SubstanceReferenceInformation — Scientific referencing

A cross-cutting block that gathers genes, genetic elements, biological targets and bibliographic references associated with a substance. The bridge between the chemistry of a substance and the pharmacology literature.

Purpose of the resource

Chemical characterisation alone does not explain a substance's pharmacological behaviour. SubstanceReferenceInformation carries the referential information that answers "what is its target?", "what gene encodes the target protein?", "which domain of that protein is involved?", "where does the information come from?".

Typical cases: trastuzumab targets HER2 (gene ERBB2, UniProt P04626) in Homo sapiens, of antagonist type. The resource does not carry activity itself, but the referential ID card that lets you retrieve it from public databases.

Key fields

JSON example

Trastuzumab targets HER2 (gene ERBB2, UniProt P04626), antagonist interaction, Kd 0.1 nM:

{
  "resourceType": "SubstanceReferenceInformation",
  "id": "example-trastuzumab-target",
  "comment": "Reference information for trastuzumab (anti-HER2 monoclonal antibody)",
  "gene": [{
    "geneSequenceOrigin": {
      "coding": [{
        "system": "http://terminology.hl7.org/CodeSystem/gene-origin",
        "code": "homo-sapiens",
        "display": "Homo sapiens"
      }]
    },
    "gene": {
      "coding": [{
        "system": "http://www.genenames.org",
        "code": "HGNC:3430",
        "display": "ERBB2"
      }]
    },
    "source": [{
      "type": "DocumentReference",
      "display": "NCBI Gene ID 2064"
    }]
  }],
  "geneElement": [{
    "type": {
      "coding": [{
        "system": "http://terminology.hl7.org/CodeSystem/gene-element-type",
        "code": "domain"
      }]
    },
    "element": {
      "system": "http://www.uniprot.org",
      "value": "P04626"
    }
  }],
  "target": [{
    "target": {
      "system": "http://www.uniprot.org",
      "value": "P04626"
    },
    "type": {
      "coding": [{
        "system": "http://terminology.hl7.org/CodeSystem/target-type",
        "code": "receptor"
      }]
    },
    "interaction": {
      "coding": [{
        "system": "http://terminology.hl7.org/CodeSystem/target-interaction",
        "code": "antagonist"
      }]
    },
    "organism": {
      "coding": [{
        "system": "http://www.ncbi.nlm.nih.gov/taxonomy",
        "code": "9606",
        "display": "Homo sapiens"
      }]
    },
    "amountQuantity": { "value": 0.1, "unit": "nM", "system": "http://unitsofmeasure.org" }
  }]
}

Typical use cases

• Target databases ChEMBL / DrugBank: import / export of substance — target associations.
• eCTD module 2.6.2: preclinical pharmacology dossier.
• Therapeutic stratification: substance — biomarker matching inside CDS (Clinical Decision Support).
• Pharmaco-genomic vigilance: correlate a substance with a patient variant through the target gene.
• R&D / repositioning: target-based search.

Common pitfalls

• Non-normative gene identifier: always use HGNC (HGNC:nnn), not the raw symbol, to avoid homonymy conflicts.
• UniProt without isoform: a UniProt identifier such as P04626 must be qualified by its isoform version when relevant (P04626-1, P04626-2).
• Mixing target & mechanism: target.type = nature (receptor, enzyme), target.interaction = mechanism (agonist). Confusing the two blurs semantics.
• Missing affinity unit: 0.1 without unit (nM, M, %) is uninterpretable. Always qualify with UCUM.
• No source: a target claim without a documentary source (DOI, PubMed) is not auditable.

Related resources

• SubstanceDefinition — references this block.
• SubstanceNucleicAcid, SubstancePolymer, SubstanceProtein, SubstanceSourceMaterial.
• MedicinalProductDefinition — the related medicinal product.
• DocumentReference — articles, dossiers, external databases.

See also: SubstanceDefinition and MedicinalProductDefinition.