Normal tissue scopes

Current adult human hazard calls are centralized in the tissue-hazard ontology, independently of reproductive membership.

oncoref uses one cited anatomical vocabulary for human, dog and mouse. A scope is a set of permitted normal anatomical/developmental contexts. A detected protein or gene is compatible with that scope only if every detection belongs to it. Tissue sets are unioned before evaluating expression patterns. Positive observations alone do not establish absence outside a scope.

Definitions and citations ship in oncoref/data/normal-tissue-taxonomy.yaml; exact dataset mappings ship in oncoref/data/normal-tissue-mappings.csv. Policy version 2026-10-21.2 and a SHA-256 identity over both files accompany each annotation. Source-artifact receipts record the bytes used to review labels. All access is offline once expression data are loaded.

Read the hierarchy

Each row below shows inclusion into successively larger tissue sets. Sibling branches are combined at their shared parent.

Starting context	Successive unions
Testis	testis → male_reproductive → reproductive → reproductive_or_disposable
Oocyte	oocyte → ovary → female_reproductive → reproductive → reproductive_or_disposable
Mammary glandular cells	mammary_glandular → mammary → female_reproductive → reproductive → reproductive_or_disposable
Placenta	placental → extraembryonic → reproductive → reproductive_or_disposable
Explicit embryo/fetus context	embryonic or fetal → reproductive → reproductive_or_disposable
Cutaneous melanocytes or hair follicles	disposable_normal → reproductive_or_disposable
Tonsil, appendix or gallbladder	permitted_normal → reproductive_or_permitted_normal

reproductive_or_disposable is a subset of the expanded reproductive_or_permitted_normal union. disposable_normal is a subset of permitted_normal; the wider name records a project screening allowance. acceptable_normal and reproductive_or_acceptable_normal are readable aliases for those existing scope identifiers. They resolve to the same sets.

For a gene detected in both testis and oocyte, the entire observed pattern fits reproductive_core and reproductive, while neither sex-specific scope contains both detections. The tissue union is evaluated before selecting genes. The aliases male_strict and female_strict name anatomical scopes; a claim of strict gene restriction additionally needs adequate negative tissue coverage.

The original CTA source and filtering report compares reproductive with reproductive + disposable using both the existing adaptive CTA policy and a strict positive-evidence sensitivity screen. It includes figures, exact gene decisions, source citations and coverage limitations. The expanded permitted-tissue report adds the requested organs, vital/protected RNA ceilings, and an independent IHC exclusion gate, with included/excluded decisions for published targets. The IHC-adaptive absolute RNA report compares those fixed ceilings with the approved tissue-specific negative-IHC ladder. These dated reports preserve their original policies and results. The tissue-tier update compares the current anatomy policy with the preceding adaptive screen, holding RNA thresholds fixed. The context and removable-organ update adds appendix/gallbladder and records the preceding four-category policy. The tissue-priority and IHC-grid report compares that baseline with the five-category policy and separates reclassification from the numerical grid change.

Reproductive scopes

The following are source contexts, not assertions of immune privilege. Anatomical subcompartments inherit their organ scope. For example, an oocyte belongs to both the oocyte and ovarian scopes, but an observation of bulk ovary does not identify oocytes.

