R6 Ballot (1st Draft)
DiagnosticsThis page is part of the FHIR Specification v6.0.0-ballot1: Release 6 Ballot (1st Draft) (see Ballot Notes). The current version is 5.0.0. For a full list of available versions, see the Directory of published versions 
| Clinical Genomics Work Group | Maturity Level: 1 | Trial Use | Security Category: Patient | Compartments: Patient |
Representation of a molecular sequence.
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 formatted 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.
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 . 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 (Global Alliance for Genomics and Health) API, and may be referenced to by the formatted element.
Structure
| Name | Flags | Card. | Type | Description & Constraints |
|---|---|---|---|---|
  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) |
 subject | Σ | 0..1 | Reference(Patient | Group | Substance | BiologicallyDerivedProduct | NutritionProduct) | Subject this sequence is associated too |
| focus | Σ | 0..* | Reference(Any) | What the molecular sequence is about, when it is not about the subject of record |
| specimen | Σ | 0..1 | Reference(Specimen) | Specimen used for sequencing |
| device | Σ | 0..1 | Reference(Device) | The method for sequencing |
| performer | Σ | 0..1 | Reference(Organization) | Who should be responsible for test result |
| literal | Σ | 0..1 | string | Sequence that was observed |
| formatted | Σ | 0..* | Attachment | Embedded file or a link (URL) which contains content to represent the sequence |
  relative | Σ | 0..* | BackboneElement | A sequence defined relative to another sequence |
 coordinateSystem | Σ | 1..1 | CodeableConcept | Ways of identifying nucleotides or amino acids within a sequence Binding: LL5323-2 (Extensible) |
| ordinalPosition | 0..1 | integer | Indicates the order in which the sequence should be considered when putting multiple 'relative' elements together | |
| sequenceRange | 0..1 | Range | Indicates the nucleotide range in the composed sequence when multiple 'relative' elements are used together | |
 startingSequence | ΣC | 0..1 | BackboneElement | A sequence used as starting sequence + Rule: Both genomeAssembly and chromosome must be both contained if either one of them is contained + Rule: Have and only have one of the following elements in startingSequence: 1. genomeAssembly; 2 sequence |
 genomeAssembly | ΣC | 0..1 | CodeableConcept | The genome assembly used for starting sequence, e.g. GRCh38 Binding: LL1040-6 (Extensible) |
| chromosome | ΣC | 0..1 | CodeableConcept | Chromosome Identifier Binding: LL2938-0 (Required) |
 sequence[x] | ΣC | 0..1 | The reference sequence that represents the starting sequence Binding: Multiple bindings acceptable (NCBI or LRG) (Example) | |
| sequenceCodeableConcept | CodeableConcept | |||
| sequenceString | string | |||
 sequenceReference | Reference(MolecularSequence) | |||
| windowStart | Σ | 0..1 | integer | Start position of the window on the starting sequence |
| windowEnd | Σ | 0..1 | integer | End position of the window on the starting sequence |
| orientation | Σ | 0..1 | code | sense | antisense Binding: orientation Type (Required) |
| strand | Σ | 0..1 | code | watson | crick Binding: strand Type (Required) |
| edit | Σ | 0..* | BackboneElement | Changes in sequence from the starting sequence |
| start | Σ | 0..1 | integer | Start position of the edit on the starting sequence |
| end | Σ | 0..1 | integer | End position of the edit on the starting sequence |
| replacementSequence | Σ | 0..1 | string | Allele that was observed |
| replacedSequence | Σ | 0..1 | string | Allele in the starting sequence |
| Documentation for this format | ||||
See the Extensions for this resource
UML Diagram (Legend)
