Consensus strategy in genes prioritization and combined bioinformatics analysis for preeclampsia pathogenesis

Abstract

BackgroundPreeclampsia is a multifactorial disease with unknown pathogenesis. Even when recent studies explored this disease using several bioinformatics tools, the main objective was not directed to pathogenesis. Additionally, consensus prioritization was proved to be highly efficient in the recognition of genes-disease association. However, not information is available about the consensus ability to early recognize genes directly involved in pathogenesis. Therefore our aim in this study is to apply several theoretical approaches to explore preeclampsia; specifically those genes directly involved in the pathogenesis.MethodsWe firstly evaluated the consensus between 12 prioritization strategies to early recognize pathogenic genes related to preeclampsia. A communality analysis in the protein-protein interaction network of previously selected genes was done including further enrichment analysis. The enrichment analysis includes metabolic pathways as well as gene ontology. Microarray data was also collected and used in order to confirm our results or as a strategy to weight the previously enriched pathways.ResultsThe consensus prioritized gene list was rationally filtered to 476 genes using several criteria. The communality analysis showed an enrichment of communities connected with VEGF-signaling pathway. This pathway is also enriched considering the microarray data. Our result point to VEGF, FLT1 and KDR as relevant pathogenic genes, as well as those connected with NO metabolism.ConclusionOur results revealed that consensus strategy improve the detection and initial enrichment of pathogenic genes, at least in preeclampsia condition. Moreover the combination of the first percent of the prioritized genes with protein-protein interaction network followed by communality analysis reduces the gene space. This approach actually identifies well known genes related with pathogenesis. However, genes like HSP90, PAK2, CD247 and others included in the first 1% of the prioritized list need to be further explored in preeclampsia pathogenesis through experimental approaches.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-017-0286-x) contains supplementary material, which is available to authorized users.

Distinct molecular processes in placentae involved in two major subtypes of preeclampsia

“…To increase the sample sizes, several meta-analyses on reported microarray datasets were published since 2012. [58][59][60][61][62][63] In 2015, Kaartokallio et al reported the first RNA-seq study on PE. 46 To obtain a consensus PE-associated genes, we collected 1,177 genes from literature, including 6 meta-analysis papers, 58-63 1 literaturecuration paper 64 and 1 RNA-seq research paper.…”

Immune‑related pathophysiological causes relevant to a subset of patients with preeclampsia (Review)

“…Second, Gene Ontology enrichment analysis and functional ingenuity pathway analysis have been used to identify potential signaling pathways, suggesting that various physiological processes, such as chronic inflammation characterized by local or systemic oxidative stress (12,16) and innate and adaptive immune system (13,14), angiogenesis, hypoxia, apoptosis and placental development are implicated in the pathophysiology of preeclampsia (15). The following biological processes are also enriched in preeclampsia: Metabolism, cell cycle regulation, implantation, decidualization, cell-cell adhesion, the response to cAMP, the transforming growth factor (TGF)-β signaling pathway, Wnt signaling pathway and the Hippo signaling pathway (35,(42)(43)(44)(45). The abnormal spiral artery remodeling leads to a state of relative ischemia and to an increase in oxidative stress.…”

Study of Preeclampsia in Placenta, Kidney, and Hepatic Diseases

“…The effects of adiponectin on the cardiovascular system in hypertensive patients are believed to be partially mediated by activation of 5' active adenosine monophosphate protein kinase and pathway cyclooxygenase-2, reduces endothelial cell apoptosis, promotes the production of nitric oxide, decreased activity in tumor necrosis factoralpha (TNF-α), and prevented atherosclerotic proliferation and smooth muscle cell migration [49]. In addition, there is a consensus strategy to improve early detection and enrichment of pathogenic genes in PE such as HSP90, PAK2, CD247, and others, included in the first 1% of the prioritized list, so it needs to be explored further on the pathogenesis of PE through an experimental approach [50]. Activation of endothelial antibodies is also a marker of cardiovascular system dysfunction and endothelial dysfunction as well as severe pathology, with multiple organ failure manifestations, which is evidence of the relevance of this area of research to a large number of patients [51].…”