Diagnostic Utility of Whole-Genome cfDNA Profiling in Pregnancy

This project aims to develop novel bioinformatic methods for noninvasive prenatal testing (NIPT) that identify genomic signatures associated with placenta-related pregnancy complications (e.g. preeclampsia, intrauterine growth restriction, preterm birth). Traditionally, ultrasonography and maternal serum protein are used as non-invasive markers of placental health. However, with the development of next-generation sequencing technologies, it is now possible to isolate placental signal in maternal plasma cfDNA using an array of approaches including single nucleotide polymorphism (SNP) genotyping, DNA methylation patterns, and nucleosome occupancy. Previous studies have shown significant elevation in the overall level of cfDNA in women with preeclampsia, intrauterine growth restriction, and preterm birth, however, these studies lack cell-type resolution. Given that the placenta is a highly heterogeneous organ with fetal and maternal components, the ability to detect cell-type-specific signatures in cfDNA will allow for a more comprehensive investigation of placental health. It is our hope that genome-wide cfDNA nucleosome profiles may be used as an early predictive marker for placental disease.