COLD SPRING HARBOR, N.Y.--(BUSINESS WIRE)--The next “next-gen” technology in genome sequencing has gotten a major boost.
A quantitative biologist at Cold Spring Harbor Laboratory (CSHL) and collaborators have published results of experiments that demonstrate the power of so-called single-molecule sequencing, which was recently introduced but whose use has so far been limited by technical issues.
The team, led by CSHL Assistant Professor Michael Schatz and Adam Phillippy and Sergey Koren of the National Biodefense Analysis and Countermeasures Center and the University of Maryland, has developed a software package that corrects a serious problem inherent in the newest sequencing technology: the fact that every fifth or sixth DNA “letter” it generates is incorrect. The high error rate is the flip side of the new method’s chief virtue: it generates much longer genome “reads” than other technologies currently used, up to 100 times longer, and thus can provide a much more complete picture of genome structure than can be obtained with current, “2nd-gen” sequencing technology.
Using mathematical algorithms, Schatz and the team have preserved the great advantage of the “3rd-gen” method while all but eliminating its chief flaw. They have reduced the error rate from about 15% or greater to less than one-tenth of one percent. This mathematical “fix” – which has been published in open-source code to the World Wide Web – greatly increases the practical utility of 3rd-gen sequencing for the entire biomedical research community.
In a paper published online July 1 in Nature Biotechnology, the team demonstrates the breadth of potential applications of single-molecule sequencing by applying their fix to sequencing tasks ranging from the tiny bacteriophage virus at one end of the difficulty scale to the large and vastly more complex genome of the parrot, at the other. The latter was the first demonstration of "3rd generation” technology in sequencing and assembling a large genome.
Obtaining superior versions of complete genomes was the objective that motivated Schatz and his collaborators. With single-molecule sequencing, the assembled genome “reads” are much longer – affording a much better picture of relatively larger genome segments. This is what Schatz and his team wanted to preserve, while at the same time boosting the error-free rate. They did so by effectively taking the best of both 2nd- and 3rd-gen technologies, a method they call ”hybrid error correction.”
The team’s major insight was to take advantage of the long-read data offered by a 3rd-gen machine like that used in their experiments, a Pacific Biosciences RS sequencer, and mixing in highly accurate short reads obtained from a separate 2nd-gen sequencer.
About Cold Spring Harbor Laboratory
Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked first in the world by Thomson Reuters for impact of its research in molecular biology and genetics. For more information, visit www.cshl.edu.