Evidence map›Paper›PMID 30992304›Full record

ArticleGenome research2019

Laboratory validation of a clinical metagenomic sequencing assay for pathogen detection in cerebrospinal fluid.

Steve Miller, Samia N Naccache, Erik Samayoa, Kevin Messacar, Shaun Arevalo, Scot Federman, Doug Stryke, Elizabeth Pham, Becky Fung, William J Bolosky and 8 more

3 registry-linked trialsOpen access · bronzeAbstract readValidation Study
In one paragraph

Article in Genome research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 393 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
393citing papers in PubMed, 6 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05085158 unknown statusnot on this mapstarted 2023, after this paper: background citation

Pathogen Detection in HIV-infected Children and Adolescents With Non-malarial Febrile Illnesses Using Metagenomic Next-generation Sequencing Approach in Uganda

TypeobservationalSponsorMakerere UniversityRan2023 to 2024Enrolled138ConditionsHIV Infection
NCT07435649 narecruitingnot on this mapstarted 2026, after this paper: background citation

Investigation of the Delve Detect Cerebrospinal Fluid (CSF) Metagenomic Next-generation Sequencing (mNGS) Test When Used for the Initial Diagnostic Workup of Patients With Suspected Central Nervous System (CNS) Infection

TypeinterventionalSponsorDelve Bio, Inc.Ran2026 to 2027Enrolled400ConditionsCentral Nervous System InfectionArmsDelve Detect CSF mNGS Test, Real-World Data
NCT07626073 enrolling by invitationnot on this mapstarted 2023, after this paper: background citation

h Can Provide the Detection Results of Pathogen Type and Resistant Gene. This Study is a Prospective Multi Centers Study to Explore Using the New Diagnostic Tool of " RPIP " and the Different Detection Methods of Next Generation Sequencing and Multiplex PC R in Patients With Pneumonia in ICU. Further Compare the Difference of Pathogen Identification and Clinical Impact by Different Diagnostic Methods.

Typeobservational_patient_registrySponsorChina Medical University HospitalRan2023 to 2028Enrolled200ConditionsRespiratory Pathogens
3 · Its place in the literature

Who cites it

393 citing papers in PubMed, 6 syntheses or guidelines pooled it, 566 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  7. Rapid diagnosis ofExperimental and therapeutic medicine · 2026
    Article
  8. First case of neonatal bloodstream infection caused byExperimental and therapeutic medicine · 2026
    Article
  9. Review
  10. Article
  11. Article
  12. Clinical utility of metagenomic next-generation sequencing in precision diagnosis of infectious diseases: a retrospective study based on bronchoalveolar lavage fluid, blood, and cerebrospinal fluid.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Metagenomic next-generation sequencing for comprehensive pathogen detection in intraocular infection.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2026
    Article
  17. Article
  18. Review
  19. Article
  20. Article

333 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors at 6 institutions in 1 country.

Steve Miller *Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Samia N Naccache *Department of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Erik SamayoaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Kevin MessacarDepartment of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Shaun ArevaloDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Scot FedermanDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Doug StrykeDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Elizabeth PhamDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Becky FungDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
William J BoloskyMicrosoft Research, Redmond, Washington 98052, USA.
Danielle IngebrigtsenDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Walter LorizioDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
Sandra M PaffDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
John A LeakeQuest Diagnostics Nichols Institute, San Juan Capistrano, California 92675, USA.
Rick PesanoQuest Diagnostics Nichols Institute, San Juan Capistrano, California 92675, USA.
Roberta DeBiasiDepartment of Pediatrics, Division of Pediatric Infectious Diseases, Children's National Health System, Washington, DC 20010, USA.
Samuel DominguezDepartment of Pediatrics, Children's Hospital Colorado and University of Colorado School of Medicine, Aurora, Colorado 80045, USA.
Charles Y ChiuDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, California 94143, USA.ORCID 0000-0003-2915-2094
University of California, San Francisco · USChildren's Hospital Colorado · USQuest Diagnostics (United States) · USChildren's Hospital of Los Angeles · USChildren's National · USMicrosoft (United States) · US

Funding

Engaging University of California Stakeholders for Biorespository ResearchUL1TR000004 · NCATS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GRANDIS, JENNIFER RUBIN · 2012 to 2015
$78.0M
NIH Prior Approval Process ProfessionalUL1TR002535 · NCATS · UNIVERSITY OF COLORADO DENVER · PI SOKOL, RONALD J. · 2018 to 2022
$51.1M
UC BRAID Center for Accelerated Innovation COVID-19 diagnostic project developmentU54HL119893 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PALAZZOLO, MICHAEL J · 2013 to 2020
$18.3M
Pan-Genomic Approaches for Comprehensive Blood Screening of Novel or Emerging Infectious AgentsR01HL105704 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIU, CHARLES YEN · 2011 to 2020
$5.9M
Real-Time Unbiased Pathogen Detection in Febrile Illnesses by Nanopore SequencingR33AI120977 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIU, CHARLES YEN · 2018 to 2020
$1.6M
Real-Time Unbiased Pathogen Detection in Febrile Illnesses by Nanopore SequencingR21AI120977 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHIU, CHARLES YEN · 2016 to 2017
$436k
NCATS NIH HHS UL1 TR000004NCATS NIH HHS UL1 TR002535NHLBI NIH HHS R01 HL105704NHLBI NIH HHS U54 HL119893NIAID NIH HHS R21 AI120977NIAID NIH HHS R33 AI120977
6 · The paper itself

Abstract

Metagenomic next-generation sequencing (mNGS) for pan-pathogen detection has been successfully tested in proof-of-concept case studies in patients with acute illness of unknown etiology but to date has been largely confined to research settings. Here, we developed and validated a clinical mNGS assay for diagnosis of infectious causes of meningitis and encephalitis from cerebrospinal fluid (CSF) in a licensed microbiology laboratory. A customized bioinformatics pipeline, SURPI+, was developed to rapidly analyze mNGS data, generate an automated summary of detected pathogens, and provide a graphical user interface for evaluating and interpreting results. We established quality metrics, threshold values, and limits of detection of 0.2-313 genomic copies or colony forming units per milliliter for each representative organism type. Gross hemolysis and excess host nucleic acid reduced assay sensitivity; however, spiked phages used as internal controls were reliable indicators of sensitivity loss. Diagnostic test accuracy was evaluated by blinded mNGS testing of 95 patient samples, revealing 73% sensitivity and 99% specificity compared to original clinical test results, and 81% positive percent agreement and 99% negative percent agreement after discrepancy analysis. Subsequent mNGS challenge testing of 20 positive CSF samples prospectively collected from a cohort of pediatric patients hospitalized with meningitis, encephalitis, and/or myelitis showed 92% sensitivity and 96% specificity relative to conventional microbiological testing of CSF in identifying the causative pathogen. These results demonstrate the analytic performance of a laboratory-validated mNGS assay for pan-pathogen detection, to be used clinically for diagnosis of neurological infections from CSF.

Indexed as

ChildComputational BiologyEncephalitisHigh-Throughput Nucleotide SequencingHumansMeningitis, AsepticMetagenomicsMyelitisSensitivity and SpecificityViruses

Identifiers

PMID30992304
PMCPMC6499319
OpenAlexW2951983907

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.