NEW YORK (GenomeWeb) – As an assortment of companies leverage various technologies for infectious disease pathogen detection, one firm has adopted a deep-sequencing approach that its CEO said can identify a broad number of infectious disease pathogens to treat people with chronic medical conditions.
The highly multiplexed service, developed by Aperiomics, incorporates Bayesian statistical analysis, along with deep sequencing.
At present, getting a test result can take a couple of weeks, partly because of the requirements imposed by deep sequencing all the microorganisms in a sample, Aperiomics CEO Crystal Icenhour said in an interview. However, within a year the company hopes to reduce the turnaround time to 24 to 48 hours.
Aperiomics is focused on achieving uptake in the market for chronic infections, when patients are not getting help through traditional medical procedures.
Icenhour noted that the Aperiomics service provides comprehensive pathogen information to clinicians.
To drive uptake, the firm has targeted integrative health centers that take a holistic view of patients’ health, and it currently has 25 customers, primarily clinicians who operate within the integrative health space.
Clinicians who work within these networks are more frequently open to the service offered by Aperiomics, Icenhour said, adding that "most patients that we deal with have chronic issues, and clinicians, in many cases, don't understand how to help them.”
In November, Aperiomics introduced the next-generation sequencing infectious disease diagnostic service at a price of $500 per sample.
The firm said that a single test of a sample accurately identifies all microbes present, including pathogens that can lead to infectious diseases. It can also identify whether the pathogens are bacterial, viral, fungal, or parasitic, and a clinician can therefore order a precise therapeutic response.
“When we analyzed data containing more than 400 microorganisms, we demonstrated sensitivity of 99 percent and specificity of 97 percent,” Icenhour said.
The test is suitable not only for use on humans, but also to identify pathogens in animal populations, and in food and water systems, and it can play a role in limiting the evolution of antibiotic-resistant super bugs, she added.
Patients generally receive results from Aperiomic's CLIA- and CAP-certified laboratory within two weeks, Icenhour said.
"We are working on modified sample preparation techniques, as well as migrating over to newer sequencers to reduce our turnaround time," Icenhour noted, and added that that because of the requirements imposed by deep sequencing, the firm still has quite a bit of work to do to get to its turnaround target.
“Once we get the data, the analytics portion takes around two hours,” so speeding up the test would require faster sequencers, she said.
The competitive environment
The total available market for chronic infectious disease testing is a difficult number to pin down, but there is clearly a market opportunity, Icenhour said. Around 75 percent of infections are never diagnosed, and the misuse of antibiotics is creating resistant pathogens for which there are no effective treatments. Icenhour noted that 380,000 Lyme disease cases are reported each year, many become chronic, and the tickborne disease market is quite large — worth more than $2 billion annually.
Aperiomics said that its proprietary database contains more than 32,000 genomes for microorganisms, and that its technologies can also be used to discover others that are unknown. The database was assembled "using public data, adding strict quality criteria, and including all sequenced microorganisms," Icenhour said.
Clinicians take samples from patients suspected of having infections — using blood, urine, stool, or swabs — and send them to Aperiomics for analysis.
“The goal is to get a high-quality sequence from every microorganism that’s present in the sample,” she added.
Icenhour noted that for a single sample, the deep-sequencing process, using Illumina sequencers, translates into a “very large, very complex data file” that can contain one terabyte of data.
The data file is then analyzed through Aperiomics’ proprietary software, which “makes sure we are only looking at sequenced data that’s of the highest integrity,” Icenhour noted. The analytics software “sorts through the information and prioritizes it in a unique way, and that enables us to align the information with our database,” she added.
Aperiomics, founded in October 2013 as a spinout from the Computational Biology Institute at George Washington University, has received around $1.5 million from the National Science Foundation within the past two years, Icenhour said, adding it expects to complete a seed round of funding valued at around $250,000 within the next few weeks, Icenhour said.
The firm introduced its service recently at the Annual Integrative Healthcare Symposium in New York City. Later this year, it expects to launch a research-use-only service to test for a pathogen’s drug resistance. A future application of Aperiomic’s service, which may be available in 2018 and has been demonstrated in an academic setting, may enable discovery of previously unknown pathogens, Icenhour said.
Susceptibility of pathogens to antimicrobial agents was front and center of a US Food and Drug Administration clearance in February. The agency cleared Accelerate Diagnostics’ test kit and instrument that provides identification and antibiotic susceptibility testing of pathogens for patients suspected of bacteremia or fungemia.
