Unveiling molecular signatures of preeclampsia and gestational diabetes mellitus with multi-omics and innovative cheminformatics visualization tools.
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ABSTRACT:
SUBMITTER: Odenkirk MT
PROVIDER: S-EPMC7736332 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:As one of the most common maternal comorbidities, gestational diabetes mellitus (GDM) and preeclampsia (PE) are associated with maternal and infant health. Although the pathogenesis of PE and GDM remains controversial, oxidative stress is thought to be involved in the underlying pathology of GDM and PE. Protein lysine acetylation (Kac) plays an important regulatory role in biological processes. There is little data regarding the association of the maternal acetylome with GDM and PE. This study aimed to assess the multi-omics (proteome and acetylome) potential value in the underlying pathology for GDM and PE by label-free quantification proteomics technology. In our study, we included placental tissue from healthy individuals (n=6), GDM patients (n=6), and PE patients (n=6). We identified 22 overlapping DEPs (differentially expressed proteins) and 192 overlapping DAPs (differentially acetylated proteins) between the GDM and PE groups. Furthermore, 192 overlapping DAPs were mainly enriched in endoplasmic reticulum stress and ferroptosis pathways. Interestingly, endoplasmic reticulum stress, ferroptosis, and oxidative stress are believed to be related to each other. We also identified that acetylation of the HSP90AA1, HSPA8, PDIA3, GPX4, TF, and CP might serve as novel markers and better therapeutic targets in both complications. We thoroughly analyzed the key characteristics of proteome and acetylome in GDM and PE placental tissues, which may be useful for exploring the underlying pathology and discovering new biomarkers and therapeutic targets.
2024-01-25 | PXD032981 | Pride
Project description:The application of multi-omic evaluations, multi-dimensional analysis methods, and new cheminformatics-based visualization tools to provide an in depth understanding of the molecular changes taking place in preeclampsia (PRE) and gestational diabetes mellitus (GDM) patients. Since PRE and GDM are two prevalent pregnancy complications that result in adverse health effects for both the mother and fetus during pregnancy and later in life, a better understanding of each is essential. The multi-omic evaluations performed here provide new insight into the end-stage molecular profiles of each disease, thereby supplying crucial information for earlier diagnosis and potential treatments.
For the Proteomics_PooledFractions datasets, peptide samples were pooled by condition and fractionated offline into 24 samples; each fraction was run via Q Exactive and Ion Mobility Mass Spectrometry for creation of an AMT tag database. Proteomics_Samples contains datasets from peptide samples that were run via Ion Mobility Mass Spectrometry. Lipidomics_Samples contains datasets from lipid samples that were run via LTQ Orbitrap Velos Mass Spectrometry.
2020-05-01 | MSV000085357 | MassIVE
Project description:The application of multi-omic evaluations, multi-dimensional analysis methods, and new cheminformatics-based visualization tools to provide an in depth understanding of the molecular changes taking place in preeclampsia (PRE) and gestational diabetes mellitus (GDM) patients. Since PRE and GDM are two prevalent pregnancy complications that result in adverse health effects for both the mother and fetus during pregnancy and later in life, a better understanding of each is essential. The multi-omic evaluations performed here provide new insight into the end-stage molecular profiles of each disease, thereby supplying crucial information for earlier diagnosis and potential treatments. Datasets here represent lipid samples analyzed via Ion Mobility Mass Spectrometry.
2020-05-02 | MSV000085361 | MassIVE
Project description:The application of multi-omic evaluations, multi-dimensional analysis methods, and new cheminformatics-based visualization tools to provide an in depth understanding of the molecular changes taking place in preeclampsia (PRE) and gestational diabetes mellitus (GDM) patients. Since PRE and GDM are two prevalent pregnancy complications that result in adverse health effects for both the mother and fetus during pregnancy and later in life, a better understanding of each is essential. The multi-omic evaluations performed here provide new insight into the end-stage molecular profiles of each disease, thereby supplying crucial information for earlier diagnosis and potential treatments.
For the Proteomics_PooledFractions datasets, peptide samples were pooled by condition and fractionated offline into 24 samples; each fraction was run via Q Exactive and Ion Mobility Mass Spectrometry for creation of an AMT tag database. Proteomics_Samples contains datasets from peptide samples that were run via Ion Mobility Mass Spectrometry. Lipidomics_Samples contains datasets from lipid samples that were run via LTQ Orbitrap Velos Mass Spectrometry.
