Gene Fusion

Definition and Information Model

Draft

May change significantly in future releases. See Maturity Model.

Computational Definition

A representation of the joining of two genes resulting in a chimeric transcript and/or novel interaction between a rearranged regulatory elements with the expression of a partner gene product (a regulatory fusion).

Information Model

Field	Flags	Type	Limits	Description
id		string	0..1	The ‘logical’ identifier of the Entity in the system of record, e.g. a UUID. This ‘id’ is unique within a given system, but may or may not be globally unique outside the system. It is used within a system to reference an object from another.
type		string	1..1	MUST be “CategoricalVariant”
name		string	1..1	A primary name for the entity.
description		string	0..1	A free-text description of the Entity.
aliases	⋮	string	0..m	Alternative name(s) for the Entity.
extensions	⋮	Extension	0..m	A list of extensions to the Entity, that allow for capture of information not directly supported by elements defined in the model.
members	⋮	Variation \| iriReference	0..m	A non-exhaustive list of VRS Variations that satisfy the constraints of this categorical variant.
constraints	⋮	Adjacency Constraint	1..m	The constraints must contain at least one item of an Adjacency Constraint.
mappings	⋮	ConceptMapping	0..m	A list of mappings to concepts in terminologies or code systems. Each mapping should include a coding and a relation.

Composes: Categorical Variant

A GeneFusion is a Categorical Variant with at least one constraint:

An Adjacency Constraint with the adjoinedElements array containing either an iriReference, MappableConcept, Location, or an UnspecifiedElement as elements.

Examples

The following example Categorical Variants satisfy this Recipe:

Implementation Guidance

Constraints

We recommend following the Variant Interpretation for Cancer Consortium (VICC)’s Gene Fusion Specification when modeling a Gene Fusion with the Adjacency 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 an 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 an UnspecifiedElement.

While they do not currently utilize Cat-VRS, the VICC FUSOR <https://github.com/cancervariants/fusor> and Fusion-Builder <https://github.com/cancervariants/fusion-builder> tools can assist with representing Gene Fusions according to the VICC Gene Fusion Specification.

Members

When modeling a Gene Fusion, members may be populated with VRS Adjacency objects, where the adjoinedSequences property can be populated with two VRS objects that are either:

VRS’ Implementation Guidance for Adjacency objects contains guidance on sequence locations and directionality, normalization, and linker sequences.

We recommend the following resources for constructing Sequence Location objects:

vrs-python is a Python package and reference implementation for VRS that can be used to generate VRS digests.
SeqRepo provides access to reference sequences and can be used to obtain Sequence Reference information, such as names and aliases, when constructing Sequence Reference objects directly.

Note

While neither the moleculeType nor residueAlphabet are required attributes for a Sequence Reference, we strongly recommend populating them within your implementation to clearly communicate to users what type of sequence your SequenceReference exists upon. Consider the following values, depending on the type of SequenceReference expressed:

Sequence reference type	moleculeType	residueAlphabet
Genomic	genomic	na
RNA	RNA	na
mRNA	mRNA	na
Protein	protein	aa

For additional Implementation Guidance, please visit VRS’ page for the Sequence Location concept.