Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies

Jiang, Fuman; Ren, Jiang; Chen, Fang‐Fang; Zhou, Yuqiu; Xie, Jiansheng; Shan, Dan; Su, Yue; Xie, Junbo; Yin, Bo; Su, Wan‐Fu; Zhang, Huakun; Wang, Weiwei; Chai, Xianghua; Lin, Linhua; Guo, Hui; Li, Qiyun; Li, Peipei; Yuan, Yuying; Pan, Xiaoyu; Li, Yihan; Liu, Lifu; Chen, Huifei; Xuan, Zhaoling; Chen, Sheng-Pei; Zhang, Chunlei; Zhang, Hongyun; Tian, Zhongming; Zhang, Zhengyu; Jiang, Huihui; Zhao, Lijian; Zheng, Wei-Mou; Li, Songgang; Li, Yingrui; Wang, Junjun; Wang, Jian; Zhang, Xiuqing

doi:10.1186/1755-8794-5-57

Cited by 148 publications

(207 citation statements)

References 35 publications

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“…The first group of studies was used for the meta-analysis on the performance of screening by cfDNA testing in screening for aneuploidies [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome; 26 studies examined prospectively collected blood or stored plasma samples obtained before invasive diagnostic testing in patients identified by conventional methods of screening as being at high-risk for aneuploidies.…”

Section: Resultsmentioning

confidence: 99%

Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Meta-Analysis

et al. 2014

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Objective: To review clinical validation or implementation studies of maternal blood cell-free (cf) DNA analysis in screening for aneuploidies and to explore the potential use of this method in clinical practice. Methods: Searches of PubMed and MEDLINE were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between 2011, when the first such study was published, and 20 December 2013. Results: Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.0% (95% CI 98.2-99.6) and 0.08% (95% CI 0.03-0.14), respectively, for trisomy 21; 96.8% (95% CI 94.5-98.4) and 0.15% (95% CI 0.08-0.25) for trisomy 18; 92.1% (95% CI 85.9-96.7) and 0.20% (95% CI 0.04-0.46) for trisomy 13; 88.6% (95% CI 83.0-93.1) and 0.12% (95% CI 0.05-0.24) for monosomy X, and 93.8% (95% CI 85.9-98.7) and 0.12% (95% CI 0.02-0.28) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR was 94.4% (95% 74.2-99.0) and the FPR was 0% (95% CI 0.00-1.84) for trisomy 21. Conclusion: An analysis of cfDNA in maternal blood provides effective screening for trisomies.

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Section: Resultsmentioning

confidence: 99%

Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Meta-Analysis

et al. 2014

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“…The remaining reads were considered unique reads for further analysis. To eliminate the effect of GC bias, we applied an integrated method for GC correction using a three-step process: LOESS regression (31), intrarun normalization (32), and linear model regression (33). Briefly, LOESS regression was used to smooth the sequencing bias produced by variable GC content on different chromosomes.…”