Scope	Exact definition
testis (male_strict)	Testis, including explicitly mapped seminiferous tubules, germ cells, Sertoli, Leydig and peritubular cells. Whole testis does not imply germ-cell-only expression.
oocyte (female_strict)	Oocytes/ova. Whole ovary, ovarian stroma and follicle-cell observations do not qualify for this narrower scope.
ovary	Whole ovary and mapped ovarian compartments: oocytes, follicles, granulosa, theca, stroma and corpus luteum.
mammary_glandular	Explicit mammary glandular epithelium, including luminal and myoepithelial cells.
mammary	Whole breast/mammary tissue and its subcompartments. Bulk tissue remains broader than glandular-cell evidence; lactating state is retained when reported.
male_reproductive (male_extended)	testis ∪ spermatozoa ∪ epididymis ∪ vas deferens ∪ prostate ∪ seminal vesicle ∪ bulbourethral gland ∪ penis, filtered for species applicability. Spermatozoa alone do not imply a testis sampling site. Mouse coagulating gland is included under prostate.
female_reproductive (female_extended)	ovary ∪ fallopian tube/oviduct ∪ uterus (including endometrium, myometrium, cervix and applicable uterine horns) ∪ vagina ∪ vulva ∪ clitoris ∪ mammary. The grouping does not infer the sample's sex.
placental	Placenta and its annotated subcompartments. A placenta-specific observation qualifies without resolving maternal versus fetal compartment.
extraembryonic	placental ∪ amnion ∪ chorion ∪ yolk sac ∪ allantois ∪ umbilical cord.
embryonic	Whole embryo or an anatomical sample explicitly labeled embryonic. Original organ, stage and age metadata remain available.
fetal	Whole fetus or an anatomical sample explicitly labeled fetal/foetal. Original organ, stage and age metadata remain available.
reproductive_core (core)	testis ∪ ovary ∪ placental, retaining the historical core organ union.
reproductive (extended, permissive)	male_reproductive ∪ female_reproductive ∪ extraembryonic ∪ embryonic ∪ fetal.

The organ groupings follow the male and female reproductive anatomy, which includes mammary glands as accessory reproductive organs. The broader embryonic/fetal inclusion is an explicit project definition, supported by retaining the source distinctions used in BarkBase and the human fetal atlas.

An embryonic liver sample can belong to embryonic and reproductive; adult liver does not. Gestational-day cutoffs are not copied between species, and pregnancy of the donor does not turn maternal organs into fetal tissue. A source's embryonic/fetal terminology is preserved rather than reinterpreted from age alone.

Conditional disposable normal scope

disposable_normal contains cutaneous melanocytes and hair-follicle compartments. reproductive_or_disposable is its union with reproductive. These are research policy names, not declarations that destruction is harmless or acceptable for every patient or treatment.

Included compartment	Source and precise boundary
Cutaneous melanocytes	The explicit example list in Blagosklonny 2003 names melanocytes, prostate, testis, breast and ovary. The four reproductive organs are assigned above. Here melanocytes are limited to skin: clinical antigen-directed T-cell therapy also caused ocular and auditory toxicity, so an unsited melanocyte label, ocular melanocytes, inner-ear cells and retinal pigment epithelium do not inherit this exception.
Hair follicles	Included as the separately requested conditional alopecia exception. NCI describes treatment-associated alopecia and variable regrowth. Purba et al. 2019 distinguishes follicular matrix and stem-cell injury. A bulk follicle observation does not establish matrix-only expression or reversible injury. This evidence does not validate immune ablation of follicles.

Whole skin, epidermis, generic keratinocytes, sebaceous/sweat glands, fibroblasts, retina, marrow, thyroid, lymphoid organs and unsited immune-cell labels do not automatically qualify. Thymus is a somatic tissue, including when expression reflects immune tolerance. No unlisted normal tissue is admitted by default.

Five categories and protection priorities

The five user-facing categories are Reproductive, Disposable, Manageable, Protected and Vital. normal_tissue_category() returns the IDs listed below. Unresolved anatomy is a QC status outside those five categories. Reproductive and Disposable share the numerical tier permitted; Manageable, Protected and Vital are screened. A candidate must have positive Reproductive evidence. Disposable expression is exempt from the RNA and IHC exclusion gates, but cannot supply that positive evidence.

Display name	Machine ID
Reproductive	reproductive
Disposable	disposable
Manageable	manageable
Protected	protected
Vital	vital

Exports include readable category labels alongside these stable IDs.

Reproductive is an anatomical/developmental grouping, not an assertion of immune privilege or tolerability in every patient. Manageable denotes the lower protection priority, where selected injuries may be manageable or functionally compensated. Protected denotes greater concern about persistent functional or structural damage. These priorities split the previous broad Protected category; manageability remains conditional on the compartment, injury extent and treatment. Vital includes major irreversible neurological or sensory disability as well as life-threatening injury. Injury in Manageable or Protected can also be serious.

