Performances of NIPT for copy number variations at different sequencing depths using the semiconductor sequencing platform

Yang, Jing; Wu, Jing; Peng, Haishan; Hou, Yaping; Guo, Fang; Wang, Dongmei; Ouyang, Haoxin; Wang, Yixia; Yin, Aihua

doi:10.1186/s40246-021-00332-5

Cited by 16 publications

(27 citation statements)

References 27 publications

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“…Surprisingly, we did observe that the larger the CNV size, the lower the PPV. While some studies have reported that the PPV of CNVs > 10 Mb is the lowest [15,24], we could not obtain strong evidence to explain this strange problem. We conjecture that this may be attributed to the interference of chromosomal location of CNVs with the PPV estimation.…”

Section: Discussioncontrasting

confidence: 91%

“…Only a few reports have assessed the detection rate of some varieties of MMs. Our study reported that the PPV for NIPS with low-coverage sequencing depth for detection of fetal CNVs (38.5%) was higher than that reported in similar studies, such as those reported by Yang (30.96%) [24], Hu (36.11%) [16] and Chen (28.99%) [15]. Recently, it has been reported that the PPV could improve with high-coverage sequencing.…”

Section: Discussioncontrasting

confidence: 50%

“…Recently, it has been reported that the PPV could improve with high-coverage sequencing. This is evident in the findings of Yang's group upon comparing the PPV of two NIPS data with different sequencing depths, where they found that the PPV of NIPS Plus (0.4X) was 12.65% higher than that of NIPS (0.15X) (43.61% vs. 30.96%) [24]. Shi et al also reported that the PPV of NIPS Plus for detection of MMs with unremarkable ultrasound findings was 50% [18].…”

Section: Discussionmentioning

confidence: 96%

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Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants

Wang

Zhang

et al. 2022

Orphanet J Rare Dis

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Objective This study explores and discusses the possible factors affecting the positive predictive value (PPV) of non-invasive prenatal screening (NIPS) for the detection of fetal copy number variants (CNVs) in pregnant women. Methods NIPS was performed for 50,972 pregnant women and 212 cases were suspected as fetal CNVs. Post additional genetic counseling for these women, 96 underwent invasive prenatal diagnosis (amniocentesis), following which they received chromosomal microarray analysis (CMA). We analyzed the PPV of NIPS for the detection of fetal CNVs and the possible interference factors that could affect the PPV. Results Among the 96 pregnant women that received prenatal diagnosis by CMA, 37 cases were confirmed to be true positive for fetal CNVs with a PPV of 38.5%. There was no significant difference between the women with different NIPS indications. Five cases were reported as the false positive and false negative of fetal CNVs and the differences were mainly reflected in the inconsistency of chromosome fragments. Depending on the sizes of the CNVs, the PPVs were 48.7% for CNVs < 3 Mb, 41.4% for CNVs falling within 3 ~ 5 Mb, 42.9% for the CNVs falling within 5 ~ 10 Mb, and 14.3% for CNVs > 10 Mb. Based on the chromosomal locations of CNVs, the PPV(4.8%) of the chromosomes of group C(including chromosomes 6 ~ 12), was lower than that of the other groups (41.2% ~ 66.7%) (p = 0.021). However, there were no significant differences in the CNV characteristics, fetal fractions, unique reads, and the Z-scores between these groups. Conclusion NIPS with a low-coverage sequencing depth has a certain effect on detection of fetal CNVs with the PPV of 38.5%. Chromosomal locations of CNVs may be the main factor that influences its effect. This study can contribute to an increased accuracy in genetic counseling and in predicting NIPS results that are positive for fetal CNVs.

