System biology approach to delineate expressional difference in the blood mononuclear cells between healthy and Turner syndrome individuals

Turner syndrome (TS) is a rare disorder associated either with complete or partial loss of one X chromosome in women. The information on the genotype–phenotype relationship in TS is inadequate. Comparing the healthy and Turner syndrome patients may help elucidate the mechanisms involved in TS pathophysiology. Gene expression differences between healthy and individuals with Turner syndrome were characterized using the systems-biology approach of weighted gene coexpression network analysis (WGCNA) on 182 microarray peripheral mononuclear blood samples (PBMC).

The coexpression networks of healthy and TS had scale-free topology that ensures network robustness. In the process, five modules were preserved between healthy and TS, which carry several genes common in each module. Two of them, SMCHD1 and PGK1, have already been reported to be involved in TS. Previously reported genes of TS, specifically, PTPN22, RPS4X, CSF2RA, and TIMP1, were missing in their respective modules. Dysfunction, differential expression, or absence of these genes could lead to a progressive disruption of molecular pathways leading to the pathophysiology of TS. Indeed, we observed a significant difference in the functions of these modules when compared within and across the healthy and TS samples. We identified four clusters in the PPI network constructed from the top 15 KME enriched in significant functions.

Overall, our work highlights the potential molecular functions, pathways, and molecular targets of TS that can be exploited therapeutically in the human healthcare system.