Section: Methodsmentioning

confidence: 99%

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing

Liao

Yin

Peng³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

114

137

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Massively parallel sequencing (MPS) of cell-free fetal DNA from maternal plasma has revolutionized our ability to perform noninvasive prenatal diagnosis. This approach avoids the risk of fetal loss associated with more invasive diagnostic procedures. The present study developed an effective method for noninvasive prenatal diagnosis of common chromosomal aneuploidies using a benchtop semiconductor sequencing platform (SSP), which relies on the MPS platform but offers advantages over existing noninvasive screening techniques. A total of 2,275 pregnant subjects was included in the study; of these, 515 subjects who had full karyotyping results were used in a retrospective analysis, and 1,760 subjects without karyotyping were analyzed in a prospective study. In the retrospective study, all 55 fetal trisomy 21 cases were identified using the SSP with a sensitivity and specificity of 99.94% and 99.46%, respectively. The SSP also detected 16 trisomy 18 cases with 100% sensitivity and 99.24% specificity and 3 trisomy 13 cases with 100% sensitivity and 100% specificity. Furthermore, 15 fetuses with sex chromosome aneuploidies (10 45,X, 2 47,XYY, 2 47,XXX, and 1 47,XXY) were detected. In the prospective study, nine fetuses with trisomy 21, three with trisomy 18, three with trisomy 13, and one with 45,X were detected. To our knowledge, this is the first large-scale clinical study to systematically identify chromosomal aneuploidies based on cell-free fetal DNA using the SSP and provides an effective strategy for large-scale noninvasive screening for chromosomal aneuploidies in a clinical setting.T he incidence of chromosomal abnormalities is as high as 1 in 160 live births in the United States (1) or 1 in 60 in China (2). The incidence increases with maternal age and can reach 2.5% with maternal age over 35 in China (2). Among autosomal abnormalities, Down syndrome (trisomy 21), Edward syndrome (trisomy 18), and Patau syndrome (trisomy 13) are most compatible with survival and therefore the most clinically significant. Sex chromosome aneuploidies occur in 1 in 500 male births and 1 in 850 female births in the United States (3-6) and 1 in 450 in China (2). Turner's syndrome (45,X), Klinefelter's syndrome (47, XXY), and 47,XYY syndrome are common sex chromosome aneuploidies that are associated with fetal loss, infertility, and language developmental delays, among other defects (7-9). Fetuses with aneuploidy account for 6-11% of all stillbirths and neonatal deaths (10). The incidence of Down syndrome increases significantly with maternal age, occurring in 25 in 100,000 births with maternal age over 35 and 30 in 100,000 births with maternal age over 40 in China. There were an estimated 27,000 babies with Down syndrome born in China in 2006, which caused an economic burden of $10,000 per capita, $48,300 per family, and a total of $2.1 billion per year (11). Diagnosis of fetal chromosomal aneuploidies is the most common indication for an invasive prenatal testing procedure such as chorionic villus sampling or amniocentesis. Curren...

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“…After normalizing the read count, one z-score per chromosome was calculated to determine fetal aneuploidy [5]. Most of published NIPT studies rely on the z-score which represents the quantitative variations of the chromosome of interest and they show the results as positive or negative by checking if the z-score exceeds the predefined threshold [6].…”

Section: Sequencing (Ngs) and Bioinformatics Led To A Novel Non-invasmentioning

confidence: 99%

Multiple z-Score Based Method for Noninvasive Prenatal Test Using Cell-Free DNA in Maternal Plasma

Kwon¹,

Goyal²,

Im³

et al. 2017

OJGen

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Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women's cell-free DNA. Methods: We proposed the multi-Z method which uses 21 z-scores for each autosomal chromosome to detect aneuploidy of the chromosome, while the conventional NIPT method uses only one z-score. To do this, mapped read numbers of a certain chromosome were normalized by those of the other 21 chromosomes. Average and standard deviation (SD), which are used for calculating z-score of each sample, were obtained with normalized values between all autosomal chromosomes of control samples. In this way, multiple z-scores can be calculated for 21 autosomal chromosomes except oneself. Results: Multi-Z method showed 100% sensitivity and specificity for 187 samples sequenced to 3 M reads while the conventional NIPT method showed 95.1% specificity. Similarly, for 216 samples sequenced to 1 M reads, Multi-Z method showed 100% sensitivity and 95.6% specificity and the conventional NIPT method showed a result of 75.1% specificity. Conclusion: Multi-Z method showed higher accuracy and robust results than the conventional method even at low coverage reads.

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Noninvasive Fetal Trisomy (NIFTY) test: an advanced noninvasive prenatal diagnosis methodology for fetal autosomal and sex chromosomal aneuploidies

Cited by 148 publications

References 35 publications

Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Meta-Analysis

Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Meta-Analysis

Noninvasive prenatal diagnosis of common aneuploidies by semiconductor sequencing

Multiple z-Score Based Method for Noninvasive Prenatal Test Using Cell-Free DNA in Maternal Plasma

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