Computational Estimation of Fetal DNA Fraction in Low Coverage Whole Genome Sequencing Data

Priit Paluoja
The aim of this thesis was to find and 'calibrate' computational methodology for estimating the proportion of cell-free fetal DNA (cffDNA) in pregnant women’s blood sample. This work was done as part of an applied research project aimed to develop a whole genome sequencing (WGS) based non-invasive prenatal testing (NIPT) medical screening test. NIPT is the most up-to-date, accurate and easily applied (non-invasive) prenatal screening method to detect fetal aneuploidies (for example trisomy 21, that causes Down syndrome) with high confidence and already during the first trimester of pregnancy. Commonly, NIPT is based on the low coverage WGS data, generated by the means of Illumina or some another platform technology. Computational tools used for aneuploidy detection can also estimate the proportion of cffDNA in maternal blood for both male and female fetus pregnancies. Fetal fraction calculation is a prerequisite to assure the technical credibility of NIPT screening test. In the current study, low coverage cell-free whole genome sequencing data from 416 pregnant women were used to develop a chromosome Y based estimator for the proportion of cffDNA in male-fetus pregnancy cases. Next, the chromosome Y based estimator was used to validate the credibility of SeqFF computational method with Estonian NIPT samples. This developed approach using SeqFF method on Estonian NIPT samples enables to estimate the proportion of cffDNA in both male and female fetus pregnancies. The SeqFF method is now integrated into the NIPT computation workflow service, validated and in daily practical use as part of the NIPTIFY® screening test.
Graduation Thesis language
Graduation Thesis type
Master - Computer Science
Priit Palta, Kaarel Krjutškov
Defence year