Comparison of Pulsed-Field Gel Electrophoresis and Whole Genome Sequencing in Clostridium difficile Typing
Bibliographic record
Abstract
Background. Pulsed-field gel electrophoresis (PFGE) is a common typing method for Clostridium difficile (C. difficile), but whole genome sequencing (WGS) may become a new gold standard. We compared the two methods by examining matched PFGE and WGS data for a set of C. difficile isolates. Methods. A total of 467 C. difficile isolates, collected in a cohort study in 2006-2007, underwent PFGE at the time of study and WGS in 2015. Strain relatedness by PFGE was identified as indistinguishable, closely related, possibly related, or different using Tenover's criteria. Numbers of single nucleotide variants (SNV) across all possible pairs were compared with PFGE categories. To assess ability to recognize clonality, isolates were considered the same type by WGS if they had 0-2 SNV, and by PFGE if indistinguishable, closely related, or possibly related. Using these definitions, adjusted Wallace coefficient was calculated to assess congruence between the methods. Simpson's index was calculated to assess discriminatory power. Results. The average number of SNV between pairs increased across increasingly dissimilar PFGE categories, but was large even for “indistinguishable” isolates (Table 1). Smaller medians suggest that a few outliers might be at play. Three isolates accounted for 97 “indistinguishable” pairs with most SNV. One also accounted for most pairs “different” by PFGE with 0 SNV. These isolates' PFGE groups were verified to be correct, and the discrepancies will require further investigation. Overall, 85.6% of pairs had concordant results. 14.3% of pairs were clonal by PFGE, but not WGS (Figure 1). The Wallace coefficient showed that isolates clonal by WGS had a 94.2% chance of sharing a PFGE group, while the converse was true for 14.2%. Compared with PFGE, WGS had a higher Simpson's index (0.973 versus 0.845). Numbers of SNV Among PFGE Categories Conclusion. C. difficile strain relatedness assessment correlated between PFGE and WGS, but WGS achieved higher levels of resolution. PFGE classified a significant portion of genomically distinct isolates as related. Disclosures. All authors: No reported disclosures
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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 | 0.027 | 0.039 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.004 | 0.003 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".