{ "release": "1.35.0", "presentation_revision": "2026-11-08.1", "catalog_review": { "version": "2026-11-06.1", "scope": "Supplementary-table matches for two additional cancer\u2013embryonic program catalogs. These proposals are separate from the 15 nomination papers used in release 1.31.0.", "catalogs": [ { "id": "chew2019", "citation": "Chew et al., 2019", "title": "DUX4 Suppresses MHC Class I to Promote Cancer Immune Evasion and Resistance to Checkpoint Blockade", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6736738/", "catalog": "Table S3: high-confidence DUX4 targets", "model": "DUX4-induced gene program evaluated in human cancers; target definition also used induced myoblast experiments.", "sources": [ { "url": "https://ars.els-cdn.com/content/image/1-s2.0-S1534580719305295-mmc4.xlsx", "sha256": "4a176f519ae81388881b0a0c459725635774684eda0ba3b28de91c3c440cfb65" }, { "url": "https://ars.els-cdn.com/content/image/1-s2.0-S1534580719305295-mmc2.xlsx", "sha256": "b8ae23bd27e6039abb2efb4a1d987fcceabe244d4e7d77e61d9f0230d7aedd6f" } ], "matches": [ { "protein": "DUXA", "entity_id": "PEG:46851e6f1fed76681cb5", "gene_id": "ENSG00000258873", "source_symbol": "DUXA", "source_gene_id": "ENSG00000258873", "sheet": "Table S3", "row": 6, "match_method": "Ensembl ID" }, { "protein": "DUXB", "entity_id": "PEG:d7c58dfc108d629cedf9", "gene_id": "ENSG00000282757", "source_symbol": "DUXB", "source_gene_id": "DUXB", "sheet": "Table S3", "row": 7, "match_method": "Exact symbol" }, { "protein": "LEUTX", "entity_id": "PEG:a4d1a78a6bc4d94dfff5", "gene_id": "ENSG00000213921", "source_symbol": "LEUTX", "source_gene_id": "ENSG00000213921", "sheet": "Table S3", "row": 11, "match_method": "Ensembl ID" }, { "protein": "PRAMEF25/6", "entity_id": "PEG:e04fe268186dedc0faed", "gene_id": "ENSG00000229571", "source_symbol": "WI2-2994D6.2", "source_gene_id": "ENSG00000229571", "sheet": "Table S3", "row": 40, "match_method": "Ensembl ID" } ], "note": "PRAMEF25 matches the historical WI2-2994D6.2 entry by Ensembl ID and is one member of the shared PRAMEF25/6 protein. DUXB matches by symbol; its source Gene ID is also DUXB. The paper reports DUXB expression in healthy tissues.", "interpretation": "Add as a cancer\u2013embryonic program catalog, preserving each gene\u2019s normal-expression findings.", "screen_table": { "total_gene_rows": 12697, "overlapping_gene_rows": 74, "interpretation": "Table S1 is the full cancer-specificity scoring table. Its 74 matches are measured genes, not 74 CTA nominations." }, "matched_proteins": 4 }, { "id": "smith2023", "citation": "Smith et al., 2023", "title": "DUX4 expression in cancer induces a metastable early embryonic totipotent program", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10578318/", "catalog": "Table S3A: zygotic gene activation and eight-cell-like gene sets", "model": "Single-cell RNA sequencing of KLE and SUSA cancer cell lines using published zygotic gene activation and eight-cell-like gene sets.", "sources": [ { "url": "https://ars.els-cdn.com/content/image/1-s2.0-S2211124723011257-mmc4.xlsx", "sha256": "70fbf0881a6ea959d28ed96f64c78bbd8133790b51c341a362ce86cde36a0394" } ], "matches": [ { "protein": "DUXA", "entity_id": "PEG:46851e6f1fed76681cb5", "gene_id": "ENSG00000258873", "source_symbol": "DUXA", "sheet": "A", "row": 6, "column": "ZGA genes", "match_method": "Exact symbol" }, { "protein": "LEUTX", "entity_id": "PEG:a4d1a78a6bc4d94dfff5", "gene_id": "ENSG00000213921", "source_symbol": "LEUTX", "sheet": "A", "row": 9, "column": "ZGA genes", "match_method": "Exact symbol" }, { "protein": "TAF11L12", "entity_id": "PEG:fdd7f0c5ad8fcef88b57", "gene_id": "ENSG00000249156", "source_symbol": "TAF11L12", "sheet": "A", "row": 20, "column": "ZGA genes", "match_method": "Exact symbol" }, { "protein": "MBD3L2B", "entity_id": "PEG:c5ea92999c5095d9ede4", "gene_id": "ENSG00000196589", "source_symbol": "MBD3L2B", "sheet": "A", "row": 9, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "OR10G3", "entity_id": "PEG:4e6ed0a98e0f954e4366", "gene_id": "ENSG00000169208", "source_symbol": "OR10G3", "sheet": "A", "row": 157, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "LEUTX", "entity_id": "PEG:a4d1a78a6bc4d94dfff5", "gene_id": "ENSG00000213921", "source_symbol": "LEUTX", "sheet": "A", "row": 186, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "ZNF280A", "entity_id": "PEG:71fe1f30ebae17ffbd03", "gene_id": "ENSG00000169548", "source_symbol": "ZNF280A", "sheet": "A", "row": 301, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "ZNF878", "entity_id": "PEG:f9a42776af304f6808d7", "gene_id": "ENSG00000257446", "source_symbol": "ZNF878", "sheet": "A", "row": 421, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "DUXA", "entity_id": "PEG:46851e6f1fed76681cb5", "gene_id": "ENSG00000258873", "source_symbol": "DUXA", "sheet": "A", "row": 494, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "C19orf85", "entity_id": "PEG:239b064b509fe82b6379", "gene_id": "ENSG00000283567", "source_symbol": "C19orf85", "sheet": "A", "row": 573, "column": "8C genes", "match_method": "Exact symbol" }, { "protein": "CPHXL", "entity_id": "PEG:8379cf8330d2c11fd9d7", "gene_id": "ENSG00000283755", "source_symbol": "CPHXL", "sheet": "A", "row": 659, "column": "8C genes", "match_method": "Exact symbol" } ], "note": "Exact gene-symbol matches to the 122. Membership records the program evaluated in cancer cells; gene-level measurements and effect sizes need separate extraction. MBD3L2 is not substituted for MBD3L2B, and H3Y is not mapped to H3Y1 in this count.", "interpretation": "Add as an early-embryo program evaluated in cancer, with the original gene-set source retained.", "matched_proteins": 9, "gene_set_source": { "citation": "Taubenschmid-Stowers et al., 2022", "title": "8C-like cells capture the human zygotic genome activation program in vitro", "url": "https://pubmed.ncbi.nlm.nih.gov/35216671/" } } ] }, "publication_funnel": [ { "source_id": "10.18632/oncotarget.21715", "citation": "da Silva et al. (2017)", "source_url": "https://doi.org/10.18632/oncotarget.21715", "evidence_scope": "At least 90% normal-tissue RNA attributable to testis; tumor positivity not required; Gene-labelled tumor proteomics; unique-locus peptide assignment is not established; RSEM >1 in at least 10% of samples in a tumor type; RNA nomination", "source_kind": "paper", "Inventory": 1017, "Normal safety + coverage": 512, "Cancer presence": 512, "Reproductive/developmental presence": 432, "Reproductive concentration": 432, "Translation qualification": 427, "Unsafe sequence containment": 418, "Final Unsafe": 466, "Final Other": 133 }, { "source_id": "10.1038/ncomms10499", "citation": "Wang et al. (2016)", "source_url": "https://doi.org/10.1038/ncomms10499", "evidence_scope": "Cancer-associated RNA nomination; no antigen validation asserted", "source_kind": "paper", "Inventory": 988, "Normal safety + coverage": 292, "Cancer presence": 292, "Reproductive/developmental presence": 279, "Reproductive concentration": 279, "Translation qualification": 276, "Unsafe sequence containment": 274, "Final Unsafe": 683, "Final Other": 31 }, { "source_id": "10.1002/cam4.2223", "citation": "Chang et al. (2019)", "source_url": "https://doi.org/10.1002/cam4.2223", "evidence_scope": "Testis-specific coding gene expressed in at least 1% of TGCT; no broad somatic-cancer claim", "source_kind": "paper", "Inventory": 985, "Normal safety + coverage": 292, "Cancer presence": 292, "Reproductive/developmental presence": 289, "Reproductive concentration": 289, "Translation qualification": 287, "Unsafe sequence containment": 287, "Final Unsafe": 676, "Final Other": 22 }, { "source_id": "10.1038/s41467-021-22695-y", "citation": "Gong et al. (2021)", "source_url": "https://doi.org/10.1038/s41467-021-22695-y", "evidence_scope": "Normal reproductive-tissue enrichment; no tumor validation; Placental RNA enrichment; no tumor-antigen validation", "source_kind": "paper", "Inventory": 729, "Normal safety + coverage": 370, "Cancer presence": 370, "Reproductive/developmental presence": 357, "Reproductive concentration": 356, "Translation qualification": 354, "Unsafe sequence containment": 351, "Final Unsafe": 343, "Final Other": 35 }, { "source_id": "10.1038/s41388-018-0357-2", "citation": "Bruggeman et al. (2018)", "source_url": "https://doi.org/10.1038/s41388-018-0357-2", "evidence_scope": "GC RNA nomination across cancer types; no antigen validation asserted; GC RNA nomination; inclusion depends on TGCT under this study's thresholds", "source_kind": "paper", "Inventory": 692, "Normal safety + coverage": 12, "Cancer presence": 12, "Reproductive/developmental presence": 12, "Reproductive concentration": 12, "Translation qualification": 12, "Unsafe sequence containment": 12, "Final Unsafe": 679, "Final Other": 1 }, { "source_id": "10.1002/1878-0261.12900", "citation": "Jamin et al. (2021)", "source_url": "https://doi.org/10.1002/1878-0261.12900", "evidence_scope": "CT-pattern microarray nomination; tumor upregulation with no corresponding normal-tissue detection; Core CT annotation; underlying microarray probes may recognize several loci", "source_kind": "paper", "Inventory": 469, "Normal safety + coverage": 39, "Cancer presence": 39, "Reproductive/developmental presence": 38, "Reproductive concentration": 38, "Translation qualification": 37, "Unsafe sequence containment": 34, "Final Unsafe": 429, "Final Other": 6 }, { "source_id": "10.1371/journal.pgen.1011734", "citation": "Loriot et al. (2025)", "source_url": "https://doi.org/10.1371/journal.pgen.1011734", "evidence_scope": "Cancer-germline RNA nomination; strict and preferential classes remain distinct", "source_kind": "paper", "Inventory": 202, "Normal safety + coverage": 86, "Cancer presence": 86, "Reproductive/developmental presence": 86, "Reproductive concentration": 86, "Translation qualification": 84, "Unsafe sequence containment": 83, "Final Unsafe": 113, "Final Other": 6 }, { "source_id": "10.1136/jitc-2023-007935", "citation": "Carter et al. (2023)", "source_url": "https://doi.org/10.1136/jitc-2023-007935", "evidence_scope": "Final CT-expression set without detectable thymic expression; functional vaccination evidence is not assigned to every gene", "source_kind": "paper", "Inventory": 103, "Normal safety + coverage": 54, "Cancer presence": 54, "Reproductive/developmental presence": 54, "Reproductive concentration": 54, "Translation qualification": 54, "Unsafe sequence containment": 54, "Final Unsafe": 47, "Final Other": 2 }, { "source_id": "10.1371/journal.pone.0144155", "citation": "Hirbo et al. (2015)", "source_url": "https://doi.org/10.1371/journal.pone.0144155", "evidence_scope": "HPA v13 placenta-enriched nominations; 30/86 fast-evolving subset retained as metadata; not tumor validation", "source_kind": "paper", "Inventory": 78, "Normal safety + coverage": 10, "Cancer presence": 10, "Reproductive/developmental presence": 10, "Reproductive concentration": 10, "Translation qualification": 10, "Unsafe sequence containment": 8, "Final Unsafe": 67, "Final Other": 3 }, { "source_id": "10.1186/s12967-024-04918-0", "citation": "Seager et al. (2024)", "source_url": "https://doi.org/10.1186/s12967-024-04918-0", "evidence_scope": "Member of the published 17-target CTA profiling panel; includes differentiation antigen MLANA", "source_kind": "paper", "Inventory": 15, "Normal safety + coverage": 11, "Cancer presence": 11, "Reproductive/developmental presence": 11, "Reproductive concentration": 11, "Translation qualification": 11, "Unsafe sequence containment": 11, "Final Unsafe": 3, "Final Other": 1 }, { "source_id": "10.4161/cbt.12.3.16260", "citation": "Sasaroli et al. (2011)", "source_url": "https://doi.org/10.4161/cbt.12.3.16260", "evidence_scope": "Tumor-vascular candidate list; includes secreted and transmembrane proteins; not a CTA-restricted list", "source_kind": "paper", "Inventory": 13, "Normal safety + coverage": 0, "Cancer presence": 0, "Reproductive/developmental presence": 0, "Reproductive concentration": 0, "Translation qualification": 0, "Unsafe sequence containment": 0, "Final Unsafe": 13, "Final Other": 0 }, { "source_id": "10.1038/s41467-020-19141-w", "citation": "Bradley et al. (2020)", "source_url": "https://doi.org/10.1038/s41467-020-19141-w", "evidence_scope": "CPA expression nominations; HLA peptide and antigen-specific T-cell validation for VGLL1", "source_kind": "paper", "Inventory": 9, "Normal safety + coverage": 0, "Cancer presence": 0, "Reproductive/developmental presence": 0, "Reproductive concentration": 0, "Translation qualification": 0, "Unsafe sequence containment": 0, "Final Unsafe": 9, "Final Other": 0 }, { "source_id": "10.1158/1078-0432.CCR-06-2340", "citation": "Garg et al. (2007)", "source_url": "https://doi.org/10.1158/1078-0432.CCR-06-2340", "evidence_scope": "Ovarian-cancer RNA/protein expression and patient antibody responses; no HLA presentation or T-cell validation claimed", "source_kind": "paper", "Inventory": 5, "Normal safety + coverage": 3, "Cancer presence": 3, "Reproductive/developmental presence": 3, "Reproductive concentration": 3, "Translation qualification": 3, "Unsafe sequence containment": 3, "Final Unsafe": 2, "Final Other": 0 }, { "source_id": "10.1016/s1074-7613(95)80053-0", "citation": "Bo\u00ebl et al. (1995)", "source_url": "https://doi.org/10.1016/s1074-7613(95)80053-0", "evidence_scope": "Original BAGE tumor-antigen nomination and autologous CTL recognition; contemporary paralog resolution is not inferred", "source_kind": "paper", "Inventory": 2, "Normal safety + coverage": 1, "Cancer presence": 1, "Reproductive/developmental presence": 1, "Reproductive concentration": 1, "Translation qualification": 1, "Unsafe sequence containment": 1, "Final Unsafe": 1, "Final Other": 0 }, { "source_id": "10.1158/0008-5472.CAN-16-0225", "citation": "Bai et al. (2016)", "source_url": "https://doi.org/10.1158/0008-5472.CAN-16-0225", "evidence_scope": "Ovarian-tumor and vascular expression/function; no normal-tissue exclusivity claim", "source_kind": "paper", "Inventory": 1, "Normal safety + coverage": 