DNA 损伤是排序错误的普遍原因,直接混变体识别
Lixin Chen1, Pingfang Liu1, Thomas C Evans2
1New England Biolabs Inc., 240 County Road, Ipswich, MA 01938-2723, USA.
概括
突变性损伤经常导致DNA测序中的错误,导致错误识别的体质变异. 这种普遍的问题影响了主要的基因组数据库,
科学领域:
- 基因组学
- 分子生物学
- 生物信息学
背景情况:
- 细胞中的体质突变导致包括癌症在内的多种病理.
- DNA测序的进步揭示了影响各种表型的细胞特异性变异.
- 准确识别体变异对于了解疾病机制至关重要.
研究的目的:
- 调查突变性损伤对低频体变异的准确识别的影响.
- 在大规模测序数据集中确定突变性损伤特征的流行率.
- 评估DNA损伤如何混体变体检测.
主要方法:
- 分析来自公共资源的DNA测序数据.
- 突变性损伤标志的识别和表征
- 测量因DNA损伤造成的测序错误.
- 在受损与未受损样本中对变异调用进行比较 (隐含).
主要成果:
- 突变性损伤是错误识别的低至中等频率变异的主要原因 (1-5%).
- 在包括1000个基因组项目和癌症基因组图谱在内的主要测序数据集中,存在DNA损伤的迹象.
- DNA损伤的程度显著混了体质变异的准确确定.
结论:
- 不仅在癌症中,而且在各种基因组研究中,
- 仅依靠当前的测序数据可能导致对体变异景观的误解.
- 未来的基因组分析必须考虑突变性损伤,以确保变异的准确性和可靠的生物学结论.
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