Genetic indicators of drug resistance in the highly repetitive genomes of <i>Trichomonas vaginalis</i> and other trichomonads
Bibliographic record
Abstract
Abstract Background Trichomonas vaginalis , the most common non-viral sexually transmitted parasite, causes ~283 million trichomoniasis infections annually and is associated with complications during pregnancy and increased risk of HIV-1 acquisition. The antimicrobial drug metronidazole is used for treatment, but has lead to widespread drug resistance. We undertook sequencing of multiple clinical isolates and lab derived lines to identify genetic markers and mechanisms of metronidazole resistance. Results Reduced representation genome sequencings of more than 100 T. vaginalis clinical isolates identified 3,923 SNP markers and presence of a bipartite population structure. Linkage disequilibrium decays rapidly, suggesting genome-wide recombination and the feasibility of genetic association studies in the parasite. We identified 72 SNPs associated with metronidazole resistance, and a comparison of SNPs within several lab-derived resistant lines revealed an overlap with the clinically resistant isolates. We identified SNPs in sets of genes for which no function has yet been assigned, as well as in functionally-characterized genes highly relevant to drug resistance ( e.g., pyruvate:ferredoxin oxidoreductase ( PFO )). Transcription profiling of these and other genes served as proxy for testing the functional consequences of multiple identified SNPs. Transcription profiles of lab-derived drug resistance strain as well as clinically resistant strain depict common regulation changes in carbohydrate metabolism and oxygen detoxification pathways correlated with Mz resistance. Finally, we identified convergent genetic changes in lab-derived resistant lines of Tritrichomonas foetus , a distantly-related species that causes venereal disease in cattle. Conclusions Our observation of shared genetic changes within and between T. vaginalis and Tr. foetus parasites suggests conservation of the pathways through which adaptation has occurred. These findings extend our knowledge of drug resistance in the parasite, providing a panel of markers that can be used as a diagnostic tool.
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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 | 0.000 | 0.001 |
| 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 | 0.000 | 0.000 |
| 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".