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2019-09-01
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CAPTURING SEQUENCE DIVERSITY IN METAGENOMES WITH COMPREHENSIVE AND SCALABLE PROBE DESIGN
Thiago M. L. Souza e Yasmine R. Vieira - Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.
Hayden C. Metsky 1,2,27*, Katherine J. Siddle1,3,27*, Adrianne Gladden-Young1, James Qu1, David K. Yang 1,3, Patrick Brehio1, Andrew Goldfarb4, Anne Piantadosi1,5, Shirlee Wohl1,3, Amber Carter1, Aaron E. Lin1,3, Kayla G. Barnes1,3,6, Damien C. Tully7, Björn Corleis7,, Scott Hennigan8, Giselle Barbosa-Lima9, Yasmine R. Vieira9, Lauren M. Paul 10, Amanda L. Tan10, Kimberly F. Garcia11, Leda A. Parham11, Ikponmwosa Odia12, Philomena Eromon13, Onikepe A. Folarin13,14, Augustine Goba15, Viral Hemorrhagic Fever Consortium16, Etienne Simon-Lorière17, Lisa Hensley18, Angel Balmaseda19, Eva Harris20, Douglas S. Kwon5,7, Todd M. Allen7, Jonathan A. Runstadler21, Sandra Smole8, Fernando A. Bozza9, Thiago M. L. Souza9, Sharon Isern10, Scott F. Michael10, Ivette Lorenzana11, Lee Gehrke22,23, Irene Bosch22, Gregory Ebel24, Donald S. Grant 15,25, Christian T. Happi6,12,13,14, Daniel J. Park1, Andreas Gnirke1, Pardis C. Sabeti1,3,6,26,28 and Christian B. Matranga1,28. 1Broad Institute of MIT and Harvard, Cambridge, MA, USA. 2Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA. 3 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. 4Faculty of Arts and Sciences, Harvard University, Cambridge, MA, USA. 5Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. 6Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. 7The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. 8Massachusetts Department of Public Health, Boston, MA, USA. 9Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. 10Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, FL, USA. 11Instituto de Investigacion en Microbiologia, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras. 12Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria. 13African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemer’s University, Ede, Nigeria. 14Department of Biological Sciences, College of Natural Sciences, Redeemer’s University, Ede, Nigeria. 15Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Sierra Leone. 16A list of members and affiliations appears in Supplementary Note 3. 17Evolutionary Genomics of RNA Viruses, Virology Department, Institut Pasteur, Paris, France. 18Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Frederick, MD, USA. 19Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua. 20Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. 21Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. 22Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. 23Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA. 24Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA. 25College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone. 26Howard Hughes Medical Institute, Chevy Chase, MD, USA. 27These authors contributed equally: Hayden C. Metsky, Katherine J. Siddle. 28These authors jointly supervised this work: Pardis C. Sabeti, Christian B. Matranga.
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Abstract
Metagenomic sequencing has the potential to transform microbial detection and characterization, but new tools are needed to improve its sensitivity. Here we present CATCH, a computational method to enhance nucleic acid capture for enrichment of diverse microbial taxa. CATCH designs optimal probe sets, with a specified number of oligonucleotides, that achieve full coverage of, and scale well with, known sequence diversity. We focus on applying CATCH to capture viral genomes in complex metagenomic samples. We design, synthesize, and validate multiple probe sets, including one that targets the whole genomes of the 356 viral species known to infect humans. Capture with these probe sets enriches unique viral content on average 18-fold, allowing us to assemble genomes that could not be recovered without enrichment, and accurately preserves within-sample diversity. We also use these probe sets to recover genomes from the 2018 Lassa fever outbreak in Nigeria and to improve detection of uncharacterized viral infections in human and mosquito samples. The results demonstrate that CATCH enables more sensitive and cost-effective metagenomic sequencing.
