Difference between revisions of "Journal:Making the leap from research laboratory to clinic: Challenges and opportunities for next-generation sequencing in infectious disease diagnostics"
Shawndouglas (talk | contribs) (Saving and adding more.) |
Shawndouglas (talk | contribs) (Saving and adding more.) |
||
Line 105: | Line 105: | ||
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.<ref name="BrownAstro15">{{cite journal |title=Astrovirus VA1/HMO-C: An increasingly recognized neurotropic pathogen in immunocompromised patients |journal=Clinical Infectious Diseases |author=Brown, J.R.; Morfopoulou, S.; Hubb, J. et al. |volume=60 |issue=6 |pages=881-8 |year=2015 |doi=10.1093/cid/ciu940 |pmid=25572899 |pmc=PMC4345817}}</ref> 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''<ref name="WilsonActionable14">{{cite journal |title=Actionable diagnosis of neuroleptospirosis by next-generation sequencing |journal=New England Journal of Medicine |author=Wilson, M.R.; Naccache, S.N.; Samayoa, E. et al. |volume=37 |issue=25 |pages=2408-17 |year=2014 |doi=10.1056/NEJMoa1401268 |pmid=24896819 |pmc=PMC4134948}}</ref>, astrovirus<ref name="NaccacheDiagnosis15">{{cite journal |title=Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing |journal=Clinical Infectious Diseases |author=Naccache, S.N.; Peggs, K.S.; Mattes, F.M. et al. |volume=60 |issue=6 |pages=919-23 |year=2015 |doi=10.1093/cid/ciu912 |pmid=25572898 |pmc=PMC4345816}}</ref>, and bornavirus.<ref name="HoffmannAVari15">{{cite journal |title=A Variegated Squirrel Bornavirus Associated with Fatal Human Encephalitis |journal=New England Journal of Medicine |author=Hoffmann, B.; Tappe, D.; Höper, D. et al. |volume=372 |issue=2 |pages=154-62 |year=2015 |doi=10.1056/NEJMoa1415627 |pmid=26154788}}</ref> 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.<ref name="WilsonActionable14" /> 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.<ref name="QuanAstro10">{{cite journal |title=Astrovirus encephalitis in boy with X-linked agammaglobulinemia |journal=Emerging Infectious Diseases |author=Quan, P.L.; Wagner, T.A.; Briese, T. et al. |volume=16 |issue=6 |pages=918-25 |year=2010 |doi=10.3201/eid1606.091536 |pmid=20507741 |pmc=PMC4102142}}</ref> | 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.<ref name="BrownAstro15">{{cite journal |title=Astrovirus VA1/HMO-C: An increasingly recognized neurotropic pathogen in immunocompromised patients |journal=Clinical Infectious Diseases |author=Brown, J.R.; Morfopoulou, S.; Hubb, J. et al. |volume=60 |issue=6 |pages=881-8 |year=2015 |doi=10.1093/cid/ciu940 |pmid=25572899 |pmc=PMC4345817}}</ref> 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''<ref name="WilsonActionable14">{{cite journal |title=Actionable diagnosis of neuroleptospirosis by next-generation sequencing |journal=New England Journal of Medicine |author=Wilson, M.R.; Naccache, S.N.; Samayoa, E. et al. |volume=37 |issue=25 |pages=2408-17 |year=2014 |doi=10.1056/NEJMoa1401268 |pmid=24896819 |pmc=PMC4134948}}</ref>, astrovirus<ref name="NaccacheDiagnosis15">{{cite journal |title=Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing |journal=Clinical Infectious Diseases |author=Naccache, S.N.; Peggs, K.S.; Mattes, F.M. et al. |volume=60 |issue=6 |pages=919-23 |year=2015 |doi=10.1093/cid/ciu912 |pmid=25572898 |pmc=PMC4345816}}</ref>, and bornavirus.<ref name="HoffmannAVari15">{{cite journal |title=A Variegated Squirrel Bornavirus Associated with Fatal Human Encephalitis |journal=New England Journal of Medicine |author=Hoffmann, B.; Tappe, D.; Höper, D. et al. |volume=372 |issue=2 |pages=154-62 |year=2015 |doi=10.1056/NEJMoa1415627 |pmid=26154788}}</ref> 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.<ref name="WilsonActionable14" /> 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.<ref name="QuanAstro10">{{cite journal |title=Astrovirus encephalitis in boy with X-linked agammaglobulinemia |journal=Emerging Infectious Diseases |author=Quan, P.L.; Wagner, T.A.; Briese, T. et al. |volume=16 |issue=6 |pages=918-25 |year=2010 |doi=10.3201/eid1606.091536 |pmid=20507741 |pmc=PMC4102142}}</ref> | ||