2020-05-01 | MSV000085357 | GNPS
Project description:ObjectiveFatty acid-binding protein 4 (FABP4) has been proposed to be a potential predictive factor of gestational hypertension or preeclampsia (GH/PE) because of its integrating metabolic and inflammatory responses. Women with gestational diabetes mellitus (GDM) are more likely to develop both GH/PE, than the normal population. The aim of our study was to examine the relationship between plasma FABP4 in the second trimester of pregnancy and the risk of GH/PE in women with GDM.MethodsThis was a nested case-control study conducted within a large on-going prospective cohort study conducted at Peking University First Hospital. A total of 1344 women, who were diagnosed with GDM, according to a 75 g oral glucose tolerance test, participated in the GDM One-Day Clinic at Peking University First Hospital from February 24, 2016 to February 9, 2017. Of the 748 GDM women who agreed to the blood sample collection, 637 were followed until their delivery. The cases included GDM patients who developed gestational hypertension or preeclampsia (GDM-GH/PE group, n = 41). Another 41 matched GDM women without major complications were selected as the control group (GDM group).ResultsThe incidence of GH/PE was 6.44% and 3.30% for preeclampsia. The level of the second trimester plasma FABP4 in the GDM-GH/PE group was significantly higher than the GDM group (17.53±11.35 vs. 12.79±6.04 ng/ml, P = 0.020). The AUC ROC for the second trimester plasma FABP4 predicted GH/PE in the GDM patients alone was 0.647 (95%CI 0.529-0.766). Multivariate analysis showed that the elevated second trimester FABP4 level was independently associated with GH/PE in the GDM patients (OR 1.136 [95% CI 1.003-1.286], P = 0.045).ConclusionsIncreased second trimester plasma FABP4 independently predicted GH/PE in GDM patients.
| S-EPMC5796716 | biostudies-literature
Project description:BackgroundIntrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies.Methods and resultsUsing Illumina's 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes, ATP5A1, MFAP4, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM.ConclusionsOur study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures.
| S-EPMC5368916 | biostudies-literature
Project description:BackgroundPreeclampsia is a multifactorial hypertensive disorder of pregnancy with multisystem involvement. Recent studies have demonstrated that preeclampsia is associated with increased placental oxidative stress at the cellular level. The nuclear factor erythroid-2-like 2 (Nrf2) / Kelch-like ECH-associated protein 1 (Keap1) signaling is an antioxidant pathway that plays an important role in protecting cells against oxidative stress. Here, we aimed to determine the possible association between the Keap1 variants and genetic susceptibility to preeclampsia.MethodsIn a case-control study, 150 preeclampsia patients and 150 women with normal pregnancy from Northern Iran were selected to evaluate the genotypes of Keap1 (rs11085735) using the polymerase chain reaction (PCR)-restriction length polymorphism (RFLP) method.ResultsA significant association between genotypes of Keap1 rs11085735 polymorphism with the renal function biomarkers and the risk of preeclampsia was not found. However, the aspartate aminotransferase (AST) level was higher in the presence of the Keap1 AA genotype compared to AC and CC genotypes. We found a significantly higher prevalence of gestational diabetes mellitus (GDM) in mild- and severe- preeclampsia and also hypothyroidism in severe preeclampsia compared to controls.ConclusionWe found an association between preeclampsia with GDM and hypothyroidism. Our findings suggest that the Keap1rs11085735 polymorphism may not be a risk factor for susceptibility to preeclampsia in our studied population; however, this polymorphism could affect the activity of AST.