Publisher
Nature Research
Citation
METSKY, Hayden C. et al. Capturing sequence diversity in metagenomes with comprehensive and scalable probe design. Nature Biotechnology, v. 37, p. 160-160, Feb. 2019.DOI
10.1038/s41587-018-0006-xISSN
1087-0156Notes
Fernando A. Bozza e Giselle Barbosa-Lima - Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.Thiago M. L. Souza e Yasmine R. Vieira - Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento.
Hayden C. Metsky 1,2,27*, Katherine J. Siddle1,3,27*, Adrianne Gladden-Young1, James Qu1, David K. Yang 1,3, Patrick Brehio1, Andrew Goldfarb4, Anne Piantadosi1,5, Shirlee Wohl1,3, Amber Carter1, Aaron E. Lin1,3, Kayla G. Barnes1,3,6, Damien C. Tully7, Björn Corleis7,, Scott Hennigan8, Giselle Barbosa-Lima9, Yasmine R. Vieira9, Lauren M. Paul 10, Amanda L. Tan10, Kimberly F. Garcia11, Leda A. Parham11, Ikponmwosa Odia12, Philomena Eromon13, Onikepe A. Folarin13,14, Augustine Goba15, Viral Hemorrhagic Fever Consortium16, Etienne Simon-Lorière17, Lisa Hensley18, Angel Balmaseda19, Eva Harris20, Douglas S. Kwon5,7, Todd M. Allen7, Jonathan A. Runstadler21, Sandra Smole8, Fernando A. Bozza9, Thiago M. L. Souza9, Sharon Isern10, Scott F. Michael10, Ivette Lorenzana11, Lee Gehrke22,23, Irene Bosch22, Gregory Ebel24, Donald S. Grant 15,25, Christian T. Happi6,12,13,14, Daniel J. Park1, Andreas Gnirke1, Pardis C. Sabeti1,3,6,26,28 and Christian B. Matranga1,28. 1Broad Institute of MIT and Harvard, Cambridge, MA, USA. 2Department of Electrical Engineering and Computer Science, Massachusetts Institute of Technology, Cambridge, MA, USA. 3 Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, MA, USA. 4Faculty of Arts and Sciences, Harvard University, Cambridge, MA, USA. 5Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA. 6Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Harvard University, Boston, MA, USA. 7The Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA. 8Massachusetts Department of Public Health, Boston, MA, USA. 9Fundacao Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Rio de Janeiro, Brazil. 10Department of Biological Sciences, College of Arts and Sciences, Florida Gulf Coast University, Fort Myers, FL, USA. 11Instituto de Investigacion en Microbiologia, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras. 12Institute of Lassa Fever Research and Control, Irrua Specialist Teaching Hospital, Irrua, Nigeria. 13African Center of Excellence for Genomics of Infectious Disease (ACEGID), Redeemer’s University, Ede, Nigeria. 14Department of Biological Sciences, College of Natural Sciences, Redeemer’s University, Ede, Nigeria. 15Lassa Fever Laboratory, Kenema Government Hospital, Kenema, Sierra Leone. 16A list of members and affiliations appears in Supplementary Note 3. 17Evolutionary Genomics of RNA Viruses, Virology Department, Institut Pasteur, Paris, France. 18Integrated Research Facility, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Frederick, MD, USA. 19Laboratorio Nacional de Virología, Centro Nacional de Diagnóstico y Referencia, Ministry of Health, Managua, Nicaragua. 20Division of Infectious Diseases and Vaccinology, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. 21Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine, Tufts University, North Grafton, MA, USA. 22Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA, USA. 23Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, USA. 24Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO, USA. 25College of Medicine and Allied Health Sciences, University of Sierra Leone, Freetown, Sierra Leone. 26Howard Hughes Medical Institute, Chevy Chase, MD, USA. 27These authors contributed equally: Hayden C. Metsky, Katherine J. Siddle. 28These authors jointly supervised this work: Pardis C. Sabeti, Christian B. Matranga.
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