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Section: Discussioncontrasting

confidence: 91%

Section: Discussioncontrasting

confidence: 50%

Section: Discussionmentioning

confidence: 96%

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Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants

Wang

Zhang

et al. 2022

Orphanet J Rare Dis

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“…The detection of chromosome abnormalities and pCNVs in pregnancies with different indications was analysed in our study. Growing evidence has revealed that NIPT dramatically improves the detection of common aneuploidies and pCNVs 25 , 26 . Consistent with these reports, the detection rates of aneuploidies and pCNVs in pregnancies with an increased NIPT risk were elevated significantly in our study.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the combined use of CNV-seq and karyotyping or QF-PCR in prenatal diagnosis: a retrospective study

Zhang

Chen

et al. 2023

Sci Rep

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To elevate the accuracy of diagnostic results, CNV-seq is usually performed simultaneously with karyotyping or QF-PCR. Although several studies have investigated the performance of the combined use of CNV-seq with karyotyping or QF-PCR, there have been no reports focusing on the comparison of these 2 diagnostic strategies. In our study, 2507 pregnant women were included to investigate these 2 strategies. The detection rates of foetal genetic abnormalities and turnaround time were compared between these 2 groups. Moreover, the detection rates of foetal genetic abnormalities in different indications were analyzed. Our results unveiled that the detection rates of numerical chromosomal abnormalities were nearly the same in these 2 groups. In addition to numerical chromosomal abnormalities, 39 balanced karyotypic changes and chromosome polymorphisms were detected via the combined use of karyotyping and CNV-seq. Further investigation revealed that the vast majority of these karyotypic changes were inherited from parents. Compared with the karyotyping group, the combination of QF-PCR and CNV-seq reduced the reporting time from 31.593 ± 4.944 days to 11.460 ± 4.894 days. Meanwhile, NIPT, maternal serum screening and ultrasound scan significantly improved the detection of foetal genetic abnormalities. In conclusion, our results revealed that parental karyotyping is a useful supplementary method for CNV-seq and systematic prenatal examinations improved the detection of foetal genetic defects.

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“…Most providers disclose CNVs that are expected to be clinically relevant and potentially actionable. The positive predictive value (PPV) for CNVs is significantly lower than that of common trisomies [ 3 , 4 ], but it is still higher than that of sex chromosomal aneuploidies, particularly monosomy X [ 5 ]. Since the vast majority of cell-free (cf) DNA is derived from the maternal genome, genome-wide approaches primarily reveal maternal imbalances with much higher resolution than fetal imbalances, even with low-coverage genomic sequencing.…”

Section: Introductionmentioning

confidence: 99%

Maternal Copy Number Imbalances in Non-Invasive Prenatal Testing: Do They Matter?

et al. 2022

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Non-invasive prenatal testing (NIPT) has become a routine practice in screening for common aneuploidies of chromosomes 21, 18, and 13 and gonosomes X and Y in fetuses worldwide since 2015 and has even expanded to include smaller subchromosomal events. In fact, the fetal fraction represents only a small proportion of cell-free DNA on a predominant background of maternal DNA. Unlike fetal findings that have to be confirmed using invasive testing, it has been well documented that NIPT provides information on maternal mosaicism, occult malignancies, and hidden health conditions due to copy number variations (CNVs) with diagnostic resolution. Although large duplications or deletions associated with certain medical conditions or syndromes are usually well recognized and easy to interpret, very little is known about small, relatively common copy number variations on the order of a few hundred kilobases and their potential impact on human health. We analyzed data from 6422 NIPT patient samples with a CNV detection resolution of 200 kb for the maternal genome and identified 942 distinct CNVs; 328 occurred repeatedly. We defined them as multiple occurring variants (MOVs). We scrutinized the most common ones, compared them with frequencies in the gnomAD SVs v2.1, dbVar, and DGV population databases, and analyzed them with an emphasis on genomic content and potential association with specific phenotypes.

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Performances of NIPT for copy number variations at different sequencing depths using the semiconductor sequencing platform

Cited by 16 publications

References 27 publications

Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants

Clinical evaluation of non-invasive prenatal screening for the detection of fetal genome-wide copy number variants

Comparison of the combined use of CNV-seq and karyotyping or QF-PCR in prenatal diagnosis: a retrospective study

Maternal Copy Number Imbalances in Non-Invasive Prenatal Testing: Do They Matter?

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