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10.7 Resource MolecularSequence - Content

Clinical Genomics icon Work GroupMaturity Level: 1 Trial UseSecurity Category: N/A Compartments: No defined compartments

Representation of a molecular sequence.

Note to Implementers: Molecular Sequence resource will be replaced by the Molecular Definition resource. Current page is temporarily available for referencing and review purposes.

10.7.1 Scope and Usage

The MolecularSequence resource is designed for representing molecular sequences. It can represent the sequence in different ways, allowing implementations to adopt the most effective one for their use case.

It is strongly encouraged to provide as much information in this resource for any reported sequences, because receiving systems (e.g. discovery research, outcomes analysis, and public health reporting) may use this information to normalize sequences over time or across sources. However, these data should not be used to dynamically correct/change sequence representations for clinical use outside of the laboratory, due to insufficient information.

The MolecularSequence resource is designed to represent a single sequence in an instance. Each sequence might have multiple representations, but implementers SHALL ensure all representations are for the same sequence. This means that if a single MolecularSequence instance contains a literal, two file files, and a relative, all four of those representations must represent the same sequence. This can be a challenge across systems, as semantic equivalency of sequences cannot be guaranteed unless there is an agreed upon standard between sending and receiving systems.

10.7.2 Boundaries and Relationships

The MolecularSequence resource should only be used to capture a molecular sequence. It will not be used for other entities such as variant, variant annotations, genotypes, haplotypes, etc. Those concepts will be captured in Observation profiles found in the Genomics Reporting Implementation Guide icon. The sequence that was observed that led to the identification of those concepts can be delivered with this resource, and will be referenced by those observations.

MolecularSequence will not be used to capture data such as precise read of DNA sequences and sequence alignment are not included; such data may be accessible through references to GA4GH icon (Global Alliance for Genomics and Health) API, and may be referenced to by the file element.

10.7.3 References to this Resource

10.7.4 Resource Content

Structure

NameFlagsCard.TypeDescription & Constraintsdoco
.. MolecularSequence TU DomainResource Representation of a molecular sequence

Elements defined in Ancestors: id, meta, implicitRules, language, text, contained, extension, modifierExtension
... identifier Σ 0..* Identifier Unique ID for this particular sequence

... type Σ 0..1 code aa | dna | rna
Binding: sequence Type (Required)
... literal Σ 0..* BackboneElement A literal representation of a Molecular Sequence

.... sequenceValue Σ 1..1 string The primary (linear) sequence, expressed as a literal string
... relative Σ 0..* BackboneElement A Molecular Sequence that is represented as an ordered series of edits on a specified starting sequence

.... startingSequence Σ 1..1 Reference(MolecularSequence) The Molecular Sequence that serves as the starting sequence, on which edits will be applied
.... edit Σ 0..* BackboneElement An edit (change) made to a sequence

..... editOrder 0..1 integer The order of this edit, relative to other edits on the starting sequence
..... coordinateSystem Σ 1..1 CodeableConcept The coordinate system used to define the edited intervals on the starting sequence. Coordinate systems are usually 0- or 1-based
Binding: LL5323-2 icon (Extensible)
..... start Σ 1..1 integer The start coordinate of the interval that will be edited
..... end Σ 1..1 integer The end coordinate of the interval that will be edited
..... replacementSequence Σ 1..1 Reference(MolecularSequence) The sequence that defines the replacement sequence used in the edit operation
..... replacedSequence Σ 0..1 Reference(MolecularSequence) The sequence on the 'starting' sequence for the edit operation, defined by the specified interval, that will be replaced during the edit
... extracted Σ 0..* BackboneElement A Molecular Sequence that is represented as an extracted portion of a different Molecular Sequence

.... startingSequence Σ 1..1 Reference(MolecularSequence) The Molecular Sequence that serves as the parent sequence, from which the intended sequence will be extracted
.... start Σ 1..1 integer The start coordinate (on the parent sequence) of the interval that defines the subsequence to be extracted
.... end Σ 1..1 integer The end coordinate (on the parent sequence) of the interval that defines the subsequence to be extracted
.... coordinateSystem Σ 1..1 CodeableConcept The coordinate system used to define the interval that defines the subsequence to be extracted. Coordinate systems are usually 0- or 1-based
.... reverseComplement Σ 0..1 boolean A flag that indicates whether the extracted sequence should be reverse complemented
... repeated Σ 0..* BackboneElement A Molecular Sequence that is represented as a repeated sequence motif

.... sequenceMotif Σ 1..1 Reference(MolecularSequence) The sequence that defines the repeated motif
.... copyCount Σ 1..1 integer The number of repeats (copies) of the sequence motif
... concatenated Σ 0..1 BackboneElement A Molecular Sequence that is represented as an ordered concatenation of two or more Molecular Sequences
.... sequenceElement Σ 1..* BackboneElement One element of a concatenated Molecular Sequence

..... sequence Σ 1..1 Reference(MolecularSequence) The Molecular Sequence corresponding to this element
..... ordinalIndex Σ 1..1 integer The ordinal position of this sequence element within the concatenated Molecular Sequence

doco Documentation for this format icon

See the Extensions for this resource

 

