基于荷兰NGS的新生儿查的未来:探索技术可能性和评估变种分类策略的评估
Gea Kiewiet1, Dineke Westra2, Eddy N de Boer1
1Department of Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands.
International journal of neonatal screening
|March 27, 2024
概括
下一代测序 (NGS) 方法,包括向面板 (tNGS),全外体测序 (WES) 和全基因组测序 (WGS),对新生儿查 (NBS) 有希望. 包括意义不明的变体 (VUS) 在内,改善了遗传代谢障碍的变体检测准确性.
科学领域:
- 基因组学就是基因组学.
- 医学遗传学 医学遗传学
- 新生儿医学 新生儿医学
背景情况:
- 新生儿查 (NBS) 对于早期发现遗传代谢障碍 (IMD) 至关重要.
- 下一代测序 (NGS) 为IMDs提供了先进的遗传分析能力.
- 评估NBS的不同NGS方法 (tNGS,WES,WGS) 是必不可少的.
研究的目的:
- 为了比较针对性小组 (tNGS),全外体测序 (WES) 和全基因组测序 (WGS) 在新生儿查中的性能.
- 评估不同变异过策略对NBS诊断准确性的影响.
- 确定在NBS工作流程中实施NGS的可行性.
主要方法:
- 来自50名IMD患者和50名对照者的DNA使用tNGS,WES和WGS进行了分析.
- 一百个IMD相关基因被作为变异分析的目标.
- 采用了两种过策略: (可能) 致病性 (L) P) 变种,以及 (L) P 变种加上未知意义的变种 (VUS).
- 变种解释定义了真假阳性和阴性,与4833个人的背景队列进行验证.
主要成果:
- 在5天内获得了可靠的结果.
- 包括VUS在过中增加了tNGS,WES和WGS的真正阳性 (TP) 率.
- 当包括VUS时,假阴性 (FN) 率下降,同卵性VUS是剩余FN的主要原因.
- 所有对照样本都是真阴性 (TN).
- 背景队列中的三个人具有与轻度表型相关的同卵性 (L) P变体.
结论:
- 基于NGS的工作流对新生儿查应用有希望.
- 临床实施需要进一步发展数据处理,自动化变体解释和成本效益.
- 将VUS纳入变异过策略可以提高NBS中IMD的检测.
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