Evidence map›Paper›PMID 39533109›Full record

ArticleNature medicine2024

Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections.

Patrick Benoit, Noah Brazer, Mikael de Lorenzi-Tognon, Emily Kelly, Venice Servellita, Miriam Oseguera, Jenny Nguyen, Jack Tang, Charles Omura, Jessica Streithorst and 10 more

Registry-linked trialAbstract read
In one paragraph

Article in Nature medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07435649 (Investigation of the Delve Detect Cerebrospinal Fluid), which is not on this map. Cited by 103 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 1 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.

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
3 · Its place in the literature

Who cites it

103 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Clinical metagenomics: a call to action.Intensive care medicine · 2026
    Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Observational
  8. Review
  9. Article
  10. Article
  11. 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
  12. Review
  13. Article
  14. Article
  15. Article
  16. Clinical utility of metagenomic next-generation sequencing in diagnosing spinal infections: a systematic review and meta-analysis.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Review
  17. Article
  18. Review
  19. Article
  20. Article

43 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

20 authors.

Patrick BenoitDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Noah BrazerDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Mikael de Lorenzi-TognonDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2969-542X
Emily KellyDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2986-0285
Venice ServellitaDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Miriam OsegueraDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0004-9621-2848
Jenny NguyenDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jack TangDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Charles OmuraDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jessica StreithorstDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Melissa HillbergDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Danielle IngebrigtsenDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Kelsey ZornDepartment of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1227-2137
Michael R WilsonWeill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-8705-5084
Tim BlicharzDelve Bio, Boston, MA, USA.ORCID http://orcid.org/0000-0002-0371-7547
Amy P WongDelve Bio, Boston, MA, USA.
Brian O'DonovanDelve Bio, Boston, MA, USA.
Brad MurrayDelve Bio, Boston, MA, USA.
Steve MillerDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA.
Charles Y ChiuDepartment of Laboratory Medicine, University of California, San Francisco, San Francisco, CA, USA. charles.chiu@ucsf.edu.ORCID http://orcid.org/0000-0003-2915-2094

Funding

U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC) 75D30121C12641U.S. Department of Health & Human Services | Centers for Disease Control and Prevention (CDC) 75D30122C15360
6 · The paper itself

Abstract

Metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) is an agnostic method for broad-based diagnosis of central nervous system (CNS) infections. Here we analyzed the 7-year performance of clinical CSF mNGS testing of 4,828 samples from June 2016 to April 2023 performed by the University of California, San Francisco (UCSF) clinical microbiology laboratory. Overall, mNGS testing detected 797 organisms from 697 (14.4%) of 4,828 samples, consisting of 363 (45.5%) DNA viruses, 211 (26.4%) RNA viruses, 132 (16.6%) bacteria, 68 (8.5%) fungi and 23 (2.9%) parasites. We also extracted clinical and laboratory metadata from a subset of the samples (n = 1,164) from 1,053 UCSF patients. Among the 220 infectious diagnoses in this subset, 48 (21.8%) were identified by mNGS alone. The sensitivity, specificity and accuracy of mNGS testing for CNS infections were 63.1%, 99.6% and 92.9%, respectively. mNGS testing exhibited higher sensitivity (63.1%) than indirect serologic testing (28.8%) and direct detection testing from both CSF (45.9%) and non-CSF (15.0%) samples (P < 0.001 for all three comparisons). When only considering diagnoses made by CSF direct detection testing, the sensitivity of mNGS testing increased to 86%. These results justify the routine use of diagnostic mNGS testing for hospitalized patients with suspected CNS infection.

Indexed as

Central Nervous System InfectionsHigh-Throughput Nucleotide SequencingMetagenomicsAdolescentAdultAgedAged, 80 and overChildChild, PreschoolFemaleHumansInfantMaleMetagenomeMiddle AgedSensitivity and Specificity

Identifiers

PMID39533109
PMCPMC11645279

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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.