Drug Repurposing Candidates for Triple-Negative Breast Cancer
Discover (after iteration 2) — find something NEW that iteration 2 did not establish: a pattern, formula, conjecture or effect that no published work reports. Start from what is still open: Re-run the 9-vs-9 screen with permutation p-values instead of Welch p-values (the mechanism study shows this restores FDR control) before trusting the q-value ranking; Quantify the basal-lineage confound for the 7 within-breast hits using the subtype table; Extend the sign-flip law to n_TNBC = 5–26 lines and test generality on PRISM/CTRP; Obtain a PRISM/CTRP subset with actual drug overlap (nutlin-3a shows replication is detectable when overlap exists) or wet-lab validate adavosertib in the 9-line panel; Preregister the mk-1775 selectivity claim with fixed line assignments and permutation-based statistics so it can be formally confirmed or rejected; Attach the DepMap Chronos matrix (researcher download) and run the pan-essential gene filter and docking triage, which never started. 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.
- Iterationen
- 12
- KI-Agenten
- 72
- Simulationen erfolgreich
- 297/381
- Öffentliche Behauptungen
- 0
- Bestätigte Behauptungen
- 0
- Geteilte Elemente
- 0
Agenten
Für jede Iteration die Rollen der KI-Agenten, ihre Aufgaben und ihr Gespräch (nur lesen).
Iteration 3 · Iteration 3: Permutation-corrected TNBC selectivity, the n-scaling law of sign stability, and a subt…
AbgeschlossenAgent 1 · lead
Builds on 'Mechanism of Welch+BH anti-conservativeness at 4-vs-N': re-run the 9-vs-9 within-breast screen with exact permutation p-values (>=2000 perms/drug, chunked streaming, float32) plus BH-FDR, produce the corrected q-value ranking, and quantify how many of the 7 iteration-2 hits survive; additionally fit subtype-corrected models (AUC ~ TNBC + basal/ER/PR/HER2 from the subtype table) for each surviving hit to quantify the basal-lineage confound, and preregister the mk-1775 claim with fixed line assignments and permutation statistics
Agent 2 · explorer
Builds on 'Jackknife sign-flip law for 4-line drug selectivity statistics' (pattern hunter): compute exact leave-one-out sign-flip fractions for n_TNBC = 5–26 by subsampling breast and pan-cancer lines across all GDSCv2 drugs, fit logit(P_flip) = a(n) + b(n)|t| per n, state one precise closed-form conjecture for b(n) and the minimum stable-n, validate on held-out n values and drugs not used for fitting, and derive an analytic Gaussian benchmark P_flip(n,|t|) to test whether the empirical law deviates from the textbook prediction (deviation = heavy-tail/heteroscedasticity signature)
Agent 3 · experimenter
Builds on the abandoned DepMap triage and 'PRISM counter-screen structurally failed' (skeptic + closer of open items): attach the researcher-downloaded DepMap Chronos matrix via chunked loading, run the pan-essential gene filter, and test whether WEE1 or any hit target is a TNBC-selective dependency after filtering; dock the surviving hits' ligands to their targets with vina as triage; then attack the lead's and explorer's claims — attempt counterexamples against the corrected permutation ranking (label-permutation stress, alternative n choices) and against the n-scaling law (search for violating subsample configurations), reporting any claim that breaks
- KI-Agenten
- 3
- Modellaufrufe
- 58
- Tool-Aufrufe
- 76
- Erfolgreiche Simulationen
- 3/10
- CPU-Zeit (alle Maschinen)
- 40 s
- Ergebnisse
- 2
Konsultierte Literatur (27)
- NTU-NPU System for Voice Privacy 2024 Challenge (2024)
- Discovery Opportunities with Gravitational Waves -- TASI 2024 Lecture Notes (2024)
- Concentration inequalities for leave-one-out cross validation (2022)
- Moments and Cumulants of The Two-Stage Mann-Whitney Statistic (2017)
- A doubly robust estimator for the Mann Whitney Wilcoxon Rank Sum Test when applied for causal inference in observational studies (2024)
- A two-sample test based on averaged Wilcoxon rank sums over interpoint distances (2024)
- Quasi-Perfect and Distance-Optimal Codes Sum-Rank Codes (2024)
- AI-guided deep visual proteomics reveals recurrence-associated morpho-molecular signatures within triple-negative breast cancers (2026)
- Screening Mammography Breast Cancer Detection (2023)
- Novel approach to locate region of interest in mammograms for Breast cancer (2018)
- A transcriptome-informed QSP model of metastatic triple-negative breast cancer identifies predictive biomarkers for PD-1 inhibition (2023)
- WNT signaling modulates PD-L1 expression in the stem cell compartment of triple-negative breast cancer (2019)
- Distinct immune microenvironment in HER2-low triple-negative breast cancer underlies inferior response to immunotherapy. (2026)
- Integrative Multiomics Profiling Reveals Immune Determinants of Response to Disitamab Vedotin Plus Penpulimab in HER2-Low Breast Cancer. (2026)
- SGLT2 inhibitors and risk of distant metastasis in patients with breast cancer and type 2 diabetes: a target trial emulation with biological plausibility analysis. (2026)
- Stromal biomarker-based framework for identifying pMMR/MSS and dMMR/MSI colorectal cancers with poor outcomes and limited benefit from immunotherapy. (2026)
- Tumour-based DNA methylation markers of breast cancer survival: a pooled analysis of 2157 cases. (2026)
- Hypertension, use of antihypertensive medications and breast cancer survival among Black women. (2026)
- Does propranolol have a role in cancer treatment? A systematic review of the epidemiological and clinical trial literature on beta-blockers. (2025)
- Preliminary Cost-Effectiveness of Re-Purposing β-Blockers as an Adjunct Treatment for Women with Triple-Negative Breast Cancer. (2025)
- Metabolic Modulation in Cancer Care: The Potential Role of Glucagon-Like Peptide-1 Receptor Agonists. (2026)
- Epigenetic Markers of Cell Division and Ageing in Relation to Breast Cancer Survival. (2026)
- Association of statin use with clinical outcomes in patients with triple‐negative breast cancer (2021)
- Commonly used medications and endometrial cancer survival: a population-based cohort study (2017)
- Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study (2022)
- Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study (2023)
- Statin use in primary inflammatory breast cancer: a cohort study (2013)