Use of Metagenomic Microbial Plasma Cell-Free DNA Next-Generation Sequencing Assay in Outpatient Rheumatology Practice
Bibliographic record
Abstract
OBJECTIVE: To assess the utility of a metagenomic microbial plasma cell-free DNA next-generation sequencing assay (Karius Test [KT]) in the evaluation of patients in an outpatient rheumatology practice. METHODS: All patients with a KT ordered and obtained by a rheumatology provider in the outpatient setting from January 1, 2020, through December 31, 2022, were retrospectively identified. Demographic, clinical, laboratory, radiologic, histopathology, and microbial studies were abstracted. Indication for KT testing was categorized. KT results were defined based on positive result and clinical relevance regarding the symptoms under investigation at the time of the rheumatologic investigation. Review of cases 3 months after KT was undertaken to determine clinical outcome. RESULTS: One hundred fifty patients with a KT were included (52.7% female, mean age 52 years). The reason for KT was evaluation of atypical presentation of rheumatic disease (80%), assessing flare vs infection in patients on immunosuppression (16.7%), and fever of unknown origin (3.3%). Twenty-four (16%) KTs were positive, 6 of which were considered clinically relevant and altered the final diagnosis and treatment. Of the 126 negative KTs, 5 (4%) were found to have a clinically relevant infection by conventional testing methodologies. CONCLUSION: In this large retrospective cohort study, the most frequent reason for KT utilization was an atypical presentation of rheumatic disease. One out of 4 positive KTs altered the final diagnosis and treatment. False negative rates were low. KT has utility in outpatient rheumatology assessments. Further delineation of which patients are best suited for KT testing remains to be defined.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.010 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".