Another promising application of NGS technology is [[hospital]] infection control surveillance programs and community outbreak investigations.<ref name="GMStaffCDC15">{{cite web |url=https://www.genomeweb.com/research-funding/cdc-earmarks-23m-ngs-bioinformatic-approaches-combat-infectious-disease |title=CDC Earmarks $2.3M for NGS, Bioinformatic Approaches to Combat Infectious Disease |author=GenomeWeb staff reporter |work=GenomeWeb |publisher=Genomeweb LLC |date=07 August 2015 |accessdate=19 September 2016}}</ref> By conducting whole-genome sequencing (WGS) (Table 1), organisms can be identified at the subspecies/strain level based on the single nucleotide polymorphisms (SNPs) (Table 1) and other variants (Table 1) in their genotype. WGS through NGS technology offers greater precision than do more-traditional typing tools such as multilocus sequence typing and pulsed-field gel electrophoresis, which may assist in refining outbreak investigations and better guide infection control interventions.<ref name="TurabelidzePrecise13">{{cite journal |title=Precise dissection of an Escherichia coli O157:H7 outbreak by single nucleotide polymorphism analysis |journal=Journal of Clinical Microbiology |author=Turabelidze, G.; Lawrence, S.J.; Gao, H. et al. |volume=51 |issue=12 |pages=3950-4 |year=2013 |doi=10.1128/JCM.01930-13 |pmid=24048526 |pmc=PMC3838074}}</ref> Because WGS analysis requires significant amounts of sequencing data, traditional sequencing methods preclude the use of WGS analysis for outbreak investigations. However, NGS platforms can generate the large volume of data needed for SNP or variant analysis and have led to a rapid expansion in the use of WGS for public health investigations. For example, WGS using NGS technology was applied to investigate an outbreak of hemolytic-uremic syndrome caused by an unusual strain of ''Escherichia coli'' in Germany<ref name="RaskoOrigins11">{{cite journal |title=Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany |journal=New England Journal of Medicine |author=Rasko, D.A.; Webster, D.R.; Sahl, J.W. et al. |volume=365 |issue=8 |pages=709-17 |year=2011 |doi=10.1056/NEJMoa1106920 |pmid=21793740 |pmc=PMC3168948}}</ref>, the origins of the 2010 Haitian ''Vibrio cholerae'' epidemic | Another promising application of NGS technology is [[hospital]] infection control surveillance programs and community outbreak investigations.<ref name="GMStaffCDC15">{{cite web |url=https://www.genomeweb.com/research-funding/cdc-earmarks-23m-ngs-bioinformatic-approaches-combat-infectious-disease |title=CDC Earmarks $2.3M for NGS, Bioinformatic Approaches to Combat Infectious Disease |author=GenomeWeb staff reporter |work=GenomeWeb |publisher=Genomeweb LLC |date=07 August 2015 |accessdate=19 September 2016}}</ref> By conducting whole-genome sequencing (WGS) (Table 1), organisms can be identified at the subspecies/strain level based on the single nucleotide polymorphisms (SNPs) (Table 1) and other variants (Table 1) in their genotype. WGS through NGS technology offers greater precision than do more-traditional typing tools such as multilocus sequence typing and pulsed-field gel electrophoresis, which may assist in refining outbreak investigations and better guide infection control interventions.