![]() Third-generation sequencing can pinpoint rare mutations by sequencing DNA without separating the two strands, but can also be inefficient and inaccurate. This process is fast, but can't tell the difference between mutations in the DNA and errors introduced by the sequencing itself, which reduces its ability to detect rare mutations accurately.Ī sample preparation method called duplex sequencing, which involves tagging individual strands of DNA, can distinguish between true mutations and errors, but is highly inefficient because it sequences each strand of the double helix independently. Next-generation sequencing is a high-throughput process in which the two strands of a DNA double helix are separated and sequenced individually. Jin Bae, a research scientist, and Ruolin Liu, a computational scientist, both in Adalsteinsson's lab, are co-first authors on the study.ĬODEC combines the advantages of two existing methods: next-generation sequencing and third-generation sequencing. "It's not something that requires new instrumentation or capital investment-it's a simple set of steps added into existing sample preparation workflows to improve the accuracy of DNA sequencing." "The beauty of this approach is that it's not an overhaul of how sequencing is done," said Viktor Adalsteinsson, senior author on the study and director of the Gerstner Center for Cancer Diagnostics and leader of the Blood Biopsy Team at the Broad. The study appears today in Nature Genetics. The method, called Concatenating Original Duplex for Error Correction (CODEC), makes next-generation sequencing about 1,000 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.
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