A representation of one of the multiple variant sequences at a contiguous region in a particular ReferenceSequence.

Scope and Usage

Genetic variation, say in a population, is usually represented with respect to an explicit reference sequence. At a locus where variation exists in the population, there are multiple alleles (subsequences), which may include both the allele that occurs in the reference, as well as one or more alternate alleles. Each one of these alleles (including the reference) would correspond to a single unique occurrence of a ContextualAllele.

ContextualAllele as here defined is similar to the SO term sequence_variant, but where that definition describes a difference with respect to a sequence, ContextualAllele explicitly allows the reference allele, so that there would not be a difference with respect to the reference sequence; note that the reference allele is not guaranteed to be the minor allele in any population.

The term ContextualAllele means that the allele should either represent a contiguous section of the ReferenceSequence, or the replacement of such a section with a new contiguous section (including an empty section for a deletion). While it would be possible to represent two widely spaced SNPs as a ContextualAllele that reproduces the ReferenceSequence between them, this would not be the intended use; such cases should be handled through the use of a ComplexCanonicalAllele.

This definition of ContextualAllele would allow for large deletions or insertions; it is left as an implementation decision whether there is a size limit above which the implementing system will no longer use this representation.

ContextualAllele is an abstract class: there are no instances of the base ContextualAllele class. Instead, each concrete example of a ContextualAllele must be either a GenomicContextualAllele, a TranscriptContextualAllele, or an AminoAcidContextualAllele.

Each ContextualAllele is the representation of an allele within a single sequence. For example, if a variant occurs along a chromosome in a location that is covered by the coding region of a transcript, there will be three different ContextualAlleles: One representing the allele in the context of the GenomeReferenceSequence, a second representing the allele in the context of the TranscriptReferenceSequence, and a third in the context of an AminoAcidReferenceSequence.

Relationships between these multiple ContextualAlleles can happen at two levels: GenomicContextualAllele and TranscriptContextualAllele are related through the construct of each being related to the same SimpleCanonicalAllele. However, an AminoAcidContextualAllele will be directly related to a TranscriptContextualAllele following a parallel construction with the relationship between the associated TranscriptReferenceSequence and the AminoAcidReferenceSequence.

Observed v. Derived

Though the main use of ContextualAllele is to record alleles at observed variant sites in the human genome, use of the ContextualAllele model does not demand that an instantiated allele actually be observed. Implementers may choose to use the model for different purposes; if a particular implementer demands that all entries to a database of ContextualAllele represent observed variation, then it is incumbent upon that implementer to add documentation to that effect.

Exclusions and Limitations

ContextualAllele as presently defined may be a poor choice for representing large insertions or deletions, as the reference and alternate alleles are stored in full.

ContextualAllele is not capable of representing the uncertainty of starting or ending coordinates of a variant.

Conceptual Model

ContextualAllele Conceptual Diagram

Resource Model: ContextualAllele