Blais Jonatan, Giroux Sylvie, Caron André, Clément Valérie, Dionne-Laporte Alexandre, Jouan Loubna, Gauthier Julie, MacLeod Tina, Moore Richard, Parker Jeremy, Swanson Lucas, Zhao Yongjun, Rouleau Guy, Karsan Aly, Langlois Sylvie, Rousseau François
Service of Medical Biochemistry, Department of Medical Biology, CHU de Québec - Université Laval, Quebec, Canada; Department of Molecular Biology, Medical Biochemistry, and Pathology, Faculty of Medicine, Université Laval, Quebec, Canada; Human and Molecular Genetics Research Unit, Research Center, CHU de Québec, Quebec, Canada.
Human and Molecular Genetics Research Unit, Research Center, CHU de Québec, Quebec, Canada.
Clin Biochem. 2018 Sep;59:69-77. doi: 10.1016/j.clinbiochem.2018.06.015. Epub 2018 Jun 27.
Non-invasive prenatal aneuploidy testing (NIPT) by next-generation sequencing of circulating cell-free DNA in maternal plasma relies on chromosomal ratio (chr) measurements to detect aneuploid values that depart from euploid ratios. Diagnostic performances are known to depend on the fraction of fetal DNA (FF) present in maternal plasma, although how this translates into specific quantitative changes in specificity/positive predictive values and which other variables might also be important is not well understood.
DESIGN & METHODS: To explore this issue, theoretical relationships between FF and various measures of diagnostic performances were assessed for a range of parameter values. Empirical data from three NIPT assays were then used to validate theoretical calculations.
For a given positivity threshold, dramatic changes in specificity and positive predictive values (PPV) as a function of both FF and the coefficient of variation (CV) of the chr measurement were observed. Theoretically predicted and observed chr z-scores agreed closely, confirming the determinant impact of small changes in both FF and chr CV.
Evaluation of NIPT assay performances therefore requires knowledge of the FF distribution in the population in which the test is intended to be used and, in particular, of the precise value of the assay chr CV for each chromosome or genomic region of interest. Laboratories offering NIPT testing should carefully measure these parameters to ensure test reliability and clinical usefulness in interpreting individual patients' results.
通过对孕妇血浆中循环游离DNA进行下一代测序的无创产前非整倍体检测（NIPT）依赖于染色体比率（chr）测量来检测偏离整倍体比率的非整倍体值。已知诊断性能取决于孕妇血浆中胎儿DNA（FF）的比例，尽管这如何转化为特异性/阳性预测值的具体定量变化以及其他哪些变量可能也很重要尚不清楚。
为探讨此问题，针对一系列参数值评估了FF与各种诊断性能指标之间的理论关系。然后使用来自三种NIPT检测的经验数据来验证理论计算。
对于给定的阳性阈值，观察到特异性和阳性预测值（PPV）随FF和chr测量变异系数（CV）的变化而发生显著变化。理论预测的和观察到的chr z分数密切一致，证实了FF和chr CV的微小变化的决定性影响。
因此，评估NIPT检测性能需要了解打算使用该检测的人群中的FF分布情况，特别是对于每个感兴趣的染色体或基因组区域的检测chr CV的精确值。提供NIPT检测的实验室应仔细测量这些参数，以确保在解释个体患者结果时检测的可靠性和临床实用性。
