Hubs in biological interaction networks exhibit low changes in expression in experimental asthma - PubMed (original) (raw)

Hubs in biological interaction networks exhibit low changes in expression in experimental asthma

Xin Lu et al. Mol Syst Biol. 2007.

Abstract

Asthma is a complex polygenic disease involving the interaction of many genes. In this study, we investigated the allergic response in experimental asthma. First, we constructed a biological interaction network using the BOND (Biomolecular Object Network Databank) database of literature curated molecular interactions. Second, we mapped differentially expressed genes from microarray data onto the network. Third, we analyzed the topological characteristics of the modulated genes. Fourth, we analyzed the correlation between the topology and biological function using the Gene Ontology classifications. Our results demonstrate that nodes with high connectivity (hubs and superhubs) tend to have low levels of change in gene expression. The significance of our observations was confirmed by permutation testing. Furthermore, our analysis indicates that hubs and superhubs have significantly different biological functions compared with peripheral nodes based on Gene Ontology classification. Our observations have important ramifications for interpreting gene expression data and understanding biological responses. Thus, our analysis suggests that a combination of differential gene expression plus topological characteristics of the interaction network provides enhanced understanding of the biology in our model of experimental asthma.

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Figures

Figure 1

Figure 1

Mouse gene network from BIND. Red and blue spots represent genes that were significantly up- or downregulated.

Figure 2

Figure 2

Scatter plot of _t_-statistics versus connectivity for genes modulated in OVA-specific allergic immune response. (A) Wild-type mice. (B) RAG KO mice. _X_-axis is the log 2 of connectivity (no. of genes directly connected) and _Y_-axis is the absolute of _t_-statistics. Red and blue spots represent genes upregulated or downregulated, respectively, in response to OVA sensitization and challenge with individual _P_-values below 0.05. Empty circles correspond to non-differentially expressed genes.

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