Evaluation of the Ultima Genomics UG 100 sequencer for low-cost, high-sensitivity metagenomic pathogen detection from cerebrospinal fluid

Metagenomic next-generation sequencing (mNGS) is a diagnostic tool allowing near universal pathogen detection directly from clinical specimens. Despite promising clinical data, broad adoption of mNGS has been hindered by high cost and reduced sensitivity relative to targeted nucleic acid amplification tests (NAATs). Recently, Ultima Genomics revealed the UG 100 NGS platform which advertises 10 billion reads per $2,400 sequencing wafer. By significantly lowering costs and improving sequencing depth, the historical value proposition of mNGS may be improved. This study evaluates the UG 100 sequencer for metagenomic pathogen detection from cerebrospinal fluid in suspected cases of meningitis and encephalitis. Of 28 specimens with a pathogen identified by routine clinical testing, reads matching to the known pathogen were identified in 93% (26/28) of cases. Near full-length genomes were recovered for three organisms (human herpesvirus-1, Streptococcus pneumonia, and Haemophilus influenzae), with the ability to detect putative antimicrobial resistance genes for H. influenzae. Recovery of Borrelia burgdorferi reads (6.1 RPM and 9.03 RPM) was achieved from clinical samples with late cycle threshold values (39.7 and 43.0, respectively). Limit of detection (LOD) studies demonstrated detection of HSV-1 and S. pneumoniae at 50 and 5 copies/mL, respectively, which is below the reported limit of detection for the orthogonal NAATs used in this study. Reducing sequencing costs and improving the analytical sensitivity removes two major hurdles for mNGS adoption by clinical laboratories. While these results are preliminary, they demonstrate a future in which mNGS may be more widely implemented. ImportanceMetagenomic next-generation sequencing has struggled to gain wider adoption for nearly a decade, due in part to concerns related to its high cost and reduced performance versus targeted molecular assays. This study demonstrates the ability of the UG100 sequencing platform to significantly reduce metagenomic sequencing costs (to approximately $12 per 50M reads) while maintaining highly sensitive pathogen detection rates. Improvements to cost and analytical performance may shift clinical metagenomics from an expensive test-of-last-resort to a front-line diagnostic for identifying infections.