Current policy and IHC matching

The baseline RNA grid is Vital 4/8/16/32, Protected 8/16/32/64, Manageable 16/32/64/128 across missing, Approved-negative, Supported-negative and Enhanced-negative IHC. There is one boundary; equality passes. Above-ceiling Vital/Protected evidence is Unsafe. Manageable excess blocks CTA but does not automatically establish Other.

Reviewed TCR-T evidence can add one RNA step, capped at Enhanced: Vital 8/16/32/32, Protected 16/32/64/64, Manageable 32/64/128/128. The IHC label stays unchanged. Clinical credit carries the exact peptide/HLA/product limits and does not override normal-protein or clinical-injury exclusions. Trial and SAE review.

RNA/IHC correspondence

The matcher records exact_cell, reviewed_compartment, same_tissue_unresolved_cell, or unmatched. Its source/version-specific crosswalk is gene-independent. Exact adult tissue/cell matches and declared histological compartment matches can receive negative-IHC credit; unrelated same-tissue cells, stimulated immune cells, fetal samples and other species cannot.

The new compartment mapping relates intestinal epithelial populations to HPA glandular cells, and bronchial basal/club/ciliated cells to respiratory epithelial cells. This is an anatomical interpretation of the histological compartment, not direct proof that every rare/stem cell was observed. The source grade is retained, and the coverage limitation is explicit. Undifferentiated intestinal populations retain a progenitor caution. This assumption affects selection and requires empirical validation; a crosswalk does not improve antibody sensitivity.

HPA colon histology, HPA bronchus histology, all matched measurements.

PRAME colon undifferentiated-cell RNA is 20.3 nTPM with 96 reads. It receives the declared epithelial-compartment match to Enhanced-negative glandular IHC. Its Vital regenerative-compartment ceiling stays capped at 32. PRAME's adrenal bulk 3.6 nTPM has a missing-IHC baseline ceiling of 4, raised to 8 by the IMA203 clinical credit. Glandular-cell staining does not supply complete coverage of the specified adrenal medullary and cortical subcompartments; the clinical credit does not change that IHC finding. Low reported adrenal protein remains a positive flag, not negative evidence.

CTAG2/LAGE-1 has Enhanced-negative heart cardiomyocyte IHC and bronchial respiratory-epithelial IHC. The revised matcher applies the latter to the basal respiratory compartment; the report retains the parent-compartment coverage assumption. Negative IHC is counterevidence, not proof of clinical safety.

Anatomy and protein

Identified fibroblasts and differentiated large-bowel epithelial cells use Protected in both RNA and HPA protein assessment; crypt/undifferentiated populations use Vital. They are not called disposable. Other cell types retain their anatomical tiers; organ-level bulk is not assigned the tier of one constituent cell type. Accepted non-Low Vital/Protected protein can independently supply Unsafe evidence. Manageable protein blocks CTA only. Uncertain staining is unresolved; explicitly Low protein remains flagged under the existing policy.

Selective fibroblast depletion in mouse contexts is not evidence that all human tissue-resident fibroblasts are dispensable. Kuwabara et al. (2022). Epithelial targeting can cause severe colitis: Parkhurst et al. (2011). The tier choices describe this screening policy's tolerance assumptions, not validated toxicity predictions.

Curated developmental nominations

The current developmental inputs are Tyser gastrulation and Petropoulos preimplantation expression. Newly identified literature sources remain outside current counts: Shaw et al. (2024) reports 157 cancer-specific targets with six oncofetal annotations, including exon-specific FN1/TNC evidence; the TRIM71 liver study contains a liver oncofetal signature. Cardoso-Moreira et al. (2019) supplies developmental organ trajectories with child/adult comparisons. Their identities, feature scope and developmental/postnatal measurements require ingestion before contributing nominations or exclusion evidence.