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- Title
Non-invasive prediction of fetal growth restriction by whole-genome promoter profiling of maternal plasma DNA: a nested case-control study.
- Authors
Xu, C; Guo, Z; Zhang, J; Lu, Q; Tian, Q; Liu, S; Li, K; Wang, K; Tao, Z; Li, C; Lv, Z; Zhang, Z; Yang, X; Yang, F
- Abstract
<bold>Objective: </bold>To predict fetal growth restriction (FGR) by whole-genome promoter profiling of maternal plasma.<bold>Design: </bold>Nested case-control study.<bold>Setting: </bold>Hospital-based.<bold>Population or Sample: </bold>810 pregnancies: 162 FGR cases and 648 controls.<bold>Methods: </bold>We identified gene promoters with a nucleosome footprint that differed between FGR cases and controls based on maternal plasma cell-free DNA (cfDNA) nucleosome profiling. Optimal classifiers were developed using support vector machine (SVM) and logistic regression (LR) models.<bold>Main Outcome Measures: </bold>Genes with differential coverages in promoter regions through the low-coverage whole-genome sequencing data analysis among FGR cases and controls. Receiver operating characteristic (ROC) analysis (area under the curve [AUC], accuracy, sensitivity and specificity) was used to evaluate the performance of classifiers.<bold>Results: </bold>Through the low-coverage whole-genome sequencing data analysis of FGR cases and controls, genes with significantly differential DNA coverage at promoter regions (-1000 to +1000 bp of transcription start sites) were identified. The non-invasive 'FGR classifier 1' (CFGR 1) had the highest classification performance (AUC, 0.803; 95% CI 0.767-0.839; accuracy, 83.2%) was developed based on 14 genes with differential promoter coverage using a support vector machine.<bold>Conclusions: </bold>A promising FGR prediction method was successfully developed for assessing the risk of FGR at an early gestational age based on maternal plasma cfDNA nucleosome profiling.<bold>Tweetable Abstract: </bold>A promising FGR prediction method was successfully developed, based on maternal plasma cfDNA nucleosome profiling.
- Subjects
CHINA; FETAL growth retardation; DNA; CASE-control method; CELL-free DNA; FETAL growth disorders; NUCLEOTIDE sequencing; SUPPORT vector machines; CHROMOSOMES; PREDICTIVE tests; GENES; LOGISTIC regression analysis; RECEIVER operating characteristic curves
- Publication
BJOG: An International Journal of Obstetrics & Gynaecology, 2021, Vol 128, Issue 2, p458
- ISSN
1470-0328
- Publication type
journal article
- DOI
10.1111/1471-0528.16292