Centre for Bioinformatics Research, Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, UKM Bangi 43600, Selangor, Malaysia.
Centre for Frontier Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, UKM Bangi 43600, Selangor, Malaysia.
Int J Mol Sci. 2019 Jun 18;20(12):2959. doi: 10.3390/ijms20122959.
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.
基于临床观察,多囊卵巢综合征(PCOS)患者易患多种其他疾病,如代谢和心血管疾病。然而,PCOS 与这些疾病之间的分子关联仍知之甚少。最近的研究表明,蛋白质-蛋白质相互作用(PPI)网络分析的信息有助于详细了解疾病的关联。本研究利用这种方法加深了对 PCOS 与其他疾病之间关联的认识。使用从 PCOSBase 获得的与 PCOS 相关的蛋白质(PCOSrp)构建了用于 PCOS 的 PPI 网络。使用 MCODE 识别 PCOS 网络中的高度连接区域,称为子网。这些子网代表蛋白质家族,其分子信息用于解释 PCOS 与其他疾病之间的关联。使用 Fisher 精确检验和共病数据识别 PCOS-疾病子网。对 PCOS-疾病子网进行通路富集分析,以确定与 PCOS-疾病关联高度相关的显著通路。偏头痛、精神分裂症、抑郁障碍、肥胖症和高血压以及其他十二种疾病被确定与 PCOS 高度相关。核糖体生物发生、抗原加工和呈递以及线粒体自噬等重要通路的鉴定表明它们参与了 PCOS 与偏头痛、精神分裂症和高血压之间的关联。