Cell-free DNA fragmentomics for preeclampsia risk assessment
Abstract
Abstract Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that could lead to serious maternal and fetal complications, yet early identification of women at risk remains challenging because reliable biomarkers are limited. Here we show that generating relatively stable cell-free DNA (cfDNA) fragmentomic metrics, including transcription start site (TSS) coverage, TSS score, and Gini coefficient, required 600 million whole-genome sequencing reads of plasma cfDNA. These metrics exhibited observable differences among genes with varying expression levels in blood cells and placental tissues. In a cohort of 1,058 pregnant women, cfDNA fragmentomics could distinguish pregnancies that subsequently developed PE. When integrated with maternal risk factors, predictive models in two independent test sets achieved mean area under the curves of 0.903 and 0.850 for early-onset and late-onset PE, respectively, with sensitivities of 0.731 and 0.607 at a 10% false positive rate. Importantly, these models also performed well in samples collected before or at 16 weeks of gestation, supporting the potential of cfDNA fragmentomics in early PE risk assessment.
Article Details
Authors (40)
Wenqiu Xu
Songchang Chen
Jia Li
Si Zhou
Guangdong Basic Research Center of Excellence for Structure and Fundamental Interactions of Matter, Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials, School of Physics
Yanning Yin
Zhixu Qiu
Jianguo Zhang
Cong Liu
Qiang Zhao
Gefei Xiao
Yan Zhou
Zhiguang Zhao
Xiao Zhang
Wenzhi Yang
Yunfang Wang
Huiqin Li
Zhen Yang
Suihua Feng
Qun Zhang
Weiping Chen
Huahua Li
Xiaohong Ruan
Hua Li
Sufen Zhang
Liqing Hu
Jie Qin
Wuyan Huang
Zhongzhe Li
Xianling Cao
Xuanyou Zhou
Naixin Xu
Dongxia Hou
Hong Dong
Jie Wang
State Key Laboratory of Molecular Oncology, Beijing Key Laboratory, CAMS Key Laboratory of Translational Research on Lung Cancer, Department of Medical Oncology Cancer Hospital, Chinese Academy of Medical Sciences Beijing China
Yaxian Liu
Department of Chemistry, Molecular Science Research Hub
Quanfu Zhang
Xiaohua Wang
Lijian Zhao
Hefeng Huang
Chenming Xu