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Research and Reviews : Journal of Computational Biology Original Research

Integrative Network Biology Analysis of GSE6011 Uncovers Molecular Signatures in Duchenne Muscular Dystrophy

  1. Shashikala Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Sec-62
  2. Vibha Rani Department of Biotechnology, Jaypee Institute of Information Technology, Noida, Sec-62
  3. Shazia Haider Department of Biosciences, Faculty of Life Sciences, Jamia Millia Islamia

Abstract

Duchenne muscular dystrophy (DMD) is a rare, severe neuromuscular disorder demonstrated by progressive skeletal muscle deterioration and premature mortality. Despite advances in supportive care, no definitive cure exists, highlighting the need to explore novel molecular targets. The current study aimed to uncover key dysregulated genes and molecular pathways in DMD through a dataset-specific network biology approach. Publicly available microarray data (GSE6011) from DMD quadriceps muscle biopsies of 22 patients and 14 age-matched healthy controls were analyzed using GEO2R to identify differentially expressed genes (DEGs) using an adjusted p-value 0.5. The Protein–protein interaction (PPI) network was constructed via STRING and analyzed in Cytoscape, with hub genes identified using the Maximal Clique Centrality method in cytoHubba. Functional and pathway enrichment analyses were explored using Enrichr. A total of 159 DEGs were identified, including 19 genes that were found to be overregulated and 140 were downregulated. The PPI network revealed highly connected hub genes. Downregulated hubs included COL1A1, COL3A1, COL1A2, POSTN, LUM, COL6A3, SPARC, FBN1, COL5A2, and COL5A1, enriched in extracellular matrix organization, collagen fibril assembly, and fibrosis-related pathways. Upregulated hubs LPIN1, LPL, and UCP3 were linked to fatty acid metabolism, mitochondrial function, and oxidative stress regulation. These expression patterns suggest late-stage ECM remodeling with a concurrent metabolic shift in dystrophic muscle. Furthermore, molecular docking was performed to evaluate the binding interactions of FDA-approved DMD drugs (Amondys 45, Emflaza, and Vyondys 53) with the upregulated hub protein LPL, revealing favorable binding affinities and potential therapeutic relevance. This network biology and docking analysis highlights ECM remodeling and metabolic regulators as key components of DMD pathology, offering potential biomarkers and therapeutic targets.

Keywords

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