title: An Optimized Method for Accurate Fetal Sex Prediction and Sex Chromosome Aneuploidy Detection in Non-Invasive Prenatal Testing.
abstract: Massively parallel sequencing (MPS) combined with bioinformatic analysis has been widely applied to detect fetal chromosomal aneuploidies such as trisomy 21, 18, 13 and sex chromosome aneuploidies (SCAs) by sequencing cell-free fetal DNA (cffDNA) from maternal plasma, so-called non-invasive prenatal testing (NIPT). However, many technical challenges, such as dependency on correct fetal sex prediction, large variations of chromosome Y measurement and high sensitivity to random reads mapping, may result in higher false negative rate (FNR) and false positive rate (FPR) in fetal sex prediction as well as in SCAs detection. Here, we developed an optimized method to improve the accuracy of the current method by filtering out randomly mapped reads in six specific regions of the Y chromosome. The method reduces the FNR and FPR of fetal sex prediction from nearly 1% to 0.01% and 0.06%, respectively and works robustly under conditions of low fetal DNA concentration (1%) in testing and simulation of 92 samples. The optimized method was further confirmed by large scale testing (1590 samples), suggesting that it is reliable and robust enough for clinical testing.
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Quanze
authors.initials: Q
authors.lastname: He
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Li
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ding
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Wen
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Xiang
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Li
authors.affiliation: Basecare Medical Device Co., Ltd., Suzhou, Jiangsu, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Xuan
authors.affiliation: Basecare Medical Device Co., Ltd., Suzhou, Jiangsu, China.
authors.forename: Lingyin
authors.initials: L
authors.lastname: Kong
authors.affiliation: Basecare Medical Device Co., Ltd., Suzhou, Jiangsu, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Basecare Medical Device Co., Ltd., Suzhou, Jiangsu, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Basecare Medical Device Co., Ltd., Suzhou, Jiangsu, China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Shen
authors.affiliation: School of Life Sciences & Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Liang
authors.affiliation: Center for Reproduction and Genetics, Nanjing Medical University Affiliated Suzhou Hospital, Suzhou, Jiangsu, 215002, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D000782:Aneuploidy; D002874:Chromosome Mapping; D041322:Chromosomes, Human, Y / Q000235:genetics; D004247:DNA / Q000235:genetics*; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D011247:Pregnancy; D011296:Prenatal Diagnosis / Q000379:methods*; D015203:Reproducibility of Results; D012730:Sex Chromosomes / Q000235:genetics*; D012732:Sex Determination Analysis / Q000379:methods*; D055815:Young Adult
chemical_list: D004247:DNA