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Abstract: Large-scale parallel gene expression analysis has provided a greater ease for investigating the underlying mechanisms of Duchenne muscular dystrophy (DMD). Previous studies typically implemented variance/regression analysis, which would be fundamentally flawed when unaccounted sources of variability in the arrays existed. Here we aim to identify genes that contribute to the pathology of DMD using partial least squares (PLS) based analysis. We carried out PLS-based analysis with two datasets downloaded from the Gene Expression Omnibus (GEO) database to identify genes contributing to the pathology of DMD. Except for the genes related to inflammation, muscle regeneration and extracellular matrix (ECM) modeling, we found some genes with high fold change, which have not been identified by previous studies, such as SRPX, GPNMB, SAT1, and LYZ. In addition, downregulation of the fatty acid metabolism pathway was found, which may be related to the progressive muscle wasting process. Our results provide a better understanding for the downstream mechanisms of DMD.

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