{ "schema_version": "1.0.0", "audit_date": "2026-07-27", "task": "BioCandidateRanker governed absolute activity training from repository-local sources", "target_model_field": "log10_activity", "status": "blocked", "decision": { "training_performed": false, "adapter_written": false, "canonical_unit_defined": false, "normalized_dataset_written": false, "family_split_written": false, "cpu_smoke_performed": false, "checkpoint_written": false, "predictions_used_as_labels": false, "fitness_used_as_labels": false, "reason_code": "INSUFFICIENT_COMPATIBLE_DIRECT_ABSOLUTE_ACTIVITY_ROWS_AND_FAMILIES", "summary": "No repository-local source provides enough compatible, governed, direct absolute activity measurements for family-aware log10_activity training. Turnover constants remain kcat labels; EnzEngDB fitness remains campaign-relative; Lunzer values have an unresolved absolute unit; RFU/min is instrument-relative; and the only shared physical activity dimension, mass-specific rate, has at most 23 rows in three families before scientific gates and at most 10 coherent rows in one family after the locally documented assay and consistency gates.", "claim_boundary": "This is a source and compatibility audit only. No labels were created, no endpoint was relabeled, no split or model was produced, and no model scoring was run." }, "search_scope": { "root": "", "repository_is_git_worktree": false, "included": [ "source adapters and curation scripts under src/ and scripts/", "repository-local tabular, JSON, archive, workbook, sequence, audit, metric, checkpoint, and prediction artifacts", "all source directories under artifacts/external/absolute-kinetics-screen", "all source directories under artifacts/external/temporal-absolute-kinetics", "all EnzEngDB v1 campaign files and audits under artifacts/external/enzengdb-v1", "existing UniKP manifests and audits under artifacts/ and configs/" ], "endpoint_terms": [ "activity", "specific activity", "Vmax", "U mg^-1", "umol min^-1 mg^-1", "RFU/min", "fitness_value", "kcat", "rate" ], "exclusion_policy": [ "Do not rename kcat, Km, kcat/Km, fitness, relative activity, inhibition, simulated flux, or predictions as activity.", "Require a finite direct experimental value, an explicit physical unit and denominator, exact sequence and defined substrate inputs, row-level provenance, and permission-compatible local evidence.", "Require assay semantics to be compatible before pooling values that happen to share dimensions.", "Require complete protein families to stay within one train, validation, or test partition." ] }, "candidate_canonical_dimension": { "dimension": "amount of product per time per mass of protein", "interconvertible_source_units": [ "U mg^-1", "umol min^-1 mg^-1" ], "possible_canonical_unit_if_unblocked": "log10(umol min^-1 mg^-1)", "defined_for_training": false, "reason_not_defined": "Dimensional convertibility is not sufficient. After directness, assay-validity, conversion-consistency, provenance, and family gates, the local pool collapses to one family with at most 10 rows. Declaring a model-wide canonical activity unit would falsely imply an adequate governed training endpoint." }, "source_buckets": [ { "source_id": "temporal-global-family-audit", "path": "artifacts/external/temporal-global-family-audit/readiness-audit.json", "endpoint": "direct steady-state kcat", "unit": "s^-1 after source-specific normalization", "records": 177, "families": 21, "substrates": 50, "activity_eligible_records": 0, "reason": "A molar turnover constant is a governed log10_kcat endpoint, not a mass-specific or condition-specific activity endpoint. Relabeling is prohibited." }, { "source_id": "UniKP-kcat-development", "path": "artifacts/unikp_audit.json", "endpoint": "kcat", "total_rows": 17010, "adapter_accepted_rows": 16838, "activity_eligible_records": 0, "reason": "The source and implemented task are log10_kcat. It also lacks row-level accessions and a bundled independent split; no kcat value was relabeled as activity." }, { "source_id": "EnzEngDB-v1", "path": "artifacts/external/enzengdb-v1/audit.json", "endpoint": "fitness_value", "total_rows": 462092, "adapter_accepted_rows": 245945, "campaigns": 160, "activity_eligible_records": 0, "reason": "Fitness has campaign-specific meaning and units. The existing adapter intentionally leaves log10_activity unset and permits only within-campaign ranking. EnzEngDB