{
  "_meta": {
    "doc": "Sniff CoverageFrames: reasoned absence as machine-readable frames. Generated, never hand-maintained. Conforms to schema/sniff-coverage-frame.yaml plus the provenance module, and is verified against them on every build.",
    "schema": "https://sniff.world/schema/coverage-frame",
    "schema_provenance": "https://sniff.world/schema/coverage-frame-provenance",
    "generated": "2026-08-13",
    "release_id": "sniff:release/2026-09-04",
    "cell_index": "sniff:artifact/coverage-cell-index",
    "cell_index_sha256": "dd107378f6969b02a55103552f3674277b3d190024a5d22ee9d42055bacedeeb"
  },
  "frames": [
    {
      "id": "sniff:frame/human-disease-gene-canine-model",
      "conforms_to": "sniff:ProvenancedCoverageFrame",
      "question": "Does a canine model foundation exist for this human disease gene under ClinVar 3-star review plus an assertable one-to-one ortholog?",
      "subject_population": "Human disease genes touched by the dog-to-human bridge",
      "object_population": "Canine orthologs",
      "predicate": "biolink:model_of",
      "expected_cardinality": 16754,
      "answered_count": 124,
      "dark_count": 16630,
      "dark_by_cause": {
        "no_disease_anchor": 11161,
        "below_bar": 5362,
        "unreachable": 107
      },
      "cell_source": "sniff:artifact/frontier-map",
      "sources_checked": [
        "infores:clinvar",
        "infores:ensembl-gene"
      ],
      "as_of": "2026-08-13",
      "release_id": "sniff:release/2026-09-04",
      "search_protocol": "sniff:protocol/human-disease-gene-canine-model@11",
      "subject_population_ref": "sniff:population/bridge-touched-human-genes@2",
      "object_population_ref": "sniff:population/canine-one2one-ortholog-space@2",
      "scope": {
        "measures": "This frame measures ClinVar 3-star review reach into canine models via dog orthology, not the canine literature.",
        "sources_queried": [
          "infores:clinvar",
          "infores:ensembl-gene"
        ],
        "sources_not_queried": [
          {
            "source": "infores:omia",
            "reason": "OMIA is the authority on documented canine Mendelian disease. This frame's answered predicate is ClinVar 3-star pathogenic or likely pathogenic plus an assertable dog ortholog, so OMIA was not queried.",
            "close_path": "Publish a parallel OMIA-scoped frame over the same subject axis (sniff:frame/human-disease-gene-canine-model/omia). Do not join OMIA into this frame's answered predicate. Narrowness is the measurement."
          }
        ]
      }
    },
    {
      "id": "sniff:frame/human-disease-gene-canine-model/omia",
      "conforms_to": "sniff:ProvenancedCoverageFrame",
      "question": "Does OMIA document a canine Mendelian disease-gene for this human disease gene?",
      "subject_population": "Human disease genes touched by the dog-to-human bridge",
      "object_population": "Canine orthologs",
      "predicate": "biolink:model_of",
      "expected_cardinality": 16754,
      "answered_count": 183,
      "dark_count": 16571,
      "dark_by_cause": {
        "no_disease_anchor": 16571
      },
      "cell_source": "sniff:artifact/coverage-stack-index",
      "sources_checked": [
        "infores:omia"
      ],
      "as_of": "2026-08-27",
      "release_id": "sniff:release/2026-09-04",
      "search_protocol": "sniff:protocol/human-disease-gene-canine-model-omia@1",
      "subject_population_ref": "sniff:population/bridge-touched-human-genes@2",
      "object_population_ref": "sniff:population/canine-one2one-ortholog-space@2",
      "scope": {
        "measures": "This frame measures OMIA's documented canine Mendelian disease-gene reach into the same human-disease-gene universe. It is not ClinVar, and it is not a combined census.",
        "sources_queried": [
          "infores:omia"
        ],
        "sources_not_queried": [
          {
            "source": "infores:clinvar",
            "reason": "This frame measures OMIA. ClinVar 3-star reach is a different frame over the same axis.",
            "close_path": "Stack with sniff:frame/human-disease-gene-canine-model. Do not join ClinVar into this answered predicate."
