Analysis Tools · MVA · BUB1B · reanalysis
704-drug NMD screen: reporter specificity
- Archived result
- Executed reanalysis
What it is not. A reporter screen in mouse cells. No BUB1B was measured; statistical significance is not therapeutic suitability and no hit establishes functional BUBR1 rescue.
Dates, kept apart
- Archived result recorded
- 2026-10-09 (snapshot mva-results-2026-10-17-immunotherapy-audit-v1, data as of 2026-10-17)
- Executions
- Execution time unknown · record packaged 2026-10-24 23:32:43 UTC · this platform
- Execution time unknown · record packaged 2026-10-24 23:32:43 UTC · this platform
- 2026-10-24 20:35:58 UTC · research repository
- 2026-10-22 18:59:19 UTC · research repository
- Repository commit
a434af9- This page rendered
- · a view date, not an execution or publication date
Values read from the files
Read from the verified outputs of execution stackfire-20261024-python312 (CPython 3.12.3, execution time unknown), whose artifacts match the archive exactly or after the documented normalisation shown in the execution record. Nothing is typed into this page.
| Quantity | Value | Unit | Source file |
|---|---|---|---|
| Drugs in the screen | 704 | drugs | summary.json (stackfire-20261024-python312) |
| Controls | 1 | control | summary.json (stackfire-20261024-python312) |
| Drugs with both published q ≤ 0.05 | Montelukast sodium, Diphenylcyclopropenone, Cladribine, Hexachlorophene, Artesunate, Topotecan hydrochloride, Albendazole, Homoharringtonine | list | summary.json (stackfire-20261024-python312) |
| Max. absolute error, recomputed Fisher p | 0.000007 | p units | summary.json (stackfire-20261024-python312) |
| Montelukast, Ptbp2 NMD / non-NMD ratio | 1.3153820850896314 | ratio | selected_candidates.csv (stackfire-20261024-python312) |
| Montelukast, Hnrnpl NMD / non-NMD ratio | 3.406494677098417 | ratio | selected_candidates.csv (stackfire-20261024-python312) |
| Montelukast, Tra2b NMD / non-NMD ratio | 1.7654686351224798 | ratio | selected_candidates.csv (stackfire-20261024-python312) |
| Montelukast, published permutation FDR (reused) | 0.02115 | q | selected_candidates.csv (stackfire-20261024-python312) |
| Rows in selected_candidates.csv | 12 | rows | selected_candidates.csv (stackfire-20261024-python312) |
Archived result · October 17 snapshot
Record MVA-NMD-003 of the frozen evidence snapshot, exactly as published on the case page. Status in the snapshot: Completed; decision: Conditional.
- Evidence class
- COMPUTATIONAL / PATHWAY EVIDENCE
- Model
- Published mouse Neuro-2a AS-NMD isoform summaries; three reporter genes, not BUB1B.
- Finding
- Montelukast has a published permutation q of 0.021150, but the response is reporter-dependent and confounded by non-NMD isoform changes. No hit establishes functional BUBR1 rescue.
- Next
- Establish L737* residual function first; any NMD candidate then needs allele-specific RNA, protein synthesis, and separate checkpoint/segregation endpoints.
- Limitations
- Normalized RNA ratios cannot isolate decay from splicing or isoform regulation.
- Replicate Ct values are unavailable. Published ratio SEM formulas do not provide valid replicate-based uncertainty; no error bars are shown.
- Translation inhibition is counterevidence for homoharringtonine. Statistical significance is not therapeutic suitability.
- Provenance in the snapshot
nmd_reanalysis_20261009/results/selected_candidates.csv· SHA-256ad7fa784e6caf2f126c9730e4edaf7dc75f0ea2ad54208661de75555ede6ab9cImported an existing analysis artifact and computed its SHA-256. This snapshot build does not rerun the original analysis or validate biological efficacy.
| Row | Ptbp2 | Hnrnpl | Tra2b | Note |
|---|---|---|---|---|
| Montelukast sodium | 1.3153820850896314 | 3.406494677098417 | 1.7654686351224798 | Published permutation q = 0.02115; not a BUBR1 endpoint. |
| Artesunate | 1.718112969537028 | 1.0078988102818638 | 4.2875477079256585 | Published permutation q = 0.010071; not a BUBR1 endpoint. |
| Cladribine | 2.126124275101715 | 2.0820411294900216 | 1.6377191943091594 | Published permutation q = 0.010071; not a BUBR1 endpoint. |
| Albendazole | 1.5634627380948676 | 1.701726223666598 | 3.2992143735876955 | Published permutation q = 0.015667; not a BUBR1 endpoint. |
| Topotecan hydrochloride | 3.9533398228039465 | 2.3994174963086077 | 0.6542839291174242 | Published permutation q = 0.0 (finite-sampling zero, not zero uncertainty); not a BUBR1 endpoint. |
| Homoharringtonine | 5.0039366160196295 | 24.97590928901173 | 11.672927661494484 | Published permutation q = 0.0 (finite-sampling zero, not zero uncertainty); not a BUBR1 endpoint. |
| Mefloquine hydrochloride | 1.181600971576268 | 1.3075083215610865 | 1.5102164979716604 | Published permutation q = 0.061224; not a BUBR1 endpoint. |
| Nicotinic acid | 1.1859031685137231 | 1.4152893426077033 | 0.9171679519898492 | Published permutation q = 0.08225; not a BUBR1 endpoint. |
Archive versus execution
The values the frozen snapshot shows, compared with the values read from the executed outputs. Exact where the snapshot stores the full number; otherwise within the decimal places the snapshot itself used.