was excluded from the activity candidate count." }, { "source_id": "Lunzer-Dryad-7nd70", "path": "artifacts/external/absolute-kinetics-screen/dryad-4964723/Lunzer Curated Biochemistry.xls", "source_identity": { "sha256": "7bfd71d78235ade06a9e117b8229ad99b1fe7adceb0a5ed72d708c3e925c2a69", "size_bytes": 38761 }, "endpoint": "derived ln(Km) + ln(kcat/Km)", "records": 1024, "families": 1, "activity_eligible_records": 0, "reason": "The absolute source-unit constant is unresolved and all 512 sequences have development-corpus homology hits. Existing use is ranking within cofactor only." }, { "source_id": "mLDHD-S-EPMC10589216", "path": "artifacts/external/temporal-absolute-kinetics/biostudies-S-EPMC10589216/exclusions.csv", "endpoint": "Michaelis-Menten Vmax reported as mass-specific activity", "unit": "umol min^-1 mg^-1", "candidate_rows": 9, "families": 1, "direct_dimensionally_compatible_rows": 9, "scientifically_eligible_rows": 0, "reason": "Every row uses a PMS-DCIP coupled assay without demonstrated saturation of either fixed electron acceptor. The local provenance audit excludes all nine apparent rates; none may become an activity label merely because Vmax has a compatible unit." }, { "source_id": "Pantoea-GDH-S-EPMC12364357", "path": "artifacts/external/temporal-absolute-kinetics/biostudies-S-EPMC12364357", "endpoint": "Michaelis-Menten Vmax reported as mass-specific activity", "unit": "U mg^-1", "candidate_rows": 10, "families": 1, "direct_dimensionally_compatible_rows": 10, "rows_passing_local_cosubstrate_saturation_rule": 1, "rows_with_development_homology": 10, "training_eligible_rows": 0, "reason": "Only one row passes the local >=5x fixed-cosubstrate Km rule, and the complete family is excluded by development homology. The ten values are useful provenance evidence but cannot support a family-aware activity split." }, { "source_id": "SlDefH-PMC13230308", "path": "artifacts/external/temporal-absolute-kinetics/europepmc-PMC13230308/blocker-evidence.json", "endpoint": "specific activity or Vmax", "unit": "U mg^-1", "candidate_rows": 4, "families": 1, "direct_dimensionally_compatible_rows": 4, "training_eligible_rows": 0, "reason": "The completed source audit found zero independently reconcilable rows. Each reported specific-activity/kcat pair implies approximately 599 kDa versus the stated 29.5 kDa sequence mass, while the article and complete supplement provide no kinetic enzyme molarity, conversion equation, oligomer measurement, active-site stoichiometry, or active-enzyme fraction. Reported values remain provenance evidence only; the local registry finalizes this source at zero rows." }, { "source_id": "Zenodo-4448337", "path": "artifacts/external/absolute-kinetics-screen/zenodo-4448337/source.zip", "source_identity": { "sha256": "8ef6d1a23ba3d5a614c5670fabc28daf8644a4d1d1320f0a0850a54f1088090a", "size_bytes": 4637 }, "endpoint": "kcat, Km, kcat/Km, and cofactor preference", "activity_eligible_records": 0, "reason": "The archive contains turnover kinetics and a dimensionless preference series, not a governed absolute activity endpoint." }, { "source_id": "Zenodo-20626217-Dataset-S1", "path": "artifacts/external/absolute-kinetics-screen/zenodo-20626217/Dataset_S1.xlsx", "source_identity": { "sha256": "83f559a75277c87c307fadb93393b6090a628055fc4c4e8a96d8e0e6e48d5338", "size_bytes": 84504 }, "endpoint": "BACE1 inhibition and instrument response rates", "units": [ "percent inhibition", "IC50 in uM", "Ki in uM", "RFU/min" ], "activity_eligible_records": 0, "reason": "RFU/min lacks a physical amount calibration and protein-mass denominator; inhibition endpoints describe peptides acting on BACE1 rather than enzyme-candidate catalytic activity." }, { "source_id": "model-and-simulation-artifacts", "paths": [ "artifacts/candidate_predictions.json", "artifacts/external/absolute-kinetics-screen/dryad-4964723/dlkcat-output.tsv", "artifacts/external/absolute-kinetics-screen/dryad-4964723/biocandidate-full-evaluation.json", "artifacts/external/enzengdb-v1/zero-shot-kcat-proxy.json", "artifacts/simulated-flux-smoke" ], "activity_eligible_records": 0, "reason": "Predictions, model metrics, checkpoints, and simulated flux are not direct experimental activity labels." } ], "mass_specific_activity_funnel": { "dimensionally_compatible_candidate_rows": 23, "candidate_sources": 3, "candidate_families": 3, "excluded_coupled_assay_rows": 