Whole-Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta-Origin Pregnancy Complications
Whole-Genome Promoter Profiling of Plasma DNA Exhibits Diagnostic Value for Placenta-Origin Pregnancy Complications
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血浆 DNA 的全基因组启动子分析对胎盘来源的妊娠并发症具有诊断价值
DOI：
10.1002/advs.201901819
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发表时间：
2020-02-18
期刊：
影响因子：
15.1
通讯作者：
Yang, Xuexi
中科院分区：
文献类型：
--
作者：
Guo, Zhiwei;Yang, Fang;Yang, Xuexi
胎盘源性妊娠并发症，包括先兆子痫（PE）、妊娠期糖尿病（GDM）、胎儿生长受限（FGR）和巨大儿（MA）是妊娠期常见的并发症，导致母亲和胎儿的显著发病率和死亡率。然而，尽管其频率，有没有可靠的方法来早期诊断这些并发症。由于cfDNA主要来源于胎盘滋养层细胞和母体造血细胞，因此它可能具有可用于疾病预测的基因表达信息。在这里，基于3,200名孕妇的回顾性队列，对2,199名孕妇的血浆DNA进行了低覆盖率全基因组测序。检查启动子区域中的读取深度以定义妊娠并发症和对照的启动子的读取深度分布模式。使用机器学习方法，开发了用于预测妊娠并发症的分类器。使用这些分类器，成功预测MA、FGR、GDM和PE的并发症，准确率分别为80.3%、78.9%、72.1%和83.0%。这些发现表明cfDNA的启动子分析可以用作预测早期妊娠并发症的生物标志物。
Placenta-origin pregnancy complications, including preeclampsia (PE), gestational diabetes mellitus (GDM), fetal growth restriction (FGR), and macrosomia (MA) are common occurrences in pregnancy, resulting in significant morbidity and mortality for both mother and fetus. However, despite their frequency, there are no reliable methods for the early diagnosis of these complications. Since cfDNA is mainly derived from placental trophoblasts and maternal hematopoietic cells, it might have information for gene expression which can be used for disease prediction. Here, low coverage whole-genome sequencing on plasma DNA from 2,199 pregnancies is performed based on retrospective cohorts of 3,200 pregnant women. Read depth in the promoter regions is examined to define read-depth distribution patterns of promoters for pregnancy complications and controls. Using machine learning methods, classifiers for predicting pregnancy complications are developed. Using these classifiers, complications are successfully predicted with an accuracy of 80.3%, 78.9%, 72.1%, and 83.0% for MA, FGR, GDM, and PE, respectively. The findings suggest that promoter profiling of cfDNA may be used as a biological biomarker for predicting pregnancy complications at early gestational age.