0, "Cancer presence": 0, "Reproductive/developmental presence": 0, "Reproductive concentration": 0, "Translation qualification": 0, "Unsafe sequence containment": 0, "Final Unsafe": 1, "Final Other": 0 }, { "source_id": "registered_union", "citation": "Registered-paper union", "source_url": "", "evidence_scope": "Unique proteins across all registered nomination papers", "source_kind": "union", "Inventory": 2514, "Normal safety + coverage": 592, "Cancer presence": 592, "Reproductive/developmental presence": 505, "Reproductive concentration": 504, "Translation qualification": 497, "Unsafe sequence containment": 487, "Final Unsafe": 1876, "Final Other": 151 }, { "source_id": "unannotated", "citation": "No registered-paper annotation", "source_url": "", "evidence_scope": "No membership in the current nomination registry; not a claim of novelty", "source_kind": "unannotated", "Inventory": 17379, "Normal safety + coverage": 526, "Cancer presence": 525, "Reproductive/developmental presence": 141, "Reproductive concentration": 138, "Translation qualification": 125, "Unsafe sequence containment": 120, "Final Unsafe": 16383, "Final Other": 876 }, { "source_id": "inventory", "citation": "Complete inventory", "source_url": "", "evidence_scope": "Every classified candidate protein record", "source_kind": "inventory", "Inventory": 19893, "Normal safety + coverage": 1118, "Cancer presence": 1117, "Reproductive/developmental presence": 646, "Reproductive concentration": 642, "Translation qualification": 622, "Unsafe sequence containment": 607, "Final Unsafe": 18259, "Final Other": 1027 } ], "out_of_universe_reasons": {}, "translation_support_reasons": { "nmd_or_cds_not_defined_only": 285, "single_study_ribo_seq": 10 }, "contract": { "schema": "oncoref.cta-decision-contract", "schema_version": 1, "contract_id": "oncoref.cta-decision-contract.2026-11-05.1", "role_policy_id": "oncoref.sequence-roles.2026-11-04.1", "title": "CTA and oncofetal candidate selection", "definition": "An OncoRef CTA candidate is a reference-resolved protein with supported cancer expression and qualifying reproductive or developmental association that passes the named normal-tissue evidence, coverage and selection rules. CTA admission requires qualifying coding annotation or supported ncORF evidence and a complete, approved MANE Select or Ensembl canonical representative, with any conflicting coding evidence resolved. Every input record is assessed, including those with insufficient translation support.", "categories": { "CTA": "Candidate under the named policy; not presentation or clinical clearance", "Unsafe": "Normal-tissue or applicable clinical evidence establishes policy exclusion", "Other": "Not admitted; inspect every reason and assessment status" }, "assessment_states": { "screened": "Declared assessment completed; not exhaustive biological coverage", "incomplete_evidence": "Required coverage or evidence resolution is incomplete", "normal_evidence_hold": "Normal evidence requires review without establishing exclusion", "translation_review": "Incomplete annotation, uncertain translation or unresolved representative-protein evidence", "unassessed": "No applicable selection policy or no completed assessment" }, "interpretation_states": { "accepted": "The specified observation is supported within its recorded scope", "unresolved": "A material identity, assay, context or interpretation question remains", "rejected": "The claimed observation is not supported; retain the rationale and source" }, "interpretation_note": "Review completion, interpretation and policy effect are separate. A completed review may retain unresolved evidence; a rejected claim is not proof of absence.", "support_routes": [ "testicular", "other_reproductive", "placental", "embryonic_fetal" ], "support_route_note": "Routes may overlap; a developmental route is not adult testis restriction", "sequence_roles": { "exclude": "Retain applicable exclusion evidence; it takes precedence across occurrences", "review": "Evidence, identity, coverage or sequence qualification needs resolution", "allow": "No exclusion from this assessed record under the named policy" }, "role_precedence": [ "exclude", "review", "allow" ], "role_scope": "selected_representative_protein", "translation_scope": "This decision interface does not qualify every translation or isoform", "consumer_scope": "Use explicitly qualified records as a reference for exact subtraction or approximate near-self screening. Preserve every source occurrence and coverage gap. Patient-HLA prediction, similarity cutoffs and intervention rules are downstream policy; exact matching does not validate approximate matching.", "prohibited_shortcuts": [ "Blanket exemption of historical CTA nominations from normal-reference evidence", "A second legacy IHC filter that silently drops exclusions from other evidence", "Interpreting Other, absent records or unmeasured panels as negative normal evidence", "Transfer of human numerical rules to another species by symbol or orthology" ], "taxon_id": 9606, "species": "human", "selection_policy_id": "oncoref.cta-selection.2026-11-08.1", "selection_status": "available", "reference_id": "openvax:reference:v1:sha256:ba6f6186a301a3ef9217ea0199ec3b851f9da2eb43558b7ba7e0d6fcd9cd85e9" }, "coverage": { "taxon_id": 9606, "species": "human", "selection_status": "available", "evidence_status": "partial", "policy_id": "oncoref.cta-selection.2026-11-08.1", "universe": "19893 classified protein-equivalence groups from 19893 input groups", "universe_counts": { "counting_unit": "selected_reference_protein_equivalence_group", "input_groups": 19893, "classified_groups": 19893, "out_of_universe_groups": 0, "input_gene_loci": 20099, "classified_gene_loci": 20099, "out_of_universe_gene_loci": 0, "gene_count_note": "Gene sets can overlap; only disjoint protein-group counts add", "translation_support_eligible_groups": 19598, "translation_support_insufficient_groups": 295, "scope_note": "Every candidate record enters classification; translation support is a CTA admission requirement, not an inventory exclusion." }, "reference": { "annotation_release": "115", "annotation_source": "Ensembl", "assembly_accession": "GCA_000001405.29", "content_provenance": { "gtf": "02df5a2a8c7a41e513209e0780c56cf197941b6b35ef8bab3e9a6317eecd17ef", "ncrna": "7825db09257902df82172928537c1da16cfe79edcca56425556f74f1507437a0", "protein": "7991ab37d09986eefdb5c77032b15370ab0e99918b78f235f3230c0302851c96", "rna": "93af088ed22a46daa9645fc6292fb120c1e4ffe791d24abbcbd35062666c03f1" }, "identifier_namespaces": { "gene": "Ensembl gene", "protein": "Ensembl protein", "transcript": "Ensembl transcript" }, "reference_id": "openvax:reference:v1:sha256:ba6f6186a301a3ef9217ea0199ec3b851f9da2eb43558b7ba7e0d6fcd9cd85e9", "schema": "openvax.reference", "schema_version": 1, "source_version": "Ensembl-115", "taxon_id": 9606 }, "limitations": [ "Research prioritization calibrated using PRAME; no clinical safety or pediatric validation", "Developmental coverage is stage-limited; gastrulation and preimplantation measurements do not cover later fetal/postnatal development", "Native RNA units remain separate and nominal thresholds lack assay-specific toxicity calibration", "Low normal protein is a tolerated flag; author descriptions and HPA categories retain different scales", "Representative-protein equivalence is not exhaustive isoform identity", "Reviewed TCR-T experience supplies at most one RNA ladder step; tested peptide/HLA/product limits apply and clinical or protein exclusions remain independent", "HPA diffuseness applies only to complete adult/placental profiles; developmental concentration is unassessed without a comparable panel", "Other includes assessed noncandidates and held/incomplete cases. Subtype does not establish evidence completeness or sequence allowance.", "Rare-cell screening uses the existing brain, spinal-cord, heart and selected lung CELLxGENE panels. At least 1% detection in a Vital population supplies exclusion evidence; Protected detection supplies a review hold. Detection frequency is not abundance. Unmeasured ages, organs and excluded lineages remain coverage limits, not allowances.", "Indirect reproductive-cell association can reflect passenger or ambient RNA; it establishes sample-site association, not the producing cell. All normal and concentration gates still apply." ], "entities": 19893, "counts": { "CTA": 607, "Unsafe": 18259, "Other": 1027, "Unassigned": 0 }, "other_subtypes": { "Nonreproductive": 573, "Translation": 380, "Nested": 28, "Held": 27, "Contained": 15, "Diffuse": 4 }, "evidence_categories": { "nomination": { "used_sources": 0, "available_sources": 22, "identified_sources": 22 }, "reproductive_expression": { "used_sources": 5, "available_sources": 5, "identified_sources": 5 }, "developmental_expression": { "used_sources": 2, "available_sources": 2, "identified_sources": 2 }, "tumor_expression": { "used_sources": 2, "available_sources": 2, "identified_sources": 2 }, "normal_bulk_rna": { "used_sources": 3, "available_sources": 3, "identified_sources": 3 }, "normal_cell_rna": { "used_sources": 7, "available_sources": 7, "identified_sources": 7 }, "immune_rna": { "used_sources": 3, "available_sources": 3, "identified_sources": 3 }, "normal_protein": { "used_sources": 4, "available_sources": 4, "identified_sources": 4 }, "clinical_safety": { "used_sources": 14, "available_sources": 14, "identified_sources": 14 }, "translation_evidence": { "used_sources": 2, "available_sources": 2, "identified_sources": 2 } } }, "counts": { "Unsafe": 18259, "Other": 1027, "CTA": 607 }, "inventory_audit": { "policy_id": "oncoref.cta-selection.2026-11-08.1", "input_records": 19893, "counts": { "Unsafe": 18259, "Other": 1027, "CTA": 607 }, "restored_records": 260, "restored_classifications": { "Other:Translation": 248, "Unsafe": 12 }, "existing_classification_changes": 452, "restored_historical_exclusions_reassessed": [ { "protein_group_label": "P2RX5-TAX1BP3", "historical_pre_diffuseness_Unsafe_reasons": "DICE immune", "classification": "Other:Translation" }, { "protein_group_label": "ENSG00000258461", "historical_pre_diffuseness_Unsafe_reasons": "DICE immune", "classification": "Other:Translation" } ], "stored_zero_rna_screen": { "cancer_present_required_bulk_complete": 19341, "adult_and_reproductive_bulk_zero": 40, "also_developmental_measured": 22, "developmental_measurement_missing": 18, "also_developmental_zero": 0, "also_no_recorded_adult_protein": 0, "interpretation": "Stored RNA summary values equal zero; no claim of whole-protein absence or exhaustive normal-cell coverage." }, "preliminary_expression_profile": { "matches": 66, "classification_counts": { "Other:Nonreproductive": 55, "Unsafe": 6, "Other:Translation": 5 }, "disposition_counts": { "normal_coverage_review_required": 40, "normal_evidence_hold": 15, "excluded_by_normal_evidence": 6, "translation_review": 5 }, "interpretation": "Existing numerical screen: replicated tumor RNA at least 10 TPM in two samples (or reviewed tumor protein), measured adult RNA below nominal 2-unit assay floors, no positive adult protein call in the profile's measurement inputs, measured developmental lineage means below 2 TPM, and no qualifying reproductive/developmental association. Curated knowledge and rare-cell counterevidence is assessed separately and overrides the screen." }, "limitations": [ "Required bulk coverage does not establish coverage of every cell type, age, physiological state or protein assay.", "Routine tissue summaries and developmental lineage means are not maxima across all donors or individual cells.", "Small positive developmental RNA values can reflect assay/mapping uncertainty; stored-zero screening is not a biological detection limit.", "Missing measurements are reported as gaps, never imputed to zero.", "No numerical RNA profile establishes translation, HLA presentation, receptor specificity or clinical safety." ] }, "sections": [ [ "What OncoRef calls a CTA", [ "An OncoRef CTA candidate is a reference-resolved protein with supported cancer expression and qualifying reproductive or developmental association that passes the named normal-tissue evidence, coverage and selection rules. CTA admission requires qualifying coding annotation or supported ncORF evidence and a complete, approved MANE Select or Ensembl canonical representative, with any conflicting coding evidence resolved. Every input record is assessed, including those with insufficient translation support.", "The current human policy produces 607 CTA, 18,259 Unsafe and 1,027 Other proteins. It evaluates 19,893 candidate proteins in the complete inventory, counting identical selected reference sequences together and retaining every member locus. Splice isoforms and post-translational modifications are outside this inventory.", "CTA admission combines cancer expression, reproductive or developmental association, translation qualification and normal-tissue assessment. The biological categories identify the tissue, cell population or developmental program associated with each protein." ], "universe-accounting" ], [ "From candidates to CTAs", [ "All 19,893 candidate records enter the same normal-evidence and admission path. The 295 records formerly removed at entry stay visible: 285 have only NMD/CDS-not-defined reference transcripts and 10 have only single-study Ribo-seq support. Translation support is assessed at CTA admission.", "CTA admission requires qualifying translation support and the separately qualified exact reference record. Applicable normal exclusion takes precedence and establishes Unsafe; otherwise insufficient translation qualification yields Other:Translation and sequence review. The translation rule accepts qualifying coding annotation and supported noncanonical ORFs.", "Apply all normal-tissue evidence independently. Accepted exclusion evidence establishes Unsafe. Unresolved findings or missing required coverage prevent admission and require review; they do not establish Unsafe. Every target must also pass reproductive/developmental