Drug Repurposing Candidates for Triple-Negative Breast Cancer
Discover (after iteration 1) — find something NEW that iteration 1 did not establish: a pattern, formula, conjecture or effect that no published work reports. Start from what is still open: Human-assisted DepMap download (researcher action): download the DepMap CRISPR gene effect (Chronos) matrix in a browser from depmap.org and attach it as a context document; Restart the screen on the Zenodo mirror: stream SuppTable1_RecalculatedProfiles.csv in ~10–25 MB range chunks, filter Database == GDSCv2 and breast lines (TNBC: MDA-MB-231, MDA-MB-468, HCC1937, BT-549), and run per-drug TNBC-vs-other Welch t-tests with BH-FDR; Use the GDSCv2|PRISM AUC Spearman ≈ 0.6 correlation as the reproducibility baseline before accepting any selectivity claim; Then proceed with the planned counter-screens (pan-essential gene filter, basal-lineage confound), docking triage, and prior-art/literature flagging — none of which has started; Validate all inputs at small scale first (schema, encoding, breast-line labels) before any large streaming run, per the mission's stated risk mitigation. Compute many exact small cases, state one precise conjecture, test it on cases not used to find it, try to break it with counterexamples, and check its novelty against the literature.
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