Unveiling transcription factor regulation and differential co-expression genes in Duchenne muscular dystrophy
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RESEARCH
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Unveiling transcription factor regulation and differential co-expression genes in Duchenne muscular dystrophy Lijun Tian*, Junhua Cao, Xingqiang Deng, Chuanling Zhang, Tong Qian, Xianxiang Song and Baoshan Huang
Abstract Background: Gene expression analysis is powerful for investigating the underlying mechanisms of Duchenne muscular dystrophy (DMD). Previous studies mainly neglected co-expression or transcription factor (TF) information. Here we integrated TF information into differential co-expression analysis (DCEA) to explore new understandings of DMD pathogenesis. Methods: Using two microarray datasets from Gene Expression Omnibus (GEO) database, we firstly detected differentially expressed genes (DEGs) and pathways enriched with DEGs. Secondly, we constructed differentially regulated networks to integrate the TF-to-target information and the differential co-expression genes. Results: A total of 454 DEGs were detected and both KEGG pathway and ingenuity pathway analysis revealed that pathways enriched with aberrantly regulated genes are mostly involved in the immune response processes. DCEA results generated 610 pairs of DEGs regulated by at least one common TF, including 78 pairs of co-expressed DEGs. A network was constructed to illustrate their relationships and a subnetwork for DMD related molecules was constructed to show genes and TFs that may play important roles in the secondary changes of DMD. Among the DEGs which shared TFs with DMD, six genes were co-expressed with DMD, including ATP1A2, C1QB, MYOF, SAT1, TRIP10, and IFI6. Conclusion: Our results may provide a new understanding of DMD and contribute potential targets for future therapeutic tests. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/ 13000_2014_210 Keywords: Duchenne muscular dystrophy, Differential co-expression analysis, Transcription factor
Background Duchenne muscular dystrophy (DMD) is a severe and progressive inherited neuromuscular disease characterized by muscle fiber degeneration and central nervous system disorders that affects 1 in 3600–6000 live male births [1]. This disease is caused by mutations or dysregulation of the X-linked dystrophin gene. Absence of or defects of dystrophin protein result in disruption of the dystrophin-associated protein complex (DAPC), resulting in chronic inflammation and progressive muscle degeneration [2].
Although mutations of the DMD protein have been identified to be primarily responsible for the pathology, comprehensive understanding of the downstream mechanisms due to dystrophin absence is still lacking. Secondary changes in DMD involve calcium homeostasis [3], nitric oxide synthase [4], inflammation [5] and mast cell degranulation [6], suggesting that the pathological process of DMD is highly complicated. Gene expression profile analysis is a powerful strategy to investigate the pathophysiological mechanisms of DMD. Several gene expression profiling studies [7-11] have been performed earlier, prov
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