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Info. Vol.9 - No.2 (2015.06.20)
Title Estimation of Dysregulated Pathway Regions in MPP+Treated Human Neuroblastoma SH-EP Cells with Structural Equation Model
Authors Daniele Pepe1 & Jin Hwan Do2,*
Institutions 1Department of Brain and Behavioural Sciences, Medical and Genomic Statistics Unit, University of Pavia, Pavia, Italy 2Department of Biomolecular and Chemical Engineering, DongYang University, Yeongju 750-711, Korea
Abstract As it is widely accepted that the cellular system is modular and complex diseases are caused by combinations of genetic alternations affecting component of the cellular system, module-centric approaches are promising in the study of Parkinson?셲 disease (PD). To identify module/pathways associated with PD, the gene signaling pathway analysis of 1-methyl-4-phenylpyridinium (MPP+) treated cells of the PD model was performed with their genome-wide gene expression data. Significant pathway perturbation was observed at 14 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. To capture differentially regulated regions by MPP+ treatment within these 14 perturbed pathways, the shortest path models linking differentially expressed genes (DEGs) were constructed for each pathway. Each shortest path model was analyzed with structural equation model (SEM) and the significant regulation structure by MPP+ treatment was observed in three shortest pathway models including cell cycle, neurotrophin and phosphatidylinositol signaling pathways. In addition, the connection of neurotrophin and phosphatidylinositol signaling pathway via CALM1 was observed. Our results suggest that the dys-regulation of these three pathways might play important role in neuronal cell death by MPP+ treatment.
Keyword Parkinson disease, Pathway perturbation, MPP+, Shortest path model, Structural equation model
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