          }
        ]
      }
    },
    {
      "id": "sniff:frame/human-disease-gene-canine-model/intersection",
      "conforms_to": "sniff:ProvenancedCoverageFrame",
      "question": "Does any scoped source document a canine model foundation for this human disease gene?",
      "subject_population": "Human disease genes touched by the dog-to-human bridge",
      "object_population": "Canine orthologs",
      "predicate": "biolink:model_of",
      "expected_cardinality": 16754,
      "answered_count": 292,
      "dark_count": 16462,
      "dark_by_cause": {},
      "cell_source": "sniff:artifact/coverage-stack-index",
      "sources_checked": [
        "infores:clinvar",
        "infores:ensembl-gene",
        "infores:omia"
      ],
      "as_of": "2026-08-13",
      "release_id": "sniff:release/2026-09-04",
      "search_protocol": "sniff:protocol/human-disease-gene-canine-model-intersection@1",
      "subject_population_ref": "sniff:population/bridge-touched-human-genes@2",
      "object_population_ref": "sniff:population/canine-one2one-ortholog-space@2",
      "constituents": [
        "sniff:frame/human-disease-gene-canine-model",
        "sniff:frame/human-disease-gene-canine-model/omia"
      ],
      "scope": {
        "measures": "This frame stacks scoped source-frames over one subject axis. A cell is answered when any constituent is lit, and dark when every constituent of this stack is dark. dark_in_all_frames is scoped to the named constituents, not to the world. Causes stay on the constituents.",
        "sources_queried": [
          "infores:clinvar",
          "infores:ensembl-gene",
          "infores:omia"
        ],
        "sources_not_queried": []
      }
    }
  ],
  "protocols": [
    {
      "id": "sniff:protocol/human-disease-gene-canine-model@11",
      "protocol_version": "11",
      "pipeline": "https://github.com/sniff-world/coverage-frame/blob/main/pipeline/build-coverage-frames.mjs",
      "match_criteria": "A cell is answered when the human gene has a 3-star ClinVar P/LP anchor AND an assertable dog ortholog (Compara one2one, or the OrthoDB/OMA moderate ladder for reachability). Dark causes per the precedence funnel; below_bar is denominated by the named dial.",
      "completeness": "exhaustive",
      "cause_precedence": [
        "unreachable",
        "method_limited",
        "no_disease_anchor",
        "unstudied",
        "below_bar",
        "absent"
      ],
      "dial_references": [
        "sniff:dial/clinvar-review-floor@1"
      ],
      "positive_controls": [
        {
          "subject": "ENSEMBL:ENSG00000141510",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "TP53: OMIA:000620-9615 (histiocytic sarcoma), canine, listed by OMIA among the genes associated with this phene, independent of this pipeline. Weaker anchor than F8 and VWF: OMIA records this phene as multifactorial with no key variant known, and removed its candidate variant from the table of likely causal variants. Retained as a control on the recorded association, not on a causal variant.",
          "basis_kind": "independent_source",
          "receipt_source": "infores:omia",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000185010",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "F8: OMIA:000437-9615 (hemophilia A), canine, documented independent of this pipeline",
          "basis_kind": "independent_source",
          "receipt_source": "infores:omia",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000110799",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "VWF: OMIA:001057-9615 (von Willebrand disease), canine, documented independent of this pipeline",
          "basis_kind": "independent_source",
          "receipt_source": "infores:omia",
          "outcome": "held"
        }
      ],
      "darkness_controls": [
        {
          "subject": "ENSEMBL:ENSG00000187191",
          "expected_cause": "unreachable",
          "observed_cause": "unreachable",
          "observed_status": "dark",
          "basis": "DAZ3: the DAZ cluster arose by transposition and amplification of autosomal DAZL onto the primate Y chromosome (Saxena et al. 1996, PMID:8896558); no non-primate genome, the dog included, carries a DAZ gene, so no ortholog exists for the assay to observe",
          "basis_kind": "independent_literature",
          "receipt_source": "PMID:8896558",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000112592",
          "expected_cause": "below_bar",
          "observed_cause": "below_bar",
          "observed_status": "dark",
          "basis": "TBP: ClinVar holds 28 germline pathogenic or likely pathogenic records for TBP (spinocerebellar ataxia 17) and none reviewed by an expert panel (E-utilities esearch, read 2026-09-04 UTC), so a human anchor exists and sits under the three-star bar",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:clinvar",
          "outcome": "held",
          "receipt_as_of": "2026-09-04"
        },
        {
          "subject": "ENSEMBL:ENSG00000121410",
          "expected_cause": "no_disease_anchor",
          "observed_cause": "no_disease_anchor",
          "observed_status": "dark",
