Discovering preservation pattern from co-expression modules in progression of HIV-1 disease: An eigengene based approach

Abstract

In recent years, microarray based gene expression analysis has emerged as a well established way to discover stage specific changes in expression pattern of a specific disease progression. In this paper we have developed a framework to analyze microarray data of three different HIV-1 infection stages and identified modules among coexpressed genes. The modules initially provided a description of coexpression patterns and an inter-relation between the infection stages. We have observed that, coexpressed modules in each HIV-1 infection stage do not exist in isolation, instead they form a network in which higher order structure reflects the relationship among them. To illustrate the relationship we have compiled module eigengene (ME) network among the modules which describes relationship between modules. We further explored the relationship between gene coexpression modules by comparing the ME networks between each pair of stages. For this, an existing preservation measure is utilized here to elucidate the expression similarity between modules across different stages of infection. Additionally, one novel preservation measure is proposed to detect the preservation pattern in modular organization of coexpressed networks. We have found that the modular organization of coexpression network remain more preserved during the transition of infection from acute to long term nonprogressor stage than to the latent chronic stage. However, the average preservation scores is little bit higher for acute and chronic stage (mean preservation score=0.7737) than for acute and nonprogressor stage (mean preservation score= 0.7307). We have also identified a higher order meta-networks by grouping coexpressed modules which exhibit similar ME expression patterns. Our findings provide a new direction for understanding the modular organization and preservation patterns of microarray expression data across different stages of HIV infection.