XML Template
<MolecularSequence xmlns="http://hl7.org/fhir"><!-- from Resource: id, meta, implicitRules, and language --> <!-- from DomainResource: text, contained, extension, and modifierExtension --> <identifier><!-- 0..* Identifier Unique ID for this particular sequence --></identifier> <type value="[code]"/><!-- 0..1 aa | dna | rna --> <subject><!-- 0..1 Reference(BiologicallyDerivedProduct|Group|NutritionProduct| Patient|Substance) Subject this sequence is associated too --></subject> <focus><!-- 0..* Reference(Any) What the molecular sequence is about, when it is not about the subject of record --></focus> <specimen><!-- 0..1 Reference(Specimen) Specimen used for sequencing --></specimen> <device><!-- 0..1 Reference(Device) The method for sequencing --></device> <performer><!-- 0..1 Reference(Organization) Who should be responsible for test result --></performer> <literal value="[string]"/><!-- 0..1 Sequence that was observed --> <formatted><!-- 0..* Attachment Embedded file or a link (URL) which contains content to represent the sequence --></formatted> <relative> <!-- 0..* A sequence defined relative to another sequence --> <coordinateSystem><!-- 1..1 CodeableConcept Ways of identifying nucleotides or amino acids within a sequence
JSON Template
{
"resourceType" : "MolecularSequence",
// from Resource: id, meta, implicitRules, and language
// from DomainResource: text, contained, extension, and modifierExtension
"identifier" : [{ Identifier }], // Unique ID for this particular sequence
"type" : "<code>", // aa | dna | rna
"subject" : { Reference(BiologicallyDerivedProduct|Group|NutritionProduct|
Patient|Substance) }, // Subject this sequence is associated too
"focus" : [{ Reference(Any) }], // What the molecular sequence is about, when it is not about the subject of record
"specimen" : { Reference(Specimen) }, // Specimen used for sequencing
"device" : { Reference(Device) }, // The method for sequencing
"performer" : { Reference(Organization) }, // Who should be responsible for test result
"literal" : "<string>", // Sequence that was observed
"formatted" : [{ Attachment }], // Embedded file or a link (URL) which contains content to represent the sequence
"relative" : [{ // A sequence defined relative to another sequence
"coordinateSystem" : { CodeableConcept }, // R! Ways of identifying nucleotides or amino acids within a sequence
"ordinalPosition" : <integer>, // Indicates the order in which the sequence should be considered when putting multiple 'relative' elements together
"sequenceRange" : { Range }, // Indicates the nucleotide range in the composed sequence when multiple 'relative' elements are used together
"startingSequence" : { // A sequence used as starting sequence
"genomeAssembly" : { CodeableConcept }, // I The genome assembly used for starting sequence, e.g. GRCh38
"chromosome" : { CodeableConcept }, // I Chromosome Identifier
// sequence[x]: The reference sequence that represents the starting sequence. One of these 3:
"sequenceCodeableConcept" : { CodeableConcept },
"sequenceString" : "<string>",
"sequenceReference" : { Reference(MolecularSequence) },
"windowStart" : <integer>, // Start position of the window on the starting sequence
"windowEnd" : <integer>, // End position of the window on the starting sequence
"orientation" : "<code>", // sense | antisense
"strand" : "<code>" // watson | crick
},
"edit" : [{ // Changes in sequence from the starting sequence
"start" : <integer>, // Start position of the edit on the starting sequence
"end" : <integer>, // End position of the edit on the starting sequence
"replacementSequence" : "<string>", // Allele that was observed
"replacedSequence" : "<string>" // Allele in the starting sequence
}]
}]
}
Turtle Template
@prefix fhir: <http://hl7.org/fhir/> .
