Performance Evaluation of NIPT in Detection of Chromosomal Copy Number Variants Using Low-Coverage Whole-Genome Sequencing of Plasma DNA

• Published in: PloS one Vol. 11; no. 7; p. e0159233
• Main Authors: Liu, Hongtai, Gao, Ya, Hu, Zhiyang, Lin, Linhua, Yin, Xuyang, Wang, Jun, Chen, Dayang, Chen, Fang, Jiang, Hui, Ren, Jinghui, Wang, Wei
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.07.2016; Public Library of Science (PLoS)
• Subjects: Adult; Age; Analysis; Biology; Biology and Life Sciences; Copy number; Copy number variations; Deoxyribonucleic acid; Disease; DNA; DNA - blood; DNA - genetics; DNA Copy Number Variations - genetics; DNA microarrays; DNA sequencing; Female; Fetuses; Gene sequencing; Genetic counseling; Genetics; Genome, Human - genetics; Genomes; Gestational Age; High-Throughput Nucleotide Sequencing - methods; Hospitals; Humans; Karyotyping; Medical diagnosis; Medicine and Health Sciences; Noninvasive diagnosis; Nucleotide sequence; Performance evaluation; Plasma; Pregnancy; Prenatal Diagnosis - methods; Reproduction (copying); Research and Analysis Methods; Sensitivity; Sensitivity analysis; Sensitivity and Specificity; Ultrasonic imaging; Young Adult; Denmark; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0159233

The aim of this study was to assess the performance of noninvasively prenatal testing (NIPT) for fetal copy number variants (CNVs) in clinical samples, using a whole-genome sequencing method. A total of 919 archived maternal plasma samples with karyotyping/microarray results, including 33 CNVs samples and 886 normal samples from September 1, 2011 to May 31, 2013, were enrolled in this study. The samples were randomly rearranged and blindly sequenced by low-coverage (about 7M reads) whole-genome sequencing of plasma DNA. Fetal CNVs were detected by Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS) to compare to the karyotyping/microarray results. Sensitivity, specificity and were evaluated. 33 samples with deletions/duplications ranging from 1 to 129 Mb were detected with the consistent CNV size and location to karyotyping/microarray results in the study. Ten false positive results and two false negative results were obtained. The sensitivity and specificity of detection deletions/duplications were 84.21% and 98.42%, respectively. Whole-genome sequencing-based NIPT has high performance in detecting genome-wide CNVs, in particular >10Mb CNVs using the current FCAPS algorithm. It is possible to implement the current method in NIPT to prenatally screening for fetal CNVs.