A virtual sequencer reveals the dephasing patterns in error-correction code DNA sequencing  

作　　者：Wenxiong Zhou Li Kang Haifeng Duan Shuo Qiao Louis Tao Zitian Chen Yanyi Huang 

机构地区：[1]Biomedical Pioneering Innovation Center(BIOPIC),School of Life Sciences,Beijing Advanced Innovation Center for Genomics(ICG),and Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China [2]Center for Bioinformatics,State Key Laboratory of Protein Engineering and Plant Genetic Engineering,Peking University,Beijing 100871,China [3]Center for Quantitative Biology,Peking University,Beijing 100871,China [4]College of Engineering,Peking University,Beijing 100871,China [5]College of Chemistry and Molecular Engineering,Peking University,Beijing 100871,China [6]Institute for Cell Analysis,Shenzhen Bay Laboratory,Guangdong 518132,China [7]Chinese Institute for Brain Research(CIBR),Beijing 102206,China

出　　处：《National Science Review》2021年第5期86-95,共10页国家科学评论（英文版）

基　　金：supported by the National Natural Science Foundation of China(21927802,21525521);the Beijing Brain Initiative(Z181100001518004);the Beijing Advanced Innovation Center for Genomics。

摘　　要：An error-correction code(ECC)sequencing approach has recently been reported to effectively reduce sequencing errors by interrogating a DNA fragment with three orthogonal degenerate sequencing-by-synthesis(SBS)reactions.However,similar to other non-single-molecule SBS methods,the reaction will gradually lose its synchronization within a molecular colony in ECC sequencing.This phenomenon,called dephasing,causes sequencing error,and in ECC sequencing,induces distinctive dephasing patterns.To understand the characteristic dephasing patterns of the dual-base flowgram in ECC sequencing and to generate a correction algorithm,we built a virtual sequencer in silico.Starting from first principles and based on sequencing chemical reactions,we simulated ECC sequencing results,identified the key factors of dephasing in ECC sequencing chemistry and designed an effective dephasing algorithm.The results show that our dephasing algorithm is applicable to sequencing signals with at least 500 cycles,or1000-bp average read length,with acceptably low error rate for further parity checks and ECC deduction.Our virtual sequencer with our dephasing algorithm can further be extended to a dichromatic form of ECC sequencing,allowing for a potentially much more accurate sequencing approach.

关 键 词：DNA sequencing error-correction code DEPHASING computer simulation sequencing-by-synthesis 

分 类 号：Q811.4[生物学—生物工程]