Journal:Making the leap from research laboratory to clinic: Challenges and opportunities for next-generation sequencing in infectious disease diagnostics
Full article title | Making the leap from research laboratory to clinic: Challenges and opportunities for next-generation sequencing in infectious disease diagnostics |
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Journal | mBio |
Author(s) | Goldberg, B.; Sichtig, H.; Geyer, C.; Ledeboer, N.; Weinstock, G.M. |
Author affiliation(s) |
Children’s National Medical Center, Food and Drug Administration, American Society for Microbiology, Medical College of Wisconsin, Jackson Laboratory for Genomic Medicine |
Primary contact | Email: George dot Weinstock at jax dot org |
Year published | 2016 |
Volume and issue | 6(6) |
Page(s) | e01888-15 |
DOI | 10.1128/mBio.01888-15 |
ISSN | 2150-7511 |
Distribution license | Creative Commons Attribution-Noncommercial-ShareAlike 3.0 Unported |
Website | http://mbio.asm.org/content/6/6/e01888-15.full |
Download | http://mbio.asm.org/content/6/6/e01888-15.full.pdf (PDF) |
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Abstract
Next-generation DNA sequencing (NGS) has progressed enormously over the past decade, transforming genomic analysis and opening up many new opportunities for applications in clinical microbiology laboratories. The impact of NGS on microbiology has been revolutionary, with new microbial genomic sequences being generated daily, leading to the development of large databases of genomes and gene sequences. The ability to analyze microbial communities without culturing organisms has created the ever-growing field of metagenomics and microbiome analysis and has generated significant new insights into the relation between host and microbe. The medical literature contains many examples of how this new technology can be used for infectious disease diagnostics and pathogen analysis. The implementation of NGS in medical practice has been a slow process due to various challenges such as clinical trials, lack of applicable regulatory guidelines, and the adaptation of the technology to the clinical environment. In April 2015, the American Academy of Microbiology (AAM) convened a colloquium to begin to define these issues, and in this document, we present some of the concepts that were generated from these discussions.
Minireview
Use of next-generation DNA sequencing (NGS) (Table 1) in infectious disease diagnostics has progressed slowly over the past 10 years despite continued advances in sequencing technology. The first commercial NGS platform, the GS20 sequencer from 454 Life Sciences, which was originally released in 2005[1][2], resulted in a more than 100-fold increase in the amount of microbial genomic sequence data produced in a day compared to preceding instruments. Despite the growing body of literature and research broadly applying sequencing-based technology to disease pathophysiology, epidemiology, and clinical diagnostics, the clinical microbiology laboratory has yet to widely adopt NGS technology. As microbiology laboratories are faced with a wealth of innovative and often costly molecular technologies, the role of NGS in clinical infectious disease diagnostics needs to be carefully evaluated.
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A number of highly publicized case reports and clinical studies have showcased the application of NGS as a single diagnostic tool with the potential to be broadly applicable to infectious disease diagnostics. Metagenomic (Table 1) sequencing has demonstrated its ability to identify microbial pathogens where traditional diagnostics have otherwise failed. For example, it is estimated that 63% of encephalitis cases go undiagnosed despite extensive testing.[3] Several cases in the literature have successfully employed NGS to diagnose rare, novel, or atypical infectious etiologies for encephalitis, including cases of infection by Leptospira (4), astrovirus (5), and bornavirus (6). In one case, 38 different diagnostic tests had been conducted and failed to yield an actionable answer before a single NGS assay was performed, which identified the pathogen (4). Similarly, the utilization of metagenomic NGS identified divergent astrovirus clades in a pair of patients with encephalitis and demonstrated the unusual zoonotic potential of a group of these viruses (7).
References
- ↑ Margulies, M.; Egholm, M.; Altman, W.E. et al. (2005). "Genome sequencing in microfabricated high-density picolitre reactors". Nature 437 (7057): 376–80. doi:10.1038/nature03959. PMC PMC1464427. PMID 16056220. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1464427.
- ↑ Liu, L.; Li, Y.; Li, S. et al. (2012). "Comparison of next-generation sequencing systems". Journal of Biomedicine and Biotechnology 2012: 251364. doi:10.1155/2012/251364. PMC PMC3398667. PMID 22829749. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3398667.
- ↑ Brown, J.R.; Morfopoulou, S.; Hubb, J. et al. (2015). "Astrovirus VA1/HMO-C: An increasingly recognized neurotropic pathogen in immunocompromised patients". Clinical Infectious Diseases 60 (6): 881-8. doi:10.1093/cid/ciu940. PMC PMC4345817. PMID 25572899. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345817.
Notes
This presentation is faithful to the original, with only a few minor changes to presentation. In some cases important information was missing from the references, and that information was added.