Abstract：
UNASSIGNED: In the current study, we sought to characterise the methylation haplotypes and nucleosome positioning patterns of placental DNA and plasma cell-free DNA of pregnant women with early-onset preeclampsia using whole genome bisulphite sequencing (WGBS) and methylation capture bisulphite sequencing (MCBS) and further develop and examine the diagnostic performance of a generalised linear model (GLM) by incorporating the epigenetic features for early-onset preeclampsia.
UNASSIGNED: This case-control study recruited pregnant women aged at least 18 years who delivered their babies at our Hospital. In addition, non-pregnant women with no previous history of diseases were included. Placental samples of the villous parenchyma were taken at the time of delivery and venous blood was drawn from pregnant women during non-invasive prenatal testing at 12-15 weeks of pregnancy and nonpregnant women during the physical check-up. WGBS and MCBS were carried out of extracted genomic DNA. Then, we established the GLM by incorporating preeclampsia-specific methylation haplotypes and nucleosome positioning patterns and examined the diagnostic performance of the model by receiver operating characteristic (ROC) curve analysis.
UNASSIGNED: The study included 135 pregnant women and 50 non-pregnant women. Our high-depth MCBS revealed notably different DNA methylation and nucleosome positioning patterns between women with and without preeclampsia. Preeclampsia-specific hypermethylated sites were found predominantly in the promoter regions and particularly enriched in CTCF on the X chromosome. Totally, 2379 preeclampsia-specific methylation haplotypes were found across the entire genome. ROC analysis showed that the area under the ROC curve (AUC) was 0.938 (95%CI 0.877, 1.000). At a GLM cut-off of 0.341, the AUC was the maximum, with a sensitivity of 95.6% and a specificity of 89.7%.
UNASSIGNED: Pregnant women with early-onset preeclampsia exhibit DNA methylation and nucleosome positioning patterns in placental and plasma DNA.
Early-onset preeclampsia is a potentially dangerous condition that can have a profound impact on the health of both the expectant mother and her unborn child. This condition is particularly concerning because it’s challenging to predict who may be affected using conventional methods such as monitoring blood pressure. In our research, we’ve developed an innovative, non-invasive approach to predict the onset of early preeclampsia. We do this by analysing the genetic material of the developing baby, which can be found in the mother’s blood. Our method has shown remarkable accuracy in our testing populations, and its implications are substantial. By providing an early warning system, this breakthrough can benefit pregnant women immensely. It means that early-onset preeclampsia can be identified and addressed well before it becomes a serious health threat. This allows for timely medical interventions and treatments, significantly improving the well-being of both mothers and their precious little ones.
UNASSIGNED: This case-control study recruited pregnant women aged at least 18 years who delivered their babies at our Hospital. In addition, non-pregnant women with no previous history of diseases were included. Placental samples of the villous parenchyma were taken at the time of delivery and venous blood was drawn from pregnant women during non-invasive prenatal testing at 12-15 weeks of pregnancy and nonpregnant women during the physical check-up. WGBS and MCBS were carried out of extracted genomic DNA. Then, we established the GLM by incorporating preeclampsia-specific methylation haplotypes and nucleosome positioning patterns and examined the diagnostic performance of the model by receiver operating characteristic (ROC) curve analysis.
UNASSIGNED: The study included 135 pregnant women and 50 non-pregnant women. Our high-depth MCBS revealed notably different DNA methylation and nucleosome positioning patterns between women with and without preeclampsia. Preeclampsia-specific hypermethylated sites were found predominantly in the promoter regions and particularly enriched in CTCF on the X chromosome. Totally, 2379 preeclampsia-specific methylation haplotypes were found across the entire genome. ROC analysis showed that the area under the ROC curve (AUC) was 0.938 (95%CI 0.877, 1.000). At a GLM cut-off of 0.341, the AUC was the maximum, with a sensitivity of 95.6% and a specificity of 89.7%.
UNASSIGNED: Pregnant women with early-onset preeclampsia exhibit DNA methylation and nucleosome positioning patterns in placental and plasma DNA.
Early-onset preeclampsia is a potentially dangerous condition that can have a profound impact on the health of both the expectant mother and her unborn child. This condition is particularly concerning because it’s challenging to predict who may be affected using conventional methods such as monitoring blood pressure. In our research, we’ve developed an innovative, non-invasive approach to predict the onset of early preeclampsia. We do this by analysing the genetic material of the developing baby, which can be found in the mother’s blood. Our method has shown remarkable accuracy in our testing populations, and its implications are substantial. By providing an early warning system, this breakthrough can benefit pregnant women immensely. It means that early-onset preeclampsia can be identified and addressed well before it becomes a serious health threat. This allows for timely medical interventions and treatments, significantly improving the well-being of both mothers and their precious little ones.
