Protein–Protein Interaction Network Analysis Reveals Several Diseases Highly Associated with Polycystic Ovarian Syndrome

Abstract

Based on clinical observations, women with polycystic ovarian syndrome (PCOS) are prone to developing several other diseases, such as metabolic and cardiovascular diseases. However, the molecular association between PCOS and these diseases remains poorly understood. Recent studies showed that the information from protein–protein interaction (PPI) network analysis are useful in understanding the disease association in detail. This study utilized this approach to deepen the knowledge on the association between PCOS and other diseases. A PPI network for PCOS was constructed using PCOS-related proteins (PCOSrp) obtained from PCOSBase. MCODE was used to identify highly connected regions in the PCOS network, known as subnetworks. These subnetworks represent protein families, where their molecular information is used to explain the association between PCOS and other diseases. Fisher’s exact test and comorbidity data were used to identify PCOS–disease subnetworks. Pathway enrichment analysis was performed on the PCOS–disease subnetworks to identify significant pathways that are highly involved in the PCOS–disease associations. Migraine, schizophrenia, depressive disorder, obesity, and hypertension, along with twelve other diseases, were identified to be highly associated with PCOS. The identification of significant pathways, such as ribosome biogenesis, antigen processing and presentation, and mitophagy, suggest their involvement in the association between PCOS and migraine, schizophrenia, and hypertension.

Network and Evolutionary Analysis of Human Epigenetic Regulators to Unravel Disease Associations

“…The functional pathways and the affected molecular mechanisms of their action are far from being fully elaborated. In the present study, we implemented a system-level approach to link ERs to gene-disease information and the PPI network [50], and generated a subnetwork that provides unique insights into the mechanisms underlying the function of ER gene members [51]. Based on the curated gene-disease information of the DisGeNET database, we first constructed a disease network enriched with compiled ER genes.…”

Oncology and Pharmacogenomics Insights in Polycystic Ovary Syndrome: An Integrative Analysis

“…This study identified that pathways in cancer (MAPK signaling pathways) and cellular functions (cell cycle and apoptosis) were enriched terms in the three diseases and might collectively contribute to their clinical course. Another research using PCOS related proteins noted that OC, endometriosis, and other 15 diseases significantly shared proteins and pathways ( 44 ). In a survival analysis, after examining PCOS differentially expressed genes (DEG) in patients with ovarian serous cystadenocarcinoma, a correlation with disease-free survival and overall survival was found.…”

Computational Systems Analysis on Polycystic Ovarian Syndrome (PCOS)

“…In the constructed network, Liu et al [134] identified 50 genes that might be key genes that involved in PCOS treatment with EXD since these genes are the EXD targets that are found to be related to PCOS [134]. Ramly et al [135] also used PPI and pathway analysis to identify protein and pathways to explain the relationships between PCOS and 17 diseases such as migraine, ovarian cancer, and schizophrenia. They used a clustering approach by MCODE [66] to identify shared proteins between PCOS and other diseases and pathway enrichment analysis to identify pathways that might connect PCOS and PCOS-associated diseases [135].…”

“…Ramly et al [135] also used PPI and pathway analysis to identify protein and pathways to explain the relationships between PCOS and 17 diseases such as migraine, ovarian cancer, and schizophrenia. They used a clustering approach by MCODE [66] to identify shared proteins between PCOS and other diseases and pathway enrichment analysis to identify pathways that might connect PCOS and PCOS-associated diseases [135].…”