High‐resolution epigenomic liquid biopsy for noninvasive phenotyping in pregnancy

Abstract

Objective We explored the potential of genome‐wide epigenomic liquid biopsy for the comprehensive analysis of cell‐free DNA (cfDNA) methylation signatures in maternal plasma in early gestation. Method We used solution phase hybridization for targeted region capture of bisulfite‐converted DNA obtained from plasma of pregnant women in early gestation and nonpregnant female controls. Results Targeted sequencing of ~80.5 Mb of the plasma methylome generated an average read depth across all 17 plasma samples of ~42x. We used these data to explore the pregnancy‐specific characteristics of cfDNA methylation in plasma and found that pregnancy resulted in clearly detectable global alterations in DNA methylation patterns that were influenced by genomic location. We analyzed similar, previously published, data from first‐trimester maternal leukocyte populations and gestational age–matched chorionic villus (CV) and confirmed that tissue‐specific DNA methylation signatures in these samples had a significant influence on global and gene‐specific methylation in the plasma of pregnant women. Conclusion We describe an approach for targeted epigenomic liquid biopsy in pregnancy and discuss our findings in the context of noninvasive prenatal testing with respect to phenotypic pregnancy monitoring and the early detection of complex gestational phenotypes such as preeclampsia and preterm birth.

Altered Epigenetic Profiles in the Placenta of Preeclamptic and Intrauterine Growth Restriction Patients

“…The potential applications of this study to human health and patient diagnostics are substantial. Past research has shown liquid biopsy as a possible diagnostic technique for PE [ 50 , 51 , 52 ]. These assays rely on cell-free nucleic acids in blood plasma to identify differentially methylated regions indicative of disease states.…”