association, cancer presence, concentration, translation qualification and sequence-containment rules.", "The chart uses cumulative counts. Of 1,118 proteins passing normal assessment, cancer presence retains 1,117; reproductive/developmental presence then narrows these to 646. The previous order showed 645 at both gates because every reproductive/developmental survivor already met cancer presence. One compatible positive tumor RNA sample or reviewed tumor protein makes cancer presence a broad gate, not an abundance or prevalence requirement.", "Every applicable evidence layer is still evaluated, including after an early exclusion. Unsafe takes precedence. Display order changes neither final classifications nor the priority used to assign Other subtypes." ], "admission-flow" ], [ "Published nominations through the funnel", [ "All 15 registered nomination papers appear in the companion funnel. Their union contains 2,514 proteins: 487 finish as CTA, 1,876 as Unsafe and 151 as Other. A protein can occur in several papers, so individual paper rows must not be summed.", "The 17,379 candidates without a registered-paper annotation undergo the same assessment and contribute 120 CTAs. Prior nomination is recorded separately from the admission gates. The evidence guide identifies additional publications for proteins outside this registry.", "A publication's measured evidence can support reproductive/developmental association, tumor expression, translation or normal-tissue counterevidence when it meets the corresponding evidence rule. A list label alone does not establish those facts. Germ-cell, testis-biased, placental and tumor-vascular lists retain their original scope alongside CTA nominations." ], "publication-funnel" ], [ "Biological categories in the historical 602-CTA snapshot", [ "The historical 1.31.0 literature tables categorize 602 CTAs by early embryo, oocyte and maternal function, reproductive secretion, testis and male germ cells, placenta and trophoblast, and gastrulation. A protein can belong to several categories. Current reference choices and coding holds are listed in the transcript-selection report.", "Each tag links to a publication or a supported RNA observation. The detail view records the species, tissue, cell population or developmental stage. Biological categories are separate from the admission route and the CTA, Unsafe or Other classification.", "Reproductive secretion currently has four manually annotated proteins: PATE1, WFDC8, RNASE9 and SEMG2. This count reflects the focused literature review; the other CTAs have not been systematically checked against reproductive-secretion catalogs." ], null ], [ "Normal-tissue consequences and expression evidence", [ "Vital, Protected, Manageable and Disposable describe the consequence and tolerability of injury to a specified tissue/cell compartment. Assignments use immediate function, repair capacity, persistent injury, anatomy and inflammatory effects.", "The central registry distinguishes 39 bulk tissues and 68 cell populations, with source-linked rationale. A cell-level exception requires resolved tissue and cell identity. An unresolved or mixed label cannot earn a narrower allowance; reproductive/developmental membership is a separate anatomical axis.", "The evidence records distinguish RNA, surface protein, peptide-HLA presentation, receptor recognition and tissue injury. Missing measurements and measured zeros have separate values." ], null ], [ "Evidence has multiple independent meanings", [ "Checks complete (screened) means the release's required assessment is complete. It describes completion, so CTA, Unsafe and Other proteins can all have this status. No sequence exclusion (allow) means the selected protein has a resolved identity, completed assessment and no Unsafe assignment. This can apply to CTA or Other; CTA admission has additional requirements. These labels describe the released checks, not every tissue, isoform or later publication.", "Review completion, interpretation and policy effect are separate. A completed review can retain an unresolved interpretation. A rejected protein claim remains visible with its rationale; rejecting that claim does not prove normal-tissue absence.", "All 196 historical findings have linked current dispositions. MAGEC2, LGALS13 and PLCZ1 retain material holds. Each record lists the source, reagent, tissue, developmental stage and unresolved question.", "Fatal neurological injury in the MAGE-A3-reactive TCR cohort remains product-specific evidence. The MAGEA12 and EPS8L2 explanations are both retained as unresolved. MAGEA12 remains Unsafe under an independent rare-cell finding. Neither receptor causality nor favorable clinical credit transfers across a gene family." ], "independent-evidence" ], [ "Translation, identity and downstream sequence use", [ "Translation qualification asks whether the exact selected primary-locus record supports target sequence use. Complete coding annotation, start/stop codons, biotype and sequence integrity are assessed separately from normal-tissue hazard. Qualification applies to the selected primary-locus record.", "The verified bundle retains original sequences, every source occurrence, qualification reasons and coverage gaps. It supplies contiguous AA20 segments with original coordinates and never joins across ambiguity, internal stops or different records. Selenocysteine-containing records require review under the AA20 sequence contract.", "Across occurrences, exclude takes precedence over review, then allow. Unsafe sequence remains exclusion evidence even in an incomplete record. Allow means no exclusion from the assessed record under this policy. Exact matching does not validate an approximate similarity cutoff or patient-HLA decision. The historical Unsafe plus additional-forbidden assets retain their older policy identity." ], "category-role-matrix" ], [ "Research parameters and coverage limits", [ "Without usable matching protein staining, the upper RNA limits start at 4 for Vital, 8 for Protected and 16 for Manageable tissues, in the source's own TPM or nTPM units. Approved, Supported and Enhanced negative IHC respectively multiply the starting limit by 2, 4 and 8. Reviewed product-specific clinical evidence can add one doubling within the same cap. A value must be above the limit to trigger this RNA rule. Corneal CP10K uses separate limits. These screening thresholds are set by OncoRef policy.", "Cancer presence requires one compatible tumor sample above zero or reviewed tumor protein. Reproductive RNA uses a 5-unit criterion with assay-specific support requirements; reliable reproductive IHC and reviewed protein provide separate routes. Adult/placental diffuseness above 10% can block identity, never establish Unsafe.", "The rare-cell panel uses a 1% detection screen with cell-support rules. Detection frequency is not abundance. Coverage is limited by sampled organs, donor age, activation states, paralog mapping and assay resolution. Optional panels remain disclosed when missing. A 95% Unsafe 9-mer overlap blocks practical candidate admission, but is not a clinical cross-reactivity validation.", "The complete gate table below retains the actual executable rules and source IDs. Human thresholds are not transferred to dog or mouse; their native nominations remain unassessed until supported by a species-specific policy." ], null ], [ "Does CTA mean expressed only in cancer?", [ "No. CTA admission requires cancer expression plus qualifying reproductive or developmental association. The CTA total is not a count of proteins absent from all normal tissues, including testis, placenta, embryo and fetus. Passing normal-tissue thresholds is not a claim of zero normal expression.", "The current data do support an observed-expression count: 40 cancer-expressed records have complete required bulk coverage and zero stored adult/reproductive RNA summaries. Of these, 22 have developmental measurements and 0 also have zero developmental RNA; 18 lack developmental measurements. Stored zeros are not proof of absent protein, and tiny positive RNA values are not validated protein production.", "The separate low-expression screen finds 66 preliminary matches. Independent normal-cell evidence excludes 6 of them. A numerical profile match is not a final cancer-only designation; remaining matches retain explicit review or coverage requirements. The inventory audit lists every record, counterevidence source and measurement gap.", "Cancer-specific altered sequences and peptides require a separate analysis from these reference-protein counts. A mutation, fusion or alternative transcript can create a target sequence even when the source gene is normally expressed; evidence for one such sequence cannot establish exclusivity of every product of the gene." ], null ], [ "Reproduction and version changes", [ "Selection policy: oncoref.cta-selection.2026-11-08.1. Role policy: oncoref.sequence-roles.2026-11-04.1. Translation policy: oncoref.translation-qualification.2026-11-04.1.", "The 1.29.0 comparison remains pinned. The evidence and translation PRs also retain adjacent baselines, separating changes in category, subtype, role, assessment status and reasons. Counts are recalculated from the evidence and rules.", "Use the public decision, finding and sequence APIs. The final release receipt binds the decision exports, ontology, curation, qualification, bundle and generated figures. Complete and cached scientific replays must be byte-identical. Historical reports keep their original inputs and policies.", "Release 1.35.0 applies MANE-first reference selection, coding-evidence review and recomputed protein identities. Its classifications and sequence roles use the current policy. The 602-protein literature analysis remains a labelled 1.31.0 snapshot." ], null ] ], "worked": [ { "label": "PRAME", "entity_id": "PEG:92c0ae3f131964f8a71d", "classification": "CTA", "assessment_status": "screened", "sequence_role": "allow", "reasons": [], "translation_qualified": true, "translation_reasons": "", "findings": [ { "id": "GK-migration-ihc-20261025-ENSG00000185686", "effect": "context", "interpretation_status": "unresolved", "finding": "Only Low raw normal annotations remain; faint intensity alone is not evidence that staining is nonspecific. The curated negative profile and passing RNA screen do not identify the molecule responsible for these raw stains. This evidence does not establish clinical toxicity, but is insufficient to clear unrestricted gene-level targeting. A separate gene-resolved publication reports adrenal-cortical protein; that accepted finding takes precedence and makes the final gene category Unsafe.", "decision_reason": "The historical blanket primary-stain hold is superseded by the current HPA level/reliability and compartment rules, including prior reagent eligibility. Original raw staining and unresolved specificity remain visible; this policy revision is not new validation of the reagent or evidence of absence. No second historical IHC veto is applied.", "source_title": "HPA v23 primary IHC; repeated family profiles are not independent studies", "source_url": "https://v23.proteinatlas.org/ENSG00000185686-PRAME/tissue/primary+data", "limitations": "Reliable gene-profile labels do not validate each raw stain. RNA/protein donors are unpaired. Retain observed intensities and identity ambiguity; the decision is a conservative research hold.", "review_depth": "All mapped positive rows, profile notes and reagent summaries reviewed; no independent histology re-read or new experiment" }, { "id": "GK-migration-review-20261025-PRAME-adrenal", "effect": "context", "interpretation_status": "accepted", "finding": "A characterized monoclonal IHC study reports normal adrenal-cortical PRAME. A later panel using different reagents was negative in adrenal; that does not falsify the positive observation or establish absence across donors. Exclude unrestricted gene targeting under the same positive-normal-protein rule used for other genes.", "decision_reason": "Reported Low intensity remains a flag without an automatic protein veto under the current policy; retain the observation and source-specific limitations.", "source_title": "33890816; 35973038", "source_url": "https://pubmed.ncbi.nlm.nih.gov/33890816/", "limitations": "Full 2021 methods unavailable; abstract-level conservative acceptance, not proven therapeutic injury. IMA203 evidence concerns a selected peptide/HLA/TCR product and is preserved separately.", "review_depth": "Primary 2021 abstract; 2022 normal-tissue methods/results inspected via primary article search excerpts" } ] }, { "label": "MAGEC2", "entity_id": "PEG:f53f189c7f70e6ff446c", "classification": "Other:Held", "assessment_status": "normal_evidence_hold", "sequence_role": "review", "reasons": [ "Reviewed normal-cell knowledge" ], "translation_qualified": true, "translation_reasons": "", "findings": [ { "id": "GK-migration-review-20261025-MAGEC2", "effect": "review", "interpretation_status": "unresolved", "finding": "The original HCA587 study reports cerebellar Purkinje-cell staining with the TC-1 polyclonal reagent, conflicting with the current curated negative normal profile.", "decision_reason": "Material normal-tissue finding remains unresolved; block CTA admission and require sequence review without establishing Unsafe. Negative bulk profiles do not resolve assay identity.", "source_title": "HCA587 antigen expression in normal tissues and cancers: correlation with tumor differentiation in hepatocellular carcinoma", "source_url": "https://pubmed.ncbi.nlm.nih.gov/12920247/", "limitations": "Abstract does not settle reagent specificity; no demonstrated target-mediated clinical injury. A neural protein conflict warrants a hold, but the historical antibody result does not establish target-mediated clinical injury or resolve MAGE-family cross-reactivity.", "review_depth": "Primary abstract rechecked; publisher full text unavailable in this review. Original tissue and antibody controls remain