Changes from both R4 and R4B
| MolecularSequence | |
| MolecularSequence.subject |
|
| MolecularSequence.focus |
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| MolecularSequence.literal |
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| MolecularSequence.formatted |
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| MolecularSequence.relative |
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| MolecularSequence.relative.coordinateSystem |
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| MolecularSequence.relative.ordinalPosition |
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| MolecularSequence.relative.sequenceRange |
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| MolecularSequence.relative.startingSequence |
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| MolecularSequence.relative.startingSequence.genomeAssembly |
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| MolecularSequence.relative.startingSequence.chromosome |
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| MolecularSequence.relative.startingSequence.sequence[x] |
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| MolecularSequence.relative.startingSequence.windowStart |
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| MolecularSequence.relative.startingSequence.windowEnd |
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| MolecularSequence.relative.startingSequence.orientation |
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| MolecularSequence.relative.startingSequence.strand |
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| MolecularSequence.relative.edit |
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| MolecularSequence.relative.edit.start |
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| MolecularSequence.relative.edit.end |
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| MolecularSequence.relative.edit.replacementSequence |
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| MolecularSequence.relative.edit.replacedSequence |
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| MolecularSequence.coordinateSystem |
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| MolecularSequence.quantity |
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| MolecularSequence.referenceSeq |
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| MolecularSequence.variant |
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| MolecularSequence.observedSeq |
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| MolecularSequence.quality |
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| MolecularSequence.readCoverage |
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| MolecularSequence.repository |
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| MolecularSequence.pointer |
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| MolecularSequence.structureVariant |
|
See the Full Difference for further information
This analysis is available for R4 as XML or JSON and for R4B as XML or JSON.
See R4 <--> R5 Conversion Maps (status = See Conversions Summary.)
Structure
| Name | Flags | Card. | Type | Description & Constraints |
|---|---|---|---|---|
| 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) |
| subject | Σ | 0..1 | Reference(Patient | Group | Substance | BiologicallyDerivedProduct | NutritionProduct) | Subject this sequence is associated too |
| focus | Σ | 0..* | Reference(Any) | What the molecular sequence is about, when it is not about the subject of record |
| specimen | Σ | 0..1 | Reference(Specimen) | Specimen used for sequencing |
| device | Σ | 0..1 | Reference(Device) | The method for sequencing |
| performer | Σ | 0..1 | Reference(Organization) | Who should be responsible for test result |
| literal | Σ | 0..1 | string | Sequence that was observed |
| formatted | Σ | 0..* | Attachment | Embedded file or a link (URL) which contains content to represent the sequence |
| relative | Σ | 0..* | BackboneElement | A sequence defined relative to another sequence |
| coordinateSystem | Σ | 1..1 | CodeableConcept | Ways of identifying nucleotides or amino acids within a sequence Binding: LL5323-2 (Extensible) |
| ordinalPosition | 0..1 | integer | Indicates the order in which the sequence should be considered when putting multiple 'relative' elements together | |
| sequenceRange | 0..1 | Range | Indicates the nucleotide range in the composed sequence when multiple 'relative' elements are used together | |
| startingSequence | ΣC | 0..1 | BackboneElement | A sequence used as starting sequence + Rule: Both genomeAssembly and chromosome must be both contained if either one of them is contained + Rule: Have and only have one of the following elements in startingSequence: 1. genomeAssembly; 2 sequence |
| genomeAssembly | ΣC | 0..1 | CodeableConcept | The genome assembly used for starting sequence, e.g. GRCh38 Binding: LL1040-6 (Extensible) |
| chromosome | ΣC | 0..1 | CodeableConcept | Chromosome Identifier Binding: LL2938-0 (Required) |
| sequence[x] | ΣC | 0..1 | The reference sequence that represents the starting sequence Binding: Multiple bindings acceptable (NCBI or LRG) (Example) | |
| sequenceCodeableConcept | CodeableConcept | |||
| sequenceString | string | |||
| sequenceReference | Reference(MolecularSequence) | |||
| windowStart | Σ | 0..1 | integer | Start position of the window on the starting sequence |
| windowEnd | Σ | 0..1 | integer | End position of the window on the starting sequence |
| orientation | Σ | 0..1 | code | sense | antisense Binding: orientation Type (Required) |
| strand | Σ | 0..1 | code | watson | crick Binding: strand Type (Required) |
