Metagenomic Next-Generation Sequencing (mNGS) enables the simultaneous detection of viruses, bacteria, parasites, and fungi from a single sample. Delve Bio has developed a robust mNGS platform for diagnosing central nervous system (CNS) infections.

mNGS-based testing for CNS infections was introduced in 2014 at the University of California San Francisco (UCSF). In partnership with UCSF, Delve Bio has advanced this legacy by developing Delve Detect, with key methodological updates designed to improve mNGS’ clinical actionability, including sample collection kits that extend sample stability, improved assay robustness, and turnaround time of 2-3 days from sample receipt. 

The Delve Detect test was validated on previously characterized, de-identified clinical remnant CSF samples and on contrived sample material. Sequencing data were analyzed with the proprietary Delve Decide pipeline. Performance metrics were assessed throughout extensive validation.

To assess analytical performance, we developed a set of matrices containing varying concentrations of human nucleic acid and clinically-relevant concentrations of pathogens. Detection sensitivity of organisms is highly dependent on the concentration of human nucleic acid, demonstrating the importance of using an appropriate matrix for assay development and validation. With an appropriate CSF matrix, analytical validation was performed, including limit of detection for various microbial organisms. Additionally, previously tested positive and negative clinical CSF remnant samples were used to evaluate sensitivity and specificity and to demonstrate the ability to identify a variety of viruses, bacteria, fungi and parasites at clinically significant levels.

Delve Bio has validated Delve Detect through robust and comprehensive studies evaluating both clinical and contrived samples. The analytical groundwork laid out in this study sets the stage for important future work harnessing the clinical utility of this unbiased technology for CNS infections and beyond.