unverified." } ] }, { "label": "LGALS13", "entity_id": "PEG:f9176091f8e56c67481e", "classification": "Other:Held", "assessment_status": "normal_evidence_hold", "sequence_role": "review", "reasons": [ "Reviewed normal-cell knowledge" ], "translation_qualified": true, "translation_reasons": "", "findings": [ { "id": "GK-migration-review-20261025-LGALS13", "effect": "review", "interpretation_status": "unresolved", "finding": "The 1999 abstract reports extra-placental immunoreactivity in a fetal/adult survey but placental-only Northern detection. The 2009 placental-galectin study supports placental restriction. Adult tissue identity and cross-reactivity remain unresolved.", "decision_reason": "Material normal-tissue finding remains unresolved; block CTA admission and require sequence review without establishing Unsafe. Negative bulk profiles do not resolve assay identity.", "source_title": "Isolation and sequence analysis of a cDNA encoding human placental tissue protein 13 (PP13)", "source_url": "https://pubmed.ncbi.nlm.nih.gov/10527825/", "limitations": "Adult versus fetal samples and original protein bands require full-paper adjudication. Conflicting assay identity is unresolved; neither a proven unsafe classification nor unconditional inclusion is justified by these abstracts alone.", "review_depth": "Primary abstracts rechecked (PMIDs 10527825 and 19497882); original adult/fetal specimen labels, bands and reagent controls not independently re-inspected." } ] }, { "label": "PLCZ1", "entity_id": "PEG:747e670b301288c00a5a", "classification": "Other:Held", "assessment_status": "normal_evidence_hold", "sequence_role": "review", "reasons": [ "Reviewed normal-cell knowledge" ], "translation_qualified": true, "translation_reasons": "", "findings": [ { "id": "GK-migration-review-20261025-PLCZ1", "effect": "context", "interpretation_status": "rejected", "finding": "The cited pancreatic result supports NYD-SP27/PLCZ1 RNA, not demonstrated normal PLCZ1 protein. The paper's antibody staining detects CFTR; it cannot supply a normal-protein veto.", "decision_reason": "Preserve rejection of the PLCZ1 protein interpretation: the immunostaining measured CFTR. The separately retained qualitative pancreatic RNA finding remains unresolved.", "source_title": "Rescuing defective pancreatic secretion in cystic fibrosis by suppression of a newly identified gene", "source_url": "https://www.cuhk.edu.hk/ecbrc/cliparts/Publication%20list/Lancet2003.pdf", "limitations": "Human pancreatic RNA is qualitative, not nTPM. Disease/cell-model functional experiments and mouse measurements do not establish healthy human protein abundance.", "review_depth": "Primary full text: Methods, normal-tissue RT-PCR/Figure 1, and CFTR immunolocalisation. Original isoform mapping and quantitative expression remain unresolved." }, { "id": "GK-migration-review-20261025-PLCZ1-RNA", "effect": "review", "interpretation_status": "unresolved", "finding": "The normal human tissue RT-PCR panel reports a pancreatic band for NYD-SP27; abundance and isoform contribution cannot be compared with the modern screening limits. Hold unrestricted gene use until this material normal-RNA evidence is reconciled.", "decision_reason": "Material normal-tissue finding remains unresolved; block CTA admission and require sequence review without establishing Unsafe. Negative bulk profiles do not resolve assay identity.", "source_title": "Rescuing defective pancreatic secretion in cystic fibrosis by suppression of a newly identified gene", "source_url": "https://www.cuhk.edu.hk/ecbrc/cliparts/Publication%20list/Lancet2003.pdf", "limitations": "Human pancreatic RNA is qualitative, not nTPM. Disease/cell-model functional experiments and mouse measurements do not establish healthy human protein abundance.", "review_depth": "Primary full text: Methods, normal-tissue RT-PCR/Figure 1, and CFTR immunolocalisation. Original isoform mapping and quantitative expression remain unresolved." } ] }, { "label": "MAGEA12", "entity_id": "PEG:4182d88ed01f30868284", "classification": "Unsafe", "assessment_status": "screened", "sequence_role": "exclude", "reasons": [ "Rare vital-tissue cell expression" ], "translation_qualified": true, "translation_reasons": "", "findings": [] }, { "label": "SERPINA2", "entity_id": "PEG:c47ae2b1751b9533d505", "classification": "Other:Translation", "assessment_status": "translation_review", "sequence_role": "review", "reasons": [ "Translation qualification" ], "translation_qualified": false, "translation_reasons": "designated_translation_incomplete | incomplete_annotation_tag | incomplete_start | incomplete_stop | noncanonical_start_residue | nonqualifying_transcript_biotype", "findings": [] }, { "label": "MROH5", "entity_id": "PEG:fce814b8a9011caef8a0", "classification": "Unsafe", "assessment_status": "screened", "sequence_role": "exclude", "reasons": [ "Translation qualification", "Rare vital-tissue cell expression" ], "translation_qualified": false, "translation_reasons": "ambiguous_or_interrupted_sequence | designated_translation_incomplete | nonqualifying_transcript_biotype", "findings": [] }, { "label": "SELENOV", "entity_id": "PEG:1fb64f61bd397bbeff51", "classification": "Other:Translation", "assessment_status": "translation_review", "sequence_role": "review", "reasons": [ "Translation qualification" ], "translation_qualified": false, "translation_reasons": "ambiguous_or_interrupted_sequence | designated_translation_incomplete", "findings": [] }, { "label": "GDPD4", "entity_id": "PEG:30014bcbfca43879e8ab", "classification": "Other:Translation", "assessment_status": "translation_review", "sequence_role": "review", "reasons": [ "Translation qualification" ], "translation_qualified": true, "translation_reasons": "unresolved_translation_evidence", "findings": [] }, { "label": "SLCO1B3-SLCO1B7", "entity_id": "PEG:712421ae3b845c315cac", "classification": "Other:Translation", "assessment_status": "translation_review", "sequence_role": "review", "reasons": [ "Translation qualification" ], "translation_qualified": true, "translation_reasons": "unresolved_translation_evidence", "findings": [] }, { "label": "FRG2", "entity_id": "PEG:1289f6cdbadac0e27067", "classification": "Other:Translation", "assessment_status": "translation_review", "sequence_role": "review", "reasons": [ "Translation qualification" ], "translation_qualified": true, "translation_reasons": "unresolved_translation_evidence", "findings": [] }, { "label": "FRG2B", "entity_id": "PEG:09779ef303c2171255f1", "classification": "Other:Translation", "assessment_status": "translation_review", "sequence_role": "review", "reasons": [ "Translation qualification" ], "translation_qualified": true, "translation_reasons": "unresolved_translation_evidence", "findings": [] } ], "bundle": { "schema": "oncoref.sequence-bundle-asset", "schema_version": 1, "bundle_id": "oncoref:sequence-bundle:v1:sha256:c8c060edab62e089fd4651065a857a8eaecb7c68816b016b3ac4c9fd06fa9525", "url": "https://github.com/pirl-unc/oncoref/releases/download/v1.35.0/oncoref-sequences-1.35.0.zip", "archive_bytes": 127896757, "archive_sha256": "0371c0fe94193b06f12bd08bb8734bd67a6adaacdf6f290629b1bfdd07c779db", "unpacked_bytes": 127896191 }, "criteria": [ { "gate_id": "reproductive_support", "stage": "Reproductive or developmental expression", "status": "evaluated", "rule": "Full Reproductive bulk \u22655 nTPM OR supported reproductive-cell RNA \u22655 nTPM (\u226520 reads; indirect sites additionally need complete outside-cluster coverage and every outside value <5, with no curated normal-induction conflict) OR reliable mapped positive reproductive IHC for every member without an antibody conflict OR reviewed human reproductive protein covering every selected member OR supported developmental stage/lineage mean \u22655 TPM; \u226520 cells, \u22655 positive and \u226510% positive at \u22651 TPM. Presence evidence never overrides normal exclusions.", "source_ids": [ "hpa_rna_consensus", "hpa_normal_tissue", "hpa_single_cell_tissue", "normal-induction-evidence", "tyser_E-MTAB-9388", "petropoulos_E-MTAB-3929" ] }, { "gate_id": "cancer_presence", "stage": "Cancer expression", "status": "evaluated", "rule": "At least one measured compatible tumor sample >0 in native TPM or HPA pTPM OR reviewed reliable tumor protein. This establishes presence, not therapeutic abundance; do not add maxima from different samples.", "source_ids": [ "oncoref_tumor_union", "hpa_cancer" ] }, { "gate_id": "normal_hpa_protein", "stage": "HPA normal protein", "status": "evaluated", "rule": "Reliable non-Low positives in Vital/Protected supply Unsafe evidence; Manageable positives block CTA only; uncertain evidence remains unresolved. Low is flagged.", "source_ids": [ "hpa_normal_tissue" ] }, { "gate_id": "required_coverage", "stage": "Required RNA coverage", "status": "evaluated", "rule": "Combined normal bulk (HPA consensus, HPA brain, GTEx v11) is the required RNA coverage panel: every nonreproductive tissue concept measured for every protein member. Missing coverage in the separate GTEx 52-context core, HPA tissue-cell, immune, DICE and cornea panels does not itself block admission; observed normal evidence from these panels still applies.", "source_ids": [ "hpa_rna_consensus", "hpa_brain", "gtex_tissue_rna", "hpa_single_cell_tissue", "hpa_immune_cell", "hpa_immune_monaco" ] }, { "gate_id": "reproductive_concentration", "stage": "Reproductive concentration", "status": "evaluated", "rule": "HPA v23 average normal/(normal+Reproductive maximum) above 10% blocks the adult/placental route when its reference is positive and the comparison is complete. Use 38 contexts/29 anatomy units, including Disposable and excluding thymus; thymus remains Protected for hazard assessment. Supported embryonic evidence remains independent; its contrast is unassessed. This is not safety evidence.", "source_ids": [ "hpa_rna_consensus" ] }, { "gate_id": "translation_qualification", "stage": "Translation qualification", "status": "evaluated", "rule": "CTA admission requires qualifying coding annotation or supported ncORF evidence and an approved reference protein: MANE Select first, Ensembl canonical second, with a complete primary-locus CDS and AA20 sequence. An incomplete designated transcript or unresolved coding conflict requires review; a shorter or alternate-locus protein cannot silently replace it. Every member must share the approved sequence. All candidates still undergo normal-evidence assessment; translation review does not establish Unsafe.", "source_ids": [ "Ensembl-115", "transcript-evidence" ] }, { "gate_id": "normal_bulk", "stage": "Normal bulk", "status": "evaluated", "rule": "One inclusive tissue/IHC ceiling: above it in Vital/Protected supplies Unsafe evidence; above it in Manageable blocks CTA, and above 128 (the top Manageable ceiling) supplies Unsafe evidence. No second RNA boundary.", "source_ids": [ "hpa_rna_consensus", "hpa_brain", "gtex_tissue_rna" ] }, { "gate_id": "normal_clusters", "stage": "HPA tissue clusters", "status": "evaluated", "rule": "RNA requires \u226520 reads and uses the single ceiling. IHC credit requires an exact or declared compartment match; unrelated cells in the same tissue cannot inherit it.", "source_ids": [ "hpa_single_cell_tissue" ] }, { "gate_id": "normal_hpa_immune", "stage": "HPA immune", "status": "evaluated", "rule": "Central cell-specific tiers with native nTPM limits and no matched negative-IHC credit; reproductive/placental location remains neutral.", "source_ids": [ "hpa_immune_cell" ] }, { "gate_id": "normal_monaco", "stage": "Monaco immune", "status": "evaluated", "rule": "Central cell-specific tiers with native TPM limits and no matched negative-IHC credit.", "source_ids": [ "hpa_immune_monaco" ] }, { "gate_id": "normal_dice", "stage": "DICE immune", "status": "evaluated", "rule": "Third-highest reported TPM value; central cell-specific tiers. Unpaired group distributions retain bounds. Missing coverage alone does not exclude.", "source_ids": [ "dice" ] }, { "gate_id": "normal_cornea", "stage": "Adult cornea", "status": "evaluated", "rule": "Recurrent native CP10K: \u22655 positive cells and \u226520 counts in \u22652 sample groups. Nominal RNA limits /100; not a TPM conversion. Missing coverage alone does not exclude.", "source_ids": [ "GSE155683_adult" ] }, { "gate_id": "normal_reviewed_protein", "stage": "Accepted normal-protein evidence", "status": "evaluated", "rule": "Accepted positive protein findings exclude unless extracted Low intensity retains a flag; unquantified does not mean negative.", "source_ids": [ "cta_policy_findings" ] }, { "gate_id": "normal_knowledge", "stage": "Reviewed normal-cell knowledge", "status": "evaluated", "rule": "Reviewed adult human normal protein, or localized RNA with orthogonal normal-cell function, in Vital/Protected supplies Unsafe evidence. Sparse RNA, uncertain species/stage or unresolved identity produces a review hold. Activation and rare-cell frequency do not exempt normal cells. Every finding retains its source and limitations.", "source_ids": [ "gene-knowledge" ] }, { "gate_id": "clinical_exclusion", "stage": "Clinical safety exclusion", "status": "evaluated", "rule": "Retain reviewed product-specific clinical injury counterevidence and causal-attribution limits; no admission shortcut from clinical use.", "source_ids": [ "cta_policy_findings" ] }, { "gate_id": "rare_vital", "stage": "Rare vital-tissue cell expression", "status": "evaluated", "rule": "At least 1% detection in a centrally assigned Vital population in the existing brain/spinal-cord/heart/lung CELLxGENE panel supplies Unsafe evidence. At least 3,000 cells and 10 expressing cells are required. Excluded or unmeasured populations are coverage limits, not allowances. Detection frequency is distinct from abundance.", "source_ids": [ "CELLxGENE" ] }, { "gate_id": "rare_protected", "stage": "Rare Protected-cell expression review", "status": "evaluated", "rule": "At least 1% detection in a centrally assigned Protected population in the existing CELLxGENE panel blocks CTA admission without itself