Crosstalk analysis of dysregulated pathways in preeclampsia

A crosstalk between multiple biological pathways has been proposed in biological processes. However, the existence and degree of this phenomenon in patients with preeclampsia (PE) have not been strictly investigated. Thus, this study explored an dysregulated pathway set (DPS) for PE based on pathway crosstalk network (PCN) related analysis. In the present study, four steps were performed in the inference of DPS: acquiring data of gene expression, pathway and protein-protein interaction (PPI) construction; building a PCN through integrating the information in these datasets and Pearson's correlation coefficient (PCC). A principal component analysis (PCA) approach was used to compute the activity of every pathway for selecting seed pathway of PCN. DPS was evaluated by measuring of an area under the receiver operating characteristics curve (AUC) and seed pathway from PCN. Consequently, a total of 420 pathways and 6,032 crosstalks were mapped to the PCN, in which RIG-I/MDA5-mediated induction of IFN-α/β pathways was identified as the seed pathway that had the greatest changes in activity scores across PE patients and normal controls. DPS was composed of 15 dysregulated pathways and 46 crosstalks, in which CLEC7A (Dectin-1) signaling possessed the highest degree of 12, which indicated it exerted an important role in the DPS. Our results revealed crosstalk between pathways and the DPS crucial for PE pathogenesis, which aid in excavating potential biomarkers of PE therapy and unveil the underlying pathological mechanism of this disease.