| S-EPMC9883022 | biostudies-literature
Project description:BackgroundThromboelastography (TEG) provides global assessment of hemostatic function and has been recommended to monitor potential coagulopathies during pregnancy in which hypercoagulable state is favored. In present study, we established the reference intervals (RIs) of the TEG parameters (R, K, MA, and α-angle) with Chinese pregnant women of third trimester. In addition, we examined the diagnostic efficacies of the TEG parameters in the patients diagnosed of gestational hypertension (GH), gestational diabetes mellitus (GDM), or preeclampsia (PE).MethodsWith specified including and excluding criteria, non-pregnant controls, healthy pregnant women, and pregnant women with GH, GDM, or PE had their venous blood drawn at Beijing Obstetrics and Gynecology Hospital, followed by TEG tests performed in the clinical laboratory.ResultsThe RIs determined with the healthy pregnant women (in third trimester) for R, K, MA, and α-angle were 4.0-7.7, 1.2-3.2, 51.9-70.1, and 41.4-74.4, respectively. When compared with the healthy pregnancy group, the K value was significantly decreased in GH patients but increased in PE patients; MA was significantly lower in the PE group. In the receiver operating characteristic curve (ROC) analyses, K value was able to efficiently distinguish normal pregnancy from the GH patients, with an AUC of 0.86 which is far better than those of R (AUC = 0.57) and MA (AUC = 0.56). For the PE patients, the AUC of MA (0.69) was significantly greater than that of R (0.50).ConclusionsThromboelastography may provide more accurate experimental basis for monitoring coagulation functions especially in pregnant women with complications of GH and PE.
| S-EPMC7891543 | biostudies-literature
Project description:Circular RNA (circRNA) plays an important role in biological processes of gestational diabetes mellitus (GDM) and preeclampsia (PE). However, the mechanisms for circRNA DMNT1 (circ-DMNT1) in GDM and PE remain unclarified. The expression levels of circ-DMNT1 and p53 in GDM and PE were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis. When the expression of circ-DMNT1 or p53 was abnormal, cell counting kit-8 (CCK-8) assay, bromodeoxyuridine (BrdU) staining, flow cytometry, cell scratch, and Transwell assays were used to assess cell viability, proliferation, cell cycle, apoptosis, migration, and invasion of trophoblast cells, respectively. Subsequently, the binding relationship between circ-DMNT1 and p53 was verified by RNA pull-down and RIP analysis, followed by the determination of JAK/STAT pathway-related protein expression levels using western blot analysis. Both circ-DMNT1 and p53 were highly expressed in GDM and PE. Upregulation of circ-DMNT1 or p53 inhibited trophoblast cell viability, proliferation, migration, and invasion, meanwhile promoting cell apoptosis but blocking cell cycle progression. However, downregulation of circ-DMNT1 or p53 induced trophoblast cell survival. In GDM and PE, circ-DMNT1 activated the JAK/STAT pathway by binding to p53, which resulted in increased expression levels of p-JAK and p-STAT. The results suggested that circ-DMNT1 was involved in the deterioration of GDM and PE, possibly through inducing p53 expression and activating the JAK/STAT signaling pathway.
| S-EPMC8927128 | biostudies-literature
Project description:Omics and meta-omics technologies are powerful approaches to explore microorganisms' functions, but the sheer size and complexity of omics datasets often turn the analysis into a challenging task. Software developed for omics and meta-omics analyses, together with knowledgebases encompassing information on genes, proteins, taxonomic and functional annotation, among other types of information, are valuable resources for analyzing omics data. Although several bioinformatics resources are available for meta-omics analyses, many require significant computational expertise. Web interfaces are more user-friendly, but often struggle to handle large data files, such as those obtained in metagenomics, metatranscriptomics, or metaproteomics experiments. In this work, we present three novel bioinformatics tools, which are available through user-friendly command-line interfaces, can be run sequentially or stand-alone, and combine popular resources for functional annotation. UPIMAPI performs sequence homology-based annotation and obtains data from UniProtKB (e.g., protein names, EC numbers, Gene Ontology, Taxonomy, cross-references to external databases). reCOGnizer performs multithreaded domain homology-based annotation of protein sequences with several functional databases (i.e., CDD, NCBIfam, Pfam, Protein Clusters, SMART, TIGRFAM, COG and KOG) and in addition, obtains information on domain names and descriptions and EC numbers. KEGGCharter represents omics results, including differential gene expression, in KEGG metabolic pathways. In addition, it shows the taxonomic assignment of the enzymes represented, which is particularly useful in metagenomics studies in which several microorganisms are present. reCOGnizer, UPIMAPI and KEGGCharter together provide a comprehensive and complete functional characterization of large datasets, facilitating the interpretation of microbial activities in nature and in biotechnological processes.
| S-EPMC9034014 | biostudies-literature