New method improves accuracy of DNA sequencing 1000-fold to detect rare genetic mutations at moderate cost

Good news! This seems to be a major progress!

"... The method, called Concatenating Original Duplex for Error Correction (CODEC), makes next-generation sequencing about 1000 times more accurate and opens up the possibility of a range of applications including detecting tiny numbers of cancer mutations in blood samples, monitoring cancer during and after treatment, and identifying mutations underlying rare diseases, all at relatively low cost. ...
To overcome these limitations, CODEC uses a specially designed adapter sequence to link one strand of the double helix with the reverse complement of the second strand. The two new strands are then sequenced together using next-generation sequencing. This allows scientists to distinguish between sequencing-induced errors and mutations and generate highly accurate sequence data at low cost.  ..."

From the abstract:

"Detecting mutations from single DNA molecules is crucial in many fields but challenging. Next-generation sequencing (NGS) affords tremendous throughput but cannot directly sequence double-stranded DNA molecules (‘single duplexes’) to discern the true mutations on both strands. Here we present Concatenating Original Duplex for Error Correction (CODEC), which confers single duplex resolution to NGS. CODEC affords 1,000-fold higher accuracy than NGS, using up to 100-fold fewer reads than duplex sequencing. CODEC revealed mutation frequencies of 2.72 × 10−8 in sperm of a 39-year-old individual, and somatic mutations acquired with age in blood cells. CODEC detected genome-wide, clonal hematopoiesis mutations from single DNA molecules, single mutated duplexes from tumor genomes and liquid biopsies, microsatellite instability with 10-fold greater sensitivity and mutational signatures, and specific tumor mutations with up to 100-fold fewer reads. CODEC enables more precise genetic testing and reveals biologically significant mutations, which are commonly obscured by NGS errors."

New method improves accuracy of DNA sequencing 1000-fold to detect rare genetic mutations | Broad Institute CODEC could help scientists find early-stage cancer from blood samples, other disease-causing mutations, and more.

Single duplex DNA sequencing with CODEC detects mutations with high sensitivity (open access)

Fig. 1: Overview of CODEC.