Binay UD, Karakeçili F, Barkay O, Sümer B. Metagenomic next-generation sequencing in the diagnosis of viral encephalitis. World J Virol 2026; 15(3): 124097 [DOI: 10.5501/wjv.124097]
Corresponding Author of This Article
Umut Devrim Binay, MD, Associate Professor, Department of Infectious Diseases and Clinical Microbiology, Erzincan Binali Yildirim University, Faculty of Medicine, Hacı Ali Akın Street, Basbaglar District, Erzincan 24000, Türkiye. umut.binay@erzincan.edu.tr
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Infectious Diseases
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Binay UD, Karakeçili F, Barkay O, Sümer B. Metagenomic next-generation sequencing in the diagnosis of viral encephalitis. World J Virol 2026; 15(3): 124097 [DOI: 10.5501/wjv.124097]
Umut Devrim Binay, Faruk Karakeçili, Orçun Barkay, Betül Sümer, Department of Infectious Diseases and Clinical Microbiology, Erzincan Binali Yildirim University, Faculty of Medicine, Erzincan 24000, Türkiye
Author contributions: Binay UD designed and wrote the paper; Karakeçili F, Barkay O, and Sümer B supervised the manuscript. All authors have read and approve the final manuscript.
AI contribution statement: OpenAI ChatGPT/Codex (GPT-5; OpenAI, San Francisco, CA, United States; accessed in July 2026) was used during the revision process. The manuscript was not generated entirely by AI. Portions of the text were drafted, translated, reorganized, or substantially reformulated with assistance from ChatGPT/Codex during revision. ChatGPT/Codex was used for English translation, language polishing, stylistic editing, structural organization, concise synthesis of source material, and drafting or rephrasing portions of the manuscript and the point-by-point response. ChatGPT/Codex did not participate in designing an original study and did not independently determine the interpretation of research findings. No generative AI image model was used. Figures 1 and 2 are original schematic diagrams created specifically for this manuscript using editable vector shapes. ChatGPT/Codex assisted with their wording and layout. All authors reviewed and approved the final manuscript and accept full responsibility for its scientific accuracy, integrity, and content.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Umut Devrim Binay, MD, Associate Professor, Department of Infectious Diseases and Clinical Microbiology, Erzincan Binali Yildirim University, Faculty of Medicine, Hacı Ali Akın Street, Basbaglar District, Erzincan 24000, Türkiye. umut.binay@erzincan.edu.tr
Received: June 8, 2026 Revised: July 27, 2026 Accepted: August 26, 2026 Published online: September 25, 2026 Processing time: 105 Days and 6.1 Hours
Abstract
Viral encephalitis requires rapid etiological assessment, yet targeted polymerase chain reaction, serology, culture, and multiplex panels leave many cases unresolved because they depend on prespecified pathogens, sampling time, and specimen biology. Metagenomic next-generation sequencing (mNGS) can interrogate DNA and RNA in cerebrospinal fluid without a predefined target and may detect unexpected, rare, opportunistic, or emerging viruses. Its clinical performance, however, is not uniform. In published cohorts, diagnostic yield varies with case selection, reference standards, pathogen burden, specimen volume, pretreatment, laboratory workflow, sequencing depth, bioinformatic thresholds, and contamination control. Short-read Illumina workflows currently have the largest clinical evidence base, whereas real-time nanopore sequencing offers speed and portability but still requires site-specific validation. The strongest role for mNGS is therefore not routine first-line replacement of polymerase chain reaction or serology, but early complementary use in severe, progressive, unexplained, atypical, or immunocompromised cases after urgent targeted testing and empirical treatment have begun. A positive result requires assessment of read distribution, genome coverage, controls, clinical plausibility, and orthogonal confirmation; a negative result cannot exclude a low-titer, serology-defined, or tissue-restricted infection. This minireview critically compares the available evidence, identifies causes of between-study variation, and proposes a practical decision pathway for integrating mNGS into the diagnosis of viral encephalitis.
Core Tip: Metagenomic next-generation sequencing broadens the diagnostic search in viral encephalitis by detecting pathogen nucleic acids without a predefined target. Its highest value is in severe, unexplained, atypical, or immunocompromised cases after urgent targeted testing and empirical treatment have started. It performs less reliably when pathogen burden is low, infection is tissue-restricted, or diagnosis depends mainly on serology. Results therefore require contamination controls, clinical correlation, and confirmatory testing. Metagenomic next-generation sequencing complements rather than replaces polymerase chain reaction, serology, and conventional microbiology.
