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Analysis Tools · MVA · BUB1B · reanalysis

L737* readthrough: exact versus nearby contexts

  • Archived result
  • Executed reanalysis

What it is not. There is no exact L737* measurement and no exact six-base match. Twelve measured rows represent eight distinct contexts; they are not BUB1B efficacy, not a patient prediction and not a rescue probability.

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
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.

QuantityValueUnitSource file
Exact six-base context matches 0 rows results.json (stackfire-20261024-python312)
Nearest measured context, Hamming distance 1 bases results.json (stackfire-20261024-python312)
Nearest measured variant rows 12 rows results.json (stackfire-20261024-python312)
Median readthrough, untreated 0.1745 % results.json (stackfire-20261024-python312)
Median readthrough, gentamicin 0.1985 % results.json (stackfire-20261024-python312)
Median paired increment (gentamicin − untreated) +0.0165 percentage points results.json (stackfire-20261024-python312)
L737* present in the measured table No boolean results.json (stackfire-20261024-python312)
BUB1B variants present in the measured table BUB1B_R114X list results.json (stackfire-20261024-python312)
Distinct six-base contexts among the nearest rows 8 contexts nearest_contexts.csv (stackfire-20261024-python312)

Archived result · October 17 snapshot

Record MVA-RT-002 of the frozen evidence snapshot, exactly as published on the case page. Status in the snapshot: Completed; decision: Deprioritized.

Evidence class
COMPUTATIONAL / PATHWAY EVIDENCE
Model
Published 144-nt PTC reporters in human cells; nearest-context subset, not endogenous BUB1B.
Finding
No exact L737* measurement or exact six-flanking-base match in the 5,837-PTC table. Twelve nearest contexts have a median paired gentamicin increment of 0.0165 percentage points.
Next
Use the exact L737* context with matched controls and independently test full-length protein, checkpoint response and segregation fidelity.
Limitations
  • Neighboring-context values are not a prediction for L737* or the child.
  • The main predictive analysis excluded gentamicin for weak signal.
  • Readthrough does not guarantee native leucine, endogenous transcript survival, or functional BUBR1. Gentamicin plus mefloquine remains an experimental branch only.
Provenance in the snapshot
l737_readthrough_gate_2026-10-09/results/results.json · SHA-256 8d1f7ca32b05f9e85cedc5d025ea04efee60b581ae4effea8fd389e6f4afbcb9Imported an existing analysis artifact and computed its SHA-256. This snapshot build does not rerun the original analysis or validate biological efficacy.
Chart “Nearby contexts are not the exact variant” of the snapshot · unit: Median reporter readthrough (%). Median paired increment: 0.0165 percentage points; it is not the difference of the two medians. The six-base analogy ignores the rest of the reporter sequence. No rescue probability is computed.
RowMedianNote
Untreated0.174512 nearest measured six-base contexts; exact L737* context absent.
Gentamicin0.1985Same 12 contexts, not BUB1B efficacy or a patient prediction.

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.

CheckArchivedExecutedToleranceResult
Untreated median, chart versus results.json 0.1745 0.1745 exact agrees
Gentamicin median, chart versus results.json 0.1985 0.1985 exact agrees
Median paired increment quoted in the snapshot (0.0165) versus results.json 0.0165 0.016500000000000015 ± 0.00005 agrees
Nearest measured rows (12) versus results.json 12 12 exact agrees
Distinct contexts (8, October 24 correction) versus nearest_contexts.csv 8 8 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 records. A matching SHA-256 is computational reproduction of a deterministic output, not biological validation.
Execution / record timeWhat ranEnvironmentInputsArtifacts versus archiveRecord
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.
  • match ptc/results/results.json SHA-256 8d1f7ca32b05…
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.
  • match ptc/results/results.json SHA-256 8d1f7ca32b05…
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.
  • match ptc/results/results.json SHA-256 8d1f7ca32b05…
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.
  • match ptc/results/results.json SHA-256 8d1f7ca32b05…
Record (JSON) At the commit

Traceability

Primary sources
Dataset
Toledano et al. 2024 Supplementary Table 3 (complete workbook, 5,837 PTC reporters) and the archived eight-row RTDetective prediction extract (bundled input).
Biological model
Published 144-nt PTC reporters in HEK293T landing-pad cells; nearest six-base contexts, not endogenous BUB1B.
Samples
Measured reporter rows nearest to the L737* six-base context (UGA, gagagt); untreated and gentamicin columns.
Parameters
  • Target context: gagagt (UGA)
  • Selection: minimum six-base Hamming distance, without using response values
  • Summaries: medians per treatment and median of within-row paired differences, in percentage points
Script
track2/reproduction/ptc/analyze.py · SHA-256 9b6e1085155fa229fa2816b56f4994541ce827008109b27f93cba33ca5c767a8 · download
Command
python analyze.py --workbook supp_tables.xlsx --predictions prediction_extracts.tsv --outdir results; python test_analysis.py
Inputs
  • ptc/supp_tables.xlsx · media.springernature.com · 9.8 MB · SHA-256 83b4661d839e7450abb3a4266a0dc7e94260fd100f9a6efcc6e2bd77683a5b64
  • ptc/prediction_extracts.tsv · doi.org · SHA-256 5db3ac1925af814552fad15153299e2dbafee484c00680a5369f7d7613a5ab5fBundled public reference: Archived exact-coordinate extract; not freshly re-extracted in this reproduction.

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.

Execution records

  • execution.json Execution record stackfire-20261024-python313 · 11.9 KB · SHA-256 3e96a613c786bd72e045f0678e9f063aa551ab0821296efe28e84cc2432d3ff9
  • execution.json Execution record stackfire-20261024-python312 · 11.9 KB · SHA-256 1356584c9c89ff15209c9af82ba5b4e1385545f7e351dcd3763772de5b73a5b7
  • deterministic_replay_check_20261024.json Deterministic replay of the four reanalyses, October 24, 2026 (cached inputs) · 1.7 KB · SHA-256 c6eb2ccde8c0fb3f297ecf715a2d1808a78a2eb6fdab5f3d7eeba0625527894a · at the commit
  • execution_check.json Execution record, October 22, 2026 (isolated environment, fresh downloads) · 1.7 KB · SHA-256 38ed7fccba9f110ac6a832a950f42a6c001d07666ec134a0e5e2f189653fbe55 · at the commit

Scripts

  • analyze.py Original PTC readthrough context script · 6.4 KB · SHA-256 9b6e1085155fa229fa2816b56f4994541ce827008109b27f93cba33ca5c767a8 · at the commit
  • test_analysis.py Original PTC analysis self-test · 771 B · SHA-256 ac47c819e5b139d343929f67e62bf79b059ec4b1482fc94a33fb141747813b20 · at the commit
  • fetch_inputs.py Input retrieval wrapper (new, October 22) · 1.4 KB · SHA-256 b12696b6387d5120d1ab49528576e7b90153cf098c29ecc06babb46797a30d99 · at the commit
  • run_reanalyses.py Runner and checker of the four reanalyses (new, October 22) · 3.4 KB · SHA-256 3ccbd544b2c119b0c2558ea4ea172bf37c4a100e569fe047b2f16d95274713ea · at the commit

Bundled public inputs

  • prediction_extracts.tsv Archived eight-row public prediction extract (RTDetective, Figshare v2) · 663 B · SHA-256 5db3ac1925af814552fad15153299e2dbafee484c00680a5369f7d7613a5ab5f · at the commit

Manifests

Environment

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