Strom Charles M, Anderson Ben, Tsao David, Zhang Ke, Liu Yan, Livingston Kayla, Elzinga Christopher, Evans Matthew, Nguyen Quoclinh, Wolfson David, Rowland Charles, Kolacki Paula, Maxwell Megan, Wang Jia-Chi, Rabin Douglas, Catanese Joseph, Owen Renius, Braastad Corey, Sun Weimin
Quest Diagnostics Nichols Institute, San Juan Capistrano, California, United States of America.
Athena Diagnostics, Marlborough, Massachusetts, United States of America.
PLoS One. 2017 Mar 1;12(3):e0167130. doi: 10.1371/journal.pone.0167130. eCollection 2017.
We evaluated performance characteristics of a laboratory-developed, non-invasive prenatal screening (NIPS) assay for fetal aneuploidies. This assay employs massively parallel shotgun sequencing with full automation. GC sequencing bias correction and statistical smoothing were performed to enhance discrimination of affected and unaffected pregnancies. Maternal plasma samples from pregnancies with known aneuploidy status were used for assay development, verification, and validation. Assay verification studies using 2,085 known samples (1873 unaffected, 69 trisomy 21, 20 trisomy 18, 17 trisomy 13) demonstrated complete discrimination between autosomal trisomy (Z scores >8) and unaffected (Z scores <4) singleton pregnancies. A validation study using 552 known samples (21 trisomy 21, 10 trisomy 18, 1 trisomy 13) confirmed complete discrimination. Twin pregnancies showed similar results. Follow-up of abnormal results from the first 10,000 clinical samples demonstrated PPVs of 98% (41/42) for trisomy 21, 92% (23/25) for trisomy 18, and 69% (9/13) for trisomy 13. Adjustment for causes of false-positive results identified during clinical testing (eg, maternal duplications) improved PPVs to 100% for trisomy 21 and 96% for trisomy 18. This NIPS test demonstrates excellent discrimination between trisomic and unaffected pregnancies. The PPVs obtained in initial clinical testing are substantially higher than previously reported NIPS methods.
我们评估了一种实验室研发的用于胎儿非整倍体检测的无创产前筛查（NIPS）检测方法的性能特征。该检测方法采用全自动化的大规模平行鸟枪法测序。进行了GC测序偏差校正和统计平滑处理，以增强对受影响和未受影响妊娠的区分能力。来自已知非整倍体状态妊娠的孕妇血浆样本用于检测方法的开发、验证和确认。使用2085份已知样本（1873份未受影响样本、69份21三体样本、20份18三体样本、17份13三体样本）进行的检测验证研究表明，常染色体三体（Z值>8）和未受影响（Z值<4）的单胎妊娠之间能够完全区分。使用552份已知样本（21份21三体样本、10份18三体样本、1份13三体样本）进行的验证研究证实了完全区分。双胎妊娠显示出类似结果。对前10000份临床样本的异常结果进行随访显示，21三体的阳性预测值为98%（41/42），18三体为92%（23/25），13三体为69%（9/13）。对临床检测期间确定的假阳性结果原因（如母体重复）进行调整后，21三体的阳性预测值提高到100%，18三体提高到96%。这种NIPS检测方法在三体妊娠和未受影响妊娠之间显示出优异的区分能力。初始临床检测中获得的阳性预测值显著高于先前报道的NIPS方法。
