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0.7087234757187972, "RMSE": 0.8578046722405808 }, "tissue_cv": { "rho": 0.0658241104055945, "status": "estimable", "MAE": 0.7087234757187972, "RMSE": 0.8578046722405808 } } } }, "macro": { "counts": { "rows": 1962, "models": 387, "origin_groups": 387, "known_tissue_models": 174, "unknown_tissue_models": 213, "known_tissue_rows": 859, "unknown_tissue_rows": 1103 }, "rho": { "molecular": { "value": 0.1805135872182654, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "status": "broad_benchmark" }, "drug_mean": { "value": null, "drugs": [], "n_drugs": 0, "status": "unavailable" }, "tissue_fixed": { "value": 0.13145549363676404, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "status": "broad_benchmark" }, "tissue_cv": { "value": 0.13145549363676404, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "status": "broad_benchmark" } }, "paired_delta_rho": { "molecular_vs_tissue_fixed": { "value": 0.04905809358150137, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "status": "broad_benchmark", "per_drug": { "123127": 0.11525050360525865, "119875": 0.155359307011882, "125973": -0.2857757817790637, "19893": 0.06433252813797796, "740": 0.13774028432915797, "141540": 0.10744172018379539 } }, "molecular_vs_tissue_cv": { "value": 0.04905809358150137, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "status": "broad_benchmark", "per_drug": { "123127": 0.11525050360525865, "119875": 0.155359307011882, "125973": -0.2857757817790637, "19893": 0.06433252813797796, "740": 0.13774028432915797, "141540": 0.10744172018379539 } } }, "endpoint_shift_errors": { "molecular": { "MAE": 0.7487252046330326, "RMSE": 0.9330359477883544, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "weighting": "equal drug; RMSE is sqrt(mean per-drug squared RMSE)", "interpretation": "predicted pGI50 versus measured pIC50; endpoint and assay shift included" }, "drug_mean": { "MAE": 0.7107047552995897, "RMSE": 0.8698350172232996, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "weighting": "equal drug; RMSE is sqrt(mean per-drug squared RMSE)", "interpretation": "predicted pGI50 versus measured pIC50; endpoint and assay shift included" }, "tissue_fixed": { "MAE": 0.7216194667003265, "RMSE": 0.883078359352529, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "weighting": "equal drug; RMSE is sqrt(mean per-drug squared RMSE)", "interpretation": "predicted pGI50 versus measured pIC50; endpoint and assay shift included" }, "tissue_cv": { "MAE": 0.7216194667003265, "RMSE": 0.883078359352529, "drugs": [ "123127", "119875", "125973", "19893", "740", "141540" ], "n_drugs": 6, "weighting": "equal drug; RMSE is sqrt(mean per-drug squared RMSE)", "interpretation": "predicted pGI50 versus measured pIC50; endpoint and assay shift included" } } }, "filter": "all finite fitted pIC50; no clipping; extrapolations retained" }, "bootstrap": { "scope": "strict in-range primary cohort", "seed": 20265002, "repetitions": 500, "origin_groups": 340, "method": "paired origin-component cluster bootstrap; integer multiplicities and average tied ranks", "confidence_level": 0.95, "interval_method": "percentile; linear interpolation", "minimum_valid_fraction": 0.9, "macro_drug_sets": "fixed at the original evaluation; all original correlations required per draw", "interpretation": "conditional descriptive uncertainty; not endpoint equivalence or unannotated-lineage assurance" }, "interpretation": [ "Primary RNA macro rho .06165 has a 95% interval including zero; tissue macro rho .10317.", "Primary paired RNA minus tissue rho -.04152 has a 95% interval including zero; no demonstrated superiority or conclusive inferiority.", "Secondary all-finite point estimates reverse the difference, including 915 out-of-range fitted responses; no secondary confidence interval was registered.", "Fixed and CV tissue baselines are identical because NCI-only CV selected shrinkage10.", "This cohort has now been evaluated; future tuning makes it development data and needs a new untouched validation cohort." ], "execution": { "runtime": { "python": "3.14.8", "numpy": "2.5.3" }, "threads": 1, "training_elapsed_seconds": 9.58931037504226, "evaluation_elapsed_seconds": 12.595848499797285, "soft_cap_seconds": 60, "downloads_and_plotting_excluded": true, "local_tests": { "rna_core_external_profile": 56, "separate_protein_profile": 20, "total": 76, "ci_record": false } }, "sources": [ { "title": "GDSC release8.5 GDSC1 fitted response", "url": "https://cog.sanger.ac.uk/cancerrxgene/GDSC_release8.5/GDSC1_fitted_dose_response_27Oct23.xlsx", "bytes": 29353210, "sha256": "837b0686500fde75179e490de08f034abd9f882d8b0253d637bafe83e156dafd" }, { "title": "Cell Model Passports RNA20191101 archive", "url": "https://cog.sanger.ac.uk/cmp/download/rnaseq_20191101.zip" }, { "title": "Sanger drug sensitivity documentation", "url": "https://depmap.sanger.ac.uk/documentation/datasets/drug-sensitivity/" }, { "title": "Sanger expression documentation", "url": "https://depmap.sanger.ac.uk/documentation/datasets/expression/" }, { "title": "Sanger data usage policy", "url": "https://depmap.sanger.ac.uk/documentation/data-usage-policy/" } ], "limitations": [ "GDSC IC50 and NCI GI50 differ in endpoint and assay conditions", "strict in-range cohort conditions on fitted effects measurable within screened concentrations", "out-of-range indicators do not establish true censoring without source flags", "drug mean has no within-drug ranking information; undefined rho is not zero", "known origin components may miss unannotated relationships", "bootstrap intervals are descriptive and conditional on frozen models and cohort", "Legacy RNA scale, processing, cell culture and assay differences remain.", "Strict filtering conditions the primary cohort on fitted response and removes 46.6% of matched rows; it is not a censoring correction.", "Drug correspondence uses source single-agent names, without independent salt or structure validation.", "No normal-cell selectivity, toxicity, patient response or clinical efficacy was tested." ], "distribution": "MAEN methods and numerical aggregates only; no source matrices, model attributes, individual responses or predictions" }