Integrative computational approach to evaluate risk genes for postmenopausal osteoporosis

In recent years, numerous studies reported over a hundred of genes playing roles in the etiology of postmenopausal osteoporosis (PO). However, many of these candidate genes were lack of replication and results were not always consistent. Here, the authors proposed a computational workflow to curate and evaluate PO related genes. They integrate large-scale literature knowledge data and gene expression data (PO case/control: 10/10) for the marker evaluation. Pathway enrichment, sub-network enrichment, and gene-gene interaction analysis were conducted to study the pathogenic profile of the candidate genes, with four metrics proposed and validated for each gene. By using the authors' approach, a scalable PO genetic database was developed; including PO related genes, diseases, pathways, and the supporting references. The PO case/control classification supported the effectiveness of the four proposed metrics, which successfully identified eight well-studied top PO genes (e.g. TGFB1, IL6, IL1B, TNF, ESR2, IGF1, HIF1A, and COL1A1) and highlighted one recently reported PO genes (e.g. IFNG). The computational biology approach and the PO database developed in this study provide a valuable resource which may facilitate understanding the genetic profile of PO.