| edit | Σ | 0..* | BackboneElement | Changes in sequence from the starting sequence |
| start | Σ | 0..1 | integer | Start position of the edit on the starting sequence |
| end | Σ | 0..1 | integer | End position of the edit on the starting sequence |
| replacementSequence | Σ | 0..1 | string | Allele that was observed |
| replacedSequence | Σ | 0..1 | string | Allele in the starting sequence |
| Documentation for this format | ||||
See the Extensions for this resource
XML Template
<MolecularSequence xmlns="http://hl7.org/fhir">
JSON Template
{
"resourceType" : "MolecularSequence",
// from Resource: id, meta, implicitRules, and language
// from DomainResource: text, contained, extension, and modifierExtension
"identifier" : [{ Identifier }], // Unique ID for this particular sequence
"type" : "<code>", // aa | dna | rna
"subject" : { Reference(BiologicallyDerivedProduct|Group|NutritionProduct|
Patient|Substance) }, // Subject this sequence is associated too
"focus" : [{ Reference(Any) }], // What the molecular sequence is about, when it is not about the subject of record
"specimen" : { Reference(Specimen) }, // Specimen used for sequencing
"device" : { Reference(Device) }, // The method for sequencing
"performer" : { Reference(Organization) }, // Who should be responsible for test result
"literal" : "<string>", // Sequence that was observed
"formatted" : [{ Attachment }], // Embedded file or a link (URL) which contains content to represent the sequence
"relative" : [{ // A sequence defined relative to another sequence
"coordinateSystem" : { CodeableConcept }, // R! Ways of identifying nucleotides or amino acids within a sequence
"ordinalPosition" : <integer>, // Indicates the order in which the sequence should be considered when putting multiple 'relative' elements together
"sequenceRange" : { Range }, // Indicates the nucleotide range in the composed sequence when multiple 'relative' elements are used together
"startingSequence" : { // A sequence used as starting sequence
"genomeAssembly" : { CodeableConcept }, // I The genome assembly used for starting sequence, e.g. GRCh38
"chromosome" : { CodeableConcept }, // I Chromosome Identifier
// sequence[x]: The reference sequence that represents the starting sequence. One of these 3:
"sequenceCodeableConcept" : { CodeableConcept },
"sequenceString" : "<string>",
"sequenceReference" : { Reference(MolecularSequence) },
"windowStart" : <integer>, // Start position of the window on the starting sequence
"windowEnd" : <integer>, // End position of the window on the starting sequence
"orientation" : "<code>", // sense | antisense
"strand" : "<code>" // watson | crick
},
"edit" : [{ // Changes in sequence from the starting sequence
"start" : <integer>, // Start position of the edit on the starting sequence
"end" : <integer>, // End position of the edit on the starting sequence
"replacementSequence" : "<string>", // Allele that was observed
"replacedSequence" : "<string>" // Allele in the starting sequence
}]
}]
}
Turtle Template
@prefix fhir: <http://hl7.org/fhir/> .
Changes from both R4 and R4B
| MolecularSequence | |
| MolecularSequence.subject |
|
| MolecularSequence.focus |
|
| MolecularSequence.literal |
|
| MolecularSequence.formatted |
|
| MolecularSequence.relative |
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| MolecularSequence.relative.coordinateSystem |
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| MolecularSequence.relative.ordinalPosition |
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| MolecularSequence.relative.sequenceRange |
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| MolecularSequence.relative.startingSequence |
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| MolecularSequence.relative.startingSequence.genomeAssembly |
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| MolecularSequence.relative.startingSequence.chromosome |
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| MolecularSequence.relative.startingSequence.sequence[x] |
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| MolecularSequence.relative.startingSequence.windowStart |
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| MolecularSequence.relative.startingSequence.windowEnd |
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| MolecularSequence.relative.startingSequence.orientation |
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| MolecularSequence.relative.startingSequence.strand |
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| MolecularSequence.relative.edit |
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| MolecularSequence.relative.edit.start |
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| MolecularSequence.relative.edit.end |
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| MolecularSequence.relative.edit.replacementSequence |
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| MolecularSequence.relative.edit.replacedSequence |
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| MolecularSequence.coordinateSystem |
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| MolecularSequence.quantity |
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| MolecularSequence.referenceSeq |
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| MolecularSequence.variant |
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| MolecularSequence.observedSeq |
|
| MolecularSequence.quality |
|
| MolecularSequence.readCoverage |
|
| MolecularSequence.repository |
|
| MolecularSequence.pointer |
|
| MolecularSequence.structureVariant |
|
See the Full Difference for further information
This analysis is available for R4 as XML or JSON and for R4B as XML or JSON.
