Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis
Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Meningitis and encephalitis are leading causes of cen...
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Published in | mBio Vol. 12; no. 4; p. e0114321 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Microbiology
31.08.2021
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Subjects | |
Online Access | Get full text |
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Abstract | Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures.
Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known (
n
= 44) or suspected (
n
= 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the
Ixodes scapularis
tick-borne pathogens Powassan virus,
Borrelia burgdorferi
, and
Anaplasma phagocytophilum
. We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis.
IMPORTANCE
Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known (
n
= 44) or suspected (
n
= 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections. |
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AbstractList | ABSTRACT Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known (n = 44) or suspected (n = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. IMPORTANCE Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known (n = 44) or suspected (n = 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections. Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known ( = 44) or suspected ( = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known ( = 44) or suspected ( = 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections. Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known ( n = 44) or suspected ( n = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi , and Anaplasma phagocytophilum . We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known ( n = 44) or suspected ( n = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi , and Anaplasma phagocytophilum . We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. IMPORTANCE Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known ( n = 44) or suspected ( n = 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections. Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known (n = 44) or suspected (n = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. IMPORTANCE Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known (n = 44) or suspected (n = 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections. Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known (n = 44) or suspected (n = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. IMPORTANCE Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known (n = 44) or suspected (n = 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections.Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional diagnostic workflows largely rely on pathogen-specific tests, sometimes over days to weeks, whereas metagenomic next-generation sequencing (mNGS) profiles all nucleic acid in a sample. In this single-center, prospective study, 68 hospitalized patients with known (n = 44) or suspected (n = 24) CNS infections underwent mNGS from RNA and DNA to identify potential pathogens and also targeted sequencing of viruses using hybrid capture. Using a computational metagenomic classification pipeline based on KrakenUniq and BLAST, we detected pathogen nucleic acid in cerebrospinal fluid (CSF) from 22 subjects, 3 of whom had no clinical diagnosis by routine workup. Among subjects diagnosed with infection by serology and/or peripheral samples, we demonstrated the utility of mNGS to detect pathogen nucleic acid in CSF, importantly for the Ixodes scapularis tick-borne pathogens Powassan virus, Borrelia burgdorferi, and Anaplasma phagocytophilum. We also evaluated two methods to enhance the detection of viral nucleic acid, hybrid capture and methylated DNA depletion. Hybrid capture nearly universally increased viral read recovery. Although results for methylated DNA depletion were mixed, it allowed the detection of varicella-zoster virus DNA in two samples that were negative by standard mNGS. Overall, mNGS is a promising approach that can test for multiple pathogens simultaneously, with efficacy similar to that of pathogen-specific tests, and can uncover geographically relevant infectious CNS disease, such as tick-borne infections in New England. With further laboratory and computational enhancements, mNGS may become a mainstay of workup for encephalitis and meningitis. IMPORTANCE Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain inefficient, requiring costly pathogen-specific assays and sometimes invasive surgical procedures. Despite intensive diagnostic efforts, 40 to 60% of people with meningitis or encephalitis have no clear cause of CNS disease identified. As diagnostic uncertainty often leads to costly inappropriate therapies, the need for novel pathogen detection methods is paramount. Metagenomic next-generation sequencing (mNGS) offers the unique opportunity to circumvent these challenges using unbiased laboratory and computational methods. Here, we performed comprehensive mNGS from 68 prospectively enrolled patients with known (n = 44) or suspected (n = 24) CNS viral infection from a single center in New England and evaluated enhanced methods to improve the detection of CNS pathogens, including those not traditionally identified in the CNS by nucleic acid detection. Overall, our work helps elucidate how mNGS can become integrated into the diagnostic toolkit for CNS infections. |
Author | Goldstein, Robert Ganesh, Vijay Goldberg, Marcia B. Freimark, Lisa M. Ye, Simon Cummins, Kaelyn C. Sabeti, Pardis Cho, Tracey A. Lemieux, Jacob Mukerji, Shibani S. Kanjilal, Sanjat Solomon, Isaac H. Ahmed, Asim A. Park, Daniel Frosch, Matthew P. Piantadosi, Anne Kinsella, Cormac M. Rosenberg, Eric Leone, Michael J. Thon, Jesse M. Adams, Gordon Ostrem, Bridget |