| Check | Archived | Executed | Tolerance | Result |
|---|---|---|---|---|
| Montelukast Ptbp2 ratio, chart versus CSV | 1.3153820850896314 | 1.3153820850896314 | exact | agrees |
| Montelukast Hnrnpl ratio, chart versus CSV | 3.406494677098417 | 3.406494677098417 | exact | agrees |
| Montelukast Tra2b ratio, chart versus CSV | 1.7654686351224798 | 1.7654686351224798 | exact | agrees |
| Montelukast permutation q quoted in the snapshot (0.02115) versus CSV | 0.02115 | 0.02115 | exact | agrees |
Execution records
Each row is a run with a record. “Match” means the output bytes hash to the archived value: deterministic computation reproduced, nothing more.
| Execution / record time | What ran | Environment | Inputs | Artifacts versus archive | Record |
|---|---|---|---|---|---|
| Execution time unknownRecord packaged The original executedAt value was generated by the packaging script, not captured from the pipeline. It is preserved as recordedAt; the actual execution time is unknown.This platform | Execution on this platform (execution time unknown, CPython 3.13.17)Same fresh inputs, CPython 3.13.17 in a new virtual environment: interpreter deliberately outside the pinned version to show which artifact depends on it. | CPython 3.13.17 not the pinned interpreter pandas 2.2.3 · numpy 2.3.5 · scipy 1.17.0 · openpyxl 3.1.5 Isolated virtual environment | 14 / 14 verified by SHA-256Inputs fetched from the public URLs of input_manifest.json over the network, plus the two bundled public references; every byte count and SHA-256 compared with the manifest. |
|
Record (JSON) |
| Execution time unknownRecord packaged The original executedAt value was generated by the packaging script, not captured from the pipeline. It is preserved as recordedAt; the actual execution time is unknown.This platform | Execution on this platform (execution time unknown, CPython 3.12.3)Fresh network downloads of all 12 public inputs on 2026-10-24, each verified against input_manifest.json; system CPython 3.12.3 in a new virtual environment (the pinned 3.12.14 build was not available on this host). | CPython 3.12.3 not the pinned interpreter pandas 2.2.3 · numpy 2.3.5 · scipy 1.17.0 · openpyxl 3.1.5 Isolated virtual environment | 14 / 14 verified by SHA-256Inputs fetched from the public URLs of input_manifest.json over the network, plus the two bundled public references; every byte count and SHA-256 compared with the manifest. |
|
Record (JSON) |
| Research repository | Deterministic replay by the research repository (October 24, 2026)Run in the existing, non-isolated Python 3.12.14 environment before the sensitivity audit. | CPython 3.12.14 pandas 2.2.3 · numpy 2.3.5 · scipy 1.17.0 · openpyxl 3.1.5 Existing environment, not isolated | 14 / 14 verified by SHA-256Previously downloaded public cached bytes, each verified against the unchanged manifest; not a fresh network download. |
|
Record (JSON) At the commit |
| Research repository | Clean reproduction by the research repository (October 22, 2026)Recorded in the research repository. Successful computational reproduction under the stated input boundaries, not biological validation. | CPython 3.12.14 pandas 2.2.3 · numpy 2.3.5 · scipy 1.17.0 · openpyxl 3.1.5 Isolated virtual environment | 12 / 12 verified by SHA-256All 12 remote inputs fetched sequentially into a brand-new isolated virtual environment and verified against input_manifest.json. |
|
Record (JSON) At the commit |
Traceability
- Primary source
- Zhao et al. — molecular profiling of NMD modulators Tables S1/S2/S4; Figures 2–5 and 7 · DOI 10.1016/j.omtn.2021.12.003 · PMID 35024243
- Dataset
- Zhao et al. 2021 supplementary tables S1, S2 and S4 (publisher workbooks).
- Biological model
- Published mouse Neuro-2a AS-NMD isoform summaries; three endogenous reporter genes (Ptbp2, Hnrnpl, Tra2b), not BUB1B.
- Samples
- 704 drugs plus one control at 5 µM for 5 h; summarised ratios without individual Ct replicates.
- Parameters
- Three NMD / non-NMD isoform ratios per drug
- Screen-wide Z and Fisher combination recomputed; Benjamini–Hochberg recomputed
- Published permutation q values reused, not rerun
- Script
track2/reproduction/nmd/reanalyze.py· SHA-2563572dc35ca41f30bfc8d115e07f04b47fa54d6374b6c4abcc6d83fcf9a7419da· download- Command
python reanalyze.py- Inputs
nmd/inputs/table_S1.xlsx· ars.els-cdn.com · 60.9 KB · SHA-25614c3c7c3c7344c365285eec39a53fd93d4a333eec83bbbbdab7eaa4348dcaf69nmd/inputs/table_S2.xlsx· ars.els-cdn.com · 485.7 KB · SHA-256f7107fa8e401cc6d1d2adbb68adca5baefe63472cfaf2f178e667d678c3b0007nmd/inputs/table_S4.xlsx· ars.els-cdn.com · 113.9 KB · SHA-256613713a81e0944d28e1b01f07a6e144ff286726d8686778efca6b1294f749e9b
Downloads
Provenance manifest (JSON)
Analysis (JSON)
The manifest lists sources, model, samples, parameters, script, commit, inputs, execution records and every file below with its SHA-256. Its generatedAt is when it was written, not an execution date.