Predicting central genes in protein-protein interaction network during mouse fibroblast to cardiomyocyte conversion

Postnatal heart fibroblasts convert to induced cardiomyocyte using combination of transcription factors. Expression pattern of genes change during direct reprogramming of mouse fibroblast to cardiomyocyte. We use system biology tools to find central genes in protein-protein interaction during direct conversion of mouse fibroblast into cardiomyocyte.Method: Data with GSE number 22292 were obtained from GEO database. RMA algorithm was used to raw data normalization. DEgenes were selected using fold change algorithm. DE genes functional clustering done using DAVID database. Interactionof DE genes with other proteins was determined using AgilentLiteratureSearch plugin and STRING database. Cytoscapewas used to construction of protein-protein interaction network. In order to detect central genes of network, degree parameter of CentiScaPe was applied to whole network. Result: We compare gene expression profile of week 2 cells versus week 4 ones and show 91 genes differentially expressedbetween these two groups of cells. Functional clustering analysis of DE genes using DAVID database shows several termssuch as signaling, glycoprotein and glycosylation as member of cluster with highest enrichment score. We construct proteinprotein interaction network of DE genes and the best network contains 45 nodes and 107 edges. In our study CCL2, PLAU, ACTN2, BGN, CCL9, SERPINE1, LOX, MYL1, CCL12 and CCL7 are the central genes during conversion of fibroblastinto cardiomyocyte based on degree parameter. Notably we find that 8 out of 10 of these genes contribute in signaling term,while ACTN2 and MYL1 is not. Conclusion: Identification of these central genes may lead to improve efficiency of this conversion

کلیدواژه ها:

Differential expressed genes ، direct reprogramming ، fibroblast ، cardiomyocyte