一种计算型DNA甲基化方法,用于从已耗尽的胚胎培养基中去除受污染的DNA,用于非侵入性植入前遗传测试
Yidong Chen1, Jin Huang1, Fuchou Tang2
1Biomedical Pioneering Innovation Center, State Key Laboratory of Female Fertility Promotion, Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Third Hospital, School of Life Sciences, Peking University, Beijing, China; Beijing Advanced Innovation Center for Genomics, Third Hospital, Peking University, Beijing, China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, China.
EBioMedicine
|March 30, 2025
概括
一种新的计算方法有效地减少了已耗尽胚胎培养基中的非胚胎DNA污染,改善了用于非侵入性植入前遗传测试 (niPGT) 的积体检测. 这提高了niPGT在辅助生殖技术 (ART) 中的潜力.
科学领域:
- 遗传学 是一个遗传学.
- 生殖生物学 生殖生物学
- 生物信息学是一种生物信息学.
背景情况:
- 辅助生殖技术 (ART) 已经导致了1200万个出生,而植入前遗传检测 (PGT) 对于胚胎选择至关重要.
- 目前的PGT方法,如托菲克托皮 (TE) 活检具有局限性,引发了人们对使用已用胚胎培养基 (SECM) 的无细胞DNA (cfDNA) 的非侵入性PGT (niPGT) 的兴趣.
- 在SECM中母体DNA污染是niPGT临床应用的重大障碍,需要创新的解决方案.
研究的目的:
- 开发和验证一种计算算法,以消除来自SECM的非胚胎DNA污染.
- 通过解决DNA污染问题,提高niPGT中形体检测的准确性和灵敏性.
主要方法:
- 一个计算算法是基于这样一个原则开发的:在全球去甲基化波中,胚胎细胞DNA被低甲基化.
- 该算法选择低甲基化cfDNA读取以丰富胚胎DNA而不是污染非胚胎DNA (积分细胞,极体,精子).
- 来自卵细胞,ICM,TE,精子,累积细胞和SECM样本的DNA甲基化数据被分析来构建和测试算法.
主要成果:
- 该算法成功丰富了胚胎细胞DNA,而不是污染了具有显著丰富因子的DNA来源.
- 模拟的SECM样本显示,虚假阴性率大幅降低,即使污染率高达75%.
- 临床SECM样本显示,随着50%的累积细胞污染,状体检测灵敏度有所提高.
结论:
- 一种新的计算策略有效地减少了SECM cfDNA中的非胚胎DNA污染.
- 这种方法增强了积体检测的灵敏度,为ART中的niPGT提供了有前途的进展.
- 开发的方法与DNA甲基化分析相结合,具有改善niPGT应用的巨大潜力.
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