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Wasatch Biolabs Bets on Nanopore Sequencing for Clinical Testing, Research Services


NEW YORK – Wasatch Biolabs is eyeing to become a high-throughput nanopore sequencing service provider for both research and clinical customers, exclusively using platforms from Oxford Nanopore Technologies.

Last month, the Brigham Young University spinoff launched one of its first commercial offerings — a targeted DNA methylation sequencing service that is based on proprietary molecular enrichment technology developed by company cofounders Tim Jenkins and Jonathon Hill, who are both professors at BYU.

"We started this company roughly two and a half ago with the goal of creating a high-throughput lab based off nanopore [sequencing]," said Wasatch CEO Chad Pollard, another company cofounder who is also currently a Ph.D. student in Jenkins' lab.

The targeted DNA methylation sequencing service enables researchers and clinicians to analyze epigenetic signatures of samples while avoiding PCR amplification biases and harsh bisulfite conversion, he said.

Jenkins, who also serves as the company's VP of research and discovery, said the workflow involves a proprietary hybridization method to pull down genomic regions of interest, which are then sequenced using the Oxford Nanopore platform.

It can currently target about 2,000 regions of interest across the genome, which typically span 1 kb to 2 kb in length. While the company offers pre-designed probes, customers can also develop their own probes with the company.

After target enrichment, sequencing libraries are prepared using Oxford Nanopore Ligation Sequencing Kit V14 protocols, followed by sequencing.

The raw data are processed using Oxford Nanopore's standard pipeline for basecalling and methylation analysis, which can detect 5mC, 5hmC, and 6mA.

For research use, the per-sample list price for the service ranges from $266 to $2,525, depending on batch size, according to the company's website.

Unlike in the traditional bisulfite sequencing approach, samples don't undergo harsh chemical treatment, which can damage them, said Hill, who now serves as Wasatch's VP of science and technology. In addition, the method requires no PCR amplification, which can be prone to errors and biases.

Besides methylation information, the service also offers insights into ​​copy number variations (CNVs), structural variations (SVs), single nucleotide polymorphisms (SNPs), and indels, Hill added.

Compared with existing target selection schemes for nanopore sequencing, such as CRISPR-Cas9-mediated approaches or adaptive sampling, Hill said the company’s method leads to "much higher enrichment" — typically in the range of 400-fold to 2,300-fold.

One application of the company's methylation assay is infertility testing, Pollard said, where it can detect the presence or absence of certain rare sperm in a sample by looking for specific DNA methylation signals.

The firm is also developing an assay to capture epigenetic signatures of neuron-derived cell-free DNA in blood as a predictor for the early onset of neurodegenerative diseases, he noted.

In general, the company wants to apply its enrichment method "in any way that's clinically impactful," Jenkins said, such as to sequence difficult regions of the genome, including pseudogenes or areas with high GC contents. Pollard said the company is in discussions with Oxford Nanopore about potentially developing the technology into a kit.

In an email, an Oxford Nanopore spokesperson said there is no partnership between the company and Wasatch at this point. She did not comment on any potential interest in commercializing Wasatch's target enrichment method.

In order to be able to offer high-throughput nanopore sequencing as a clinical service, the company is currently building out a 20,000-square-foot CLIA lab in Salt Lake City.

Wasatch also plans to move its headquarters to Salt Lake City from its current location in Heber City, Utah, where it operates an R&D sequencing lab that also offers nanopore research sequencing services, such as whole-genome sequencing and RNA-seq.

Currently, Wasatch employs 12 full-time employees and plans to expand its workforce to 40 by the end of this year. It is completely privately owned, and the only ongoing relationship with BYU is a sponsored research agreement, under which the company helps fund relevant research projects within Jenkins' and Hill's labs. 

The firm has licensed its founding technologies from BYU, according to Pollard, who noted that it is working on six other patents.

To date, Wasatch has raised $11 million in Series A funding, supported by its parent company Renew Biotechnologies, a biotech incubator.

While Wasatch is betting on nanopore sequencing for methylation analysis, other companies have also been making strides on alternatives to bisulfite sequencing, using short-read sequencing platforms.

New England Biolabs, for instance, recently launched the NEBNext Enzymatic 5hmC-seq kit that promises to detect 5hmC at single-base resolution. The kit follows the company’s existing NEBNext Enzymatic Methyl-seq (EM-seq) product, which can analyze both 5mC and 5hmC but does not distinguish between them. By subtracting E5hmC-seq data from EM-seq, researchers can now determine individual 5mC and 5hmC sites, according to the company.

Additionally, Cambridge, UK-based Biomodal also recently launched a new version of its epigenetic sequencing and sample prep kit that enables researchers to achieve single-base resolution sequencing of the four standard DNA bases, 5-methylcytosine (5mC), and 5-hydroxymethylcytosine (5hmC) from the same DNA molecule and in the same workflow.

With limited benchmarking data publicly available, it remains to be seen how Wasatch's workflow will fare against other players in the space.

Still, with the data quality of nanopore sequencing continuing to improve, Wasatch management thinks the opportunity is ripe for the company to venture into the nanopore clinical sequencing service market, which is vastly untapped at this point.

"If we tried this a couple of years ago, it would not have been ready, and I think if we waited a couple more years, then others would have beat us to it," Hill said. "We're trying to catch that wave just right, where the technology is just getting to the point where it's ready for prime time."