Using a new technique, DNA sequencing accuracy is increased by 1,000 times to find rare genetic mutations.

A novel method for detecting genetic mutations within individual DNA molecules has been developed by a group of researchers from Harvard, the Broad Institute, MIT, and other institutions.

Concatenating Original Duplex for Error Correction (CODEC) is a method that increases the accuracy of next-generation sequencing by about 1,000 times and opens the door to a wide range of applications at a relatively low cost, such as finding mutations that cause rare diseases, monitoring cancer during and after treatment, and detecting a small number of cancer mutations in blood samples. Today, the study was published in Nature Genetics.

“The magnificence of this approach is that it’s anything but an update of how sequencing is finished,” said Viktor Adalsteinsson, senior creator on the review and head of the Gerstner Community for Disease Diagnostics and head of the Blood Biopsy Group at the Expansive. “Not something that requires new instrumentation or capital speculation — it’s a basic arrangement of steps added into existing example planning work processes to work on the exactness of DNA sequencing.”

“This technology is allowing us to see things that we couldn’t see before with DNA sequencing, and that’s tremendously exciting,”

Jin Bae, a research scientist, and Ruolin Liu, a computational scientist, both in Adalsteinsson’s lab,

The co-first authors of the study are Jin Bae, a researcher, and Ruolin Liu, a computational scientist, both of whom work in Adalsteinsson’s lab.

Sequencing difficulties
CODEC joins the upsides of two existing strategies: cutting-edge sequencing and third-age sequencing.

The process of separating and sequencing each of the two strands of a DNA double helix is known as next-generation sequencing, and it uses high throughput. This process is quick, but it can’t tell the difference between DNA mutations and mistakes made by sequencing, which makes it less accurate at finding rare mutations.

Due to the fact that it sequences each strand of the double helix independently, the sample preparation method known as duplex sequencing can differentiate between genuine mutations and errors. However, it is extremely inefficient because it involves tagging individual strands of DNA.

By sequencing DNA without separating the two strands, third-generation sequencing can identify rare mutations, but it can also be ineffective and inaccurate.

CODEC utilizes a specialized adapter sequence to link one strand of the double helix to the reverse complement of the second strand in order to circumvent these limitations. Next-generation sequencing is used to sequence the two new strands together. This permits researchers to recognize sequencing-incited blunders and transformations and produce exceptionally precise succession information for a minimal price.

Mutation detection

The researchers used CODEC to look for mutations in single molecules of DNA from tumors and other patient samples, as well as age-related mutations in blood cells and mutation frequencies in sperm. They tried CODEC with cutting-edge sequencing of either the whole genome or just a designated board of qualities. They discovered that CODEC was more efficient than duplex sequencing and distinguished between genuine mutations and errors with the same precision as duplex sequencing while requiring less DNA to analyze.

The team led by Adalsteinsson has applied for a patent on the technology and is currently thinking of ways to make CODEC even more effective. Since depicting their technique in June 2021 in a preprint, Adalsteinsson says they’ve been reached by a variety of specialists wanting to utilize CODEC.

Adalsteinsson stated, “This technology is enabling us to see things that we could never have seen before with DNA sequencing, and that’s tremendously exciting.”

More information: Jin H. Bae et al, Single duplex DNA sequencing with CODEC detects mutations with high sensitivity, Nature Genetics (2023). DOI: 10.1038/s41588-023-01376-0

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