Tejera Eduardo, Bernardes João, Rebelo Irene
Department of Biological Sciences, Biochemistry, University of Porto, Portugal/Institute for Molecular and Cell Biology (IBMC), Porto, Portugal.
BMC Syst Biol. 2012 Aug 8;6:97. doi: 10.1186/1752-0509-6-97.
In this study we explored preeclampsia through a bioinformatics approach. We create a comprehensive genes/proteins dataset by the analysis of both public proteomic data and text mining of public scientific literature. From this dataset the associated protein-protein interaction network has been obtained. Several indexes of centrality have been explored for hubs detection as well as the enrichment statistical analysis of metabolic pathway and disease.
We confirmed the well known relationship between preeclampsia and cardiovascular diseases but also identified statistically significant relationships with respect to cancer and aging. Moreover, significant metabolic pathways such as apoptosis, cancer and cytokine-cytokine receptor interaction have also been identified by enrichment analysis. We obtained FLT1, VEGFA, FN1, F2 and PGF genes with the highest scores by hubs analysis; however, we also found other genes as PDIA3, LYN, SH2B2 and NDRG1 with high scores.
The applied methodology not only led to the identification of well known genes related to preeclampsia but also to propose new candidates poorly explored or completely unknown in the pathogenesis of preeclampsia, which eventually need to be validated experimentally. Moreover, new possible connections were detected between preeclampsia and other diseases that could open new areas of research. More must be done in this area to resolve the identification of unknown interactions of proteins/genes and also for a better integration of metabolic pathways and diseases.
在本研究中，我们通过生物信息学方法探索了子痫前期。我们通过分析公共蛋白质组数据和对公共科学文献进行文本挖掘，创建了一个全面的基因/蛋白质数据集。从该数据集中获得了相关的蛋白质-蛋白质相互作用网络。我们探索了几种中心性指标以检测枢纽节点，并对代谢途径和疾病进行了富集统计分析。
我们证实了子痫前期与心血管疾病之间众所周知的关系，但也发现了与癌症和衰老相关的具有统计学意义的关系。此外，通过富集分析还确定了诸如凋亡、癌症和细胞因子-细胞因子受体相互作用等重要的代谢途径。通过枢纽节点分析，我们获得了得分最高的FLT1、VEGFA、FN1、F2和PGF基因；然而，我们也发现了其他得分较高的基因，如PDIA3、LYN、SH2B2和NDRG1。
所应用的方法不仅导致了与子痫前期相关的已知基因的鉴定，还提出了在子痫前期发病机制中探索较少或完全未知的新候选基因，最终需要通过实验进行验证。此外，还检测到子痫前期与其他疾病之间新的可能联系，这可能开辟新的研究领域。在这一领域还需要做更多的工作，以解决蛋白质/基因未知相互作用的鉴定问题，并更好地整合代谢途径和疾病。
