DNA-Damage

背景概念

生物学真实损伤和实验引入损伤间的差异。

DNA易受多种损伤,其中之一就是氧化损伤。随着时间的推移,这种类型的损害会逐渐累积,破坏修复系统,导致健康问题,最终导致疾病。

在生理环境下,一旦某一个碱基发生改变如果没有被错配修复蛋白处理掉,这种错配可以传递给子代,形成突变,一个真实的突变正模板链和对应负模板链应同时被替换

如果碱基改变是发生在实验阶段,那么其对应链不会发生改变,正链发生G>8-oxoG的改变时,由于其可与A配对,易被测序仪读成T,但对应的负链C碱基,仍会被读为C,而不是A

正负链 真实突变 假突变
正链:5’-3’ 5’- ATC$\color{red}{G}$ATCG-3 5’- ATC$\color{red}{G}$ATCG-3
负链:3’-5’ 3’- TAG$\color{red}{A}$TAGC-5 3’- TAG$\color{red}{C}$TAGC-5

NGS识别氧化损伤的技术基础

处理方式

参考文献[16]

参考资料

文献

  1. Characterization of background noise in capture-based targeted sequencing data
  2. FIREVAT: finding reliable variants without artifacts in human cancer samples using etiologically relevant mutational signatures
  3. Sequence Neighborhoods Enable Reliable Prediction of Pathogenic Mutations in Cancer Genomes
  4. Needlestack: an ultra-sensitive variant caller for multi-sample next generation sequencing data
  5. Location analysis of 8-oxo-7,8-dihydroguanine in DNA by polymerase-mediated differential coding
  6. Targeted Single Primer Enrichment Sequencing with Single End Duplex-UMI
  7. Analysis of error profiles in deep next-generation sequencing data
  8. The use of technical replication for detection of low-level somatic mutations in next-generation sequencing
  9. Allele balance bias identifies systematic genotyping errors and false disease associations
  10. Overview of Next-Generation Sequencing Technologies
  11. Detecting Somatic Mutations in Normal Cells
  12. Detecting Rare Mutations and DNA Damage with Sequencing-Based Methods
  13. IMPUTOR: Phylogenetically Aware Software for Imputation of Errors in Next-Generation Sequencing
  14. UDiTaS™, a genome editing detection method for indels and genome rearrangements
  15. Reference standards for next-generation sequencing
  16. Discovery and characterization of artifactual mutations in deep coverage targeted capture sequencing data due to oxidative DNA damage during sample preparation

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