Identification of Transcriptional Modules and Key Genes in Chickens Infected with Salmonella enterica Serovar Pullorum Using Integrated Coexpression Analyses

Abstract

Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA) and differential coexpression analysis (DCEA) to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S. enterica infection. A total of 19 modules from 13,538 genes were associated with the Jak-STAT signaling pathway, the extracellular matrix, cytoskeleton organization, the regulation of the actin cytoskeleton, G-protein coupled receptor activity, Toll-like receptor signaling pathways, and immune system processes; among them, 14 differentially coexpressed modules (DCMs) and 2,856 differentially coexpressed genes (DCGs) were identified. The global expression of module genes between infected and uninfected chickens showed slight differences but considerable changes for global coexpression. Furthermore, DCGs were consistently linked to the hubs of the modules. These results will help prioritize candidate genes for future studies of Salmonella infection.

Figure 1

Workflow of the comprehensive gene coexpression network analysis.

Figure 2

Module expression patterns.

Figure 3

Correlation of intramodule connectivity for each module after 100 samplings.

Figure 4

(a) Violin plot showing the gene expression differences between modules in the infected and control groups. (b) Violin plot showing the gene coexpression connectivity differences between modules in the infected and control groups.   .i represents the module in the infected group, and  .c represents the module in the control group.

Figure 5

Violin plot of gene coexpression connectivity for significantly differentially coexpressed modules.

Figure 6

(a) Hub genes' network in the infected group. The node colors represent the module colors: the nodes with shape of rectangle are DCGs and the elliptical nodes are non-DCGs. (b) Hub genes' network in the control group. The node colors represent the module colors: the nodes with shape of rectangle are DCGs and the elliptical nodes are non-DCGs.