Print Email Facebook Twitter Calculating the fetal fraction for noninvasive prenatal testing based on genome-wide nucleosome profiles Title Calculating the fetal fraction for noninvasive prenatal testing based on genome-wide nucleosome profiles Author Straver, R. (Amsterdam UMC) Oudejans, Cees B.M. (Amsterdam UMC) Sistermans, Erik A. (Amsterdam UMC) Reinders, M.J.T. (TU Delft Pattern Recognition and Bioinformatics; Amsterdam UMC) Date 2016 Abstract Objective While large fetal copy number aberrations can generally be detected through sequencing of DNA in maternal blood, the reliability of tests depends on the fraction of DNA that originates from the fetus. Existing methods to determine this fetal fraction require additional work or are limited to male fetuses. We aimed to create a sex-independent approach without additional work. Methods DNA fragments used for noninvasive prenatal testing are cut only by natural processes; thus, influences on cutting by the packaging of DNA in nucleosomes will be preserved in sequencing. As cuts are expected to be made preferentially in linker regions, the shorter fetal fragments should be enriched for reads starting in nucleosome covered positions. Results We generated genome-wide nucleosome profiles based on single end sequencing of cell-free DNA. We found a difference between DNA digestion of fetal cell-free DNA and maternal cell-free DNA and used this to calculate the fraction of fetal DNA in maternal plasma for both male and female fetuses. Conclusion Our method facilitates cost-effective noninvasive prenatal testing, as the fetal DNA fraction can be estimated without the need for expensive paired-end sequencing or additional tests. The methodology is implemented as a tool, which we called SANEFALCON (Single reAds Nucleosome-basEd FetAL fraCtiON). It is available for academic and non-profit purposes under Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License. github.com/rstraver/sanefalcon. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd. To reference this document use: http://resolver.tudelft.nl/uuid:514cb194-b08b-48bf-b2e7-d2d9931fb431 DOI https://doi.org/10.1002/pd.4816 ISSN 0197-3851 Source Prenatal Diagnosis, 36 (7), 614-621 Part of collection Institutional Repository Document type journal article Rights © 2016 R. Straver, Cees B.M. Oudejans, Erik A. Sistermans, M.J.T. Reinders Files PDF 11717731.pdf 932.59 KB Close viewer /islandora/object/uuid:514cb194-b08b-48bf-b2e7-d2d9931fb431/datastream/OBJ/view