Benn Peter, Cuckle Howard
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT, USA.
Prenat Diagn. 2014 Aug;34(8):778-83. doi: 10.1002/pd.4366. Epub 2014 Apr 30.
The aim of this study was to calculate the theoretical performance of non-invasive prenatal testing based on counting methods.
The calculations were based on Gaussian distributions of the percent cell-free DNA from selected chromosome regions in affected and normal pregnancies. The means were derived from the relative genomic size of the chromosome region and the fetal fraction. The standard deviations were derived from the bivariate distributions of proportional counts. Depth of sequencing was varied from 50,000,000 to 100,000 and fetal fraction from 20% to 3%. Detection rate was estimated for a fixed 0.13% false-positive rate.
When either depth or fetal fraction is high, expected Down syndrome screening detection rates are high. However, when fetal fraction is low, deeper sequencing is required to obtain high detection rates. For microdeletion and microduplication screening, deeper sequencing is routinely required to consistently achieve high detection rates. There are small differences in the ability to detect a microdeletion compared with a duplication of the same size.
While the theoretical calculations do not necessarily reflect the performance of currently available non-invasive prenatal testing tests, it confirms that fetal fraction is a key factor. Efficacy can be substantially altered depending on the abnormality under investigation and the depth of sequencing.
本研究旨在计算基于计数方法的无创产前检测的理论性能。
计算基于受影响和正常妊娠中选定染色体区域的游离DNA百分比的高斯分布。均值来自染色体区域的相对基因组大小和胎儿游离DNA比例。标准差来自比例计数的双变量分布。测序深度从50000000变化到100000，胎儿游离DNA比例从20%变化到3%。在固定的0.13%假阳性率下估计检测率。
当深度或胎儿游离DNA比例较高时，预期的唐氏综合征筛查检测率较高。然而，当胎儿游离DNA比例较低时，需要更深的测序才能获得高检测率。对于微缺失和微重复筛查，通常需要更深的测序才能持续获得高检测率。检测相同大小的微缺失与微重复的能力存在细微差异。
虽然理论计算不一定反映当前可用的无创产前检测的性能，但它证实了胎儿游离DNA比例是一个关键因素。根据所研究的异常情况和测序深度，效能可能会有很大改变。