establishing Unsafe. The same cell-support criteria apply. Source age restrictions and detection artifacts remain limitations.", "source_ids": [ "CELLxGENE" ] }, { "gate_id": "normal_external_protein", "stage": "External validated normal protein", "status": "evaluated", "rule": "Use categorical/quantitative staining only within verified reagent, tissue and cell scope; no inherited HPA reliability label.", "source_ids": [ "external_ihc" ] }, { "gate_id": "unsafe_containment", "stage": "Unsafe sequence containment", "status": "evaluated", "rule": "A would-be CTA with at least 95% of its 9-mers also present in Unsafe proteins becomes Other:Contained: Unsafe sequence is blacklisted, so almost no peptide survives. Computed over all protein-coding transcripts of Ensembl 115. This is a sequence rule, not expression evidence.", "source_ids": [ "Ensembl-115", "unsafe_sequences" ] }, { "gate_id": "final_assignment", "stage": "CTA and Other assignments", "status": "evaluated", "rule": "CTA requires all applicable admission gates, required coverage and resolved normal evidence. Unsafe exclusion takes precedence. Other includes assessed noncandidates, held/incomplete evidence, nested microproteins and sequence-contained candidates. Subtype and assessment_status answer different questions; an identity failure cannot erase a normal-evidence hold. Sequence roles require that independent status.", "source_ids": [ "current_decisions" ] } ], "registry_references": 50, "tier_definitions": { "vital": "Highest protection priority: plausible life-threatening failure, major irreversible neurological/sensory loss, or loss of indispensable regenerative support.", "protected": "Persistent functional or structural injury is a major concern; compensation is incomplete or direct immune-depletion evidence is insufficient.", "manageable": "A defined compartment has credible replacement, compensation or supportive-treatment precedent; acute inflammation and persistent recognition still require review.", "disposable": "Narrow conditional allowance for loss of a specified compartment; does not imply painless, reversible or inflammation-free ablation." }, "source_guide": [ { "taxon_id": 9606, "source_id": "gene-knowledge", "name": "Reviewed human gene knowledge: normal cells and reproductive protein", "evidence_category": "normal_protein, normal_cell_rna, reproductive_expression", "status": "used_in_selection", "native_unit": "source-native qualitative and quantitative observations", "stage": "explicit per-finding stage and activation state", "source_url": "https://pirl-unc.github.io/oncoref/audits/cta-other-literature-20261030/", "limitations": "Exact gene/protein attribution; sparse RNA and unresolved species/isoforms remain review holds. Search leads are not accepted findings." }, { "taxon_id": 9606, "source_id": "olfactory_durante_supplement", "name": "Durante et al. 2020 adult human olfactory atlas supplementary tables", "evidence_category": "normal_cell_rna", "status": "used_in_selection", "native_unit": "positive neurons; cluster detection fraction", "stage": "adult", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7065961/", "limitations": "Exact reported genes enter knowledge review holds; sparse detection is not TPM, protein, donor replication or proof of absence for unlisted genes." }, { "taxon_id": 9606, "source_id": "olfactory_verbeurgt_cq", "name": "Verbeurgt et al. 2014 whole human olfactory mucosa", "evidence_category": "normal_cell_rna", "status": "used_in_selection", "native_unit": "native qPCR Cq; assay IDs and donor identity", "stage": "adult; 26 donor samples", "source_url": "https://doi.org/10.1371/journal.pone.0096333", "limitations": "OR10A4 normal RNA supplies a reviewed hold. Native values are not TPM, protein or a clinical toxicity estimate; unlisted genes are not measured zero." }, { "taxon_id": 9606, "source_id": "olfactory_verbeurgt_copies", "name": "Verbeurgt et al. 2014 whole human olfactory mucosa", "evidence_category": "normal_cell_rna", "status": "used_in_selection", "native_unit": "estimated RNA copies per 20 ng total RNA", "stage": "adult; 26 donor samples", "source_url": "https://doi.org/10.1371/journal.pone.0096333", "limitations": "OR10A4 normal RNA supplies a reviewed hold. Native values are not TPM, protein or a clinical toxicity estimate; unlisted genes are not measured zero." }, { "taxon_id": 9606, "source_id": "normal-induction-evidence", "name": "Published human normal immune induction contexts", "evidence_category": "reproductive_expression, normal_cell_rna", "status": "used_in_selection", "native_unit": "qualitative reported RNA induction", "stage": "adult; activated", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6457222/", "limitations": "Qualitative counterevidence to indirect reproductive-site restriction; no TPM or clinical-toxicity inference" }, { "taxon_id": 9606, "source_id": "hpa_rna_consensus", "name": "HPA v23 / GTEx consensus", "evidence_category": "normal_bulk_rna, reproductive_expression", "status": "used_in_selection", "native_unit": "nTPM", "stage": "adult; placenta handled separately", "source_url": "https://v23.proteinatlas.org/about/download", "limitations": "Bulk source summaries; not exhaustive pediatric, pregnancy or rare-cell coverage" }, { "taxon_id": 9606, "source_id": "tyser_E-MTAB-9388", "name": "Tyser human gastrulation atlas", "evidence_category": "developmental_expression", "status": "used_in_selection", "native_unit": "TPM", "stage": "Carnegie stage 7", "source_url": "https://doi.org/10.1038/s41586-021-04158-y", "limitations": "One embryo; cell support does not establish independent-donor replication" }, { "taxon_id": 9606, "source_id": "petropoulos_E-MTAB-3929", "name": "Petropoulos preimplantation atlas", "evidence_category": "developmental_expression", "status": "used_in_selection", "native_unit": "TPM", "stage": "3\u20137 days, stage \u00d7 inferred lineage", "source_url": "https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-3929/Results", "limitations": "1,519 measured cells; stage and embryo counts retained; not coverage of all fetal stages" }, { "taxon_id": 9606, "source_id": "hpa_brain", "name": "HPA v23 human brain, 193 subregions", "evidence_category": "normal_bulk_rna", "status": "used_in_selection", "native_unit": "nTPM", "stage": "adult", "source_url": "https://v23.proteinatlas.org/download/rna_brain_hpa.tsv.zip", "limitations": "Maximum subregion mean after within-context group sums; no automatic negative-IHC credit" }, { "taxon_id": 9606, "source_id": "gtex_tissue_rna", "name": "Direct GTEx v11 tissue medians", "evidence_category": "normal_bulk_rna", "status": "used_in_selection", "native_unit": "TPM", "stage": "adult", "source_url": "https://gtexportal.org/home/downloads/adult-gtex", "limitations": "52 native whole-organ contexts; 14 microdissected and two cultured/transformed contexts remain outside this adapter. Exact whole-organ HPA negative-IHC grades apply; donor medians do not exclude donor outliers. Native reader preserves all 68 contexts." }, { "taxon_id": 9606, "source_id": "oncoref_tumor_union", "name": "OncoRef source-mapped tumor union", "evidence_category": "tumor_expression", "status": "used_in_selection", "native_unit": "TPM", "stage": "cohort-specific", "source_url": "https://github.com/pirl-unc/oncoref/tree/v1.21.0/docs/audits/cta-expanded-funnel-20261027/tumor-union", "limitations": "132 compatible cohorts; source namespaces deduplicate views, not patients across studies" }, { "taxon_id": 9606, "source_id": "hpa_cancer", "name": "HPA v23 cancer sample measurements", "evidence_category": "tumor_expression", "status": "used_in_selection", "native_unit": "pTPM", "stage": "cohort-specific", "source_url": "https://v23.proteinatlas.org/about/download", "limitations": "Protein-coding RNA denominator; no numerical protein or peptide abundance" }, { "taxon_id": 9606, "source_id": "hpa_single_cell_tissue", "name": "HPA v23 tissue/cell clusters", "evidence_category": "normal_cell_rna, reproductive_expression", "status": "used_in_selection", "native_unit": "nTPM", "stage": "source-labelled adult; reproductive locations explicit", "source_url": "https://v23.proteinatlas.org/about/download", "limitations": "At least 20 reads; missing cell types and disease states remain uncovered" }, { "taxon_id": 9606, "source_id": "hpa_immune_cell", "name": "HPA v23 immune summaries", "evidence_category": "immune_rna", "status": "used_in_selection", "native_unit": "nTPM", "stage": "adult", "source_url": "https://v23.proteinatlas.org/about/download", "limitations": "Sorted populations retain native units; no matched negative-IHC relaxation" }, { "taxon_id": 9606, "source_id": "hpa_immune_monaco", "name": "Monaco immune summaries via HPA v23", "evidence_category": "immune_rna", "status": "used_in_selection", "native_unit": "TPM", "stage": "adult", "source_url": "https://v23.proteinatlas.org/about/download", "limitations": "Sorted populations retain native units; no matched negative-IHC relaxation" }, { "taxon_id": 9606, "source_id": "dice", "name": "DICE immune distributions", "evidence_category": "immune_rna", "status": "used_in_selection", "native_unit": "TPM", "stage": "adult", "source_url": "https://dice-database.org/", "limitations": "15 distributions; third-highest value; unpaired locus distributions retain bounds; optional coverage" }, { "taxon_id": 9606, "source_id": "GSE155683_adult", "name": "Collin adult corneal atlas", "evidence_category": "normal_cell_rna", "status": "used_in_selection", "native_unit": "CP10K", "stage": "adult", "source_url": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE155683", "limitations": "Two supported sample groups; optional coverage; CP10K is not length-normalized TPM" }, { "taxon_id": 9606, "source_id": "hpa_normal_tissue", "name": "HPA v23 normal-tissue IHC", "evidence_category": "normal_protein, reproductive_expression", "status": "used_in_selection", "native_unit": "HPA categorical level and reliability", "stage": "adult", "source_url": "https://v23.proteinatlas.org/about/assays%2Bannotation", "limitations": "Reliability describes evidence support, not a calibrated false-negative probability" }, { "taxon_id": 9606, "source_id": "external_ihc", "name": "Curated external staining observations", "evidence_category": "normal_protein", "status": "used_in_selection", "native_unit": "native categorical findings", "stage": "source-specific", "source_url": "https://github.com/pirl-unc/oncoref/tree/v1.21.0/docs/audits/external-ihc-20261027", "limitations": "Reagent, tissue, cell type and validation scope remain explicit; no inherited HPA grade" }, { "taxon_id": 9606, "source_id": "cta_policy_findings", "name": "Reviewed normal protein and clinical exclusions", "evidence_category": "normal_protein, clinical_safety", "status": "used_in_selection", "native_unit": "categorical reviewed findings", "stage": "source-specific", "source_url": "https://github.com/pirl-unc/oncoref/blob/v1.21.0/oncoref/data/cta-policy-findings.csv", "limitations": "Qualitative reported Low is distinct from HPA Low and numerical intensity; clinical evidence is product-specific" }, { "taxon_id": 9606, "source_id": "tcr_trial_lete_mrcls_2025", "name": "Letetresgene Autoleucel in Advanced/Metastatic Myxoid/Round Cell Liposarcoma", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1200/JCO-24-01466", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_ima203_2025", "name": "Autologous T cell therapy for PRAME+ advanced solid tumors in HLA-A*02+ patients: a phase 1 trial", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1038/s41591-025-03650-6", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_afami_phase1_2023", "name": "Autologous T cell therapy for MAGE-A4+ solid cancers in HLA-A*02+ patients: a phase 1 trial", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1038/s41591-022-02128-z", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_spearhead1_2024", "name": "SPEARHEAD-1: a single-arm phase 2 trial of afamitresgene autoleucel in advanced synovial sarcoma and myxoid/round cell liposarcoma", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1016/S0140-6736(24)00319-2", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_magea3_titin_2013", "name": "Identification of a Titin-Derived HLA-A1-Presented Peptide as a Cross-Reactive Target for Engineered MAGE A3-Directed T Cells", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1126/scitranslmed.3006034", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_lete_gbs_2019", "name": "Guillain-Barre syndrome observed with adoptive transfer of lymphocytes genetically engineered with an NY-ESO-1 reactive T-cell receptor", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1186/s40425-019-0759-x", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_lete_protocol", "name": "NCT03709706 protocol: NY-ESO-1/LAGE-1A shared peptide and c259 receptor", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://cdn.clinicaltrials.gov/large-docs/06/NCT03709706/Prot_000.pdf", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_afami_protocol", "name": "NCT03132922 protocol: MAGE-A4 c1032 target peptide", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://cdn.clinicaltrials.gov/large-docs/22/NCT03132922/Prot_000.pdf", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_magea1_2024", "name": "First-in-human dose escalation trial to evaluate the clinical safety and efficacy of an anti-MAGEA1 autologous TCR-transgenic T cell therapy in relapsed and refractory solid tumors", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1136/jitc-2023-008668", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_magea10_2022", "name": "Phase I clinical trial evaluating the safety and efficacy of ADP-A2M10 SPEAR T cells in patients with MAGE-A10+ advanced non-small cell lung cancer", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1136/jitc-2021-003581", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_tbi1301_2022", "name": "NY-ESO-1-specific redirected T cells with endogenous TCR knockdown mediate tumor response and