ArticleJournal of clinical microbiology2018
Development and Optimization of Metagenomic Next-Generation Sequencing Methods for Cerebrospinal Fluid Diagnostics.
Article in Journal of clinical microbiology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Who cites it
56 citing papers in PubMed, 3 syntheses or guidelines pooled it.
- The added value of metagenomic next-generation sequencing in central nervous system infections: a systematic review of case reports.Infection · 2025Pooled it
- Metagenomics next-generation sequencing for the diagnosis of central nervous system infection: A systematic review and meta-analysis.Frontiers in neurology · 2022Pooled it
- Application of Metagenomic Next-Generation Sequencing inFrontiers in medicine · 2022Pooled it
- Validation of an integrated metagenomic pipeline combining optimized wet-lab processing and tiered reporting for CSF pathogen detection.Microbiology spectrum · 2026Article
- Pathogen detection in central nervous system infections: moving metagenomic sequencing closer to clinical practice.BMC infectious diseases · 2026Article
- Bridging the Gap: Opsoclonus-Myoclonus Syndrome: Human Pegivirus Encephalomyelitis Diagnosed Through Metagenomic Next-Generation Sequencing.Neurology · 2025Article
- Unveiling the Future of Infective Endocarditis Diagnosis: The Transformative Role of Metagenomic Next-Generation Sequencing in Culture-Negative Cases.Journal of epidemiology and global health · 2025Review
- Benefits and challenges of host depletion methods in profiling the upper and lower respiratory microbiome.NPJ biofilms and microbiomes · 2025Article
- Exploring the role of T cells in Alzheimer's and other neurodegenerative diseases: Emerging therapeutic insights from the T Cells in the Brain symposium.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Metagenomic Analysis of Lung Microbiome in Patients With Interstitial Lung Diseases and Sarcoidosis: An Experimental Study.Health science reports · 2025Article
- Diagnosis and management of invasive fungal diseases by next-generation sequencing: are we there yet?Expert review of molecular diagnostics · 2024Review
- Seven-year performance of a clinical metagenomic next-generation sequencing test for diagnosis of central nervous system infections.Nature medicine · 2024Article
- Diagnostic Value of Targeted Next-generation Sequencing in Pulmonary Mycobacterial Infections.Current medical science · 2024Article
- No Evidence of Chronic Infection in a Metagenomic Sequencing Study of the Keratoconus Corneal Epithelium.Journal of clinical medicine · 2024Article
- Clinical application of nanopore-targeted sequencing technology in bronchoalveolar lavage fluid from patients with pulmonary infections.Microbiology spectrum · 2024Article
- Development of an automated amplicon-based next-generation sequencing pipeline for rapid detection of bacteria and fungi directly from clinical specimens.Journal of clinical microbiology · 2024Article
- Development of a Targeted NGS Assay for the Detection of Respiratory Pathogens including SARS-CoV-2 in Felines.Pathogens (Basel, Switzerland) · 2024Article
- Epstein-Barr virus-positive iris diffuse large B-cell lymphoma detected by metagenomic next-generation sequencing.BMC ophthalmology · 2024Article
- Laboratory diagnosis of CNS infections in children due to emerging and re-emerging neurotropic viruses.Pediatric research · 2024Review
- Application of Host-Depleted Nanopore Metagenomic Sequencing in the Clinical Detection of Pathogens in Pigs and Cats.Animals : an open access journal from MDPI · 2023Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
The purpose of this study was to develop and optimize different processing, extraction, amplification, and sequencing methods for metagenomic next-generation sequencing (mNGS) of cerebrospinal fluid (CSF) specimens. We applied mNGS to 10 CSF samples with known standard-of-care testing (SoC) results (8 positive and 2 negative). Each sample was subjected to nine different methods by varying the sample processing protocols (supernatant, pellet, neat CSF), sample pretreatment (with or without bead beating), and the requirement of nucleic acid amplification steps using DNA sequencing (DNASeq) (with or without whole-genome amplification [WGA]) and RNA sequencing (RNASeq) methods. Negative extraction controls (NECs) were used for each method variation (4/CSF sample). Host depletion (HD) was performed on a subset of samples. We correctly determined the pathogen in 7 of 8 positive samples by mNGS compared to SoC. The two negative samples were correctly interpreted as negative. The processing protocol applied to neat CSF specimens was found to be the most successful technique for all pathogen types. While bead beating introduced bias, we found it increased the detection yield of certain organism groups. WGA prior to DNASeq was beneficial for defining pathogens at the positive threshold, and a combined DNA and RNA approach yielded results with a higher confidence when detected by both methods. HD was required for detection of a low-level-positive enterovirus sample. We demonstrate that NECs are required for interpretation of these complex results and that it is important to understand the common contaminants introduced during mNGS. Optimizing mNGS requires the use of a combination of techniques to achieve the most sensitive, agnostic approach that nonetheless may be less sensitive than SoC tools.
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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.