Complete root assignment

Mapped descendants inherit their root assignment, with explicit permitted compartments taking precedence. Thus cutaneous melanocytes and follicles are Disposable, while bulk skin is Protected; resolved differentiated keratinocytes can be Manageable. A broad measurement never establishes the narrower compartment's restriction.

Category	Complete root list
Reproductive	Testis and male reproductive organs; ovary/oocytes and female reproductive tract; mammary; placenta; other extraembryonic; explicitly embryonic/fetal contexts, as defined above.
Disposable	Cutaneous melanocytes; hair follicles; tonsil; human appendix; gallbladder.
Manageable	Thyroid gland; adipose tissue. Mammary tissue retains Reproductive membership while its independent functional hazard is Manageable. Narrow cell rules are recorded separately in the central ontology.
Protected	Skin; spleen; thymus; salivary gland (including parotid); parathyroid gland; lymph node; esophagus; stomach; colon; rectum; urinary bladder; ureter; cartilage; oral mucosa; nasopharynx; tongue.
Vital	Heart; lung; bronchus; brain; spinal cord; liver; kidney; bone marrow; blood; adrenal gland; pituitary gland; pancreas; small intestine; skeletal muscle; smooth muscle; peripheral nerve; vascular endothelium; retina; eye; inner ear.
Unresolved	Head; foot; generic soft tissue; unrecognized, conflicting or unsited anatomy.

The current human hazard inventory records functional tiers independently of permitted membership. The historical human/dog/mouse inventories list every concept and native source mapping, its category, species applicability, policy references and review flags. A concept's anatomy citation and the project's category-policy citations are kept in separate export fields. Mapping rows and canonical concepts are not evidence of measured expression or absence.

Literature basis and limits

Bradley et al. (2020), Supplementary Table 2 provides a direct precedent for Caution versus Hazard, alongside Danger and Non-essential groups. Spleen and thyroid were Caution, esophagus and other GI tissues Hazard, and skin/adipose Non-essential in that study. Our categories are an explicit adaptation: the study does not classify thymus or cartilage for us, and its GTEx TPM values do not validate HPA nTPM thresholds.

• Skin: Protected recognizes extensive barrier-injury consequences, preserving RNA and positive-IHC exclusion gates. Only explicit cutaneous melanocyte/follicle compartments remain permitted. Local treatment evidence concerns selected manifestations, not guaranteed control of all skin-directed T-cell injury.
• Spleen: Protected recognizes persistent infection and thrombotic concerns. Long-term splenectomy cohort
• Thymus: Protected is a project inference, with an age/immune-reserve flag. Adult thymectomy was associated with mortality and cancer in an observational study; it is not evidence that thymic immune injury is locally controllable. Kooshesh et al.
• Salivary glands: Protected because secretion can remain very low after immune injury despite symptom improvement. Warner et al.
• Cartilage: Protected for persistent structural injury concerns. Mature articular collagen turnover and chronic inflammatory arthritis provide indirect support, not direct validation of antigen-specific chondrocyte targeting. Generic cartilage does not identify a joint or rule out airway cartilage; its site needs review. Heinemeier et al., Braaten et al.

The manageability review explains the distinction between functional consequences, permanence and local-control evidence. These priorities concern significant immune injury; surgical tolerance is one source of indirect evidence. They are adult-oriented research choices. Pediatric, pregnancy, modality-specific and nonhuman tolerability require separate assessment.

Conditional organ allowances and review flags

permitted_normal now contains disposable_normal (the historical narrow cutaneous scope) plus tonsil, appendix and gallbladder. reproductive_or_permitted_normal is its union with Reproductive. Scope IDs and readable aliases remain available; their versioned memberships changed in policy 2026-10-20.4. Historical reports retain previous memberships. Cached annotations must be resolved against the new taxonomy.