cytokine release syndrome", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://doi.org/10.1136/jitc-2021-003811", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_magea3_neuro_2013", "name": "Cancer regression and neurological toxicity following anti-MAGE-A3 TCR gene therapy", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://pubmed.ncbi.nlm.nih.gov/23377668/", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "tcr_trial_magea3_reexamination_2021", "name": "Re-examination of MAGE-A3 as a T-cell Therapeutic Target", "evidence_category": "clinical_safety", "status": "used_in_selection", "native_unit": "reviewed clinical attribution", "stage": "adult clinical cohort", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7946352/", "limitations": "Peptide/HLA/receptor scope; targeted review, not all trials; no species transfer" }, { "taxon_id": 9606, "source_id": "Gong2021_placenta_PC", "name": "Gong et al., Nature Communications (2021)", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/s41467-021-22695-y", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Gong2021_placenta_ncRNA", "name": "Gong et al., Nature Communications (2021)", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/s41467-021-22695-y", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Bradley2020_CPA", "name": "Bradley et al., Nature Communications (2020)", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/s41467-020-19141-w", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Wang2016_CT", "name": "Wang 2016", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/ncomms10499", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Bruggeman2018_GC", "name": "Bruggeman 2018", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/s41388-018-0357-2", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "daSilva2017_testis_biased", "name": "da Silva 2017 \u00b7 testis-biased", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.18632/oncotarget.21715", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "daSilva2017_CT", "name": "da Silva 2017 \u00b7 CT", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.18632/oncotarget.21715", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Jamin2021_CT", "name": "Jamin 2021", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1002/1878-0261.12900", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Jamin2021_core", "name": "Jamin 2021 \u00b7 core", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1002/1878-0261.12900", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Chang2019_TGCT", "name": "Chang 2019 \u00b7 TGCT", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1002/cam4.2223", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Carter2023_CT", "name": "Carter 2023", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1136/jitc-2023-007935", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Seager2024_CTA", "name": "Seager 2024 \u00b7 panel", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1186/s12967-024-04918-0", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Loriot2025_S1", "name": "Loriot 2025 \u00b7 strict", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1371/journal.pgen.1011734", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Loriot2025_S2", "name": "Loriot 2025 \u00b7 preferential", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1371/journal.pgen.1011734", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Gong2021_reproductive_PC", "name": "Gong 2021 \u00b7 reproductive coding", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/s41467-021-22695-y", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Gong2021_reproductive_ncRNA", "name": "Gong 2021 \u00b7 reproductive noncoding", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1038/s41467-021-22695-y", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "daSilva2017_tumor_proteomics", "name": "da Silva 2017 \u00b7 tumor proteomics", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.18632/oncotarget.21715", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Bai2016_EGFL6", "name": "Bai 2016", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1158/0008-5472.CAN-16-0225", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Boel1995_BAGE", "name": "Bo\u00ebl et al., Immunity (1995)", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1016/s1074-7613(95)80053-0", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Garg2007_SPAG9", "name": "Garg et al., Clinical Cancer Research (2007)", "evidence_category": "nomination", "status": "annotation", "native_unit": "gene-list membership", "stage": "publication-specific", "source_url": "https://doi.org/10.1158/1078-0432.CCR-06-2340", "limitations": "Comparison annotation only; no membership bypass of the quantitative funnel" }, { "taxon_id": 9606, "source_id": "Sasaroli2011_vascular", "name": "Sasaroli et al. 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(1995)", "native_unit": "publication membership", "source_url": "https://doi.org/10.1016/s1074-7613(95)80053-0", "limitations": "Original BAGE tumor-antigen nomination and autologous CTL recognition; contemporary paralog resolution is not inferred", "stage": "publication-specific", "evidence_category": "nomination", "status": "annotation" }, { "source_id": "10.1158/0008-5472.CAN-16-0225", "name": "Bai et al. (2016)", "native_unit": "publication membership", "source_url": "https://doi.org/10.1158/0008-5472.CAN-16-0225", "limitations": "Ovarian-tumor and vascular expression/function; no normal-tissue exclusivity claim", "stage": "publication-specific", "evidence_category": "nomination", "status": "annotation" } ], "tier_references": { "pardo2015": { "title": "Parent stem cells can serve as niches for their daughter cells", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4521991/", "model": "mouse", "design": "selective_ablation", "finding": "Approximately 79% ciliated-cell depletion did not accelerate replacement; basal and secretory populations persisted.", "limitation": "Large-airway homeostasis experiment, not human immune killing or a validated tolerability threshold.", "checked": "2026-11-03" }, "dumm2019": { "title": "Non-lytic clearance of influenza B virus from infected cells preserves epithelial barrier function", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6377627/", "model": "mouse", "design": "infection_and_ablation", "finding": "Depletion of infection-surviving, predominantly ciliated-like cells worsened epithelial permeability and recovery.", "limitation": "Mixed survivor population in an infected lung; not selective depletion of healthy mature ciliated cells.", "checked": "2026-11-03" }, "perl2011": { "title": "Conditional Depletion of Airway Progenitor Cells Induces Peribronchiolar Fibrosis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3056226/", "model": "mouse", "design": "selective_ablation", "finding": "Sustained club-compartment depletion caused persistent peribronchiolar fibrosis despite later epithelial regeneration.", "limitation": "Promoter-defined compartment and toxin exposure do not quantify human receptor-specific risk.", "checked": "2026-11-03" }, "guild2023": { "title": "Evidence for lung barrier regeneration by differentiation prior to binucleated and stem cell division", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10579698/", "model": "mouse", "design": "selective_ablation", "finding": "AT2 differentiation rapidly compensated AT1 loss; repeated injury produced abnormal epithelial hyperplasia.", "limitation": "Intact repair under finite experimental insults is not proof of tolerance to persistent T-cell attack.", "checked": "2026-11-03" }, "garcia2016": { "title": "Targeted Type 2 Alveolar Cell Depletion: A Dynamic Functional Model for Lung Injury Repair", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4821031/", "model": "mouse", "design": "selective_ablation", "finding": "AT2 depletion produced recovery, fibrosis or lethal edema depending on severity and kinetics.", "limitation": "Drug toxicity and model kinetics prevent transfer of depletion percentages to clinical thresholds.", "checked": "2026-11-03" }, "zhao2000": { "title": "Alveolar epithelial cell chemokine expression triggered by antigen-specific cytolytic CD8+ T cell recognition", "url": "https://www.jci.org/articles/view/9786", "model": "mouse", "design": "antigen_specific_t_cells", "finding": "Alveolar antigen recognition initiated inflammatory recruitment and progressive lethal lung injury.", "limitation": "Transgenic antigen and transferred T cells; not a human engineered-TCR clinical risk estimate.", "checked": "2026-11-03" }, "haas2023": { "title": "Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10422001/", "model": "human", "design": "cell_therapy_clinical", "finding": "Two severe pulmonary toxicities, one fatal, implicated benign pneumocyte expression in injured lung.", "limitation": "AT1 versus AT2 initiation was not resolved; product, dose and pre-existing injury matter.", "checked": "2026-11-03" }, "halbeisen2022": { "title": "Lung function from school age to adulthood in primary ciliary dyskinesia", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9582507/", "model": "human", "design": "functional_disease_cohort", "finding": "Lung function declined on average in 486 patients, with heterogeneous trajectories despite treatment.", "limitation": "Inherited ciliary dysfunction is not epithelial ablation or an immune-toxicity model.", "checked": "2026-11-03" }, "roy2014": { "title": "Muc5b is required for airway defence", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4001806/", "model": "mouse", "design": "functional_gene_deletion", "finding": "Muc5b deficiency impaired clearance and host defence, unlike Muc5ac deficiency.", "limitation": "Mucin deletion is not goblet-cell killing; multiple secretory populations produce MUC5B.", "checked": "2026-11-03" }, "tata2013": { "title": "Dedifferentiation of committed epithelial cells into stem cells in vivo", "url": "https://www.nature.com/articles/nature12777", "model": "mouse", "design": "selective_ablation_and_lineage_tracing", "finding": "Secretory cells restored basal stem cells after basal-cell depletion.", "limitation": "Alternative repair depends on surviving populations and does not establish tolerance to repeated recognition.", "checked": "2026-11-03" }, "clad2023": { "title": "JAK-STAT activation contributes to cytotoxic T cell-mediated basal cell death in human chronic lung allograft dysfunction", "url": "https://pubmed.ncbi.nlm.nih.gov/36946463/", "model": "human", "design": "disease_tissue_and_mechanistic", "finding": "Basal-cell MHC-I induction and cytotoxic T-cell killing were linked to airway-centered allograft injury.", "limitation": "Alloreactivity affects multiple compartments and is not an isolated engineered-receptor trial.", "checked": "2026-11-03" }, "bergmann2009": { "title": "Evidence for cardiomyocyte renewal in humans", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2991140/", "model": "human", "design": "cell_turnover", "finding": "Carbon dating demonstrated limited adult cardiomyocyte renewal.", "limitation": "Renewal is nonzero; a turnover estimate does not measure replacement during acute destructive injury.", "checked": "2026-11-03" }, "linette2013": { "title": "Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3743463/", "model": "human", "design": "cell_therapy_clinical", "finding": "Titin cross-recognition by an engineered TCR caused fatal cardiac toxicity.", "limitation": "Receptor-specific cross-reactivity; not evidence that every MAGEA3-directed receptor recognizes heart.", "checked": "2026-11-03" }, "morgan2013": { "title": "Cancer regression and neurologic toxicity following anti-MAGE-A3 TCR gene therapy", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3581823/", "model": "human", "design": "cell_therapy_clinical", "finding": "Severe neurological injury was associated with a cross-reactive TCR and neural MAGEA12 expression.", "limitation": "Peptide and receptor specificity matter; rare RNA detection alone does not reproduce this evidence.", "checked": "2026-11-03" }, "wharram2005": { "title": "Podocyte depletion causes glomerulosclerosis", "url": "https://pubmed.ncbi.nlm.nih.gov/16107576/", "model": "rat", "design": "selective_ablation", "finding": "Increasing podocyte depletion caused persistent proteinuria, sclerosis and renal dysfunction.", "limitation": "Model depletion thresholds are not human safety cutoffs.", "checked": "2026-11-03" }, "grgic2012": { "title": "Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3480325/", "model": "mouse", "design": "selective_ablation", "finding": "Repeated tubular injury caused chronic atrophy, fibrosis and secondary glomerular injury.", "limitation": "Cre distribution and toxin sensitivity qualify compartment specificity; not clinical immune targeting.", "checked": "2026-11-03" }, "raven2017": { "title": "Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration", "url": "https://www.nature.com/articles/nature23015", "model": "mouse", "design": "lineage_tracing_and_injury", "finding": "Biliary cells contributed hepatocytes when hepatocyte proliferation was impaired.", "limitation": "Compensatory plasticity does not establish tolerance of combined biliary and hepatocyte destruction.", "checked": "2026-11-03" }, "parkhurst2011": { "title": "T cells targeting carcinoembryonic antigen can mediate regression of metastatic colorectal cancer but induce severe transient colitis", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3048186/", "model": "human", "design": "cell_therapy_clinical", "finding": "CEA-directed TCR treatment caused severe transient colitis in all three treated patients.", "limitation": "Recovery in a small product-specific trial does not establish general controllability of persistent mucosal targeting.", "checked": "2026-11-03" }, "tian2011": { "title": "A reserve stem cell population in small intestine renders Lgr5-positive cells dispensable", "url": "https://www.nature.com/articles/nature10408", "model": "mouse", "design": "selective_ablation", "finding": "Alternative