Evidence map›Paper›PMID 27340685›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2016

Next-generation sequencing in neuropathologic diagnosis of infections of the nervous system.

Steven L Salzberg, Florian P Breitwieser, Anupama Kumar, Haiping Hao, Peter Burger, Fausto J Rodriguez, Michael Lim, Alfredo Quiñones-Hinojosa, Gary L Gallia, Jeffrey A Tornheim and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology(R) neuroimmunology & neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 2 pooled it
16.9field-weighted citation impact, top 1% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 179 citations in OpenAlex.

  1. Pooled it
  2. The etiological spectrum of multiple ring-enhancing lesions of the brain: a systematic review of published cases and case series.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2024
    Pooled it
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  18. Novel metagenomics analysis of stony coral tissue loss disease.bioRxiv : the preprint server for biology · 2024
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38 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

13 authors at 1 institution in 2 countries.

Steven L SalzbergCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Florian P BreitwieserCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Anupama KumarCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Haiping HaoCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Peter BurgerCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Fausto J RodriguezCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Michael LimCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Alfredo Quiñones-HinojosaCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Gary L GalliaCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Jeffrey A TornheimCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Michael T MeliaCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Cynthia L SearsCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Carlos A PardoCenter for Computational Biology, McKusick-Nathans Institute of Genetic Medicine (S.L.S., F.P.B.), Department of Neurology (A.K., C.A.P.), Deep Sequencing and Microarray Core (H.H.), and Departments of Pathology (P.B., F.J.R., C.A.P.), Neurosurgery (M.L., A.Q.-H., G.L.G.), and Medicine (J.A.T., M.T.M., C.L.S.), School of Medicine, and Departments of Biomedical Engineering, Computer Science, and Biostatistics (S.L.S.), Johns Hopkins University, Baltimore, MD.
Institute of Applied Physics · UA

Funding

Translational Research Enhancement CoreP30DK089502 · NIDDK · JOHNS HOPKINS UNIVERSITY · PI ZACHOS, NICHOLAS CONSTANTINE · 2011 to 2020
$12.0M
Computational Methods for Genome Assembly, Transcript Assembly, and Variant DiscoveryR01HG006677 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI SALZBERG, STEVEN L. · 2011 to 2025
$10.7M
NHGRI NIH HHS R01 HG006677NIDDK NIH HHS P30 DK089502
6 · The paper itself

Abstract

objectiveTo determine the feasibility of next-generation sequencing (NGS) microbiome approaches in the diagnosis of infectious disorders in brain or spinal cord biopsies in patients with suspected CNS infections.

methodsIn a prospective pilot study, we applied NGS in combination with a new computational analysis pipeline to detect the presence of pathogenic microbes in brain or spinal cord biopsies from 10 patients with neurologic problems indicating possible infection but for whom conventional clinical and microbiology studies yielded negative or inconclusive results.

resultsDirect DNA and RNA sequencing of brain tissue biopsies generated 8.3 million to 29.1 million sequence reads per sample, which successfully identified with high confidence the infectious agent in 3 patients for whom validation techniques confirmed the pathogens identified by NGS. Although NGS was unable to identify with precision infectious agents in the remaining cases, it contributed to the understanding of neuropathologic processes in 5 others, demonstrating the power of large-scale unbiased sequencing as a novel diagnostic tool. Clinical outcomes were consistent with the findings yielded by NGS on the presence or absence of an infectious pathogenic process in 8 of 10 cases, and were noncontributory in the remaining 2.

conclusionsNGS-guided metagenomic studies of brain, spinal cord, or meningeal biopsies offer the possibility for dramatic improvements in our ability to detect (or rule out) a wide range of CNS pathogens, with potential benefits in speed, sensitivity, and cost. NGS-based microbiome approaches present a major new opportunity to investigate the potential role of infectious pathogens in the pathogenesis of neuroinflammatory disorders.

Identifiers

PMID27340685
PMCPMC4907805
OpenAlexW2419984687

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.