Additional definitions: Master Definition XML + JSON, XML Schema/Schematron + JSON Schema, ShEx (for Turtle) + see the extensions, the spreadsheet version & the dependency analysis

10.7.4.1 Terminology Bindings

Path ValueSet Type Documentation
MolecularSequence.type SequenceType Required

Type if a sequence -- DNA, RNA, or amino acid sequence.
MolecularSequence.relative.edit.coordinateSystem http://loinc.org/LL5323-2/ icon Extensible

10.7.5 Notes

10.7.5.1 Representing the Sequence

This resource supports three patterns for representing a sequence of interest:

  • By providing a literal string of IUPAC codes representing nucleotides or amino acids.
  • By linking to a formatted file or link containing the sequence information (e.g. FASTA file or GA4GH sequence repository).
  • By providing a list of edits from a starting sequence.

The MolecularSequence resource is designed to represent a single sequence in an instance. Each sequence might have multiple representations, but implementers SHALL ensure all representations are for the same sequence.

10.7.5.1.1 Sequence as a literal string

literal: This string element can be used to hold the sequence as a string of characters.

10.7.5.1.2 Sequence as a file or URL

file: This Attachment is used to refer to the sequence as embedded file content or via a URL reference.

This method can be used to refer to sequence data from in an external source. If the sequence is referring to a GA4GH repository, the file.url should refer to a GA4GH compliant endpoint that conforms to GA4GH data models.

10.7.5.1.3 Sequence as a series of edits from a known sequence

relative: This complex element is used for encoding sequence. When the information of starting sequence and edits are provided, the observed sequence will be derived. Here is a picture below:

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10.7.5.1.3.1 Composing multiple relative sequences into one new sequence

relative.ordinalPosition: Indicates the order in which the sequence should be considered when putting multiple relative instances together.

relative.sequenceRange: Indicates the nucleotide range in the composed sequence when multiple relative instances are used together.

These attributes help to clarify what sequence is being represented with less computation/inference on the recipient side. Implementers SHOULD use sequenceRange first to determine order as the most reliable. If sequenceRange is not present then ordinalPosition SHOULD be used. Finally, if both sequenceRange and ordinalPosition are absent, then the order of the relative data elements SHOULD be used to calculate a composition. It is the responsibility of the data sender to ensure the message can be consistently understood. Additionally, gaps in sequenceRange are considered intentional (i.e. the composed sequence contains a sequence of N's, the placeholder nucleotide, for the gap range).

10.7.5.1.3.2 Representing the Starting Sequence

relative.startingSequence: There are four optional ways to represent a starting sequence in MolecularSequence resource:

  1. relative.startingSequence.sequenceCodeableConcept: Starting sequence id in public database;
  2. relative.startingSequence.sequenceString: Starting sequence string;
  3. relative.startingSequence.sequenceReference: Reference to starting sequence stored in another sequence entity;
  4. relative.startingSequence.genomeAssembly, relative.startingSequence.chromosome: The combination of genome assembly and chromosome.

The relative.startingSequence.windowStart and relative.startingSequence.windowEnddefines a range from the starting sequence that is used to define a subsequence used as the starting sequence.

10.7.5.1.3.3 Coordinate System

When saving the sequence information, the nucleic acid will be numbered with order. Some representations use a 0-based system (e.g. GA4GH API, BAM files) while some use a 1-based system (e.g. VCF file format). The element coordinateSystem contains this information.

relative.coordinateSystem binds to a LOINC answer list, please review those answers here icon as well as the detailed description found here icon.

10.7.5.1.3.4 Choice of Strand

There are many considerations concerning the directionality of DNA or RNA. Here we are using relative.startingSequence.orientation and relative.startingSequence.strand. Orientation represents the sense of the sequence, which has different meanings depending on the type. Strand represents the sequence writing order. Watson strand refers to 5' to 3' top strand (5' -> 3'), whereas Crick strand refers to 5' to 3' bottom strand (3' <- 5').

Only two possible values can be made by strand, watson and crick. Since the directionality of the sequence string might be represented in different ways in different omics scenario, below are examples of how to map other expressions into its correlated value:

Watson Crick
5′-to-3′ direction 3′-to-5′ direction
+1 -1
Sense Antisense
Positive Negative

10.7.5.2 Character usage for sequence as strings

There are attributes where the sequence is represented as a string of characters.

  • relative.startingSequence.sequenceString
  • relative.edit.replacementSequence
  • relative.edit.replacedSequence
  • literal

The characters used in these string representations of a sequence should be constrained to the IUPAC codes found here https://www.bioinformatics.org/sms2/iupac.html icon.

10.7.6 Search Parameters

Search parameters for this resource. See also the full list of search parameters for this resource, and check the Extensions registry for search parameters on extensions related to this resource. The common parameters also apply. See Searching for more information about searching in REST, messaging, and services.

Name Type Description Expression In Common
identifier token The unique identity for a particular sequence MolecularSequence.identifier 65 Resources
type token Amino Acid Sequence/ DNA Sequence / RNA Sequence MolecularSequence.type 11 Resources