{ "date": "2026-10-13", "m5": { "model": "M5", "scope": "Qualified external gene-disjoint HeLa transfer, with completed declared source/sample audit", "source": "https://doi.org/10.1038/s41587-025-02712-x", "evaluatedGenes": 973, "missingOutcomeExclusions": 27, "metrics": { "M5": 0.32212213065746126, "Kozak-only linear": 0.4325089591655537, "UTR length/GC ridge": 0.17134823952787723 }, "metricCi95": { "M5": [ 0.2621620972030185, 0.37414599996830666 ], "Kozak-only linear": [ 0.3767862549540821, 0.48568555103101446 ], "UTR length/GC ridge": [ 0.10822374622321172, 0.23095167865660154 ] }, "comparisons": [ { "baseline": "Kozak-only linear", "deltaSpearman": -0.11038682850809245, "adjustedPairedCi": [ -0.18602824664546488, -0.04217946685394352 ], "supportsSuperiority": false }, { "baseline": "UTR length/GC ridge", "deltaSpearman": 0.15077389112958403, "adjustedPairedCi": [ 0.07934390178025225, 0.22411475813807888 ], "supportsSuperiority": true } ], "statisticalWinWithinCohort": false, 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Davis uses incompatible 20/50 inputs and modified constructs.", "next": "A source-family-disjoint panel with measured efficacy, documented guide orientation and genuine 19/57 inputs." }, { "model": "M2", "status": "No new qualified independent cohort", "candidate": "ASO-RASAR; WFDC1 validation", "source": "https://doi.org/10.1021/acs.jcim.6c01314", "blocker": "22,536/22,845 MOE and 36,121/36,428 cEt descriptor rows overlap development sequences. WFDC1 eight-compound figure lacks exact sequence/assay rows.", "next": "Source-backed WFDC1 constructs, positional chemistry, context, complete assay membership and numerical measurements; then freeze predictions before opening outcomes." }, { "model": "M3", "status": "Candidate identified; not yet qualified or scored", "candidate": "MFASS experimental splicing", "source": "https://github.com/KosuriLab/MFASS", "blocker": "Requires variant-level ClinVar calibration-overlap audit, matching reference context and verified raw SpliceAI predictions. Minigene disruption differs from clinical labeling used in calibration.", "next": "Qualify variant identities and labels; compare raw versus calibrated SpliceAI on a separately defined experimental endpoint." }, { "model": "M4", "status": "Legacy held-out diagnostic; geometry quality gate fails", "candidate": "GENCODE v50 existing test partition", "source": "https://www.gencodegenes.org/human/release_50.html", "blocker": "21,508 of 53,116 test rows fail the deployed input contract. Historical builder uses union indices and mismatched representative transcripts. Higher scores on the valid subset do not resolve this source defect.", "next": "Use the tested transcript-local geometry extractor for a separately identified corrected dataset and validate a new model; existing weights and outputs remain historical." }, { "model": "M5", "status": "Qualified external gene-disjoint transfer evaluated", "candidate": "Published HeLa translation-efficiency aggregate", "source": "https://doi.org/10.1038/s41587-025-02712-x", "blocker": "973 evaluable unseen-development genes. M5 beats length/GC, loses to Kozak-only. Study-specific uncertainty cannot be recovered from the aggregate table.", "next": "Investigate transportability and transcript-choice mismatch in development data; reserve a different cohort for any later revised model." }, { "model": "M6", "status": "New coverage benchmark blocked by qualified potency inputs", "candidate": "Independent RNase-H assay sets", "source": "https://github.com/barneyhill/aso_atlas", "blocker": "Coverage requires genuinely unseen model predictions, distinct calibration/test groups and complete assay membership. Historical outcome-derived coverage is not a deployment guarantee.", "next": "Qualify enough independent RNase-H groups, freeze calibration and test partitions, and evaluate both coverage and selected-set size." }, { "model": "M7", "status": "No qualified independent OOD-labeled cohort", "candidate": "External transcript distribution-shift cases", "source": "https://huggingface.co/multimolecule/rinalmo-giga", "blocker": "Sequence-file availability or stored human-index replay does not establish OOD detection accuracy. Novel-gene labels alone are not applicability ground truth.", "next": "Define intended in/out-of-support labels before scoring and exclude stored index membership; verify fresh encoder execution." }, { "model": "Recovered exp11/exp12", "status": "Reference replay; no independent accuracy result", "candidate": "Sciabola external source for Huesken-trained legacy folds", "source": "https://doi.org/10.1093/nar/gks1191", "blocker": "Requires original supplement reconciliation, correct-strand core/context preparation and external fresh-feature validation. Cannot inherit current-M1 metrics.", "next": "Verify primary table rows and assay endpoint before separately identified external legacy-fold evaluation." }, { "model": "Recovered pooled-v4", "status": "Public training-reference replay only", "candidate": "New source-family-disjoint pooled-model rows", "source": "https://github.com/barneyhill/aso_atlas", "blocker": "External-holdout checkpoint identities and fresh-input parity are unresolved. Loading five pooled checkpoints is not independent accuracy.", "next": "Obtain verified external-holdout exports and full preprocessing/vocabulary identities." }, { "model": "Reconstructed KRAIG + OligoAI", "status": "New matched independent comparison blocked", "candidate": "DNA/MOE/cEt public validation panels", "source": "https://github.com/barneyhill/OligoAI", "blocker": "LNA candidate panels are incompatible; ASO-RASAR development collections overlap. Global OligoAI source membership must also be checked for each candidate.", "next": "Training-disjoint supported complete assay sets with documented chemistry/context, then matched prediction locks and paired study-family evaluation." }, { "model": "Original full KRAIG", "status": "Unavailable", "candidate": "Original historical fold exports", "source": "https://github.com/barneyhill/OligoAI", "blocker": "Historical aligned-raw, bag-raw and LambdaRank fold exports and original OligoAI fold identities are missing.", "next": "Recover authentic deployable exports; do not replace them with pooled/reconstructed weights under the historical identity." }, { "model": "SAR-FiLM", "status": "Unavailable", "candidate": "Verified deployment bundle", "source": "", "blocker": "No deployment bundle containing weights and required feature/support schemas.", "next": "Recover an authentic bundle or authorize a separately identified new training effort." } ], "m4": { "model": "M4", "evaluatedGenes": 1851, "evaluatedExons": 31608, "inputContractExclusions": 21508, "metrics": { "M4": { "averagePrecision": 0.9367084105533253, "brier": 0.08700236283730954 }, "Logistic same geometry": { "averagePrecision": 0.9056310325457861, "brier": 0.11431278350330375 }, "55-nt stop rule": { "averagePrecision": 0.5477722603863683, "brier": 0.3638003037205771 }, "Training prevalence": { "averagePrecision": 0.44071121235130345, "brier": 0.2473925323493433 } }, "comparisons": [ { "baseline": "Logistic same geometry", "deltaAveragePrecision": 0.03107737800753918, "adjustedPairedCi": [ 0.025562957848341977, 0.037031592096431705 ], "supportsSuperiority": true }, { "baseline": "55-nt stop rule", "deltaAveragePrecision": 0.38893615016695704, "adjustedPairedCi": [ 0.37084236720139113, 0.405550399042917 ], "supportsSuperiority": true } ], "heldoutAnnotationSuperiority": true, "newExternalSuperiority": false, "scope": "Existing gene-disjoint GENCODE annotation test; 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