Metagenomic sequencing with spiked primer enrichment for viral diagnostics and genomic surveillance


Por: Deng X., Achari A., Federman S., Yu G., Somasekar S., Bártolo I., Yagi S., Mbala-Kingebeni P., Kapetshi J., Ahuka-Mundeke S., Muyembe-Tamfum J.-J., Ahmed A.A., Ganesh V., Tamhankar M., Patterson J.L., Ndembi N., Mbanya D., Kaptue L., McArthur C., Muñoz-Medina J.E., Gonzalez-Bonilla C.R., López S., Arias C.F., Arevalo S., Miller S., Stone M., Busch M., Hsieh K., Messenger S., Wadford D.A., Rodgers M., Cloherty G., Faria N.R., Thézé J., Pybus O.G., Neto Z., Morais J., Taveira N., R. Hackett J., Jr., Chiu C.Y.

Publicada: 1 ene 2020
Resumen:
Metagenomic next-generation sequencing (mNGS), the shotgun sequencing of RNA and DNA from clinical samples, has proved useful for broad-spectrum pathogen detection and the genomic surveillance of viral outbreaks. An additional target enrichment step is generally needed for high-sensitivity pathogen identification in low-titre infections, yet available methods using PCR or capture probes can be limited by high cost, narrow scope of detection, lengthy protocols and/or cross-contamination. Here, we developed metagenomic sequencing with spiked primer enrichment (MSSPE), a method for enriching targeted RNA viral sequences while simultaneously retaining metagenomic sensitivity for other pathogens. We evaluated MSSPE for 14 different viruses, yielding a median tenfold enrichment and mean 47% (±16%) increase in the breadth of genome coverage over mNGS alone. Virus detection using MSSPE arboviral or haemorrhagic fever viral panels was comparable in sensitivity to specific PCR, demonstrating 95% accuracy for the detection of Zika, Ebola, dengue, chikungunya and yellow fever viruses in plasma samples from infected patients. Notably, sequences from re-emerging and/or co-infecting viruses that have not been specifically targeted a priori, including Powassan and Usutu, were successfully enriched using MSSPE. MSSPE is simple, low cost, fast and deployable on either benchtop or portable nanopore sequencers, making this method directly applicable for diagnostic laboratory and field use. © 2020, The Author(s), under exclusive licence to Springer Nature Limited.

Filiaciones:
Deng X.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

 UCSF–Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, United States

Achari A.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

 UCSF–Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, United States

Federman S.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

 UCSF–Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, United States

Yu G.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

 UCSF–Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, United States

Somasekar S.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

 UCSF–Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, United States

Bártolo I.:
 Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

Yagi S.:
 Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA, United States

Mbala-Kingebeni P.:
 Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic Congo

Kapetshi J.:
 Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic Congo

Ahuka-Mundeke S.:
 Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic Congo

Muyembe-Tamfum J.-J.:
 Institut National de Recherche Biomédicale, Kinshasa, Democratic Republic Congo

Ahmed A.A.:
 Boston Children’s Hospital, Boston, MA, United States

 Harvard Medical School, Boston, MA, United States

Ganesh V.:
 Massachussetts General Hospital, Boston, MA, United States

Tamhankar M.:
 Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX, United States

Patterson J.L.:
 Department of Virology and Immunology, Texas Biomedical Research Institute, San Antonio, TX, United States

Ndembi N.:
 Institute for Human Virology Nigeria, Abuja, Nigeria

 Institute of Human Virology, University of Maryland School of Medicine, Baltimore, MD, United States

Mbanya D.:
 Universite de Yaoundé I, Yaoundé, Cameroon

 University of Bamenda, Bamenda, Cameroon

Kaptue L.:
 Université des Montagnes, Bangangté, Cameroon

McArthur C.:
 University of Missouri-Kansas City, Kansas City, MO, United States

Muñoz-Medina J.E.:
 Instituto Mexicano del Seguro Social, Mexico City, Mexico

Gonzalez-Bonilla C.R.:
 Instituto Mexicano del Seguro Social, Mexico City, Mexico

López S.:
 Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico

Arias C.F.:
 Instituto de Biotecnología, Universidad Nacional Autónoma de México, Cuernavaca, Mexico

Arevalo S.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

Miller S.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

Stone M.:
 Blood Systems Research Institute, San Francisco, CA, United States

Busch M.:
 Blood Systems Research Institute, San Francisco, CA, United States

Hsieh K.:
 Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA, United States

Messenger S.:
 Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA, United States

Wadford D.A.:
 Viral and Rickettsial Disease Laboratory, California Department of Public Health, Richmond, CA, United States

Rodgers M.:
 Abbott Laboratories, Abbott Park, IL, United States

Cloherty G.:
 Abbott Laboratories, Abbott Park, IL, United States

Faria N.R.:
 Department of Zoology, University of Oxford, Oxford, United Kingdom

Thézé J.:
 Department of Zoology, University of Oxford, Oxford, United Kingdom

Pybus O.G.:
 Department of Zoology, University of Oxford, Oxford, United Kingdom

Neto Z.:
 Angolan National Institute of Health Research, Luanda, Angola

Morais J.:
 Angolan National Institute of Health Research, Luanda, Angola

Taveira N.:
 Research Institute for Medicines, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal

 Instituto Universitário Egas Moniz (IUEM), Monte de Caparica, Portugal

R. Hackett J.:
 Abbott Laboratories, Abbott Park, IL, United States

Jr.:
 Abbott Laboratories, Abbott Park, IL, United States

Chiu C.Y.:
 Department of Laboratory Medicine, University of California San Francisco, San Francisco, CA, United States

 UCSF–Abbott Viral Diagnostics and Discovery Center, San Francisco, CA, United States

 Department of Medicine, Division of Infectious Diseases, University of California San Francisco, San Francisco, CA, United States
ISSN: 20585276
Editorial
Nature Publishing Group, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND, Reino Unido
Tipo de documento: Article
Volumen: 5 Número: 3
Páginas: 443-454
WOS Id: 000508513600001
ID de PubMed: 31932713