Author(s)

Hyuk Jung Kwon, Amit Goyal, Heesu Im, Kichan Lee, Seon Young Yun, Yoon Hee Kim, Sungjong Lee, Mi-Gyeong Lee, Hyuna Lee, Reena Garg, Boram Park, Soyoung Choi, Joungsu Joo, Jin-Sik Bae, Min-Jeong Kim, Min Seob Lee, Sunghoon Lee^*

EONE-DIAGNOMICS Genome Center Co. Ltd., Inchon, Korea.

Objective: To improve the detecting accuracy of chromosomal aneuploidy of fetus by non-invasive prenatal testing (NIPT) using next generation sequencing data of pregnant women’s cell-free DNA. Methods: We proposed the multi-Z method which uses 21 z-scores for each autosomal chromosome to detect aneuploidy of the chromosome, while the conventional NIPT method uses only one z-score. To do this, mapped read numbers of a certain chromosome were normalized by those of the other 21 chromosomes. Average and standard deviation (SD), which are used for calculating z-score of each sample, were obtained with normalized values between all autosomal chromosomes of control samples. In this way, multiple z-scores can be calculated for 21 autosomal chromosomes except oneself. Results: Multi-Z method showed 100% sensitivity and specificity for 187 samples sequenced to 3 M reads while the conventional NIPT method showed 95.1% specificity. Similarly, for 216 samples sequenced to 1 M reads, Multi-Z method showed 100% sensitivity and 95.6% specificity and the conventional NIPT method showed a result of 75.1% specificity. Conclusion: Multi-Z method showed higher accuracy and robust results than the conventional method even at low coverage reads.

Cell-Free DNA, z-Score, Multiple Thresholds, Coefficient of Variance, Noninvasive Prenatal Testing, NIPT

Kwon, H. , Goyal, A. , Im, H. , Lee, K. , Young Yun, S. , Hee Kim, Y. , Lee, S. , Lee, M. , Lee, H. , Garg, R. , Park, B. , Choi, S. , Joo, J. , Bae, J. , Kim, M. , Lee, M. and Lee, S. (2017) Multiple z-Score Based Method for Noninvasive Prenatal Test Using Cell-Free DNA in Maternal Plasma. Open Journal of Genetics, 7, 1-8. doi: 10.4236/ojgen.2017.71001.