed June 2017).
[5] IRAN: Tehran. 2011; (Accessed January 2017).
[6] John Annett, Hierarchical task analysis. Handbook of cognitive task design (2003) 2: 17-35.
[7] F Hajibabaee, S Joolaee, H Peyravi, and H Haghani, The relationship of medication errors among nurses with some organizational and demographic characteristics. Iran. J. Nurs. Res. (2011) 6: 83-92.
[8] MS Yousefi, Z Abed Saeedi, M Maleki, and P Sarbakhsh, Frequency and causes of medication errors of nurses in different shift works in educational hospitals affiliated to Shahid Beheshti University of Medical Sciences. Iran. J. Nurs Midwifery Res. (2014) 24 (86): 8454.
[9] Michelle A Chui and David A Mott, Community pharmacists' subjective workload and perceived task performance: a human factors approach. J. Am. Pharm. Assoc. (2012) 52 (6): e153.
[10] Fatemeh Dabaghzadeh, Arash Rashidian, Hassan Torkamandi, Sara Alahyari, Somayeh Hanafi, Shadi Farsaei, and Mohammadreza Javadi, Medication errors in an emergency department in a large teaching hospital in Tehran. Iran. J. Pharm. Res. (2013) 12 (4): 937-942.
[11] S Joolaee, F Hajibabaee, H Peyrovi, H Haghani, and N Bahrani, The relationship between incidence and report of medication errors and working conditions. Int. Nurs. Rev. (2011) 58 (1): 37-44.
[12] Reza Kazemi, Rashid Haidarimoghadam, Majid Motamedzadeh, Rostam Golmohammadi, Alireza Soltanian, and Mohammad Reza Zoghipaydar, Effects of Shift Work on Cognitive Performance, Sleep Quality, and Sleepiness among Petrochemical Control Room Operators. J. Circadian Rhythms (2016) 14 (1).
[13] Pamela B de Cordova, Michelle A Bradford, and Patricia W Stone, Increased errors and decreased performance at night: A systematic review of the evidence concerning shift work and quality. Work (2016) (Preprint): 1-9.
[14] Benjamin Bar-Oz, Michael Goldman, Eliezer Lahat, Revital Greenberg, Meytal Avgil, Ami Blay, Amir Herman, et al., Medication errors and response bias: the tip of the iceberg. Isr. Med. Assoc. J. (2008) 10 (11): 771.
[15] Ava Mansouri, Alireza Ahmadvand, Molouk Hadjibabaie, Mona Kargar, Mohammadreza Javadi, and Kheirollah Gholami, Types and severity of medication errors in Iran; a review of the current literature. DARU J. Pharma. Sci. (2013) 21 (1): 49.
[16] Ahuva Lustig, Medication error prevention by pharmacists ‐ An Israeli solution. Pharm. World Sci. (2000) 22 (1): 21-25.
[17] S. Mahdikhani and F. Dabaghzadeh, Benefits of Pharmacist's Participation on Hospitalist Team. Acta Med. Iran (2016) 54 (2): 140-5.
[18] NA Qureshi, Y Neyaz, T Khoja, MA Magzoub, A Haycox, and T Walley, Physicians' medication prescribing in primary care in Riyadh city, Saudi Arabia. Literature review, part 3: prescribing errors. East Mediterr Health J. (2011) 17 (2): 140.
[19] Zayed Alsulami, Sharon Conroy, and Imti Choonara, Medication errors in the Middle East countries: A systematic review of the literature. Eur. J. Clin. Pharmacol. (2013) 69 (4): 995-1008.
[20] S. Salmasi, T. M. Khan, Y. H. Hong, L. C. Ming, and T. W. Wong, Medication Errors in the Southeast Asian Countries: A Systematic Review. PLoS One (2015) 10 (9): e0136545.
[21] Giampaolo P. Velo and Pietro Minuz, Medication errors: prescribing faults and prescription errors. British J. Clinic. Pharmacol. (2009) 67 (6): 624-628.
[22] Linda J Dodds, Pharmacist contributions to ensuring safe and accurate transfer of written medicines-related discharge information: lessons from a collaborative audit and service evaluation involving 45 hospitals in England. EUR. J .HOSP. PHARM-S P Journal (2014) 21 (3): 150-155.
[23] RS Poudel, RM Piryani, S Shrestha, A Prajapati, and B Adhikari, Prescription errors and pharmacist intervention at outpatient pharmacy of Chitwan Medical College. J. Chitwan Med. College (2015) 5 (2): 20-24.