See R4 <--> R5 Conversion Maps (status = See Conversions Summary.)
Additional definitions: Master Definition XML + JSON, XML Schema/Schematron + JSON Schema, ShEx (for Turtle) + see the extensions, the spreadsheet version & the dependency analysis
| Path | ValueSet | Type | Documentation |
|---|---|---|---|
| MolecularSequence.type | SequenceType | Required | Type if a sequence -- DNA, RNA, or amino acid sequence. |
| MolecularSequence.relative.coordinateSystem | http://loinc.org/LL5323-2/ | Extensible | |
| MolecularSequence.relative.startingSequence.genomeAssembly | http://loinc.org/LL1040-6/ | Extensible | |
| MolecularSequence.relative.startingSequence.chromosome | http://loinc.org/LL2938-0/ | Required | |
| MolecularSequence.relative.startingSequence.sequence[x] | ?? | Example | |
| MolecularSequence.relative.startingSequence.orientation | OrientationType | Required | Type for orientation. |
| MolecularSequence.relative.startingSequence.strand | StrandType | Required | Type for strand. |
| UniqueKey | Level | Location | Description | Expression |
 msq-5 | Rule | MolecularSequence.relative.startingSequence | Both genomeAssembly and chromosome must be both contained if either one of them is contained | chromosome.exists() = genomeAssembly.exists() |
| msq-6 | Rule | MolecularSequence.relative.startingSequence | Have and only have one of the following elements in startingSequence: 1. genomeAssembly; 2 sequence | genomeAssembly.exists() xor sequence.exists() |
This resource supports three patterns for representing a sequence of interest:
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.
literal: This string element can be used to hold the sequence as a string of characters.
formatted: 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 formatted.url should refer to a GA4GH compliant endpoint that conforms to GA4GH data models.
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:
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).
In a FGFR2:MET Fusion use case, where the fusion was uncovered through RNA sequencing, a partial representation can be found here.
relative.startingSequence: There are four optional ways to represent a starting sequence in MolecularSequence resource:
relative.startingSequence.sequenceCodeableConcept: Starting sequence id in public database;relative.startingSequence.sequenceString: Starting sequence string; relative.startingSequence.sequenceReference: Reference to starting sequence stored in another sequence entity; 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.
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 as well as the detailed description found here .
Here are two examples:
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 |
There are attributes where the sequence is represented as a string of characters.
relative.startingSequence.sequenceStringrelative.edit.replacementSequencerelative.edit.replacedSequenceliteral
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 .
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 |
| focus | reference | What the molecular sequence is about, when it is not about the subject of record | MolecularSequence.focus (Any) | |
| identifier | token | The unique identity for a particular sequence | MolecularSequence.identifier | 65 Resources |
| patient | reference | The subject that the sequence is about | MolecularSequence.subject.where(resolve() is Patient) (Patient) | 66 Resources |
| subject | reference | The subject that the sequence is about | MolecularSequence.subject (Group, BiologicallyDerivedProduct, NutritionProduct, Patient, Substance) | |
| type | token | Amino Acid Sequence/ DNA Sequence / RNA Sequence | MolecularSequence.type | 11 Resources |
FHIR ®© HL7.org 2011+. FHIR R6 hl7.fhir.core#6.0.0-ballot1 generated on Mon, Dec 18, 2023 15:17+1100.
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