Systematic Prediction of Antifungal Drug Synergy by Chemogenomic Screening in Saccharomyces cerevisiae
Bibliographic record
Abstract
Since the earliest days of using natural remedies, combining therapies for disease treatment has been standard practice. Combination treatments exhibit synergistic effects, broadly defined as a greater-than-additive effect of two or more therapeutic agents. Clinicians often use their experience and expertise to tailor such combinations to maximize the therapeutic effect. Although understanding and predicting biophysical underpinnings of synergy have benefitted from high-throughput screening and computational studies, one challenge is how to best design and analyze the results of synergy studies, especially because the number of possible combinations to test quickly becomes unmanageable. Nevertheless, the benefits of such studies are clear-by combining multiple drugs in the treatment of infectious disease and cancer, for instance, one can lessen host toxicity and simultaneously reduce the likelihood of resistance to treatment. This study introduces a new approach to characterize drug synergy, in which we extend the widely validated chemogenomic HIP-HOP assay to drug combinations; this assay involves parallel screening of comprehensive collections of barcoded deletion mutants. We identify a class of "combination-specific sensitive strains" that introduces mechanisms for the synergies we observe and further suggest focused follow-up studies.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".