A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing
A method for noninvasive detection of fetal large deletions/duplications by low coverage massively parallel sequencing
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DOI：
10.1002/pd.4110
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发表时间：
2013-06-01
影响因子：
3
通讯作者：
Zhang, Xiuqing
中科院分区：
文献类型：
--
作者：
Chen, Shengpei;Lau, Tze Kin;Zhang, Xiuqing
目的 报告利用母体血浆低覆盖度全基因组测序的新型生物信息学方法检测胎儿染色体缺失/重复的可行性。方法 开发了一种实用的母体血浆测序胎儿拷贝数分析 (FCAPS) 方法，结合 GC 偏差校正、二元分割算法和动态阈值策略，通过低覆盖度全基因组测序（约 0.08 倍）检测 >10Mb 的胎儿染色体缺失/重复。首先通过计算机评估所得到的 FCAPS 算法在检测缺失/重复方面的敏感性/特异性，然后在来自已知胎儿 G 带核型分析结果的 1311 个母体血浆样本中进行测试。结果 1311份样本中，4份疑似存在缺失/重复，范围为9.01～28.46Mb，其中3份与胎儿核型分析结果一致。在一例中，疑似异常并未通过核型分析得到证实，属于假阳性病例。其余1307份低风险样本中未发现假阴性病例。检测 >10 Mb 染色体缺失/重复的灵敏度和特异性分别为 100% 和 99.92%。结论 我们的研究表明，FCAPS 具有利用目前用于胎儿非整倍体检测的低覆盖率母体血浆 DNA 测序来检测胎儿大缺失/重复 (>10Mb) 的潜力。 (c) 2013 约翰·威利父子有限公司
Objective To report the feasibility of fetal chromosomal deletion/duplication detection using a novel bioinformatic method of low coverage whole genome sequencing of maternal plasma. Method A practical method Fetal Copy-number Analysis through Maternal Plasma Sequencing (FCAPS), integrated with GC-bias correction, binary segmentation algorithm and dynamic threshold strategy, was developed to detect fetal chromosomal deletions/duplications of >10Mb by low coverage whole genome sequencing (about 0.08-fold). The sensitivity/specificity of the resultant FCAPS algorithm in detecting deletions/duplications was firstly assessed in silico and then tested in 1311 maternal plasma samples from those with known G-banding karyotyping results of the fetus. Results Deletions/duplications, ranged from 9.01 to 28.46Mb, were suspected in four of the 1311 samples, of which three were consistent with the results of fetal karyotyping. In one case, the suspected abnormality was not confirmed by karyotyping, representing a false positive case. No false negative case was observed in the remaining 1307 low-risk samples. The sensitivity and specificity for detection of >10-Mb chromosomal deletions/duplications were100% and 99.92%, respectively. Conclusion Our study demonstrated FCAPS has the potential to detect fetal large deletions/duplications (>10Mb) with low coverage maternal plasma DNA sequencing currently used for fetal aneuploidy detection. (c) 2013 John Wiley & Sons, Ltd.