Context	Boundary and review condition
Tonsil	Conditional allowance, with palatine tonsillectomy as the human rationale. Native tonsil labels retain their source resolution; adenoids, all mucosal lymphoid tissue and mouse NALT are not inferred. Review age, immune reserve and expressing-cell distribution.
Appendix / gallbladder	Conditional allowance based on removal tolerance. In-situ inflammation, leakage or obstruction still requires review. Adjacent bowel, liver and bile ducts are not included.
Spleen / thymus	Protected, with positive-IHC veto and RNA ceilings. Review immune-cell distribution, age and immune reserve; spleen also carries infection-risk review.
Lymph nodes	Protected. Regional removal does not justify systemic depletion or injury to lymphatic stroma.
Blood / marrow	Vital. No general immune-lineage exception; unsited B/T-cell labels remain unresolved.

Sources: tonsillectomy decision aid, NHS appendix, NIDDK gallbladder, CDC asplenia, NCI lymph nodes.

Review conditions are machine-readable in context_reviews and returned by normal_tissue_screening_details(). Reports flag RNA >0 nTPM or positive IHC in these contexts. A review flag is not an additional numerical gate or completed clinical review. The same cell population measured elsewhere receives that site's independent classification and gates. Fetal/embryonic samples retain the requested Reproductive grouping; maternal organs are not reclassified by pregnancy.

Fixed baseline screen

Category	Maximum RNA (human HPA v23 nTPM)	IHC rule
Reproductive / Disposable	No upper ceiling	Positive staining allowed within selected scope; review flags retained
Manageable	10	Any positive staining excludes, including Low
Protected	6	Any positive staining excludes, including Low
Vital	2	Any positive staining excludes, including Low
Unresolved	No imputed allowance	Positive evidence blocks retention

RNA comparisons are inclusive, per observation, with no deflation or averaging. The complete screen combines these absolute limits with the selectivity limits below. A candidate needs valid RNA strictly >0 nTPM or positive IHC in Reproductive tissue and complete coverage of the 50 routine bulk RNA contexts. Missing/partial IHC remains explicit; 80 routine tissue/cell pairs define routine-complete IHC, not exhaustive biological coverage. Unknown anatomy, unusable measurements and reviewed-unreliable IHC block retention. Family and nomination/manual-review gates remain independent.

from oncoref.normal_tissues import (
    normal_tissue_screening_details,
    resolve_normal_tissue,
)

skin = normal_tissue_screening_details(resolve_normal_tissue("skin", species="human"))
assert skin["tissue_category"] == "protected"
cartilage = normal_tissue_screening_details(resolve_normal_tissue("cartilage", species="human"))
assert cartilage["tissue_category"] == "protected"
melanocyte = normal_tissue_screening_details(
    resolve_normal_tissue("cutaneous melanocytes", species="human")
)
assert melanocyte["tissue_category"] == "disposable"

IHC-adaptive absolute RNA ceilings

The ihc_adaptive_cta policy uses the same permitted union and anatomical tiers, with these inclusive maximum human HPA v23 nTPM values:

IHC evidence in the RNA tissue	Vital	Protected	Manageable
Missing, incomplete, uncertain or unusable	2	6	10
Approved, all routine contexts Not detected	4	8	20
Supported, all routine contexts Not detected	6	12	30
Enhanced, all routine contexts Not detected	12	24	60

Tissue-by-tissue selectivity

The same tissue's IHC evidence also selects a minimum selectivity. Both conditions must pass for every Manageable, Protected and Vital RNA observation:

Rmax = highest valid raw nTPM in a mapped Reproductive tissue for this gene
selectivity[tissue] = Rmax / (Rmax + raw nTPM[tissue])
pass[tissue] = RNA[tissue] <= ceiling AND selectivity[tissue] >= minimum

Disposable contributes neither to Rmax nor to the screened tissue set. The reference is identified in every audit row. Values remain within one species, source and version; there is no pooling of atlases or species. No tissue sums, deflation or rounding precede comparison. Missing or zero reproductive RNA makes selectivity unresolved, even if reproductive IHC supplies positive admission evidence.