<ref name="TurabelidzePrecise13">{{cite journal |title=Precise dissection of an Escherichia coli O157:H7 outbreak by single nucleotide polymorphism analysis |journal=Journal of Clinical Microbiology |author=Turabelidze, G.; Lawrence, S.J.; Gao, H. et al. |volume=51 |issue=12 |pages=3950-4 |year=2013 |doi=10.1128/JCM.01930-13 |pmid=24048526 |pmc=PMC3838074}}</ref> Because WGS analysis requires significant amounts of sequencing data, traditional sequencing methods preclude the use of WGS analysis for outbreak investigations. However, NGS platforms can generate the large volume of data needed for SNP or variant analysis and have led to a rapid expansion in the use of WGS for public health investigations. For example, WGS using NGS technology was applied to investigate an outbreak of hemolytic-uremic syndrome caused by an unusual strain of ''Escherichia coli'' in Germany<ref name="RaskoOrigins11">{{cite journal |title=Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany |journal=New England Journal of Medicine |author=Rasko, D.A.; Webster, D.R.; Sahl, J.W. et al. |volume=365 |issue=8 |pages=709-17 |year=2011 |doi=10.1056/NEJMoa1106920 |pmid=21793740 |pmc=PMC3168948}}</ref>, the origins of the 2010 Haitian ''Vibrio cholerae'' epidemic<ref name="ChinTheOrigin11">{{cite journal |title=The origin of the Haitian cholera outbreak strain |journal=New England Journal of Medicine |author=Chin, C.S.; Sorenson, J.; Harris, J.B. et al. |volume=364 |issue=1 |pages=33–42 |year=2011 |doi=10.1056/NEJMoa1012928 |pmid=21142692 |pmc=PMC3030187}}</ref>, a series of methicillin-resistant ''Staphylococcus aureus'' infections in a neonatal intensive care unit<ref name="AzarianWhole15">{{cite journal |title=Whole-genome sequencing for outbreak investigations of methicillin-resistant ''Staphylococcus aureus'' in the neonatal intensive care unit: Time for routine practice? |journal=Infection Control and Hospital Epidemiology |author=Azarian, T.; Cook, R.L.; Johnson, J.A. et al. |volume=36 |issue=7 |pages=777–785 |year=2015 |doi=10.1017/ice.2015.73 |pmid=25998499 |pmc=PMC4507300}}</ref>, and the origins of a series of nosocomial carbapenem-resistant ''Klebsiella pneumoniae'' infections<ref name="SnitkinTracking12">{{cite journal |title=Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing |journal=Science Translational Medicine |author=Snitkin, E.S.; Zelazny, A.M.; Thomas, P.J. et al. |volume=4 |issue=148 |pages=148ra116 |year=2012 |doi=10.1126/scitranslmed.3004129 |pmid=22914622 |pmc=PMC3521604}}</ref>, among many others. | ||
==References== | ==References== | ||
{{Reflist|colwidth=30em}} | {{Reflist|colwidth=30em}} |
Revision as of 20:09, 19 September 2016
Full article title | Making the leap from research laboratory to clinic: Challenges and opportunities for next-generation sequencing in infectious disease diagnostics |
---|---|
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) |
This article should not be considered complete until this message box has been removed. This is a work in progress. |
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.
|
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]
Another promising application of NGS technology is hospital infection control surveillance programs and community outbreak investigations.[8] By conducting whole-genome sequencing (WGS) (Table 1), organisms can be identified at the subspecies/strain level based on the single nucleotide polymorphisms (SNPs) (Table 1) and other variants (Table 1) in their genotype. WGS through NGS technology offers greater precision than do more-traditional typing tools such as multilocus sequence typing and pulsed-field gel electrophoresis, which may assist in refining outbreak investigations and better guide infection control interventions.[9] Because WGS analysis requires significant amounts of sequencing data, traditional sequencing methods preclude the use of WGS analysis for outbreak investigations. However, NGS platforms can generate the large volume of data needed for SNP or variant analysis and have led to a rapid expansion in the use of WGS for public health investigations. For example, WGS using NGS technology was applied to investigate an outbreak of hemolytic-uremic syndrome caused by an unusual strain of Escherichia coli in Germany[10], the origins of the 2010 Haitian Vibrio cholerae epidemic[11], a series of methicillin-resistant Staphylococcus aureus infections in a neonatal intensive care unit[12], and the origins of a series of nosocomial carbapenem-resistant Klebsiella pneumoniae infections[13], among many others.
