Calculating the Fetal Fraction for Noninvasive Prenatal Testing Based on Genome-wide Nucleosome Profiles

Overview

Journal Prenat Diagn

Publisher Wiley

Specialty Gynecology & Obstetrics

Date 2016 Mar 22

PMID 26996738

Citations 47

Authors

Roy Straver

Cees B M Oudejans

Erik A Sistermans

Marcel J T Reinders

Affiliations

Soon will be listed here.

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.

Citing Articles

Artificial intelligence and machine learning in cell-free-DNA-based diagnostics.

Tsui W, Ding S, Jiang P, Lo Y Genome Res. 2025; 35(1):1-19.

PMID: 39843210 PMC: 11789496. DOI: 10.1101/gr.278413.123.

Non-invasive prenatal diagnosis (NIPD): current and emerging technologies.

Hanson B, Paternoster B, Povarnitsyn N, Scotchman E, Chitty L, Chandler N Extracell Vesicles Circ Nucl Acids. 2024; 4(1):3-26.

PMID: 39698301 PMC: 11648410. DOI: 10.20517/evcna.2022.44.

Expanded knowledge of cell-free DNA biology: potential to broaden the clinical utility.

Che H, Stanley K, Jatsenko T, Thienpont B, Vermeesch J Extracell Vesicles Circ Nucl Acids. 2024; 3(3):216-234.

PMID: 39697489 PMC: 11648412. DOI: 10.20517/evcna.2022.21.

Emerging frontiers of cell-free DNA fragmentomics.

Hu X, Ding S, Jiang P Extracell Vesicles Circ Nucl Acids. 2024; 3(4):380-392.

PMID: 39697357 PMC: 11648524. DOI: 10.20517/evcna.2022.34.

Cell-free placental DNA: What do we really know?.

Yuen N, Lemaire M, Wilson S PLoS Genet. 2024; 20(12):e1011484.

PMID: 39652523 PMC: 11627368. DOI: 10.1371/journal.pgen.1011484.

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