Shan Yu1, Huani Yi1, Zhimin Wang1, Juan Dong1. 1. Department of Obstetrics, Jinan Maternity and Child Care Hospital Jinan 250001, Shandong Province, P.R. China.
Abstract
BACKGROUND: Down syndrome (DS) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Forty to fifty percent of newborns with DS have some form of congenital heart defects (CHD). The genome of CHD in DS has already been obtained, but the underlying genomic or gene expression variation that contributes to the manifestation of a CHD in DS is still unknown. OBJECTIVE: This study was aimed to analyze key genes of patients with CHD in DS. METHODS: Differential expression network (DEN) approach was employed to analyze the dyeregulated genes and pathways in this study. First, the differentially expressed genes (DEGs) between CHD in DS and normal subjects were screened based on the microarray expression data. Next, the differential interactions were identified using spearman correlation coefficients of edges in different conditions. The DEN was then constructed combining both DEGs and differential interactions, and HUB genes were gained by degree centrality analysis of DEN. Meanwhile, disease genes included in the DEN were also ascertained. RESULTS: When analyzing gene expression values in different conditions, no DEGs were identified. While, a total of 984 gene pairs with significant differential expression were identified. Finally, the DEN was constructed only using differential edges in our study. In this network, eight HUB genes were identified, and thereinto four genes (UBC, APP, HUWE1 and SRC) were both HUB genes and disease genes. CONCLUSIONS: DEN approach should be taken as a useful complement to traditional differential genes methods. We provide several potential underlying biomarkers for CHD in DS.
BACKGROUND: Down syndrome (DS) is the most common viable chromosomal disorder with intellectual impairment and several other developmental abnormalities. Forty to fifty percent of newborns with DS have some form of congenital heart defects (CHD). The genome of CHD in DS has already been obtained, but the underlying genomic or gene expression variation that contributes to the manifestation of a CHD in DS is still unknown. OBJECTIVE: This study was aimed to analyze key genes of patients with CHD in DS. METHODS: Differential expression network (DEN) approach was employed to analyze the dyeregulated genes and pathways in this study. First, the differentially expressed genes (DEGs) between CHD in DS and normal subjects were screened based on the microarray expression data. Next, the differential interactions were identified using spearman correlation coefficients of edges in different conditions. The DEN was then constructed combining both DEGs and differential interactions, and HUB genes were gained by degree centrality analysis of DEN. Meanwhile, disease genes included in the DEN were also ascertained. RESULTS: When analyzing gene expression values in different conditions, no DEGs were identified. While, a total of 984 gene pairs with significant differential expression were identified. Finally, the DEN was constructed only using differential edges in our study. In this network, eight HUB genes were identified, and thereinto four genes (UBC, APP, HUWE1 and SRC) were both HUB genes and disease genes. CONCLUSIONS:DEN approach should be taken as a useful complement to traditional differential genes methods. We provide several potential underlying biomarkers for CHD in DS.
Authors: Eva Albertsen Malt; Renate Charlotte Dahl; Trine Marie Haugsand; Ingebjørg H Ulvestad; Nina Merete Emilsen; Børre Hansen; Yon Eduin Galezo Cardenas; Rolf Olof Skøld; Anne Tove Berge Thorsen; Eva Merete Male Davidsen Journal: Tidsskr Nor Laegeforen Date: 2013-02-05
Authors: Manway Liu; Arthur Liberzon; Sek Won Kong; Weil R Lai; Peter J Park; Isaac S Kohane; Simon Kasif Journal: PLoS Genet Date: 2007-06 Impact factor: 5.917