CONCH
conch_tum_tissue_stain_tail_20260603
valid localized public crc tum tail boundary / weak independent site generalization
CONCH zero-shot CRC ROI classification shows a claim-valid but localized degradation boundary: true TUM recall falls in the low-similarity tail of a prospective tissue/stain-fraction axis. The result is bounded to public CRC ROI tiles and the CONCH CRC prompt ensemble. It is not an all-class, whole-slide, independent-site, non-CRC, or medical deployment claim.
Primary Axis
TUM tissue/stain-fraction proximity tail
Euclidean distance in tissue, white/background, dark, and high-saturation pixel fractions from the class-balanced NCT-CRC-HE-100K reference median. Higher numbered levels mean lower similarity; split membership is frozen before CONCH scoring.
Discovery tiles7,180
CRC-VAL balanced accuracy0.785
Confirmation TUM tiles1,800
Expanded TUM tiles4,000
Low-tail recall gap0.223
Expanded Spearman-0.77
Claim Boundary
Public CRC 224x224 H&E ROI tiles scored with the CONCH CRC prompt ensemble. Confirmation and expansion are fresh relative to CRC-VAL discovery but still from the public Kather/NCT source family, so independent-site or clinical deployment generalization remains weak.
Limitations
- Confirmation and expansion are still from the public Kather/NCT source family rather than an independent site cohort.
- The primary result is TUM-class localized, not an all-class or deployment-wide generalizability statement.
- The expanded curve is threshold-shaped rather than strictly monotone; levels 8-10 are degraded but levels 9 and 10 rebound slightly relative to level 8.
Downgraded Axes
- broader NCT color/texture proximity: split-valid but not claim-closing
- all-class CRC ROI generalizability: not supported as broad closure
Key MCP artifact IDs
conch:final_report.md
conch:artifacts:tum_expansion:expanded_finding_report.md
conch:artifacts:tum_expansion:expanded_metrics.json
conch:artifacts:tum_expansion:analysis.json
conch:artifacts:tum_expansion:scored_tum_expansion_with_baselines.csv
conch:artifacts:tum_expansion:target_model_results_tum_expansion.csv
conch:artifacts:tum_confirmation:analysis.json
conch:artifacts:tum_confirmation:decile_densification.json- and 7 more key artifacts in the MCP store
ESMFold2
esmfold2_high_disulfide_boundary_20260602
valid current pool confirmed
Across accumulated CAMEO and RCSB-derived ESMFold2 evaluations, high disulfide/cysteine capacity is a broad prospective risk proxy for reduced structural accuracy. Class-II-like viral E/E2/envelope-E proteins form a sharper localized failure mode. The failures are generally accompanied by low ESMFold2 confidence, so the result is a calibrated low-confidence generalization boundary rather than a hidden overconfident failure regime.
Primary Axis
high disulfide/cysteine capacity
disulfide_capacity_per100 = floor(number_of_cysteines / 2) / sequence_length * 100
Primary rows652
High-disulfide n134
Lower-disulfide n518
Raw CA-lDDT gap-0.149
Matched-control gap-0.061
Class-II CA-lDDT gap-0.407
Claim Boundary
Supported for accumulated ESMFold2 target-level evaluations across CAMEO/CAMEO follow-up, external RCSB, fresh general RCSB, and viral RCSB panels. MSA depth was claim-valid in CAMEO but not globally comparable across later panels.
Limitations
- Global table mixes scaled ESMFold2 inference with a smaller earlier CAMEO/default subset.
- Cluster-aware validation used approximate k-mer clustering; publication could replace this with MMseqs2 or CD-HIT.
- Class-II E/E2 is metadata-defined and localized, not a global all-protein sequence axis.
Downgraded Axes
- MSA depth: CAMEO-claim-valid but not global
- flexible/non-helical composition: CAMEO-local, not broad portable
- reference geometry/topology: invalid as deployment axis
Key MCP artifact IDs
esmfold2:FINAL_ESMFOLD2_RESULT.md
esmfold2:data:primary_exact_sequence_dedup.csv
esmfold2:data:all_esmfold2_scored_evaluations.csv
esmfold2:tables:global_hypothesis_effects_primary_sequence.csv
esmfold2:tables:global_hypothesis_adjusted_effects_primary_sequence.csv
esmfold2:tables:global_hypothesis_level_curves_primary_sequence.csv
esmfold2:tables:per_source_high_disulfide_summary.csv
esmfold2:tables:cluster_aware_disulfide_effects.csv- and 5 more key artifacts in the MCP store
STATE
state_pathway_module_train_support_20260603
valid current pool confirmed
STATE generalizes worse for Replogle held-out gene perturbations whose pathways/modules are sparsely represented among training perturbations. The effect was discovered in hepg2 and k562, confirmed in jurkat and rpe1, checked in Replogle zero-shot, and extended beyond Reactome to independent gene-set systems.
Primary Axis
pathway/module train-support density
For each held-out gene perturbation, support is the mean log(1 + number of same-context training genes sharing each pathway/module annotation of the target gene). Higher support means the target gene is closer to known training biology in that context.
Scored rows39,808
Few-shot HVG gap0.128
Few-shot SE gap0.109
Zero-shot HVG gap0.068
Zero-shot SE gap0.044
OLS support coefficient0.028
Claim Boundary
Current-pool confirmed using official precomputed STATE scored CSVs and official split definitions, not fresh STATE inference or raw single-cell matrices. The main reviewer-facing gap is a fixed baseline/raw-label rerun.
Limitations
- Used official precomputed scored CSVs rather than fresh STATE inference.
- Fixed baseline/raw-label rerun still needed for reviewer-facing closure.
- Perturbation strength measured by DE-count severity is a strong mediator/confound and should remain in claim framing.
Downgraded Axes
- Tahoe target-context chemical Tanimoto support: split-valid but negative/weak
- Parse-PBMC ligand-family training support: reversed direction
- GO Molecular Function support: positive but weaker
Key MCP artifact IDs
state:state_spectra_report.md
state:target_model_results.csv
state:spectra_loop_state.json
state:axis_ledger_prior.json
state:artifacts:spc_replogle_best_refined_axis.csv
state:artifacts:spc_replogle_best_refined_axis_trends.csv
state:artifacts:spc_replogle_best_refined_axis_context_trends.csv
state:artifacts:spc_replogle_zeroshot_reactome_support_confirmation.csv- and 6 more key artifacts in the MCP store