By Bio-IT World Staff
July 11, 2012 | Complete Genomics has published details of its long-awaited Long Fragment Read (LFR) technology for whole genome sequencing in this week’s issue of Nature.
The company says that the LFR method dramatically improves accuracy, enables the assembly of fully-phased genomes, and significantly reduces the amount of DNA required for testing – all factors that should buttress the company’s avowed intent to move into the clinical genome market.
“We expect the introduction of this technological breakthrough to accelerate the move of whole genome sequencing into patient care, which in turn will begin to change the face of medicine,” said Clifford Reid, Complete Genomics’ chairman, president and CEO.
In a typical whole-genome sequencing experiment using the new LFR technology, the resulting sequence will have just one error/10 million basepairs, or 600 errors in an entire human genome. “This represents a 10-fold increase in accuracy for Complete and is unmatched by any high-sensitivity method currently available,” says Rade Drmanac, Complete Genomics chief science officer, co-founder, and co-developer of the LFR technology.
With most next-gen sequencing methods favoring short read approaches, including the Complete Genomics method, it has been difficult if not impossible to determine whether two disease-associated variants were physically linked on the same chromosome or sitting on different parental chromosomes.
The LFR technology includes phasing information that reveals which mutations are sitting together on the same parental chromosome. This would allow a physician to determine whether a patient with two pathogenic variants in a recessively inherited gene is affected or merely a carrier of the trait.
Moreover, Complete says its LFR technology provides accurate WGS from as few as 10 to 20 cells (requiring only 100 picograms of DNA), making it an ideal choice for small sample clinical sequencing applications including circulating tumor cells, fine needle aspirations, and pre-implantation genetic diagnostics.
“In the not-too-distant future, failure to use phasing when providing genomic diagnoses in patient care will be seen as unacceptably inaccurate,” says George Church, professor of genetics at Harvard Medical School. “I also suspect that LFR will reveal surprising things we didn’t know were missing because we didn’t have a tool to see them.”
The U.S. Patent and Trademark Office has issued Complete Genomics two patents on LFR technology, and additional patent applications, including miniaturization using nanodrops, are pending. Complete Genomics plans to incorporate the new technology into its sequencing offerings in early 2013.