IHC evidence	Vital: max nTPM / min selectivity	Protected: max nTPM / min selectivity	Manageable: max nTPM / min selectivity
Missing, uncertain, incomplete or unusable	2 / 75%	6 / 70%	10 / 65%
Approved, complete negative	4 / 70%	8 / 65%	20 / 60%
Supported, complete negative	6 / 65%	12 / 60%	30 / 55%
Enhanced, complete negative	12 / 60%	24 / 55%	60 / 50%

These percentages are pairwise expression selectivity, not percent of all RNA, protein or the body. For example, 75% requires Rmax to be at least three times that tissue's RNA. High reproductive expression cannot override the absolute ceiling or the positive-IHC veto. Adding additional sampled tissues cannot change an existing tissue's score; newly measured tissues still receive their own gates. Adding a higher reproductive observation can change Rmax, so the complete reference panel and its coverage remain part of the audit.

HPA v23 specificity definitions provide a precedent for enrichment comparisons against other tissues. The reproductive reference and both numerical grids are project definitions approved for this screen. The percentages were recalibrated for the pairwise metric after the previous 99% baseline excluded trace outside expression even below its absolute ceiling. The later update doubles every absolute ceiling, making 2 nTPM the lowest outside-tissue limit; reproductive admission and percentage limits stay unchanged. These are target-informed research settings, not validated safety limits; recovery of named targets is a calibration check, not independent validation. Category summaries use the worst margin against each tissue's own threshold; negative IHC in another tissue cannot relax a failing observation.

The earlier comparison separates the effects of >0 reproductive admission, revised selectivity, the Protected ceiling and explicit holdback reviews, and shows fixed-baseline and IHC-adaptive results. adaptive_normal_rna_limits() returns the observed selectivity, its minimum, margin, and reference alongside the absolute ceiling. Its output is an audit, not an overall pass: callers must apply both gates, the positive-IHC veto, reproductive admission, coverage and curation rules.

The routine tissue/cell inventory is independent of the candidate being assessed: the report freezes contexts measured for at least half of the source's measured genes (80 IHC tissue/cell pairs). This inventory is not exhaustive biological coverage. Every expected context for that anatomical tissue must be measured and negative; the weakest reliability among all its IHC observations determines the ceiling. Additional positive or invalid observations also prevent relaxation. Kidney RNA requires both routine glomerular and tubular IHC contexts. Stomach RNA requires both source labels, stomach 1 and stomach 2. Caudate-only IHC cannot relax broader basal-ganglia RNA. Negative staining in another organ supplies no support.

Positive IHC anywhere outside the permitted set still excludes, including Low. Complete routine RNA, positive Reproductive evidence, source resolution, and the existing family/manual-review gates still apply. Missing IHC remains a coverage limitation. The ladder is a project screening policy: HPA's Enhanced label does not establish a quantitative detection limit or absence of peptide-HLA presentation, and these numbers are not validated clinical limits.

from oncoref.cta_normal_screen import adaptive_normal_rna_limits
from oncoref.normal_tissues import normal_tissue_screening_policy

policy = normal_tissue_screening_policy("ihc_adaptive_cta")
assert policy["negative_ihc_rna_limits"]["Enhanced"] == {
    "vital": 12, "protected": 24, "manageable": 60,
}

# One gene's annotated HPA v23 observation table; an independently specified
# inventory of expected source tissue/cell pairs is required.
audit = adaptive_normal_rna_limits(
    observations,
    routine_ihc_contexts=routine_ihc_contexts,
)

The archived comparison preserves each RNA value, ceiling, supporting IHC and exclusion under the five-category policy. The historical adaptive report preserves each RNA value, ceiling, supporting IHC and exclusion. It also explains CTAG2's pinned consensus heart value of 5.1 nTPM: HPA's own cohort and the separately displayed GTEx estimates are different datasets. Current portal values do not replace the pinned release. The combined absolute/selectivity screen is separate from the older IHC-conditioned global deflated RNA fraction used by the frozen core/extended CTA panels. Numerical adaptation is currently implemented only for human HPA v23; cross-species anatomical definitions do not transfer these assay thresholds.

