Uncertainty of fetal fraction determination in Non-Invasive Prenatal Screening by highly polymorphic SNPs

Grendár, Marian; Loderer, Dušan; Laučeková, Zuzana; Svecova, Iveta; Hrtánková, M; Horňáková, Andrea; Nagy, Bálint; Žúbor, Pavol; Lasabová, Zora; Danko, Ján

doi:10.1016/j.jbiotec.2019.04.020

Cited by 4 publications

(5 citation statements)

References 21 publications

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“…Compared with the most reliable method FFY (4, 34), SNPFF underestimated FF by 7% (105), which was similar to the results of another study in which SNPFF underestimated FF by 10% (106). Moreover, Song et al found that SNPFF underestimated the full range of FF (73).…”

Section: Methods For Calculation Ffsupporting

confidence: 80%

“…In addition, SANEFALCON had high false positives rates for FF. The SeqFF method cannot be limited to the evaluation of FF in male or female fetuses but may underestimate this parameter in high and low limits (105). Therefore, Hestand et al concluded that DEFRAG_W was the best-tested method for calculating FF in male fetuses and SeqFF in female fetuses, although the latter still needs improvement (26).…”

Section: Methods For Calculation Ffmentioning

confidence: 99%

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Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Deng

Liu

2022

Front. Pediatr.

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A paradigm shift in noninvasive prenatal screening has been made with the discovery of cell-free fetal DNA in maternal plasma. Noninvasive prenatal screening is primarily used to screen for fetal aneuploidies, and has been used globally. Fetal fraction, an important parameter in the analysis of noninvasive prenatal screening results, is the proportion of fetal cell-free DNA present in the total maternal plasma cell-free DNA. It combines biological factors and bioinformatics algorithms to interpret noninvasive prenatal screening results and is an integral part of quality control. Maternal and fetal factors may influence fetal fraction. To date, there is no broad consensus on the factors that affect fetal fraction. There are many different approaches to evaluate this parameter, each with its advantages and disadvantages. Different fetal fraction calculation methods may be used in different testing platforms or laboratories. This review includes numerous publications that focused on the understanding of the significance, influencing factors, and interpretation of fetal fraction to provide a deeper understanding of this parameter.

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Section: Methods For Calculation Ffsupporting

confidence: 80%

Section: Methods For Calculation Ffmentioning

confidence: 99%

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Deng

Liu

2022

Front. Pediatr.

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“…Numerous techniques for FF measurement are currently in use, including the seqFF method, the seqFFY method, the chromosome Y-based method ffy, and the SNP method. 49 When comparing these techniques, each method can generate a different FF depending on differing maternal and fetal characteristics, and the methods should be used in conjunction. 50 Although the patients enrolled in this study had their blood samples sent to different commercial laboratories, the majority of patients, with the exception of four, had MPSS-based cfDNA analysis as the basis for their FF calculation, but the details of how Abbreviations: OR = odds ratio and CI = confidence interval.…”

Section: Discussionmentioning

confidence: 99%

“…An important consideration that cannot be overlooked is the variability of measurement of FF between labs. Numerous techniques for FF measurement are currently in use, including the seqFF method, the seqFFY method, the chromosome Y‐based method ffy, and the SNP method 49 . When comparing these techniques, each method can generate a different FF depending on differing maternal and fetal characteristics, and the methods should be used in conjunction 50 .…”

Section: Discussionmentioning

confidence: 99%

Lower fetal fraction in clinical cell‐free DNA screening results is associated with increased risk of hypertensive disorders of pregnancy

et al. 2022

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Objective: To evaluate if fetal fraction (FF) reported on cell-free DNA (cfDNA) screening is a marker for adverse obstetric outcomes. Methods:We retrospectively reviewed medical records from a cohort of women with singleton pregnancies who had cfDNA screening. We evaluated if reported FF could predict the following pregnancy complications: hypertensive disorders of pregnancy (HDP), fetal growth restriction, preterm delivery, gestational diabetes mellitus, or a composite maternal morbidity, defined as the presence of at least one of these outcomes.Results: Receiver operating curve analysis was performed on FF from 534 women to define the FF that differentiated a low FF group (<10%; N = 259) and a high FF group (≥10%; N = 275). Hypertensive disorders of pregnancy were more common for women in the low FF group (32.0% vs. 11.6% and p < 0.001), who had a two-fold odds of developing HDP (p = 0.006). Composite maternal morbidity was also more common for women in the low FF group (51.4% vs. 30.2% and p < 0.001), who had a 1.7-fold odds of developing any of the adverse obstetrical outcomes (p = 0.014). Conclusion:We found that low FF on cfDNA screening is associated with an increased risk of HDP. Fetal fraction reported that cfDNA screening reports have potential as a predictive marker for the development of HDP and adverse outcomes. Key pointsWhat is already known about this topic? � Analysis of cell-free DNA circulating in maternal blood is used for noninvasive prenatal screening for fetal aneuploidies. � The fetal fraction (FF) is the proportion of circulating cell-free DNA (cfDNA) that is of fetal (placental) origin. � Several maternal and fetal factors such as maternal weight and fetal gestational age can affect FF. Deeksha Madala, Mohamad Ali Maktabi contributed equally to the work.

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“…Moreover, allelic read counts for different underlying genotypes could be analyzed together after such linear transformations, and a robust linear regression could be fitted, which was insensitive to outliers. On the contrary, methods current available for estimating fetal fractions 17,24,25 were based on either medians or statistical distributions, whereas only median values were used or models sensitive to outliers were applied. Hence the method for estimating fetal fraction using a robust linear regression model should be accurate inherently as all data points were included and the effects of outliers were minimized, and fetal fractions even at the level of 1% were consistently and accurately measured for repetitive samples (Fig.…”

Section: Discussionmentioning

confidence: 99%

Noninvasive Detection of Fetal Genetic Variations through Polymorphic Sites Sequencing of Maternal Plasma DNA

Gao

2021

Preprint

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Non-invasive prenatal testing (NIPT) for common fetal aneuploidies using circulating cell free DNA in maternal plasma has been widely adopted in clinical practice for its sensitivity and accuracy. However, the detection of subchromosomal abnormalities or monogenetic variations using such a method showed no cost-effectiveness or satisfactory accuracy. Here we show that with the aid of polymorphic sites sequencing, fetal fraction of the sample and genotype of the target site were determined with high accuracy. Then genetic variations at the chromosomal, subchromosomal and nucleotide levels were detected using the overall allelic goodness-of-fit test of all target polymorphic sites to each possible genetic model. Finally, relative allelic distributions for each amplicon were visualized and genetic variations at the chromosomal, subchromosomal and nucleotide levels were determined by distinct characteristic clusters on allelic distribution plot of each possible genetic model. As no parental genetic information was required and all allelic information retained for amplicon sequencing, the reported approach has the potential to simultaneously detect genetic variations at different levels, facilitating the extension of NIPT to all common genetic conditions for general low-risk pregnancies and target variations for certain high-risk pregnancy groups.

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Uncertainty of fetal fraction determination in Non-Invasive Prenatal Screening by highly polymorphic SNPs

Cited by 4 publications

References 21 publications

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Factors Affecting the Fetal Fraction in Noninvasive Prenatal Screening: A Review

Lower fetal fraction in clinical cell‐free DNA screening results is associated with increased risk of hypertensive disorders of pregnancy

Noninvasive Detection of Fetal Genetic Variations through Polymorphic Sites Sequencing of Maternal Plasma DNA

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