Adjacency Constraint
Definition and Information Model
Warning
This data class is at a draft maturity level and may change significantly in future releases. Maturity levels are described in the GKS Maturity Model.
Computational Definition
Components that define a molecular adjacency of congruent elements.
Information Model
Some AdjacencyConstraint attributes are inherited from Constraint.
Field |
Flags |
Type |
Limits |
Description |
|---|---|---|---|---|
type |
string |
1..1 |
MUST be “AdjacencyConstraint” |
|
adjoinedElements |
↓ | iriReference | MappableConcept | Location | Terminus | UnspecifiedElement |
2..2 |
The elements of the adjacency. |
functionalDomains |
⋮ | 0..m |
Functional domains whose presence or absence is required to satisfy the adjacency. |
|
linker |
0..1 |
The sequence found between the adjoined elements. |
||
orderKnown |
boolean |
1..1 |
When orderKnown is true, the order of adjoinedElements is assumed to denote the 5’ partner first and the 3’ partner second. If orderKnown is false, then the order of adjoinedElements assumed not in fact to be known, as in the case of a fusion where only one or both partners are known, but not their relative order. This field is redundant and may be set to true when using Sequence Locations and following the VRS 2 Adjacency model, as the order is implied by the usage of start and end on respective adjoinedElements. |
Examples
The following are example implementations of AdjacencyConstraint:
BCR(ncbi:613)::ABL1(ncbi:25)
"constraints": [
{
"type": "AdjacencyConstraint",
"orderKnown": true,
"adjoinedElements": [
{
"id": "ncbi:613",
"conceptType": "Gene",
"name": "BCR",
"primaryCoding": {
"id": "ncbi:613",
"name": "BCR",
"system": "https://www.ncbi.nlm.nih.gov/gene",
"code": "613",
"iris": [
"https://www.ncbi.nlm.nih.gov/gene/613"
]
}
},
{
"id": "ncbi:25",
"conceptType": "Gene",
"name": "ABL1",
"primaryCoding": {
"id": "ncbi:25",
"name": "ABL1",
"system": "https://www.ncbi.nlm.nih.gov/gene",
"code": "25",
"iris": [
"https://www.ncbi.nlm.nih.gov/gene/25"
]
}
}
]
v::NTRK1(hgnc:8031)
{
"type": "AdjacencyConstraint",
"orderKnown": false,
"adjoinedElements": [
{
"type": "UnspecifiedElement"
},
{
"id": "hgnc:8031",
"conceptType": "Gene",
"name": "NTRK1",
"primaryCoding": {
"id": "hgnc:8031",
"name": "NTRK1",
"system": "https://genenames.org",
"code": "HGNC:8031",
"iris": [
"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:7230"
]
}
}
]
}
?::ZNF384(ncbi:171017)
{
"type": "AdjacencyConstraint",
"orderKnown": true,
"adjoinedElements": [
{
"type": "UnspecifiedElement"
},
{
"id": "ncbi:171017",
"conceptType": "Gene",
"name": "ZNF384",
"primaryCoding": {
"id": "ncbi:171017",
"name": "ZNF384",
"system": "https://www.ncbi.nlm.nih.gov/gene",
"code": "171017",
"iris": [
"https://www.ncbi.nlm.nih.gov/gene/171017"
]
}
}
]
}
FGFR2(hgnc:3689)::v
{
"type": "AdjacencyConstraint",
"orderKnown": true,
"adjoinedElements": [
{
"id": "hgnc:3689",
"conceptType": "Gene",
"name": "FGFR2",
"primaryCoding": {
"id": "hgnc:3689",
"name": "FGFR2",
"system": "https://genenames.org",
"code": "HGNC:3689",
"iris": [
"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:3689"
]
}
},
{
"type": "UnspecifiedElement"
}
],
"functionalDomains": [
{
"name": "FGFR2 protein product (refseq:NP_000132.3) protein tyrosine kinase domain",
"type": "FunctionalDomain",
"location": {
"id": "ga4gh:SL.6VpekQsGUz74aAgQ0RklrrgJVwYNK8xx",
"type": "SequenceLocation",
"description": "Amino acid positions 456 - 768 within the FGFR2 protein (refseq:NP_000132.3), which is the protein product of the MANE Select coding transcript for FGFR2 (refseq:NM_000141.5). This sequence corresponds to the catalytic domain of the Protein Tyrosine Kinase.",
"digest": "6VpekQsGUz74aAgQ0RklrrgJVwYNK8xx",
"sequenceReference": {
"id": "refseq:NP_000132.3",
"type": "SequenceReference",
"name": "NP_000132.3",
"description": "The protein product of the MANE Select coding transcript for FGFR2 (refseq:NM_000141.5), corresponding to the RefSeq protein accession NP_000132.3.",
"aliases": [
"ensembl:ENSP00000351276.5",
"ga4gh:SQ.hAWsXlUEul8pcUbRmOHRQ6osiUdGIiWs"
],
"refgetAccession": "SQ.hAWsXlUEul8pcUbRmOHRQ6osiUdGIiWs",
"residueAlphabet": "aa"
},
"start": 455,
"end": 768
},
"status": "preserved"
},
{
"name": "FGFR2(refseq:NM_000141.5) kinase domain",
"type": "FunctionalDomain",
"location": {
"id": "ga4gh:SL.511EV3zYjlFNE3CEUMfu9YtuO7q6mOoG",
"description": "Positions 1999 - 2937 of the FGFR2 MANE Select transcript (refseq:NM_000141.5), corresponding to FGFR2's kinase domain on the product protein (refseq:NP_000132.3).",
"type": "SequenceLocation",
"digest": "511EV3zYjlFNE3CEUMfu9YtuO7q6mOoG",
"sequenceReference": {
"id": "refseq:NM_000141.5",
"name": "NM_000141.5",
"description": "The MANE Select coding transcript for FGFR2.",
"aliases": [
"ga4gh:SQ.MHz9sixiWHMnZDi0pTaEqEM6nf08v2Vu"
],
"type": "SequenceReference",
"refgetAccession": "SQ.MHz9sixiWHMnZDi0pTaEqEM6nf08v2Vu",
"residueAlphabet": "na"
},
"start": 1998,
"end": 2937
},
"status": "preserved"
}
]
}
Implementation Guidance
The Adjacency Constraint is similar to VRS’ Adjacency class, except that the adjoinedElements field supports data types in addition to iriReference and Location.
We recommend following the Variant Interpretation for Cancer Consortium’s Gene Fusion Specification when modeling a Gene Fusion using this constraint. Specifically by:
Representing Named Gene Components as a MappableConcept with the conceptType field set to “Gene”; the Gene Normalizer can help.
Representing Multiple Possible Gene Components as a UnspecifiedElement within the Adjacency Constraint. An exhaustive or non-exhaustive list of possible elements can be included as an Extension. We recommend setting the value to be a ConceptSet with the membershipOperator field set to “OR”.
Representing an Unknown Gene Component as a UnspecifiedElement.