          "basis": "A1BG: ClinVar holds no germline pathogenic or likely pathogenic record for A1BG (E-utilities esearch, read 2026-09-04 UTC) while a one-to-one dog ortholog exists, so the question cannot be asked of this gene from a human anchor",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:clinvar",
          "outcome": "held",
          "receipt_as_of": "2026-09-04"
        }
      ],
      "executed_at": "2026-08-13"
    },
    {
      "id": "sniff:protocol/human-disease-gene-canine-model-omia@1",
      "protocol_version": "1",
      "pipeline": "https://github.com/sniff-world/coverage-frame/blob/main/pipeline/build-coverage-composition.mjs",
      "match_criteria": "A cell is answered when a recorded OMIA canine (NCBI taxon 9615) disease-gene identifier exists for this human gene symbol, mapped onto the shared subject axis. Dark cells are no_disease_anchor under OMIA: no such record. This frame does not assign below_bar.",
      "completeness": "exhaustive",
      "cause_precedence": [
        "unreachable",
        "method_limited",
        "no_disease_anchor",
        "unstudied",
        "below_bar",
        "absent"
      ],
      "dial_references": [],
      "positive_controls": [
        {
          "subject": "ENSEMBL:ENSG00000142168",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "SOD1: OMIA:000263-9615 degenerative myelopathy, canine, documented independent of this pipeline",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "receipt_as_of": "2026-08-27",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000185010",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "F8: OMIA:000437-9615 haemophilia A, canine, documented independent of this pipeline",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "receipt_as_of": "2026-08-27",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000110799",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "VWF: OMIA:001057-9615 von Willebrand disease, canine, documented independent of this pipeline",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "receipt_as_of": "2026-08-27",
          "outcome": "held"
        }
      ],
      "darkness_controls": [
        {
          "subject": "ENSEMBL:ENSG00000121410",
          "expected_cause": "no_disease_anchor",
          "observed_cause": "no_disease_anchor",
          "observed_status": "dark",
          "basis": "A1BG: no OMIA canine phene lists this gene (OMIA phene table, read directly 2026-09-04) while a one-to-one dog ortholog exists",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "receipt_as_of": "2026-08-27",
          "outcome": "held"
        }
      ],
      "executed_at": "2026-08-27"
    },
    {
      "id": "sniff:protocol/human-disease-gene-canine-model-intersection@1",
      "protocol_version": "1",
      "pipeline": "https://github.com/sniff-world/coverage-frame/blob/main/pipeline/build-coverage-composition.mjs",
      "match_criteria": "A cell is answered when ANY constituent frame is answered (lit in at least one scoped source). A cell is dark when EVERY constituent is dark. Causes are not assigned here; they remain on the constituents. Constituents must share one subject axis.",
      "completeness": "exhaustive",
      "cause_precedence": [
        "unreachable",
        "method_limited",
        "no_disease_anchor",
        "unstudied",
        "below_bar",
        "absent"
      ],
      "dial_references": [],
      "positive_controls": [
        {
          "subject": "ENSEMBL:ENSG00000142168",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "SOD1: OMIA:000263-9615 degenerative myelopathy, canine, documented independent of this pipeline Intersection control: lit in at least one constituent.",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000185010",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "F8: OMIA:000437-9615 haemophilia A, canine, documented independent of this pipeline Intersection control: lit in at least one constituent.",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "outcome": "held"
        },
        {
          "subject": "ENSEMBL:ENSG00000110799",
          "expected_status": "answered",
          "observed_status": "answered",
          "basis": "VWF: OMIA:001057-9615 von Willebrand disease, canine, documented independent of this pipeline Intersection control: lit in at least one constituent.",
          "basis_kind": "same_source_hand_verified",
          "receipt_source": "infores:omia",
          "outcome": "held"
        }
      ],
      "executed_at": "2026-08-13"
    }
  ],
  "populations": [
    {
      "id": "sniff:population/bridge-touched-human-genes@2",
      "source": "infores:clinvar",
      "source_version": "sniff:release/2026-08-13",
      "selection": "Every human gene touched by the dog-to-human bridge: ClinVar P/LP disease-gene atoms (3-star anchors kept, below-expert-bar signal retained as below_bar) joined to the dog orthology ladder; the human-gene selection funnel total (the human-gene selection funnel total).",
      "count": 16754
    },
    {
      "id": "sniff:population/canine-one2one-ortholog-space@2",
      "source": "infores:ensembl-gene",
      "source_version": "Ensembl Compara release 116",
      "selection": "Dog genes with ortholog_status=one2one in the Ensembl Compara one-to-one set; the moderate OrthoDB/OMA ladder used for reachability is stated in match_criteria, not double-counted here.",
      "count": 17239
    }
  ]
}