TranscriptReferenceCoordinate

Scope and Usage

ReferenceCoordinate represents a particular continguous location at which different alleles may be defined with ContextualAllele. TranscriptReferenceCoordinate is a ReferenceCoordinate where the underlying reference sequence is a TranscriptReferenceSequence.

TranscriptReferenceCoordinates may refer to either exonic or intronic locations. Because exonic locations are in the TranscriptReferenceSequence, the coordinate may be defined as described in ReferenceCoordinate.

However, intronic locations are not part of the TranscriptReferenceSequence, and cannot be simply described using a start and end. In HGVS, intronic variants are described in a transcript by using two integers. The first is a location in the transcript, which is supposed to be the first or last base in an exon. The second number is a coordinate into the intron from that location. This assumes an alignment of this transcript to a particular GenomicReferenceSequence. There may be multiple such alignments to multiple GenomicReferenceSequences, though this is not modeled in HGVS expressions.

TranscriptReferenceCoordinate uses a similar system to refer to intronic positions. Each TranscriptReferenceCoordinate, like any ReferenceCoordinate, has two Position elements, one for each end of the coordinate. Each of these Positions may be either an InternalPosition (for an exonic Position) or an ExternalPosition (for an intronicPosition). An ExternalPosition entity contains two integer attributes, which are the position in the transcript of the intron/exon boundary (called the index), and the distance into the intron (the offsetDirection). In addition, the ExternalPosition contains a reference to a GenomicReferenceSequence where the transcript was mapped.

If an allele occurs in an intron, the allele does not occur in the transcript, but in a genomic sequence; the relation to this sequence is managed by ExternalPosition. Note that the transcript may be mapped to multiple genomic sequences. Rather than allow a multiplicity of start and ends for a single TranscriptContextualAllele, we allow only one. Each mapping is represented by the creation of a new TranscriptContextualAllele with its start and end corresponding to that specific mapping. These TranscriptContextualAlleles are then aggregated at the SimpleCanonicalAllele level.

Exclusions and Limitations

The relationship between the transcript and the genomic sequence to which it is mapped is partially modeled, the details of the mapping are not modeled. In other words, for intronic coordinates, using only the data modeled here, it will be impossible to calculate the reference allele.

Attributes

When describing observations a concise and interoperable method is required to reduce ambiguity as well as clarify the semantics of nature language and biological meaning. The use of a formal, stable ontological structure allows highly detailed descriptions as well as a logically ordered interrelationship between concepts.

Related Entities

The TranscriptReferenceCoordinate inherits both the start and end entities from ReferenceCoordinate(reference_coordinate.html). However, unlike other ReferenceCoordinates, the start and end of a TranscriptReferenceCoordinate can be either an InternalPosition or an ExternalPosition.