Dataset mappings and coverage

Mappings are keyed by taxon + source ID + source version + tissue + cell type. The original labels are always returned. Matching normalizes case and whitespace; it does not guess using substrings. Unknown labels or versions remain unresolved. A known organ can support an organ-level annotation when the cell subtype is unresolved; that mapping cannot support a narrower cell-type scope.

Data source	Mapping behavior
HPA hpa_rna_consensus, v23	Whole-organ labels, including breast, testis, ovary and placenta. Skin RNA cannot resolve follicles or melanocytes.
HPA hpa_normal_tissue, v23	Preserves tissue and cell type together. breast / glandular cells and breast / myoepithelial cells map to glandular mammary tissue; breast / adipocytes retains whole-organ context. skin 1/skin 2 with melanocytes or hair follicles map to the corresponding disposable compartment. The hair tissue's annotated epithelial compartments also map to hair follicle. endometrium 1 and endometrium 2 map to endometrium while preserving the original label.
HPA hpa_single_cell, v23	Oocytes, testicular cell types, mammary glandular cells, trophoblasts and other anatomically resolved cell labels map individually. HPA's skin-derived Melanocytes label maps to cutaneous melanocytes. Generic fibroblasts, ductal cells and other unsited cell types remain unresolved.
Canine bgee-srp009687, bgee-srp181218, Bgee 15.2	Uses the bundled curated tissue fields, including testis and ovary. Original anatomical IDs, source labels and any corrections remain in sample metadata. life cycle does not imply adult or fetal.
Canine barkbase, retrieved-2026-10-08	Native labels such as frontalcortex and kidneycortex retain their labels and map to frontal cortex and renal cortex. Explicit embryonic versus adult sample stages are preserved in annotation and tissue summaries.
Canine pfizer-dog-protein, MSV000099744-update-2026-03-23	Breast/Mammary → whole mammary tissue; Fallopian_Tube → fallopian tube; Uterus_Cervix → cervix; Uterus_Endometrium → endometrium; ovary, prostate and testis map directly. Bulk Skin does not qualify for the disposable scope.
Canine hindriks2025, 2025-05-06-publisher-version; nemec2019, 2019-article-abstract-europepmc-2026-10-13	Curated normal observation labels map at their reported resolution. Placenta qualifies directly. Tumor observations are excluded from normal-scope annotation.
Mouse	Canonical anatomical categories are available now. No native mouse expression/CTA atlas is bundled yet; no source mapping or measured coverage is fabricated.

Every CSV row cites its source. The HPA vocabulary is checked against the pinned v23 source files; HPA histology and pigment-cell documentation support the compartment distinctions. Canine source evidence and checksum receipts remain in the existing species metadata.

Species filtering excludes seminal vesicles and bulbourethral glands in dogs, consistent with comparative veterinary anatomy. Mouse reproductive anatomy follows the Jackson Laboratory anatomy resource. Anatomical transfer does not transfer evidence of expression or clinical tolerability: animal annotations explicitly report that tolerability is unvalidated.

The complete registry audit exports every canonical concept for each species and every bundled native mapping. normal_tissue_inventory(species=...) includes inapplicable anatomy explicitly; normal_tissue_mapping_inventory(species=..., source_id=..., source_version=...) reports native labels, mapping precision, citations and five-way categories. No mapping inventory for a source means not bundled, never expression absent. Species applicability is validated through every anatomical parent.

Source sex and physiological state can be supplied separately from anatomy. Unknown sex stays unknown; the grouping of mammary tissue with female reproductive anatomy never proves the donor is female. Unknown stage labels now remain unresolved instead of inheriting an adult allowance. No gestational cutoffs or ortholog expression calls are copied between species.

The patient-context gene filters evaluate actual sex/stage/source-specific detections and declared negative coverage. Their names describe expression restrictions, not pregnancy or fertility safety.