Author_xml | – sequence: 1 givenname: Anne orcidid: 0000-0002-5942-1534 surname: Piantadosi fullname: Piantadosi, Anne organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Emory University School of Medicine, Atlanta, Georgia, USA – sequence: 2 givenname: Shibani S. surname: Mukerji fullname: Mukerji, Shibani S. organization: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA – sequence: 3 givenname: Simon surname: Ye fullname: Ye, Simon organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Harvard-MIT Program of Health Sciences and Technology, Cambridge, Massachusetts, USA – sequence: 4 givenname: Michael J. surname: Leone fullname: Leone, Michael J. organization: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA – sequence: 5 givenname: Lisa M. surname: Freimark fullname: Freimark, Lisa M. organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA – sequence: 6 givenname: Daniel surname: Park fullname: Park, Daniel organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA – sequence: 7 givenname: Gordon surname: Adams fullname: Adams, Gordon organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA – sequence: 8 givenname: Jacob surname: Lemieux fullname: Lemieux, Jacob organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA – sequence: 9 givenname: Sanjat orcidid: 0000-0002-1221-5725 surname: Kanjilal fullname: Kanjilal, Sanjat organization: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA, Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA – sequence: 10 givenname: Isaac H. surname: Solomon fullname: Solomon, Isaac H. organization: Harvard Medical School, Boston, Massachusetts, USA, Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts, USA – sequence: 11 givenname: Asim A. surname: Ahmed fullname: Ahmed, Asim A. organization: Harvard Medical School, Boston, Massachusetts, USA, Department of Pediatrics, Harvard Medical School, Children’s Hospital, Boston, Massachusetts, USA – sequence: 12 givenname: Robert surname: Goldstein fullname: Goldstein, Robert organization: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA – sequence: 13 givenname: Vijay surname: Ganesh fullname: Ganesh, Vijay organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA, Department of Neurology, Brigham and Women’s Hospital, Boston, Massachusetts, USA – sequence: 14 givenname: Bridget surname: Ostrem fullname: Ostrem, Bridget organization: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA – sequence: 15 givenname: Kaelyn C. surname: Cummins fullname: Cummins, Kaelyn C. organization: Division of Infectious Diseases, Brigham and Women’s Hospital, Boston, Massachusetts, USA – sequence: 16 givenname: Jesse M. surname: Thon fullname: Thon, Jesse M. organization: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA – sequence: 17 givenname: Cormac M. surname: Kinsella fullname: Kinsella, Cormac M. organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA – sequence: 18 givenname: Eric surname: Rosenberg fullname: Rosenberg, Eric organization: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA – sequence: 19 givenname: Matthew P. surname: Frosch fullname: Frosch, Matthew P. organization: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA, Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts, USA – sequence: 20 givenname: Marcia B. surname: Goldberg fullname: Goldberg, Marcia B. organization: Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA – sequence: 21 givenname: Tracey A. surname: Cho fullname: Cho, Tracey A. organization: Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA, University of Iowa, Department of Neurology, Iowa City, Iowa, USA – sequence: 22 givenname: Pardis surname: Sabeti fullname: Sabeti, Pardis organization: Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA, Division of Infectious Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA, Harvard Medical School, Boston, Massachusetts, USA, Department of Organismic and Evolutionary Biology, Harvard University, Cambridge, Massachusetts, USA, Department of Immunology and Infectious Disease, Harvard T. H. Chan School of Public Health, Boston, Massachusetts, USA |
BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34465023$$D View this record in MEDLINE/PubMed |
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Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Tracey A. Cho and Pardis Sabeti contributed equally. Present address: Kaelyn C. Cummins, Baylor College of Medicine, Houston, Texas, USA; Jesse M. Thon, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA; Cormac M. Kinsella, Amsterdam UMC, Amsterdam, The Netherlands. Anne Piantadosi, Shibani S. Mukerji, and Simon Ye all contributed equally to this work. Author order was determined by mutual agreement among first authors. |
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Snippet | Meningitis and encephalitis are leading global causes of central nervous system (CNS) disability and mortality. Current diagnostic workflows remain... Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death. Traditional... ABSTRACT Meningitis and encephalitis are leading causes of central nervous system (CNS) disease and often result in severe neurological compromise or death.... |
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SubjectTerms | Adult Aged Central Nervous System Viral Diseases - cerebrospinal fluid Central Nervous System Viral Diseases - diagnosis Central Nervous System Viral Diseases - virology encephalitis Encephalitis - cerebrospinal fluid Encephalitis - diagnosis Encephalitis - virology Female High-Throughput Nucleotide Sequencing - methods Humans hybrid capture Male meningitis Meningitis - cerebrospinal fluid Meningitis - diagnosis Meningitis - virology Metagenome metagenomic sequencing Metagenomics - methods Middle Aged next-generation sequencing (NGS) Prospective Studies Research Article Virology virus Viruses - classification Viruses - genetics Viruses - isolation & purification Viruses - pathogenicity |
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Title | Enhanced Virus Detection and Metagenomic Sequencing in Patients with Meningitis and Encephalitis |
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