Systematic evaluation of NIPT aneuploidy detection software tools with clinically validated NIPT samples

• Main Authors: Ardeshirdavani, A. (Author), Bayindir, B. (Author), Krjutškov, K. (Author), Palta, P. (Author), Paluoja, P. (Author), Salumets, A. (Author), Teder, H. (Author), Vermeesch, J. (Author)
• Format: Article
• Language: English
• Published: Public Library of Science 2021
• Subjects: aneuploidy; Aneuploidy; Article; biology; Computational Biology; computer assisted diagnosis; controlled study; Diagnosis, Computer-Assisted; diagnostic accuracy; diagnostic test accuracy study; diagnostic value; Down syndrome; Edwards syndrome; false negative result; female; Female; fetus; human; Humans; major clinical study; male; mathematical model; noninvasive prenatal testing; Noninvasive Prenatal Testing; pregnancy; Pregnancy; procedures; software; Software; trisomy 13; trisomy 18; trisomy 21; whole genome sequencing; Whole Genome Sequencing
• Online Access: View Fulltext in Publisher

 Non-invasive prenatal testing (NIPT) is a powerful screening method for fetal aneuploidy detection, relying on laboratory and computational analysis of cell-free DNA. Although several published computational NIPT analysis tools are available, no prior comprehensive, head-to-head accuracy comparison of the various tools has been published. Here, we compared the outcome accuracies obtained for clinically validated samples with five commonly used computational NIPT aneuploidy analysis tools (WisecondorX, NIPTeR, NIPTmer, RAPIDR, and GIPseq) across various sequencing depths (coverage) and fetal DNA fractions. The sample set included cases of fetal trisomy 21 (Down syndrome), trisomy 18 (Edwards syndrome), and trisomy 13 (Patau syndrome). We determined that all of the compared tools were considerably affected by lower sequencing depths, such that increasing proportions of undetected trisomy cases (false negatives) were observed as the sequencing depth decreased. We summarised our benchmarking results and highlighted the advantages and disadvantages of each computational NIPT software. To conclude, trisomy detection for lower coverage NIPT samples (e.g. 2.5M reads per sample) is technically possible but can, with some NIPT tools, produce troubling rates of inaccurate trisomy detection, especially in low-FF samples. © 2021 Paluoja et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.