9, "excluded_internal_conversion_inconsistency_rows": 4, "coherent_direct_rows_before_homology_and_saturation_gates": 10, "coherent_direct_families_before_homology_and_saturation_gates": 1, "rows_passing_existing_saturation_and_homology_gates": 0, "families_passing_existing_saturation_and_homology_gates": 0, "maximum_rows_if_homology_exclusion_were_ignored": 1, "maximum_families_if_homology_exclusion_were_ignored": 1 }, "family_split_audit": { "required_partitions": [ "train", "validation", "test" ], "assignment_unit": "complete protein homology family", "label_independent_assignment_required": true, "candidate_families_before_scientific_gates": 3, "eligible_families_after_scientific_gates": 0, "split_feasible": false, "reason": "Even the permissive dimensional pool would place only one family in each partition with no within-partition family diversity. After existing scientific gates there are no eligible families, so a leakage-aware split cannot be written." }, "incompatibility_counts": { "heterogeneous_fitness_rows_explicitly_excluded": 245945, "governed_kcat_rows_not_relabelled": 177, "unikp_kcat_adapter_rows_not_relabelled": 16838, "unit_ambiguous_lunzer_rows_not_relabelled": 1024, "mass_specific_candidate_rows": 23, "mass_specific_candidate_families": 3, "mass_specific_rows_rejected_by_assay_or_consistency": 13, "mass_specific_rows_rejected_by_existing_saturation_or_homology_gates": 10, "eligible_activity_rows": 0, "eligible_activity_families": 0 }, "blocking_findings": [ { "code": "ENDPOINT_SEMANTICS_INCOMPATIBLE", "severity": "fatal", "detail": "kcat, kcat/Km, fitness, inhibition, instrument response, relative activity, and simulated flux are distinct endpoints and cannot be pooled as log10_activity." }, { "code": "MASS_SPECIFIC_POOL_TOO_SMALL", "severity": "fatal", "detail": "Only 23 dimensionally compatible candidate rows in three families exist before scientific gates; at most 10 coherent rows remain in one family before homology and saturation gates." }, { "code": "NO_ELIGIBLE_FAMILY_SPLIT", "severity": "fatal", "detail": "No family remains eligible after the locally documented assay-validity, conversion-consistency, saturation, and development-homology gates." }, { "code": "CANONICAL_UNIT_PREMATURE", "severity": "fatal", "detail": "Defining log10(umol min^-1 mg^-1) as a training endpoint would imply unsupported comparability across apparent Vmax, coupled assays, fixed-condition specific activity, and inconsistent conversions." } ], "conditions_to_unblock": [ "Acquire direct purified-enzyme activity rows with a single prespecified physical denominator and auditable conversion to it; do not substitute kcat or fitness.", "Preserve per-row source file/cell, DOI or stable record, exact construct sequence, defined substrate structure, assay conditions, replicate/error semantics, evidence tier, and license provenance.", "Prespecify whether the endpoint is saturating mass-specific Vmax or activity at a fixed substrate protocol; do not pool those assay semantics without a validated normalization model.", "Resolve coupled-assay saturation and SlDefH conversion inconsistencies before admission.", "Acquire enough independent homology families to populate train, validation, and test with meaningful family diversity, then freeze a label-independent family assignment.", "Only after those gates pass, define the canonical unit, implement a strict activity-specific adapter, and run a CPU training smoke." ], "evidence_files": [ "README.md", "src/biocandidate/data/normalized_kinetics.py", "src/biocandidate/data/enzengdb.py", "src/biocandidate/data/lunzer.py", "configs/temporal_absolute_kinetics_protocol.json", "artifacts/unikp_audit.json", "artifacts/external/enzengdb-v1/audit.json", "artifacts/external/absolute-kinetics-screen/dryad-4964723/selection.json", "artifacts/external/absolute-kinetics-screen/dryad-4964723/homology-audit.json", "artifacts/external/temporal-absolute-kinetics/registry-readiness-audit.json", "artifacts/external/temporal-global-family-audit/readiness-audit.json", "artifacts/external/temporal-absolute-kinetics/biostudies-S-EPMC10589216/provenance.json", "artifacts/external/temporal-absolute-kinetics/biostudies-S-EPMC12364357/provenance.json", "artifacts/external/temporal-absolute-kinetics/candidate_registry.json", "artifacts/external/temporal-absolute-kinetics/third_round_discovery_registry.json" ] }