Accelerate's service is illustrative of the competition Aperiomics will face from diagnostic test companies as it pushes for uptake in mainstream infectious disease testing. The Accelerate PhenoTest BC Kit is a highly-multiplexed panel that targets more than 80 percent of the "routine and significant pathogens" that cause bloodstream infections, and more than 90 percent of the antibiotics useful in treating those pathogens, the firm said recently.
The test can identify 14 different bacterial species and two yeast species that cause bloodstream infections and provides antibiotic sensitivity information on 18 selected antibiotics for a subset of identified organisms deemed as appropriate.
The antimicrobial and infectious disease testing space also includes large incumbent companies in the diagnostics industry, such as Abbott, Danaher, BioMérieux, and Becton Dickinson, among others.
PathoQuest, a spinout from Institut Pasteur, is a more direct competitor to Aperiomics from a technology perspective. The firm offers a metagenomics approach to improving pathogen detection in biological samples.
PathoQuest’s technology combines an NGS platform and "a proprietary sample preparation process which is applicable to several types of samples with a proprietary pathogen genome sequence database and automated analysis pipeline," the firm said in a statement, and added that its solution provides microbiologists and clinicians with a "comprehensive analysis covering all known clinically relevant human pathogens."
PathoQuest's iDTECT blood test, CE marked in October 2016, is a proprietary sample-to-report service that provides "a significantly improved method for detecting bacteria and viruses in blood samples from patients with suspected infections, especially immunocompromised patients," the firm added.
Menlo Park, California-based Karius provides a plasma-based next generation sequencing test for the detection of bacteria, viruses, and eukaryotic pathogens, including yeasts, molds, and protozoa.
And ARUP Laboratories is planning to make available a CLIA-validated test for pneumonia within a few months. It’s an informatics package for analysis of metagenomic sequence data as a clinical microbiology detection tool that was developed by Robert Schlaberg, an assistant professor of pathology at the University of Utah and medical director of infectious diseases at ARUP Laboratories, and Mark Yandell, a professor of human genetics at the University of Utah School of Medicine.
Several academic groups are doing infectious disease sequencing.
Researchers at the University of California, San Francisco are preparing to launch a clinical metagenomic next-generation sequencing-based test this month for meningitis and encephalitis, according to Charles Chiu, director of UCSF's Viral Diagnostics and Discovery Center.
In addition, his lab is involved in an infectious disease sequencing project to develop a better test for Lyme based on targeted RNA sequencing.
Also, researchers from Johns Hopkins University have prospectively demonstrated that next-generation sequencing of brain or spinal cord biopsies can identify pathogenic microbes in individuals suspected of having an infection-induced neurologic disorder.
In June 2016, the group reported pilot study results of the metagenomic sequencing assay on 10 individuals in the journal Neurology: Neuroimmunology & Neuroinflammation. For three individuals, the assay was able to give a definitive diagnosis that was confirmed via diagnostic testing. For an additional five patients, the NGS approach helped the clinician understand the neuropathology of the patients' disorders, and in two patients the technique did not contribute to a diagnosis.
Carlos Pardo-Villamizar, associate professor of neurology and pathology at Johns Hopkins and a senior author of the study, told 360Dx sister publication GenomeWeb that an eventual test could be run in about 72 hours for a cost per sample of about $1,000.
Several groups, including Mount Sinai Health System, the UK's National Health Service, and the NIH Clinical Center, are also investigating using NGS for outbreak surveillance purposes in hospitals, and the Centers for Disease Control and Prevention earmarked roughly $2.3 million in fiscal 2016 to support the rollout of next-generation sequencing and bioinformatics technologies for the advanced detection of infectious disease outbreaks in select US states.
Meanwhile, a new study supports the notion that genome sequencing can offer insights into potential infection sources and transmission patterns for infectious microbes such as vancomycin-resistant Enterococcus faecium, a bug implicated in hospital-acquired or nosocomial infections.
Researchers operating in the field of NGS testing for infectious diseases declined to comment on Aperiomics' service, saying they have not seen any data related to its performance and clinical utility. Icenhour said that the company is "planning publications."
She noted that the path to regulatory clearance through FDA for Aperiomics and other similar services is unclear. While the firm's service is marketed for research use only, clinicians can use it for clinical purposes.
"At this time, the FDA has no path that allows this kind of device to be approved," Icenhour said, adding that as diagnostic companies and others await FDA rules and guidance, "people are suffering from chronic conditions because of pathogen-based infections and are not able to get a diagnosis."
Icenhour noted that the firm can market its service as a research use only tool "so long as it is clearly marked as such…The research-use-only indication is frequently used in the LDT space, and this is analogous to that space."