Metagenomics can look across the entire genomic sequence of more than 50,000 species of organisms that may be present in a patient sample and compare millions of sequences from a patient with millions of reference sequences.
IDbyDNA’s Explify platform for metagenomics analysis is transforming highly sophisticated research-only laboratory tools into practical diagnostics tools for routine hospital use. Now physicians can determine not just whether a patient has COVID-19, but also – in the same test – whether that patient has other respiratory pathogens that are exacerbating illness.
Metagenomics can look across the entire genomic sequence of more than 50,000 species of organisms that may be present in a patient sample and compare millions of sequences from a patient with millions of reference sequences. Having a diagnostic profile of possibly causative pathogens in a given sample helps physicians determine whether there is a genetic basis for the phenotype.
“That’s the broadest way you can test. But, if you have a hypothesis, you can use targeted metagenomics panels that address certain categories of disease,” Robert Schlaberg, MD, PhD, MPH - IDbyDNA co-founder and CMO, told BioSpace.
IDbyDNA is developing a targeted respiratory pathogen panel to identify the presence of the SARS-CoV-2 virus and approximately 250 additional pathogens that can be tested in parallel. “People are concerned about the flu season coinciding with the COVID-19 pandemic, so we expect to launch before October,” he said.
For metagenomics, that’s a huge leap forward.
“A few years ago, metagenomics was technically challenging, even for researchers,” Schlaberg said. “Compute times were long and biologists needed expertise across the whole tree of life.”
With such hurdles, metagenomics analysis was usually performed by only the most sophisticated labs, such as those at the Centers for Disease Control & Prevention (CDC). Therefore, it was used to analyze unexplained disease outbreaks rather than routine diagnostics.
IDbyDNA’s Explify platform simplifies the process. “It turns diagnosis into a computational problem rather than a lab testing exercise.” It starts by digitizing the sample. “It takes all the RNA from the patient and from other bacteria in the sample, so it’s a mix that represents all the living things in that sample,” Dr. Schlaberg said. “We generate DNA sequences for that whole mix.” Then, the application scans the sample for known pathogens or closely related sequences. From sample to report takes less than 24 hours, he said. From sequencing to report takes less than one hour.
Dr. Schlaberg developed the basis of this platform during his work at the University of Utah. “I had been a medical director at a large, national reference lab and was responsible for molecular testing. I knew the limitations of the current tests,” he recalled. From his time in research labs, he also knew what was possible, based on the technology. “The gap was apparent.”
His team launched a retrospective research project that looked at child pneumonia patients who had tested negative for other pathogens. In a high percentage, “We found infections that traditional testing methods had missed. Sometimes they were things no one would have thought to have looked for.”
More recent research reported at the 2017 Annual Meeting of the American Thoracic Society used metagenomics to detect pathogens in children with respiratory disease. Metagenomics confirmed the results of standard tests, but also identified undetected pathogens in 44% of the children who had negative microbiology test results. That study helped underscore the validity of metagenomics as a diagnostic tool and has been followed by other studies with similar findings.
In 2014 Dr. Schlaberg incorporated IDbyNDA and continued developing the Explify platform. Now that’s it’s in commercial use, he aims to democratize metagenomics testing, bringing it to as many labs and as many patients as possible. The focused pathogen panels IDbyDNA is developing will help tremendously, by bringing a practical, cost-effective element to metagenomics that so far has been lacking. The benefits extend beyond just diagnosis.
The ability to detect 50,000 organisms, including 6,000 known pathogen, based on the entire genome. “…helps you identify transmission throughout the community and to characterize the virus, determining, for instance, whether it is evolving, becoming more pathogenic, or becoming resistant to treatment,” he said. For perspective, “Existing diagnostic tests, like PRC, look for a single short piece of the genome – often shorter than 100 nucleotides – of a particular pathogen, such as the SARS-CoV-2 virus. Then you infer whether this is the virus.”
Dr. Schlaberg understands that for the purposes of diagnosis, having a catalog of every pathogen in a sample could be overwhelming and counterproductive. Therefore, the analysis interprets the findings, finding and prioritizing variants.
Labs can access the Explify metagenomics platform in either of two ways. They can send samples to IDbyDNA’s CLIA-certified lab in Salt Lake City for analysis, or they can install the testing solution developed jointly by Illumina and IdbyDNA and thus create their own lab-developed tests.
“Illumina provides the next gen sequencing instruments and reagents. We offer the application-specific pieces – the materials and protocols – to digitize the sample and the software to turn the data into a diagnostic report,” Dr. Schlaberg said.
One of the benefits of the in-house solution developed with Illumina is the elimination of shipping time. “We partner with the labs,” he said, “working with them throughout the development of their test and its validation – suggesting quality control processes, qualified reagents or optimized protocols, for example.” Post-launch, the company can help labs with data analysis.” The Explify platform can run on premises or in the cloud. Either way, it uses machine learning to continuously improve.
Metagenomics enables physicians to learn about the pathogen in context, putting them in a better diagnostic position, he said, “but learning still needs to occur,” Dr. Schlaberg said. The platform is involved in clinical trials to correlate findings from samples to patients’ conditions. “We can provide a lot of actionable information today, and also generate information we can use to become better at interpreting results.”
