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

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…

• AL
  Abbott Laboratories
• NI
  National Institutes of Health

  Awards: U54 HL119893, UL1 TR000004, TR000004, R21/R33, R21/R33 AI120977, R01 HL105704
• UO
  University of California, San Francisco

  Awards: UL1 TR000004, TR000004
• AD
  Abbott Diagnostics
• NC
  National Center for Advancing Translational Sciences

  Awards: UL1 TR000004, TR000004, UCSF-CTSI grant UL1 TR000004