progenitors maintained intestinal epithelium during Lgr5-cell depletion.", "limitation": "An Lgr5-specific insult is narrower than destroying all crypt regenerative populations.", "checked": "2026-11-03" }, "maude2018": { "title": "Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5996391/", "model": "human", "design": "cell_therapy_clinical", "finding": "Responders developed B-cell aplasia; immunoglobulin replacement was commonly used.", "limitation": "Manageability requires support; this does not generalize to all lymphocytes or marrow progenitors.", "checked": "2026-11-03" }, "tran2013": { "title": "Immune targeting of fibroblast activation protein triggers recognition of multipotent bone marrow stromal cells and cachexia", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3674706/", "model": "mouse", "design": "car_t_experiment", "finding": "FAP-reactive T cells recognized marrow stromal cells and caused severe systemic toxicity.", "limitation": "Target distribution and receptor properties matter; not all fibroblasts or all FAP products have equivalent effects.", "checked": "2026-11-03" }, "roberts2013": { "title": "Depletion of stromal cells expressing fibroblast activation protein-alpha from skeletal muscle and bone marrow results in cachexia and anemia", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3674708/", "model": "mouse", "design": "selective_ablation", "finding": "Distributed FAP-positive stromal depletion disrupted muscle and hematopoietic support.", "limitation": "Distributed target-defined cells differ from a localized dermal fibroblast population.", "checked": "2026-11-03" }, "wang2014": { "title": "Targeting Fibroblast Activation Protein in Tumor Stroma with Chimeric Antigen Receptor T Cells Can Inhibit Tumor Growth and Augment Host Immunity Without Severe Toxicity", "url": "https://pubmed.ncbi.nlm.nih.gov/24778279/", "model": "mouse", "design": "car_t_experiment", "finding": "A different FAP CAR achieved antitumor effects without the severe toxicity of other models.", "limitation": "Counterevidence emphasizes receptor/epitope and target-density dependence, not universal stromal safety.", "checked": "2026-11-03" }, "sambasivan2011": { "title": "Pax7-expressing satellite cells are indispensable for adult skeletal muscle regeneration", "url": "https://pubmed.ncbi.nlm.nih.gov/21828093/", "model": "mouse", "design": "selective_ablation", "finding": "Satellite-cell depletion prevented normal muscle regeneration after injury.", "limitation": "Localized experimental depletion does not estimate human systemic immune toxicity.", "checked": "2026-11-03" }, "murphy2011": { "title": "Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3152921/", "model": "mouse", "design": "selective_ablation", "finding": "Fibroblast depletion altered satellite-cell dynamics and impaired regenerated myofibers.", "limitation": "Niche-specific dependence cannot be generalized to all fibroblast populations.", "checked": "2026-11-03" }, "stamatouli2018": { "title": "Collateral Damage: Insulin-Dependent Diabetes Induced With Checkpoint Inhibitors", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6054443/", "model": "human", "design": "checkpoint_clinical_cohort", "finding": "Checkpoint treatment was associated with insulin deficiency and frequent ketoacidosis at presentation.", "limitation": "Checkpoint autoimmunity is not selective engineered-TCR beta-cell killing; insulin replacement is ongoing support.", "checked": "2026-11-03" }, "iyer2018": { "title": "Immune-Related Thyroiditis with Immune Checkpoint Inhibitors", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC6157359/", "model": "human", "design": "checkpoint_clinical_cohort", "finding": "Destructive thyroiditis often progressed to hypothyroidism requiring hormone replacement.", "limitation": "Controlling hormone deficiency does not establish control of acute inflammatory injury.", "checked": "2026-11-03" }, "hypophysitis2021": { "title": "Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8183642/", "model": "human", "design": "checkpoint_clinical_cohort", "finding": "Pituitary hormone deficits showed limited recovery, particularly the adrenal axis.", "limitation": "Anatomical swelling, affected axes and hormone support distinguish patients; not a cell-specific ablation trial.", "checked": "2026-11-03" }, "rama2010": { "title": "Limbal Stem-Cell Therapy and Long-Term Corneal Regeneration", "url": "https://www.nejm.org/doi/abs/10.1056/NEJMoa0905955", "model": "human", "design": "regenerative_clinical", "finding": "Limbal-cell grafts restored corneal epithelial maintenance after destructive injury.", "limitation": "Successful transplantation does not make spontaneous limbal recovery reliable or treat retinal injury.", "checked": "2026-11-03" }, "golub2012": { "title": "Hair Cell Replacement in Adult Mouse Utricles after Targeted Ablation of Hair Cells with Diphtheria Toxin", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC3544304/", "model": "mouse", "design": "selective_ablation", "finding": "Adult vestibular hair-cell loss was followed by limited replacement.", "limitation": "Utricular findings do not establish restoration of human cochlear hearing.", "checked": "2026-11-03" }, "shin2011": { "title": "Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder", "url": "https://www.nature.com/articles/nature09851", "model": "mouse", "design": "injury_and_lineage_tracing", "finding": "Urothelial and stromal signaling supported epithelial regeneration after injury.", "limitation": "Repair after finite injury is not evidence that continuous urothelial killing is tolerable.", "checked": "2026-11-03" }, "spalding2008": { "title": "Dynamics of fat cell turnover in humans", "url": "https://www.nature.com/articles/nature06902", "model": "human", "design": "cell_turnover", "finding": "Adult adipocytes turn over while population size is regulated.", "limitation": "Turnover does not establish the metabolic tolerability of generalized adipocyte destruction.", "checked": "2026-11-03" }, "johnson2009": { "title": "Gene therapy with human and mouse T-cell receptors mediates cancer regression and targets normal tissues expressing cognate antigen", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2929689/", "model": "human", "design": "cell_therapy_clinical", "finding": "Melanocyte-antigen TCR therapy injured skin, eye and ear compartments.", "limitation": "Cutaneous depigmentation cannot justify ocular or cochlear melanocyte depletion.", "checked": "2026-11-03" }, "warner2019": { "title": "Sicca Syndrome Associated with Immune Checkpoint Inhibitor Therapy", "url": "https://pubmed.ncbi.nlm.nih.gov/30996010/", "model": "human", "design": "checkpoint_clinical_cohort", "finding": "Checkpoint-associated sicca included persistent salivary hypofunction.", "limitation": "Symptom improvement did not guarantee restoration of secretion; not selective receptor targeting.", "checked": "2026-11-03" }, "kristinsson2014": { "title": "Long-term risks after splenectomy among 8149 cancer-free American veterans", "url": "https://haematologica.org/article/view/6942", "model": "human", "design": "surgical_cohort", "finding": "Splenectomy was associated with lasting infection and thromboembolic risks.", "limitation": "Observational organ-removal evidence is not systemic immune-cell depletion.", "checked": "2026-11-03" }, "kooshesh2023": { "title": "Health Consequences of Thymus Removal in Adults", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC10557034/", "model": "human", "design": "surgical_cohort", "finding": "Adult thymectomy was associated with adverse long-term health outcomes.", "limitation": "Observational association, potential confounding and adult context limit causal inference.", "checked": "2026-11-03" }, "heinemeier2016": { "title": "Radiocarbon dating reveals minimal collagen turnover in both healthy and osteoarthritic human cartilage", "url": "https://pubmed.ncbi.nlm.nih.gov/27384346/", "model": "human", "design": "matrix_turnover", "finding": "Adult articular collagen showed very limited turnover.", "limitation": "Matrix turnover is not chondrocyte turnover or a direct immune-injury experiment.", "checked": "2026-11-03" }, "braaten2020": { "title": "Immune checkpoint inhibitor-induced inflammatory arthritis persists after immunotherapy cessation", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7031780/", "model": "human", "design": "checkpoint_clinical_cohort", "finding": "Inflammatory arthritis could persist after checkpoint treatment stopped.", "limitation": "Mixed joint tissues; not selective cartilage-cell ablation.", "checked": "2026-11-03" }, "nhs_tonsillectomy": { "title": "Making a decision about recurrent tonsillitis in children and adults", "url": "https://www.england.nhs.uk/wp-content/uploads/2023/10/decision-support-tool-making-a-decision-about-recurrent-tonsillitis-in-children-and-adults.pdf", "model": "human", "design": "clinical_guidance", "finding": "Tonsil removal is an established treatment with recognized procedural risks.", "limitation": "Local removal is not systemic lymphocyte depletion.", "checked": "2026-11-03" }, "nhs_appendix": { "title": "Appendicitis", "url": "https://www.nhs.uk/conditions/appendicitis/", "model": "human", "design": "clinical_guidance", "finding": "Appendectomy permits survival without the appendix.", "limitation": "Removal does not establish tolerance of in-situ perforation or shared intestinal targeting.", "checked": "2026-11-03" }, "niddk_gallbladder": { "title": "Treatment for Gallstones", "url": "https://www.niddk.nih.gov/health-information/digestive-diseases/gallstones/treatment", "model": "human", "design": "clinical_guidance", "finding": "Cholecystectomy is an established treatment for symptomatic gallstones.", "limitation": "Does not justify bile-duct or liver targeting, or uncontrolled in-situ inflammation.", "checked": "2026-11-03" }, "niddk_adrenal": { "title": "Definition and Facts of Adrenal Insufficiency and Addison's Disease", "url": "https://www.niddk.nih.gov/health-information/endocrine-diseases/adrenal-insufficiency-addisons-disease/definition-facts", "model": "human", "design": "clinical_guidance", "finding": "Adrenal insufficiency can cause crisis and requires hormone replacement.", "limitation": "Replacement availability does not establish acute-injury control.", "checked": "2026-11-03" }, "nci_lymph_nodes": { "title": "Sentinel Lymph Node Biopsy", "url": "https://www.cancer.gov/about-cancer/diagnosis-staging/staging/sentinel-node-biopsy-fact-sheet", "model": "human", "design": "clinical_guidance", "finding": "Regional nodal surgery can cause lymphatic morbidity.", "limitation": "Regional excision is narrower than distributed lymphatic injury.", "checked": "2026-11-03" }, "sitc2021": { "title": "SITC clinical practice guideline on immune checkpoint inhibitor-related adverse events", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8237720/", "model": "human", "design": "clinical_guidance", "finding": "Immune injuries span organ-specific acute and persistent consequences.", "limitation": "Checkpoint-toxicity management cannot validate engineered-cell killing for an untested compartment.", "checked": "2026-11-03" }, "hpa_tissues": { "title": "Human Protein Atlas tissue and cell-type definitions", "url": "https://www.proteinatlas.org/humanproteome/tissue/data", "model": "human", "design": "anatomy_reference", "finding": "Defines tissue and cell annotations used for expression mapping.", "limitation": "Anatomy supports identity, not tolerability or receptor recognition.", "checked": "2026-11-03" }, "openstax_female": { "title": "Anatomy and Physiology: Female Reproductive System", "url": "https://openstax.org/books/anatomy-and-physiology/pages/27-2-anatomy-and-physiology-of-the-female-reproductive-system", "model": "human", "design": "anatomy_reference", "finding": "Defines female reproductive organs and physiological functions.", "limitation": "Reproductive membership is independent of clinical hazard.", "checked": "2026-11-03" }, "openstax_male": { "title": "Anatomy and Physiology: Male Reproductive System", "url": "https://openstax.org/books/anatomy-and-physiology/pages/27-1-anatomy-and-physiology-of-the-male-reproductive-system", "model": "human", "design": "anatomy_reference", "finding": "Defines male reproductive organs and physiological functions.", "limitation": "Reproductive membership is independent of clinical hazard.", "checked": "2026-11-03" }, "purba2019": { "title": "CDK4/6 inhibition mitigates stem cell damage in a novel model for taxane-induced alopecia", "url": "https://pubmed.ncbi.nlm.nih.gov/31512803/", "model": "human_ex_vivo", "design": "injury_experiment", "finding": "Hair-follicle stem-cell injury was investigated in an experimental chemotherapy model.", "limitation": "Chemotherapy injury is not immune ablation; permanent alopecia remains possible.", "checked": "2026-11-03" }, "collin2021": { "title": "A single cell atlas of human cornea that defines its development, limbal progenitor cells and their interactions with the immune cells", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC8343164/", "model": "human", "design": "cell_atlas", "finding": "Distinguishes corneal and limbal cell populations.", "limitation": "Cell identity and expression alone do not measure toxicity.", "checked": "2026-11-03" }, "wang2021_bcma": { "title": "Humoral immune reconstitution after anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma", "url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9153033/", "model": "human", "design": "cell_therapy_clinical", "finding": "Normal marrow plasma-cell aplasia and prolonged hypogammaglobulinemia followed BCMA-directed CAR T-cell therapy.", "limitation": "Myeloma, prior therapies and conditioning affect immune recovery; this is not an isolated healthy-plasma-cell ablation trial.", "checked": "2026-11-03" } }, "unlisted_comparison": { "registered": { "proteins": 480, "loci": 523, "routes": { "Adult