Identifying dysregulated pathways in postmenopausal osteoporosis through investigation of crosstalk between pathways

Abstract

The present study aimed to identify potential dysregulated pathways to further reveal the molecular mechanisms of postmenopausal osteoporosis (PMOP) based on pathway-interaction network (PIN) analysis, which considers crosstalk between pathways. Protein-protein interaction (PPI) data and pathway information were derived from STRING and Reactome Pathway databases, respectively. According to the gene expression profiles, pathway data and PPI information, a PIN was constructed with each node representing a biological pathway. Principal component analysis was used to compute the pathway activity for each pathway, and the seed pathway was selected. Subsequently, dysregulated pathways were extracted from the PIN based on the seed pathway and the increased classification accuracy, which was measured using the area under the curve (AUC) index according to 5-fold cross validation. A PIN comprising 2,725 interactions was constructed, which was used to detect dysregulated pathways. Notably, the 'mitotic prometaphase' pathway was selected and defined as a seed pathway. Starting with the seed pathway, network-based analysis successfully identified one pathway set for PMOP comprising eight dysregulated pathways (such as mitotic prometaphase, resolution of sister chromatid cohesion, mRNA splicing and mRNA splicing-major) with an AUC score of 0.85, which may provide potential biomarkers for targeted therapy for PMOP.