An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.

With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it a...

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Main Authors: Xiongbin Kang, Jun Xia, Yicong Wang, Huixin Xu, Haojun Jiang, Weiwei Xie, Fang Chen, Peng Zeng, Xuchao Li, Yifan Xie, Hongtai Liu, Guodong Huang, Dayang Chen, Ping Liu, Hui Jiang, Xiuqing Zhang
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5035032?pdf=render
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spelling doaj-b79b618f0cb345d5bf00349e04be9f852020-11-24T22:03:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01119e016192810.1371/journal.pone.0161928An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.Xiongbin KangJun XiaYicong WangHuixin XuHaojun JiangWeiwei XieFang ChenPeng ZengXuchao LiYifan XieHongtai LiuGuodong HuangDayang ChenPing LiuHui JiangXiuqing ZhangWith the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses.In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%.Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome.http://europepmc.org/articles/PMC5035032?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Xiongbin Kang
Jun Xia
Yicong Wang
Huixin Xu
Haojun Jiang
Weiwei Xie
Fang Chen
Peng Zeng
Xuchao Li
Yifan Xie
Hongtai Liu
Guodong Huang
Dayang Chen
Ping Liu
Hui Jiang
Xiuqing Zhang
spellingShingle Xiongbin Kang
Jun Xia
Yicong Wang
Huixin Xu
Haojun Jiang
Weiwei Xie
Fang Chen
Peng Zeng
Xuchao Li
Yifan Xie
Hongtai Liu
Guodong Huang
Dayang Chen
Ping Liu
Hui Jiang
Xiuqing Zhang
An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
PLoS ONE
author_facet Xiongbin Kang
Jun Xia
Yicong Wang
Huixin Xu
Haojun Jiang
Weiwei Xie
Fang Chen
Peng Zeng
Xuchao Li
Yifan Xie
Hongtai Liu
Guodong Huang
Dayang Chen
Ping Liu
Hui Jiang
Xiuqing Zhang
author_sort Xiongbin Kang
title An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
title_short An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
title_full An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
title_fullStr An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
title_full_unstemmed An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
title_sort advanced model to precisely estimate the cell-free fetal dna concentration in maternal plasma.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2016-01-01
description With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses.In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%.Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome.
url http://europepmc.org/articles/PMC5035032?pdf=render
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