July 7, 2019  |  

Highly accurate fluorogenic DNA sequencing with information theory-based error correction.

Authors: Chen, Zitian and Zhou, Wenxiong and Qiao, Shuo and Kang, Li and Duan, Haifeng and Xie, X Sunney and Huang, Yanyi

Eliminating errors in next-generation DNA sequencing has proved challenging. Here we present error-correction code (ECC) sequencing, a method to greatly improve sequencing accuracy by combining fluorogenic sequencing-by-synthesis (SBS) with an information theory-based error-correction algorithm. ECC embeds redundancy in sequencing reads by creating three orthogonal degenerate sequences, generated by alternate dual-base reactions. This is similar to encoding and decoding strategies that have proved effective in detecting and correcting errors in information communication and storage. We show that, when combined with a fluorogenic SBS chemistry with raw accuracy of 98.1%, ECC sequencing provides single-end, error-free sequences up to 200 bp. ECC approaches should enable accurate identification of extremely rare genomic variations in various applications in biology and medicine.

Journal: Nature biotechnology
DOI: 10.1038/nbt.3982
Year: 2017

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