SAN FRANCISCO (GenomeWeb) – Fry Laboratories is developing next-generation sequencing-based infectious disease tests using a proprietary bioinformatics pipeline and said it is in discussions with Qiagen to develop its tests for the firm's GeneReader instrument.
Earlier this month the Scottsdale, Arizona-based company was issued a patent on its method, dubbed RIDI (rapid infectious disease identification), which Fry CSO Jeremy Ellis described as being "targeted on the front end, but broad on the backend." It also holds a patent on its algorithms, which was issued in 2017.
The firm currently offers two lab-developed clinical NGS tests — a pan-bacterial assay and a pan-eukaryotic assay — that involve 16S rRNA sequencing and 18S rRNA sequencing, respectively. Fry offers its assays from its CLIA-certified laboratory for $1,495 per test. CEO Judith Joseph said that it does receive reimbursement from insurance companies. Importantly, the clinical tests have a turnaround time of less than 12 hours, and the company is working to reduce that to six hours or less.
The lab runs its assays on Thermo Fisher Scientific's Ion Torrent instruments, but has also validated the method on Illumina and Pacific Biosciences instruments.
Ellis said that later this year, the company aims to offer its RIDI bioinformatics pipeline in the cloud and to develop research-use only kits, which would enable researchers to run the assay in their own labs on any sequencing platform.
Fry is also working on developing a pan-viral assay in collaboration with a government-funded laboratory and is working on an assay that screens for antibiotic resistance genes and virulence factors, Ellis said.
It also is discussing with Qiagen the potential to develop assays for Qiagen's GeneReader NGS instrument. The initial goal is to establish and validate Fry's existing assays on the GeneReader, which is attractive because Qiagen "has put a lot of effort into making the system user friendly with a push-button approach," Ellis said.
In a statement, Thierry Bernard, head of Qiagen's molecular diagnostics business area, said that although oncology is the main application for NGS at the moment, Qiagen "is convinced that infectious diseases, in particular microbial identification, or the microbiome, will greatly benefit from NGS technologies."
Qiagen declined to elaborate further on how it plans to collaborate with Fry.
Joseph added that ultimately Fry hopes that integrating its assays with the GeneReader will enable an integrated system to be offered off the shelf as a cleared kit. "But, we're in the early stages of this project, so that's hard to predict," she said.
Fry described its RIDI platform in a 2016 study published in the Journal of Microbiological Methods, where it validated it using American Type Culture Collection reference standards of 27 species.
One key to the assay is the RIDI bioinformatics pipeline and database of over 47 million entries, Ellis said. The software can detect which sequencing platform is being used and set up quality thresholds and filters tailored for the specific instrument. The software performs the data-processing steps, including read filtering and trimming, and uses a BLAST strategy to match sequence reads to the more than 47 million microorganisms in the database.
RIDI also generates a final report where it lists any matches to known species as well as close matches and potential novel species. Ellis explained that while the goal is to call known species, the software is set up to flag potentially novel species in cases where a sequence is sufficiently divergent from a known organism.
Ellis said that specificity and sensitivity vary slightly depending on the organism, but on average are in the mid to upper 90 percent range.
The field of NGS-based infectious disease diagnostics is still relatively young, but many researchers think the technology can improve upon existing infectious disease diagnostic methods. The problem with current standard diagnostic methods is that they rely on being able to culture bacteria, Ellis said. Not only is that method time consuming, taking days rather than hours, but many bacteria cannot be cultured.
Ellis described an example of a patient who was admitted to the hospital with an unspecified illness that was thought to be tick-borne. Culture-based testing took four days and was not able to identify the cause beyond saying it was bacterial. Within 24 hours Fry identified the organism down to the species level and explained an unusual resistance pattern. Using that information, the physician was able to change the patient's treatment, Ellis said.
Ellis said that it will be challenging to educate a medical community about the advantages of NGS-based tests for infectious disease diagnostics. He said that molecular tests based on PCR have started to pave the way, but those tests are still too targeted — physicians have to have a good idea about what the infection is.
Some companies that have traditionally marketed PCR-based assays,— like the German-based molecular diagnostic firm Curetis — are beginning to move into the NGS space due to its potential for hypothesis-free diagnostics.
In addition, an academic group at the University of California, San Francisco now offers a clinical NGS test that involves metagenomic sequencing for meningitis and encephalitis; and startup Karius recently raised $50 million to support development of a cell-free DNA-based infectious disease test that it plans to target for sepsis.
"I think we're on the cusp of the next renaissance in infectious disease diagnostics, which will be led by NGS," Ellis said.