Use

from oncoref import human, canine, mouse
from oncoref.normal_tissues import classify_normal_tissue_pattern

mouse.normal_tissue_scopes()
observations = [
    mouse.resolve_normal_tissue("testis"),
    mouse.resolve_normal_tissue("mammary gland"),
]
pattern = classify_normal_tissue_pattern(observations)
assert pattern["narrowest_scopes"] == ("reproductive",)
assert pattern["absence_evidence"] == "not_assessed"

follicles = human.resolve_normal_tissue(
    "skin 1", cell_type="hair follicles",
    source_id="hpa_normal_tissue", source_version="v23",
)
assert "disposable_normal" in follicles.scopes

canine.cta_tissue_annotations(candidate_id="CTCFL")
# dataset = canine.expression.read("barkbase", offline=True)
# dataset.tissue_annotations()  # current taxonomy, indexed by original sample ID
# dataset.tissue_summary()      # groups tissue AND source stage

matching_scopes includes all ancestors, and narrowest_scopes identifies the minimal compatible scopes (more than one is possible for overlapping anatomy and stage). Testis + oocyte qualifies for the reproductive core and broader reproductive unions, but neither male-only nor female-only. Testis + skin melanocytes qualifies with the combined reproductive-or-disposable union as its narrowest scope. Testis + adult heart qualifies for none of these scopes. Empty detections never qualify vacuously; unmapped detections block a supported pattern classification.

Detection thresholds remain assay-specific. The caller supplies detected observations; no shared numerical threshold is applied to RNA, IHC or PCR. Coverage of negative observations must be assessed separately before claiming strict restriction. The cta_tissue_annotations() view explicitly applies the current taxonomy; saved CTA v1/v2 facts, roles and source values are not rewritten. Human summaries carry an explicit HPA:v23 lineage marker for source mapping; an older archive without a declared HPA version remains unresolved in this view.

Existing human CTA tables

Both HPA-derived tables are regenerated with the corrected anatomy. The extended RNA numerator now includes breast. permissive is an alias of extended in the shared taxonomy, and the legacy tier audit's two columns now agree. Thymus is counted in somatic maxima/detection counts and cannot establish reproductive protein restriction. Explicit *_and_thymus_frac summaries retain their name and meaning.

Single-organ labels now require the complete detected-tissue set to match that organ. Testis + prostate or testis + breast yields REPRODUCTIVE, not TESTIS. RNA restriction considers all detected normal tissues for either numerator scope. The synthesized label unions RNA/protein scope evidence; somatic counterevidence cannot retain a testis-only label merely by lowering confidence. These legacy labels summarize observations and are not substitutes for adequate negative tissue coverage. The richer shared scopes are available through the new API.

The core panel remains 624 genes. The extended panel is now 695 genes, gaining ABCC11, CSN2, CSN3, CST9, LALBA, ROPN1 and ROPN1B. The low-expression rescue requires positive evidence inside the selected scope, so an accessory-only trace cannot enter the core panel through an all-zero deflated denominator.

The v1.10.0 reports retain their original labels and checksums: “Manageable risk” and “High consequence” correspond to Manageable and Protected. The naming change leaves category membership, RNA ceilings and IHC gates unchanged. The new positive-evidence rule additionally requires Reproductive expression; Disposable expression alone no longer meets the admission requirement.

The current selection guide documents the active tissue/IHC ceilings and separate safety, cancer, association and restriction requirements. The 2026-10-21 curation report retains its doubled RNA ceilings, readable gene results and searchable explorer as a historical comparison. Disjoint gene and protein sets provide the separately versioned basis for subsequent k-mer subtraction.

Permissive expression-profile role

The diffuseness policy assigns adult thymus a Permissive role: exclude it from both the normal comparator and the Reproductive reference. Its RNA remains visible and it is not Disposable. This is orthogonal to its adult human Protected safety tier. Resolved thymic anatomy and descendants use this identity role across human, dog and mouse; the quantitative score is currently implemented for human HPA v23. Explicit embryonic/fetal stage retains the Reproductive umbrella. This profile role is distinct from the historical permissive alias for the extended reproductive scope.

The rationale is thymic expression of peripheral antigens during central tolerance: Projection of an Immunological Self Shadow Within the Thymus by the Aire Protein. Spleen, lymph node, tonsil and Disposable anatomy remain comparator tissues.