{
  "policy_id": "oncoref.target-selection.2026-11-10.1",
  "status": "research_catalog_rebuilt",
  "species": "human",
  "categories": [
    "CTA",
    "Cancer Antigen only",
    "Reproductive Antigen only",
    "Other",
    "Unsafe"
  ],
  "shared_checks": [
    "normal_screen_pass",
    "required_coverage_complete",
    "identity_translation_pass",
    "evidence_resolved",
    "expression_bounds_pass",
    "sequence_pass"
  ],
  "sets": {
    "Cancer Antigens": "eligible AND cancer evidence qualifies",
    "Reproductive Antigens": "eligible AND reproductive/developmental evidence qualifies",
    "CTA": "Cancer Antigens INTERSECTION Reproductive Antigens",
    "Target candidates": "Cancer Antigens UNION Reproductive Antigens"
  },
  "precedence": [
    "Unsafe",
    "Other:Review",
    "Other:Sequence",
    "set memberships"
  ],
  "other_subtypes": {
    "Review": "Required evidence is missing, unresolved, or fails a shared admission check.",
    "Sequence": "Nested protein without independent support or >=95% Unsafe 9-mer containment.",
    "Expression": "Neither positive expression route qualifies, or the target maximum or Disposable cap fails."
  },
  "expression_bounds": {
    "target_maximum": "max(tumor, adult reproductive, developmental) >= 1 and above every measured nonreproductive normal and Disposable value on the comparison scale.",
    "disposable_cap_tpm": 32.0,
    "disposable_cap_ntpm": 32.0,
    "cap_scope": "Each source scale separately; a screening convention, not a tolerance.",
    "failure": "Other:Expression"
  },
  "rare_cell_rna": {
    "unit": "One adult donor x one named Vital or Protected cell population, UMI counts",
    "signal": ">= 1% of a donor's cells and >= 10 cells carry >= 2 molecules.",
    "replication": "The signal in >= 2 independent studies of the same organ, which agree on a cell type or include >= 3 donors. Donors of one study share its libraries and reference; one donor in each of two studies, in different cell types, agrees on nothing but the organ.",
    "single_study": "Without replication, a signal counts only when >= 5% of a donor's cells carry multiple molecules.",
    "protected": "Protected populations need 2 times these frequencies.",
    "single_molecules": "Cells with one molecule never change a category. A mis-assigned read from a paralog, pseudogene or overlapping gene produces exactly this pattern.",
    "mapping_risk": "Shared transcript sequence with another locus, or an exon inside another same-strand gene. Counts for a flagged gene cannot be attributed to it.",
    "confirmation": "Bulk RNA >= 1 native TPM in the same organ in both the HPA and GTEx sample sets, a different assay with its own read assignment.",
    "established": "A replicated signal at a locus without mapping risk, or any signal with bulk confirmation. Unsafe.",
    "dismissed": "A signal that is neither: counts at a flagged locus, or from one study, that no other assay confirms. Recorded with its reason; no category effect.",
    "literature": "Where a reviewed publication reports the gene in the same organ by a gene-specific assay, 1% detection in one donor is established, single molecules included: two assay types then agree. Published protein in a Vital or Protected tissue excludes through the knowledge layer without any counts.",
    "consequences": {
      "established": "Unsafe",
      "dismissed": "No finding; the reason and counts stay in the record.",
      "below_screen": "No finding. Not a demonstration of absence or safety.",
      "unassessed": "Recorded as unmeasured; never treated as negative."
    },
    "reported_sensitivity_cutoffs_pct": [
      1,
      2,
      5
    ],
    "interpretation": "Detection frequency measures captured RNA, not the fraction of cells producing protein. No cutoff is a calibrated toxicity threshold."
  },
  "cancer_rna": {
    "detection_floor": 1.0,
    "independent_participants_required": 2,
    "repeated_rule": "T >= 1 AND T > N in at least two independent participants",
    "single_tumor_fold": 10.0,
    "single_rule": "T >= 10 * max(N, 1) in at least one qualified tumor sample",
    "normal_reference": "Maximum QC-passing, identity-resolved measurement in the declared compatible normal panel, excluding specifically allowed Disposable and reproductive compartments.",
    "comparability": "One documented comparison scale and complete required normal contexts. Equal unit names alone do not establish comparability. No TPM/nTPM/pTPM/CP10K pooling.",
    "missing_reference": "unassessed, never zero",
    "alternative": "Reviewed reliable tumor protein with exact identity and source scope."
  },
  "reproductive_evidence": {
    "branches": [
      "adult reproductive",
      "placental",
      "extraembryonic",
      "embryonic",
      "fetal"
    ],
    "rna_detection_floor": 1.0,
    "bulk": "Mapped human reproductive compartment >=1 native TPM/nTPM.",
    "cell": "Mapped reproductive cells >=1 native TPM/nTPM and >=20 reads.",
    "developmental": "Human stage/lineage mean >=1 TPM, >=20 cells, >=5 cells at >=1 TPM, and >=10% cells at >=1 TPM. Retain embryos, donors and stage.",
    "protein": "Reliable mapped reproductive IHC or reviewed human reproductive protein.",
    "concentration": "Descriptive measurement; not an admission gate for either set."
  },
  "shared_normal_policy": {
    "policy_id": "oncoref.cta-selection.2026-11-08.1",
    "scope": "Normal assessment only; legacy cancer, reproductive and concentration gates excluded.",
    "allowances": "Same resolved reproductive and Disposable compartment allowances for both sets. Immune, endothelial and other protected cells do not inherit an organ's allowance.",
    "threshold_interpretation": "RNA/IHC cutoffs are screening conventions, not measured injury thresholds. Negative IHC does not establish a calibrated safety margin."
  },
  "translation": "Qualifying coding reference or supported noncanonical ORF plus complete approved MANE-first/canonical representative; resolve conflicting coding evidence. Experimental protein detection is retained separately.",
  "published_target_support": "Positive evidence annotation for a curated, exact-scope target nomination. Preserve every protein-paper link and its attested claim; biology or background-table coverage alone is not a target nomination. Publication cannot override an exclusion or hold.",
  "only_meaning": "Membership in one qualified set, not proven absence from the other context."
}