Cell-free fetal DNA fraction (FF) in maternal plasma is a key parameter affecting the performance of noninvasive prenatal testing (NIPT). Accurate quantitation of FF plays a pivotal role in these tests. However, there are few methods that could determine FF with high accuracy using shallow-depth whole-genome sequencing data. In this study, we hypothesized that the actual FF in maternal plasma should be proportional to the discrepancy rate between the observed genotypes and inferred genotypes based on the linkage disequilibrium rule in certain polymorphism sites. Based on this hypothesis, we developed a method named Linkage Disequilibrium information-based cell-free Fetal DNA Fraction (LDFF) to accurately quantify FF in maternal plasma. This method achieves a high performance and outperforms existing methods in the fetal DNA fraction estimation. As LDFF is a gender-independent method and developed on shallow-depth samples, it can be easily incorporated into routine NIPT test and may enhance the current NIPT performance.
Keyphrases
- cell free
- circulating tumor
- birth weight
- pregnancy outcomes
- genome wide
- mass spectrometry
- hiv testing
- ms ms
- gestational age
- high resolution
- gene expression
- liquid chromatography
- liquid chromatography tandem mass spectrometry
- dna methylation
- weight gain
- high performance liquid chromatography
- hiv infected
- solid phase extraction