Prenatal Screening and Diagnosis Center, Nantong Municipal Maternal and Child Health Hospital, Nantong, 226010 Jiangsu, China.
Basecare Medical Device Co., Ltd., Suzhou, Jiangsu, China.
Biomed Res Int. 2020 Jul 25;2020:4712657. doi: 10.1155/2020/4712657. eCollection 2020.
Noninvasive Prenatal Testing (NIPT) has advanced the detection of fetal chromosomal aneuploidy by analyzing cell-free DNA in peripheral maternal blood. The statistic -test that it utilizes, which measures the deviation of each chromosome dosage from its negative control, is now widely accepted in clinical practice. However, when a chromosome has loss and gain regions which offset each other in the -score calculation, merely using the -test for the result tends to be erroneous. To improve the performance of NIPT in this aspect, a novel graphic-aided algorithm (gNIPT) that requires no extra experiment procedures is reported in this study. In addition to the -test, this method provides a detailed analysis of each chromosome by dividing each chromosome into multiple 2 Mb size windows, calculating the -score and copy number variation of each window, and visualizing the -scores for each chromosome in a line chart. Data from 13537 singleton pregnancy women were analyzed and compared using both the normal NIPT (nNIPT) analysis and the gNIPT method. The gNIPT method had significantly improved the overall positive predictive value (PPV) of nNIPT (88.14% vs. 68.00%, = 0.0041) and the PPV for trisomy 21 (T21) detection (93.02% vs. 71.43%, = 0.0037). There were no significant differences between gNIPT and nNIPT in PPV for trisomy 18 (T18) detection (88.89% vs. 63.64%, = 0.1974) and in PPV for trisomy 13 (T13) detection (57.14% vs. 50.00%, = 0.8004). One false-negative T18 case in nNIPT was detected by gNIPT, which demonstrates the potency of gNIPT in discerning chromosomes that have variation in multiple regions with an offsetting effect in -score calculation. The gNIPT was also able to detect copy number variation (CNV) in chromosomes, and one case with pathogenic CNV was detected during the study. With no additional test requirement, gNIPT presents a reasonable solution in improving the accuracy of normal NIPT.
非侵入性产前检测 (NIPT) 通过分析母体外周血中的游离 DNA 来提高胎儿染色体非整倍体的检测率。目前，该检测方法利用统计检验来测量每个染色体剂量与阴性对照之间的偏差，在临床实践中得到广泛认可。然而，当染色体存在相互抵消的缺失和增益区域时，仅使用 -检验进行结果分析往往会出现错误。为了提高 NIPT 在这方面的性能，本研究报告了一种不需要额外实验程序的新型图形辅助算法 (gNIPT)。除了 -检验外，该方法还通过将每条染色体分为多个 2 Mb 大小的窗口，计算每个窗口的 -评分和拷贝数变异，并在线性图中显示每条染色体的 -评分，从而对每条染色体进行详细分析。对 13537 例单胎妊娠女性的数据进行了分析，并分别采用正常 NIPT (nNIPT) 分析和 gNIPT 方法进行了比较。gNIPT 方法显著提高了 nNIPT 的总体阳性预测值 (PPV) (88.14% 比 68.00%， = 0.0041)，以及检测三体 21 (T21) 的 PPV (93.02% 比 71.43%， = 0.0037)。gNIPT 与 nNIPT 在检测三体 18 (T18) 的 PPV (88.89% 比 63.64%， = 0.1974)和检测三体 13 (T13) 的 PPV (57.14% 比 50.00%， = 0.8004) 方面没有显著差异。nNIPT 中一个假阴性 T18 病例被 gNIPT 检测到，这表明 gNIPT 在辨别 -评分计算中存在多个区域变化且相互抵消影响的染色体方面具有潜力。gNIPT 还能够检测染色体的拷贝数变异 (CNV)，研究期间检测到一个致病性 CNV 病例。gNIPT 无需额外的测试要求，为提高正常 NIPT 的准确性提供了合理的解决方案。
