Format

Send to

Choose Destination
BMC Med Genomics. 2016 Oct 3;9(1):61.

An adaptive detection method for fetal chromosomal aneuploidy using cell-free DNA from 447 Korean women.

Author information

1
GenomeCare, Suwon, Republic of Korea.
2
Mirae & Heemang OB/GYN Clinic, Seoul, Republic of Korea.
3
Seoul Clinical Laboratories (SCL), Yongin, Republic of Korea.
4
Namujungwon Maternity Hospital, Yangju, Republic of Korea.
5
GN Maternity Hospital, Pyeongtak, Republic of Korea.
6
Department of Nanobiomedical Science, BK21 PLUS NBM Global Research Center for, Regenerative Medicine, Dankook University, Cheonan, Republic of Korea.
7
TheragenEtex, Suwon, Republic of Korea.
8
The Genomics Institute (TGI), BioMedical Engineering, UNIST, Ulsan, 687-798, Republic of Korea.
9
Xiamen Vangenes BioTech, Xiamen, Fujian, China.
10
Xiamen Vangenes BioTech, Xiamen, Fujian, China. chenhl@vangenes.com.
11
GenomeCare, Suwon, Republic of Korea. jongbhak@genomics.org.
12
The Genomics Institute (TGI), BioMedical Engineering, UNIST, Ulsan, 687-798, Republic of Korea. jongbhak@genomics.org.
13
Geromics, Ulsan, 687-798, Republic of Korea. jongbhak@genomics.org.
14
Genome Research Foundation, Osong, Chungbuk, Republic of Korea. jongbhak@genomics.org.

Abstract

BACKGROUND:

Noninvasive prenatal testing (NIPT) using massively parallel sequencing of cell-free DNA (cfDNA) is increasingly being used to predict fetal chromosomal abnormalities. However, concerns over erroneous predictions which occur while performing NIPT still exist in pregnant women at high risk for fetal aneuploidy. We performed the largest-scale clinical NIPT study in Korea to date to assess the risk of false negatives and false positives using next-generation sequencing.

METHODS:

A total of 447 pregnant women at high risk for fetal aneuploidy were enrolled at 12 hospitals in Korea. They underwent definitive diagnoses by full karyotyping by blind analysis and received aneuploidy screening at 11-22 weeks of gestation. Three steps were employed for cfDNA analyses. First, cfDNA was sequenced. Second, the effect of GC bias was corrected using normalization of samples as well as LOESS and linear regressions. Finally, statistical analysis was performed after selecting a set of reference samples optimally adapted to a test sample from the whole reference samples. We evaluated our approach by performing cfDNA testing to assess the risk of trisomies 13, 18, and 21 using the sets of extracted reference samples.

RESULTS:

The adaptive selection algorithm presented here was used to choose a more optimized reference sample, which was evaluated by the coefficient of variation (CV), demonstrated a lower CV and higher sensitivity than standard approaches. Our adaptive approach also showed that fetal aneuploidies could be detected correctly by clearly splitting the z scores obtained for positive and negative samples.

CONCLUSIONS:

We show that our adaptive reference selection algorithm for optimizing trisomy detection showed improved reliability and will further support practitioners in reducing both false negative and positive results.

KEYWORDS:

Adaptive detection algorithm; Circulating fetal DNA; Genome; Non-invasive prenatal testing; Sequencing; Trisomy

PMID:
27716407
PMCID:
PMC5048604
DOI:
10.1186/s12920-016-0222-5
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center