Dataset Information

Crosstalk analysis of dysregulated pathways in preeclampsia.

ABSTRACT: A crosstalk between multiple biological pathways has been proposed in biological processes. However, the existence and degree of this phenomenon in patients with preeclampsia (PE) have not been strictly investigated. Thus, this study explored an dysregulated pathway set (DPS) for PE based on pathway crosstalk network (PCN) related analysis. In the present study, four steps were performed in the inference of DPS: acquiring data of gene expression, pathway and protein-protein interaction (PPI) construction; building a PCN through integrating the information in these datasets and Pearson's correlation coefficient (PCC). A principal component analysis (PCA) approach was used to compute the activity of every pathway for selecting seed pathway of PCN. DPS was evaluated by measuring of an area under the receiver operating characteristics curve (AUC) and seed pathway from PCN. Consequently, a total of 420 pathways and 6,032 crosstalks were mapped to the PCN, in which RIG-I/MDA5-mediated induction of IFN-?/? pathways was identified as the seed pathway that had the greatest changes in activity scores across PE patients and normal controls. DPS was composed of 15 dysregulated pathways and 46 crosstalks, in which CLEC7A (Dectin-1) signaling possessed the highest degree of 12, which indicated it exerted an important role in the DPS. Our results revealed crosstalk between pathways and the DPS crucial for PE pathogenesis, which aid in excavating potential biomarkers of PE therapy and unveil the underlying pathological mechanism of this disease.

SUBMITTER: Wang T

PROVIDER: S-EPMC6395964 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Crosstalk analysis of dysregulated pathways in preeclampsia.

Wang Tao T Shi Xing-Zhen XZ Wu Wen-Hua WH

Experimental and therapeutic medicine 20190116 3

A crosstalk between multiple biological pathways has been proposed in biological processes. However, the existence and degree of this phenomenon in patients with preeclampsia (PE) have not been strictly investigated. Thus, this study explored an dysregulated pathway set (DPS) for PE based on pathway crosstalk network (PCN) related analysis. In the present study, four steps were performed in the inference of DPS: acquiring data of gene expression, pathway and protein-protein interaction (PPI) con ...[more]

PMID: 30867714

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Project description:BackgroundThe extensive spread of coronavirus disease 2019 (COVID-19) has led to a rapid increase in global mortality. Preeclampsia is a commonly observed pregnancy ailment characterized by high maternal morbidity and mortality rates, in addition to the restriction of fetal growth within the uterine environment. Pregnant individuals afflicted with vascular disorders, including preeclampsia, exhibit an increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection via mechanisms that have not been fully delineated. Additionally, the intricate molecular mechanisms underlying preeclampsia and COVID-19 have not been fully elucidated. This study aimed to discern commonalities in gene expression, regulators, and pathways shared between COVID-19 and preeclampsia. The objective was to uncover potential insights that could contribute to novel treatment strategies for both COVID-19 and preeclampsia.MethodTranscriptomic datasets for COVID-19 peripheral blood (GSE152418) and preeclampsia blood (GSE48424) were initially sourced from the Gene Expression Omnibus (GEO) database. Subsequent to that, we conducted a subanalysis by selecting females from the GSE152418 dataset and employed the "Deseq2" package to identify genes that exhibited differential expression. Simultaneously, the "limma" package was applied to identify differentially expressed genes (DEGs) in the preeclampsia dataset (GSE48424). Following that, an intersection analysis was conducted to identify the common DEGs obtained from both the COVID-19 and preeclampsia datasets. The identified shared DEGs were subsequently utilized for functional enrichment analysis, transcription factor (TF) and microRNAs (miRNA) prediction, pathway analysis, and identification of potential candidate drugs. Finally, to validate the bioinformatics findings, we collected peripheral blood mononuclear cell (PBMC) samples from healthy individuals, COVID-19 patients, and Preeclampsia patients. The abundance of the top 10 Hub genes in both diseases was assessed using real-time quantitative polymerase chain reaction (RT-qPCR).ResultA total of 355 overlapping DEGs were identified in both preeclampsia and COVID-19 datasets. Subsequent ontological analysis, encompassing Gene Ontology (GO) functional assessment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, revealed a significant association between the two conditions. Protein-protein interactions (PPIs) were constructed using the STRING database. Additionally, the top 10 hub genes (MRPL11, MRPS12, UQCRH, ATP5I, UQCRQ, ATP5D, COX6B1, ATP5O, ATP5H, NDUFA6) were selected based on their ranking scores using the degree algorithm, which considered the shared DEGs. Moreover, transcription factor-gene interactions, protein-drug interactions, co-regulatory networks of DEGs and miRNAs, and protein-drug interactions involving the shared DEGs were also identified in the datasets. Finally, RT-PCR results confirmed that 10 hub genes do exhibit distinct expression profiles in the two diseases.ConclusionThis study successfully identified overlapping DEGs, functional pathways, and regulatory elements between COVID-19 and preeclampsia. The findings provide valuable insights into the shared molecular mechanisms and potential therapeutic targets for both diseases. The validation through RT-qPCR further supports the distinct expression profiles of the identified hub genes in COVID-19 and preeclampsia, emphasizing their potential roles as biomarkers or therapeutic targets in these conditions.

Project description:In normal human placentation, uterine invasion by trophoblast cells and subsequent spiral artery remodeling depend on cooperation among fetal trophoblasts and maternal decidual, myometrial, immune and vascular cells in the uterine wall. Therefore, aberrant function of anyone or several of these cell-types could theoretically impair placentation leading to the development of preeclampsia. Because trophoblast invasion and spiral artery remodeling occur during the first half of pregnancy, the molecular pathology of fetal placental and maternal decidual tissues following delivery may not be informative about the genesis of impaired placentation, which transpired months earlier. Therefore, in this review, we focus on the emerging prospective evidence supporting the concept that deficient or defective endometrial maturation in the late secretory phase and during early pregnancy, i.e., pre-decidualization and decidualization, respectively, may contribute to the genesis of preeclampsia. The first prospectively-acquired data directly supporting this concept were unexpectedly revealed in transcriptomic analyses of chorionic villous samples (CVS) obtained during the first trimester of women who developed preeclampsia 5 months later. Additional supportive evidence arose from investigations of Natural Killer cells in first trimester decidua from elective terminations of women with high resistance uterine artery indices, a surrogate for deficient trophoblast invasion. Last, circulating insulin growth factor binding protein-1, which is secreted by decidual stromal cells was decreased during early pregnancy in women who developed preeclampsia. We conclude this review by making recommendations for further prospectively-designed studies to corroborate the concept of endometrial antecedents of preeclampsia. These studies could also enable identification of women at increased risk for developing preeclampsia, unveil the molecular mechanisms of deficient or defective (pre)decidualization, and lead to preventative strategies designed to improve (pre)decidualization, thereby reducing risk for preeclampsia development.

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Crosstalk analysis of dysregulated pathways in preeclampsia.

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Crosstalk analysis of dysregulated pathways in preeclampsia.

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