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SeqWell Aims to Drive Down NGS Library Prep Costs

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SAN FRANCISCO (GenomeWeb) – SeqWell, a Beverly, Massachusetts-based company that launched in 2014, will soon commercialize its first kit for next-generation sequencing library prep to enable low-cost sequencing of large numbers of samples.

Founder and CEO Joseph Mellor said recently that many researchers are not able to fully realize the drastic reductions in costs and time that advances in NGS technology have brought over the last several years because the cost of library prep has not fallen at nearly the same rate as the costs of sequencing.

"As multiplex sequencing of many samples becomes more common, the challenges are before the samples even go on the sequencer, in getting them through the library prep workflow," he said.

To address that problem, SeqWell's library prep technology, which it has dubbed PlexWell, involves two rounds of transposase-based barcoding to enable pooling and normalization of samples.

The company has been offering its technology as a service but plans to launch a kit in the second quarter of this year.  The firm currently has 13 employees and closed a round of equity financing in June 2016 for an undisclosed amount.

The PlexWell technology's initial application will be for multiplexing large numbers of samples, for instance to sequence large numbers of plasmids, PCR products, or small bacterial genomes. In the second half of the year, the firm will scale up the technology to enable human genome applications.

Keith Robison, who described the technology on his Omics! Omics! Blog, said that he has used SeqWell's service to validate large numbers of synthetic biology constructs and that the data has been reliable.

In addition, he said the technology helps solve a problem. "Sequencing costs have come down quickly, but library costs have not," he said. When sequencing large numbers of small constructs, library construction costs can quickly soar past the actual data generation costs, he said. SeqWell's technology brings the "costs of the library down close to or below the sequencing costs," he said.

The technique enables normalization, Robison said, so that all the samples can be quality controlled in one single tube. He added that it would be useful for designing synthetic biology constructs and small microbial genomes — "large markets that have not been well served by existing technologies."

The PlexWell workflow involves loading input DNA from 96 samples onto a 96-well plate that has been pre-loaded with transposase-based barcoded adaptors such that each sample has a unique well-specific barcode, Jack Leonard, SeqWell's chief technology officer, explained. That enables the 96 samples to be pooled into a single tube. Then a plate-specific barcode is added via a second transposase-based adaptor. These tagging steps are done in such a way that regardless of how much starting DNA is added from each sample, read count and size distribution is normalized among the samples.

Last year, researchers from SeqWell and the University of British Columbia published a study in PLOS Genetics showing that the technique could be used to simultaneously screen 200,000 mutant cells to identify mechanisms of drug resistance.

The version of the kit SeqWell plans to launch in Q2 will enable multiplexing of 384 samples. Mellor did not disclose what the cost of the kit would be, but said it would be "significantly less expensive than conventional library prep technologies."

The company has also been collaborating with researchers at the Dana Farber Cancer Institute and presented a poster at the Advances in Genome Biology and Technology meeting in Hollywood Beach, Florida last month showing that the technology is comparable to the Nextera XT kit.

Aside from its PlexWell technology, the company is developing a single-tube library prep technology called LongBow that will enable phasing. At AGBT, it presented a poster describing its reagent-based method for haplotyping, which it calls Tethered Synaptic Complexes. The library prep reagent contains 480 molecular scaffolds in a single tube, each of which contains identical barcode adapators that are inserted into regions of target DNA in such a way to maintain the phase information.

The technology is still in "early development," Mellor said, but the firm plans to start commercializing it by the end of the year.

In addition, Mellor said that the company will develop additional products using its PlexWell technology and look to partner with a distributor.