Human structural proteome-wide characterization of Cyclosporine A targets
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
MOTIVATION: Off-target interactions of a popular immunosuppressant Cyclosporine A (CSA) with several proteins besides its molecular target, cyclophilin A, are implicated in the activation of signaling pathways that lead to numerous side effects of this drug. RESULTS: Using structural human proteome and a novel algorithm for inverse ligand binding prediction, ILbind, we determined a comprehensive set of 100+ putative partners of CSA. We empirically show that predictive quality of ILbind is better compared with other available predictors for this compound. We linked the putative target proteins, which include many new partners of CSA, with cellular functions, canonical pathways and toxicities that are typical for patients who take this drug. We used complementary approaches (molecular docking, molecular dynamics, surface plasmon resonance binding analysis and enzymatic assays) to validate and characterize three novel CSA targets: calpain 2, caspase 3 and p38 MAP kinase 14. The three targets are involved in the apoptotic pathways, are interconnected and are implicated in nephrotoxicity.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.000 | 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 it