reproductive only": 351, "Adult reproductive + developmental": 95, "Developmental only": 34 }, "tumor_max_median_tpm": 33.52667324030507, "reproductive_max_median_ntpm": 13.05, "developmental_max_median_tpm": 0.8716235610292445, "normal_max_median_ntpm": 0.7, "unconfirmed_normal_signal": 7, "tumor_max_below_1": 0, "tumor_max_below_10": 80, "reviewed_tumor_protein": 0 }, "unlisted": { "proteins": 122, "loci": 123, "routes": { "Developmental only": 60, "Adult reproductive only": 49, "Adult reproductive + developmental": 13 }, "tumor_max_median_tpm": 35.64472154572741, "reproductive_max_median_ntpm": 0.4, "developmental_max_median_tpm": 11.204421797454327, "normal_max_median_ntpm": 1.4, "unconfirmed_normal_signal": 7, "tumor_max_below_1": 1, "tumor_max_below_10": 23, "reviewed_tumor_protein": 0 } }, "biology": { "version": "2026-11-06.1", "categories": [ { "id": "early_embryo", "label": "Early embryo", "definition": "Human preimplantation embryo RNA or published embryo gene-activation evidence." }, { "id": "oocyte_maternal", "label": "Oocyte / maternal", "definition": "Oocyte RNA, oocyte protein, or published maternal-effect function; species is recorded for each finding." }, { "id": "reproductive_secretion", "label": "Reproductive secretion", "definition": "Reproductive-tract secretions or sperm-associated proteins identified in the focused publication review. Four proteins are currently annotated; a systematic secretion-catalog review is pending." }, { "id": "testis", "label": "Testis / male germ cells", "definition": "RNA in testis tissue or cells, including male germ cells." }, { "id": "placenta", "label": "Placenta / trophoblast", "definition": "RNA in placental tissue or cells, including trophoblast populations." }, { "id": "gastrulation", "label": "Gastrulation", "definition": "RNA in the human Carnegie-stage-7 embryo dataset." }, { "id": "other_reproductive", "label": "Other reproductive", "definition": "Released reproductive association without one of the more specific reproductive tags above." }, { "id": "other_developmental", "label": "Other developmental", "definition": "Released developmental association without a stage-specific tag in this annotation." }, { "id": "uncategorized", "label": "Not categorized", "definition": "No biological category has been assigned in this annotation." } ], "rules": { "rna_minimum": 5, "rna_units": [ "TPM", "nTPM" ], "normal_context_input": "All supported testis, placenta and oocyte contexts from the pinned normal-expression replay, before the display top-five limit", "developmental_support": "At least 20 cells, 5 positive cells and 10% positive at 1 TPM; lineage mean at least 5 TPM", "assignment": "Multiple tags per protein; evidence records retain the study, stage, compartment and measured value. Biological tags do not change CTA admission." }, "curated_assignments": [ { "gene_ids": [ "ENSG00000213921" ], "label": "LEUTX", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5087614/", "source_title": "The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation", "model": "Human embryos and human embryonic stem-cell overexpression", "basis": "LEUTX and DPRX regulate an early-embryo transcriptional program. The paper also examines cancer-cell-line expression." }, { "gene_ids": [ "ENSG00000204595" ], "label": "DPRX", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5087614/", "source_title": "The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation", "model": "Human embryos and human embryonic stem-cell overexpression", "basis": "LEUTX and DPRX regulate an early-embryo transcriptional program. The paper also examines cancer-cell-line expression." }, { "gene_ids": [ "ENSG00000204595" ], "label": "DPRX", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4944136/", "source_title": "Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos", "model": "Human embryo transcripts and human stem-cell functional assays", "basis": "DPRX, DUXA, DUXB and TPRX2 are included in a study of human preimplantation homeobox factors." }, { "gene_ids": [ "ENSG00000258873" ], "label": "DUXA", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4944136/", "source_title": "Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos", "model": "Human embryo transcripts and human stem-cell functional assays", "basis": "DPRX, DUXA, DUXB and TPRX2 are included in a study of human preimplantation homeobox factors." }, { "gene_ids": [ "ENSG00000282757" ], "label": "DUXB", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4944136/", "source_title": "Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos", "model": "Human embryo transcripts and human stem-cell functional assays", "basis": "DPRX, DUXA, DUXB and TPRX2 are included in a study of human preimplantation homeobox factors." }, { "gene_ids": [ "ENSG00000259009" ], "label": "TPRX2", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4944136/", "source_title": "Characterization and target genes of nine human PRD-like homeobox domain genes expressed exclusively in early embryos", "model": "Human embryo transcripts and human stem-cell functional assays", "basis": "DPRX, DUXA, DUXB and TPRX2 are included in a study of human preimplantation homeobox factors." }, { "gene_ids": [ "ENSG00000213921" ], "label": "LEUTX", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9978639/", "source_title": "Comprehensive characterization of the embryonic factor LEUTX", "model": "Human cell models, proteomics and transcriptional assays", "basis": "LEUTX regulates ZNF280A and TPRX2. The study reports TPRX2 transcription and function despite its historical pseudogene annotation." }, { "gene_ids": [ "ENSG00000169548" ], "label": "ZNF280A", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9978639/", "source_title": "Comprehensive characterization of the embryonic factor LEUTX", "model": "Human cell models, proteomics and transcriptional assays", "basis": "LEUTX regulates ZNF280A and TPRX2. The study reports TPRX2 transcription and function despite its historical pseudogene annotation." }, { "gene_ids": [ "ENSG00000259009" ], "label": "TPRX2", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9978639/", "source_title": "Comprehensive characterization of the embryonic factor LEUTX", "model": "Human cell models, proteomics and transcriptional assays", "basis": "LEUTX regulates ZNF280A and TPRX2. The study reports TPRX2 transcription and function despite its historical pseudogene annotation." }, { "gene_ids": [ "ENSG00000282757" ], "label": "DUXB", "category_id": "early_embryo", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC9978639/", "source_title": "Comprehensive characterization of the embryonic factor LEUTX", "model": "Human cell models, proteomics and transcriptional assays", "basis": "LEUTX regulates ZNF280A and TPRX2. The study reports TPRX2 transcription and function despite its historical pseudogene annotation." }, { "gene_ids": [ "ENSG00000214102" ], "label": "WEE2", "category_id": "oocyte_maternal", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC5985286/", "source_title": "Homozygous Mutations in WEE2 Cause Fertilization Failure and Female Infertility", "model": "Human genetics, affected oocytes and rescue experiments", "basis": "WEE2 mutations caused fertilization failure in human oocytes. The study measured WEE2 protein and tested experimental rescue." }, { "gene_ids": [ "ENSG00000203908" ], "label": "KHDC3L", "category_id": "oocyte_maternal", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC4974340/", "source_title": "Identification of Maturation-Specific Proteins by Single-Cell Proteomics of Human Oocytes", "model": "Human oocyte proteomics", "basis": "KHDC3L/ECAT1 was identified by proteomics in human oocytes." }, { "gene_ids": [ "ENSG00000158077" ], "label": "NLRP14", "category_id": "oocyte_maternal", "source_url": "https://www.sciencedirect.com/science/article/pii/S2211124723015437", "source_title": "NLRP14 deficiency causes female infertility with oocyte maturation defects and early embryonic arrest by impairing cytoplasmic UHRF1 abundance", "model": "Human infertility investigation and mechanistic experiments", "basis": "NLRP14 deficiency was associated with female infertility, oocyte maturation defects and early embryonic arrest." }, { "gene_ids": [ "ENSG00000205022" ], "label": "PABPN1L", "category_id": "oocyte_maternal", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC7403729/", "source_title": "PABPN1L mediates cytoplasmic mRNA decay as a placeholder during the maternal-to-zygotic transition", "model": "Mouse oocytes and embryos", "basis": "Pabpn1l knockout disrupted the maternal-to-zygotic transition and early embryonic development in mice." }, { "gene_ids": [ "ENSG00000171053" ], "label": "PATE1", "category_id": "reproductive_secretion", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/pmid/25760095/", "source_title": "In-depth mapping of human testicular and epididymal proteins and their functional association with spermatozoa", "model": "Human reproductive tissues and proteins", "basis": "Human reproductive-tissue proteomics identified epididymal enrichment of PATE1 and WFDC8." }, { "gene_ids": [ "ENSG00000158901" ], "label": "WFDC8", "category_id": "reproductive_secretion", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/pmid/25760095/", "source_title": "In-depth mapping of human testicular and epididymal proteins and their functional association with spermatozoa", "model": "Human reproductive tissues and proteins", "basis": "Human reproductive-tissue proteomics identified epididymal enrichment of PATE1 and WFDC8." }, { "gene_ids": [ "ENSG00000188655" ], "label": "RNASE9", "category_id": "reproductive_secretion", "source_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC2669477/", "source_title": "Cloning, expression and location of RNase9 in human epididymis", "model": "Human tissue RNA and immunolocalization", "basis": "RNASE9 was cloned and localized in human epididymis; the study also reported sperm-associated protein." }, { "gene_ids": [ "ENSG00000124157" ], "label": "SEMG2", "category_id": "reproductive_secretion", "source_url": "https://pubmed.ncbi.nlm.nih.gov/12200457/", "source_title": "Semenogelin I and II, the predominant human seminal plasma proteins, are also expressed in non-genital tissues", "model": "Human tissue RT-PCR and immunohistochemistry", "basis": "Semenogelin II is a seminal-plasma protein." } ], "counts": [ { "id": "early_embryo", "label": "Early embryo", "definition": "Human preimplantation embryo RNA or published embryo gene-activation evidence.", "all": 184, "registered": 125, "unlisted": 59 }, { "id": "oocyte_maternal", "label": "Oocyte / maternal", "definition": "Oocyte RNA, oocyte protein, or published maternal-effect function; species is recorded for each finding.", "all": 37, "registered": 27, "unlisted": 10 }, { "id": "reproductive_secretion", "label": "Reproductive secretion", "definition": "Reproductive-tract secretions or sperm-associated proteins identified in the focused publication review. Four proteins are currently annotated; a systematic secretion-catalog review is pending.", "all": 4, "registered": 0, "unlisted": 4 }, { "id": "testis", "label": "Testis / male germ cells", "definition": "RNA in testis tissue or cells, including male germ cells.", "all": 435, "registered": 404, "unlisted": 31 }, { "id": "placenta", "label": "Placenta / trophoblast", "definition": "RNA in placental tissue or cells, including trophoblast populations.", "all": 25, "registered": 17, "unlisted": 8 }, { "id": "gastrulation", "label": "Gastrulation", "definition": "RNA in the human Carnegie-stage-7 embryo dataset.", "all": 26, "registered": 7, "unlisted": 19 }, { "id": "other_reproductive", "label": "Other reproductive", "definition": "Released reproductive association without one of the more specific reproductive tags above.", "all": 49, "registered": 34, "unlisted": 15 }, { "id": "other_developmental", "label": "Other developmental", "definition": "Released developmental association without a stage-specific tag in this annotation.", "all": 3, "registered": 3, "unlisted": 0 }, { "id": "uncategorized", "label": "Not categorized", "definition": "No biological category has been assigned in this annotation.", "all": 0, "registered": 0, "unlisted": 0 } ] }, "rows": [ { "entity_id": "PEG:950a3f7bfa727dab8bd4", "label": "AKAP17A", "classification": "Unsafe", "assessment_status": "screened", "shared_sequence": "exclude", "gene_ids": [ "ENSG00000197976", "ENSG00000292343" ], "reasons": [ "HPA normal protein", "Required RNA coverage", "Normal bulk", "HPA tissue clusters", "Monaco immune", "Rare vital-tissue cell expression", "Rare Protected-cell expression review" ] }, { "entity_id": "PEG:84cbaaf7a02d7fb10d06", "label": "AMY1A/B/C", "classification": "Unsafe", "assessment_status": "screened", "shared_sequence": "exclude", "gene_ids": [ "ENSG00000174876", "ENSG00000187733", "ENSG00000237763" ], "reasons": [ "HPA normal protein", "Normal bulk", "HPA tissue clusters", "Rare Protected-cell expression review" ] }, { "entity_id": "PEG:914ce8b7272e9121e04c", "label": "APOBEC3D/ENSG00000284554", "classification": "Unsafe", "assessment_status": "screened", "shared_sequence": "exclude", "gene_ids": [ "ENSG00000243811", "ENSG00000284554" ], "reasons": [ "HPA normal protein", "Normal bulk", "HPA tissue clusters", "HPA immune", "Monaco immune" ] }, { "entity_id": "PEG:b1df643c52fab062e84f", "label": "ARHGAP11B/ENSG00000284906", "classification": "Unsafe", "assessment_status": "screened", "shared_sequence": "exclude", "gene_ids": [ "ENSG00000284906", "ENSG00000285077" ], "reasons": [ "Required RNA coverage", "Normal bulk", "HPA tissue clusters", "Monaco immune", "Rare vital-tissue cell expression" ] }, { "entity_id": "PEG:003f20cddfc1ec107377", "label": "ARL17A/B", "classification": "Unsafe", "assessment_status": "screened", "shared_sequence": "exclude", "gene_ids": [ "ENSG00000185829", "ENSG00000228696" ], "reasons": [ "HPA normal protein", "Normal bulk", "HPA 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