摘要：
■在当前的研究中，我们试图使用全基因组亚硫酸氢盐测序(WGBS)和甲基化捕获亚硫酸氢盐测序(MCBS)来表征早发型先兆子痫孕妇胎盘DNA和浆细胞游离DNA的甲基化单倍型和核小体定位模式,并通过纳入早发型先兆子痫的表观遗传学特征来进一步发展和检验广义线性模型(GLM)的诊断性能.
这项病例对照研究招募了在我们医院分娩的18岁以上的孕妇。此外,纳入既往无疾病史的非孕妇.分娩时采集绒毛实质的胎盘样本，并在怀孕12-15周时进行非侵入性产前检查时从孕妇和体格检查中未怀孕的妇女中抽取静脉血。对提取的基因组DNA进行WGBS和MCBS。然后，我们通过纳入子痫前期特异性甲基化单倍型和核小体定位模式建立了GLM,并通过受试者工作特征(ROC)曲线分析检查了该模型的诊断性能.
■该研究包括135名孕妇和50名非孕妇。我们的深度MCBS揭示了有和没有先兆子痫的女性之间明显不同的DNA甲基化和核小体定位模式。先兆子痫特异性高甲基化位点主要在启动子区域中发现，特别是在X染色体上的CTCF中富集。完全正确,在整个基因组中发现了2379个先兆子痫特异性甲基化单倍型。ROC分析显示ROC曲线下面积(AUC)为0.938(95CI0.877,1.000)。在0.341的GLM截止值下，AUC最大，敏感性为95.6%，特异性为89.7%。
■早发型先兆子痫孕妇在胎盘和血浆DNA中表现出DNA甲基化和核小体定位模式。
早发型先兆子痫是一种潜在的危险疾病，可以对孕妇和未出生的孩子的健康产生深远的影响。这种情况尤其令人担忧，因为使用常规方法（如监测血压）来预测谁可能受到影响是具有挑战性的。在我们的研究中,我们开发了一种创新的，非侵入性方法预测早期先兆子痫的发病。我们通过分析发育中的婴儿的遗传物质来做到这一点，可以在母亲的血液中找到.我们的方法在我们的测试人群中显示出惊人的准确性，其影响是巨大的。通过提供预警系统，这一突破可以极大地造福孕妇。这意味着早发型先兆子痫可以在其成为严重的健康威胁之前被识别和解决。这可以及时进行医疗干预和治疗，显着改善母亲和她们宝贵的孩子的福祉。
这项病例对照研究招募了在我们医院分娩的18岁以上的孕妇。此外,纳入既往无疾病史的非孕妇.分娩时采集绒毛实质的胎盘样本，并在怀孕12-15周时进行非侵入性产前检查时从孕妇和体格检查中未怀孕的妇女中抽取静脉血。对提取的基因组DNA进行WGBS和MCBS。然后，我们通过纳入子痫前期特异性甲基化单倍型和核小体定位模式建立了GLM,并通过受试者工作特征(ROC)曲线分析检查了该模型的诊断性能.
■该研究包括135名孕妇和50名非孕妇。我们的深度MCBS揭示了有和没有先兆子痫的女性之间明显不同的DNA甲基化和核小体定位模式。先兆子痫特异性高甲基化位点主要在启动子区域中发现，特别是在X染色体上的CTCF中富集。完全正确,在整个基因组中发现了2379个先兆子痫特异性甲基化单倍型。ROC分析显示ROC曲线下面积(AUC)为0.938(95CI0.877,1.000)。在0.341的GLM截止值下，AUC最大，敏感性为95.6%，特异性为89.7%。
■早发型先兆子痫孕妇在胎盘和血浆DNA中表现出DNA甲基化和核小体定位模式。
早发型先兆子痫是一种潜在的危险疾病，可以对孕妇和未出生的孩子的健康产生深远的影响。这种情况尤其令人担忧，因为使用常规方法（如监测血压）来预测谁可能受到影响是具有挑战性的。在我们的研究中,我们开发了一种创新的，非侵入性方法预测早期先兆子痫的发病。我们通过分析发育中的婴儿的遗传物质来做到这一点，可以在母亲的血液中找到.我们的方法在我们的测试人群中显示出惊人的准确性，其影响是巨大的。通过提供预警系统，这一突破可以极大地造福孕妇。这意味着早发型先兆子痫可以在其成为严重的健康威胁之前被识别和解决。这可以及时进行医疗干预和治疗，显着改善母亲和她们宝贵的孩子的福祉。