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.
- ↑ 4.0 4.1 Wilson, M.R.; Naccache, S.N.; Samayoa, E. et al. (2014). "Actionable diagnosis of neuroleptospirosis by next-generation sequencing". New England Journal of Medicine 37 (25): 2408-17. doi:10.1056/NEJMoa1401268. PMC PMC4134948. PMID 24896819. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134948.
- ↑ Naccache, S.N.; Peggs, K.S.; Mattes, F.M. et al. (2015). "Diagnosis of neuroinvasive astrovirus infection in an immunocompromised adult with encephalitis by unbiased next-generation sequencing". Clinical Infectious Diseases 60 (6): 919-23. doi:10.1093/cid/ciu912. PMC PMC4345816. PMID 25572898. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4345816.
- ↑ Hoffmann, B.; Tappe, D.; Höper, D. et al. (2015). "A Variegated Squirrel Bornavirus Associated with Fatal Human Encephalitis". New England Journal of Medicine 372 (2): 154-62. doi:10.1056/NEJMoa1415627. PMID 26154788.
- ↑ Quan, P.L.; Wagner, T.A.; Briese, T. et al. (2010). "Astrovirus encephalitis in boy with X-linked agammaglobulinemia". Emerging Infectious Diseases 16 (6): 918-25. doi:10.3201/eid1606.091536. PMC PMC4102142. PMID 20507741. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4102142.
- ↑ GenomeWeb staff reporter (7 August 2015). "CDC Earmarks $2.3M for NGS, Bioinformatic Approaches to Combat Infectious Disease". GenomeWeb. Genomeweb LLC. https://www.genomeweb.com/research-funding/cdc-earmarks-23m-ngs-bioinformatic-approaches-combat-infectious-disease. Retrieved 19 September 2016.
- ↑ Turabelidze, G.; Lawrence, S.J.; Gao, H. et al. (2013). "Precise dissection of an Escherichia coli O157:H7 outbreak by single nucleotide polymorphism analysis". Journal of Clinical Microbiology 51 (12): 3950-4. doi:10.1128/JCM.01930-13. PMC PMC3838074. PMID 24048526. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838074.
- ↑ Rasko, D.A.; Webster, D.R.; Sahl, J.W. et al. (2011). "Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany". New England Journal of Medicine 365 (8): 709-17. doi:10.1056/NEJMoa1106920. PMC PMC3168948. PMID 21793740. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168948.
- ↑ Chin, C.S.; Sorenson, J.; Harris, J.B. et al. (2011). "The origin of the Haitian cholera outbreak strain". New England Journal of Medicine 364 (1): 33–42. doi:10.1056/NEJMoa1012928. PMC PMC3030187. PMID 21142692. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3030187.
- ↑ Azarian, T.; Cook, R.L.; Johnson, J.A. et al. (2015). "Whole-genome sequencing for outbreak investigations of methicillin-resistant Staphylococcus aureus in the neonatal intensive care unit: Time for routine practice?". Infection Control and Hospital Epidemiology 36 (7): 777–785. doi:10.1017/ice.2015.73. PMC PMC4507300. PMID 25998499. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4507300.
- ↑ Snitkin, E.S.; Zelazny, A.M.; Thomas, P.J. et al. (2012). "Tracking a hospital outbreak of carbapenem-resistant Klebsiella pneumoniae with whole-genome sequencing". Science Translational Medicine 4 (148): 148ra116. doi:10.1126/scitranslmed.3004129. PMC PMC3521604. PMID 22914622. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3521604.
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.