Next-generation sequencing (NGS) is moving beyond core research applications and playing a larger role in biodefense research. A review in the March issue of Clinical Chemistry describes NGS’ current and future applications in this area, the limitations associated with using this technology, and the regulatory challenges it faces.
“While NGS is not the panacea replacing all molecular techniques, it will greatly enhance the ability to detect, characterize, and diagnose biowarfare agents, thus providing an excellent addition to the biodefense toolbox of biosurveillance, bioforensics, and biothreat diagnosis,” summarized review authors Timothy D. Minogue, PhD, Jeffrey W. Koehler, MS, PhD, Christopher P. Stefan, PhD, and Turner A. Conrad.
The authors describe NGS’ progression as an in vitro diagnostic from specialized sequencing centers to clinics, smaller laboratories, and austere environments. “In particular, NGS has greatly expanded the capabilities of detecting biothreats, unexpected pathogens, or even the completely novel, previously unknown threat,” the authors observed. Its sequencing capabilities can produce detailed genomic information for both molecular epidemiological studies and bioforensics analysis, “which is critical for source agent identification in a biothreat outbreak,” they wrote.
NGS has three main biothreat applications:
- biosurveillance, which involves active data gathering of biosphere data to detect biothreat at the early stages.
- bioforensics, which analyzes evidence related to bioterrorism, biocrime, or release of an etiologic agency to provide attribution.
- biothreat clinical NGS diagnostics, which generates actionable information to identify underlying disease, based on a patient’s complaints.
NGS is disrupting paradigms in many ways within biodetection, bioforensics, and clinical detection of biothreat agents, said Minogue, the study’s corresponding author and department chief of the United States Army Medical Research Institute for Infectious Diseases’ Diagnostic Systems Division. “Nanopore sequencing is pushing biodetection farther than even before towards the point-of-need. NGS is being directly applied to samples for attribution and microbial forensics. Lab-developed tests (LDTs) are being applied to impact patient treatment,” he told CLN Stat.
The recent Ebola virus disease (EVD) outbreak in West Africa exemplifies how NGS was applied in biosurveillance. Investigators used the technology to characterize the genome of the emerging pathogen and determine the path of transmission. “Implementation of NGS in near real time allowed for a better understanding of the Ebola virus transmission dynamics and aided in controlling the outbreak,” wrote the authors. In one breakthrough, NGS and genomic analysis were able to confirm a hypothesis that the disease could be transmitted sexually.
Investigators did face some hurdles in using NGS as a point-of-care device during the West Africa EVD outbreak, involving shipping, validating, and maintaining the technology. To complete the sequencing run, they also needed an uninterrupted power supply.
In general, NGS biothreat/infectious disease diagnostics are lagging behind similar applications in biodetection and bioforensics, said Minogue. “The technology is on the cusp of providing substantial impact to patient treatment, but until NGS assays move past the LDT context to Food and Drug Administration-cleared assays, NGS for biodefense will remain outside the realm of routine clinical application,” he said.
Pick up the March Clinical Chemistry to learn more about the growing importance of NGS in biodefense.