metakb_moa_cdm_20260108.json

{
  "assertions":{
    "id":"metakb:id that sums up the proposition parts",
    "type":"Statement",
    "specifiedBy":{
      "id":"metakb.method:2026",
      "type":"Method",
      "name":"MetaKB (2026)",
      "reportedIn":{
        "type":"Document",
        "name":"Wagnerds et al",
        "title":"MetaKB v2",
        "doi":"10.1038/1111-1-1111-111-1111",
        "pmid":"9999999"
      }
    },
    "proposition":{
      "type":"VariantTherapeuticResponseProposition",
      "subjectVariant":{
        "id":"catvar:ga4gh:VA.D6NzpWXKqBnbcZZrXNSXj4tMUwROKbsQ",
        "type":"CategoricalVariant",
        "name":"ABL1 T315I",
        "constraints":[
          {
            "type":"DefiningAlleleConstraint",
            "allele":{
              "id":"ga4gh:VA.D6NzpWXKqBnbcZZrXNSXj4tMUwROKbsQ",
              "type":"Allele",
              "digest":"D6NzpWXKqBnbcZZrXNSXj4tMUwROKbsQ",
              "location":{
                "id":"ga4gh:SL.jGElwyBPYNWI-BkFFHKfgLJynt9zuNPs",
                "type":"SequenceLocation",
                "digest":"jGElwyBPYNWI-BkFFHKfgLJynt9zuNPs",
                "sequenceReference":{
                  "type":"SequenceReference",
                  "refgetAccession":"SQ.dmFigTG-0fY6I54swb7PoDuxCeT6O3Wg"
                },
                "start":314,
                "end":315,
                "sequence":"T"
              },
              "state":{
                "type":"LiteralSequenceExpression",
                "sequence":"I"
              }
            }
          }
        ]
      },
      "geneContextQualifier":{
        "id":"normalize.gene.hgnc:76",
        "conceptType":"Gene",
        "name":"ABL1",
        "primaryCoding":{
          "id":"hgnc:76",
          "system":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/",
          "code":"HGNC:76"
        }
      },
      "predicate":"predictsResistanceTo",
      "objectTherapeutic":{
        "id":"normalize.therapy.rxcui:282388",
        "extensions":[
          
        ],
        "conceptType":"Therapy",
        "name":"imatinib",
        "primaryCoding":{
          "id":"rxcui:282388",
          "system":"https://mor.nlm.nih.gov/RxNav/search?searchBy=RXCUI&searchTerm=",
          "code":"282388"
        },
        "mappings":[
          
        ]
      },
      "conditionQualifier":{
        "id":"normalize.disease.ncit:C3174",
        "extensions":[
          
        ],
        "conceptType":"Disease",
        "name":"Chronic Myeloid Leukemia, BCR-ABL1 Positive",
        "primaryCoding":{
          "id":"ncit:C3174",
          "system":"https://ncit.nci.nih.gov/ncitbrowser/ConceptReport.jsp?dictionary=NCI_Thesaurus&code=",
          "code":"C3174"
        },
        "mappings":[
          
        ]
      }
    },
    "direction":"supports",
    "classification":{
      "id":"metakb.classification:1",
      "name":"tmp metakb tr classification",
      "primaryCoding":{
        "system":"AMP/ASCO/CAP (AAC) Guidelines, 2017",
        "code":"Tier I"
      }
    },
    "hasEvidenceLines":[
      {
        "type":"EvidenceLine",
        "hasEvidenceItems":[
          {
            "id":"moa.assertion:66",
            "type":"Statement",
            "description":"T315I mutant ABL1 in p210 BCR-ABL cells resulted in retained high levels of phosphotyrosine at increasing concentrations of inhibitor STI-571, whereas wildtype appropriately received inhibition.",
            "specifiedBy":{
              "id":"moa.method:2021",
              "type":"Method",
              "name":"MOAlmanac (2021)",
              "reportedIn":{
                "type":"Document",
                "name":"Reardon, B., Moore, N.D., Moore, N.S. et al.",
                "title":"Integrating molecular profiles into clinical frameworks through the Molecular Oncology Almanac to prospectively guide precision oncology",
                "doi":"10.1038/s43018-021-00243-3",
                "pmid":"35121878"
              }
            },
            "reportedIn":[
              {
                "id":"moa.source:45",
                "type":"Document",
                "extensions":[
                  {
                    "name":"source_type",
                    "value":"Journal"
                  }
                ],
                "title":"Gorre, Mercedes E., et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293.5531 (2001): 876-880.",
                "urls":[
                  "https://doi.org/10.1126/science.1062538"
                ],
                "doi":"10.1126/science.1062538",
                "pmid":"11423618"
              }
            ],
            "proposition":{
              "type":"VariantTherapeuticResponseProposition",
              "subjectVariant":{
                "id":"moa.variant:66",
                "type":"CategoricalVariant",
                "name":"ABL1 p.T315I (Missense)",
                "extensions":[
                  {
                    "name":"MOA representative coordinate",
                    "value":{
                      "chromosome":"9",
                      "start_position":"133748283",
                      "end_position":"133748283",
                      "reference_allele":"C",
                      "alternate_allele":"T",
                      "cdna_change":"c.944C>T",
                      "protein_change":"p.T315I",
                      "exon":"5"
                    }
                  }
                ],
                "members":[
                  {
                    "id":"ga4gh:VA.HUJOQCml0LngKmUf5IJIYQk9CfKmagbf",
                    "type":"Allele",
                    "name":"9-133748283-C-T",
                    "digest":"HUJOQCml0LngKmUf5IJIYQk9CfKmagbf",
                    "location":{
                      "id":"ga4gh:SL.vd9Kb9rCPWBEUZ_wbBxZyulgOAq-jk0P",
                      "type":"SequenceLocation",
                      "digest":"vd9Kb9rCPWBEUZ_wbBxZyulgOAq-jk0P",
                      "sequenceReference":{
                        "type":"SequenceReference",
                        "refgetAccession":"SQ.KEO-4XBcm1cxeo_DIQ8_ofqGUkp4iZhI"
                      },
                      "start":133748282,
                      "end":133748283,
                      "sequence":"C"
                    },
                    "state":{
                      "type":"LiteralSequenceExpression",
                      "sequence":"T"
                    }
                  }
                ],
                "mappings":[
                  {
                    "coding":{
                      "system":"https://www.ncbi.nlm.nih.gov/snp/",
                      "code":"rs121913459"
                    },
                    "relation":"relatedMatch"
                  }
                ]
              },
              "geneContextQualifier":{
                "id":"moa.gene:ABL1",
                "name":"ABL1"
              },
              "predicate":"predictsResistanceTo",
              "objectTherapeutic":{
                "id":"moa.drug:Imatinib",
                "conceptType":"Drug",
                "name":"Imatinib"
              },
              "conditionQualifier":{
                "id":"moa.disease:Chronic Myelogenous Leukemia",
                "conceptType":"Disease",
                "name":"Chronic Myelogenous Leukemia",
                "mappings":[
                  {
                    "coding":{
                      "id":"oncotree:CML",
                      "name":"Chronic Myelogenous Leukemia",
                      "system":"https://oncotree.mskcc.org/?version=oncotree_latest_stable&field=CODE&search=",
                      "code":"CML"
                    },
                    "relation":"exactMatch"
                  }
                ]
              }
            },
            "direction":"supports"
          }
        ],
        "directionOfEvidenceProvided":"supports"
      }
    ]
  }
}