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10.7 Resource MolecularSequence - Content

Clinical Genomics icon

Work Group

Maturity Level: 1

Trial Use

Security Category: Patient

Compartments: Patient

Representation of a molecular sequence.

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 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.

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 formatted element.

10.7.3 References to this Resource

Resource References: itself and Observation

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	Σ C	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	Σ C	0..1	CodeableConcept	The genome assembly used for starting sequence, e.g. GRCh38 Binding: LL1040-6 (Extensible)
chromosome	Σ C	0..1	CodeableConcept	Chromosome Identifier Binding: LL2938-0 (Required)
sequence[x]	Σ C	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  --></coordinateSystem>
  <ordinalPosition value="[integer]"/><!-- 0..1 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 --></sequenceRange>
  <startingSequence>  <!-- 0..1 A sequence used as starting sequence -->
   <genomeAssembly><!-- I 0..1 CodeableConcept The genome assembly used for starting sequence, e.g. GRCh38  --></genomeAssembly>
   <chromosome><!-- I 0..1 CodeableConcept Chromosome Identifier  --></chromosome>
   <sequence[x]><!-- I 0..1 CodeableConcept|string|Reference(MolecularSequence) The reference sequence that represents the starting sequence --></sequence[x]>
   <windowStart value="[integer]"/><!-- 0..1 Start position of the window on the starting sequence -->
   <windowEnd value="[integer]"/><!-- 0..1 End position of the window on the starting sequence -->
   <orientation value="[code]"/><!-- 0..1 sense | antisense -->
   <strand value="[code]"/><!-- 0..1 watson | crick -->
  </startingSequence>
  <edit>  <!-- 0..* Changes in sequence from the starting sequence -->
   <start value="[integer]"/><!-- 0..1 Start position of the edit on the starting sequence -->
   <end value="[integer]"/><!-- 0..1 End position of the edit on the starting sequence -->
   <replacementSequence value="[string]"/><!-- 0..1 Allele that was observed -->
   <replacedSequence value="[string]"/><!-- 0..1 Allele in the starting sequence -->
  </edit>
 </relative>
</MolecularSequence>

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/> .


[ a fhir:MolecularSequence;
  fhir:nodeRole fhir:treeRoot; # if this is the parser root

  # from Resource: .id, .meta, .implicitRules, and .language
  # from DomainResource: .text, .contained, .extension, and .modifierExtension
  fhir:identifier  ( [ Identifier ] ... ) ; # 0..* Unique ID for this particular sequence
  fhir:type [ code ] ; # 0..1 aa | dna | rna
  fhir:subject [ Reference(BiologicallyDerivedProduct|Group|NutritionProduct|Patient|Substance) ] ; # 0..1 Subject this sequence is associated too
  fhir:focus  ( [ Reference(Any) ] ... ) ; # 0..* What the molecular sequence is about, when it is not about the subject of record
  fhir:specimen [ Reference(Specimen) ] ; # 0..1 Specimen used for sequencing
  fhir:device [ Reference(Device) ] ; # 0..1 The method for sequencing
  fhir:performer [ Reference(Organization) ] ; # 0..1 Who should be responsible for test result
  fhir:literal [ string ] ; # 0..1 Sequence that was observed
  fhir:formatted  ( [ Attachment ] ... ) ; # 0..* Embedded file or a link (URL) which contains content to represent the sequence
  fhir:relative ( [ # 0..* A sequence defined relative to another sequence
    fhir:coordinateSystem [ CodeableConcept ] ; # 1..1 Ways of identifying nucleotides or amino acids within a sequence
    fhir:ordinalPosition [ integer ] ; # 0..1 Indicates the order in which the sequence should be considered when putting multiple 'relative' elements together
    fhir:sequenceRange [ Range ] ; # 0..1 Indicates the nucleotide range in the composed sequence when multiple 'relative' elements are used together
    fhir:startingSequence [ # 0..1 A sequence used as starting sequence
      fhir:genomeAssembly [ CodeableConcept ] ; # 0..1 I The genome assembly used for starting sequence, e.g. GRCh38
      fhir:chromosome [ CodeableConcept ] ; # 0..1 I Chromosome Identifier
      # sequence[x] : 0..1 I The reference sequence that represents the starting sequence. One of these 3
        fhir:sequence [  a fhir:CodeableConcept ; CodeableConcept ]
        fhir:sequence [  a fhir:string ; string ]
        fhir:sequence [  a fhir:Reference ; Reference(MolecularSequence) ]
      fhir:windowStart [ integer ] ; # 0..1 Start position of the window on the starting sequence
      fhir:windowEnd [ integer ] ; # 0..1 End position of the window on the starting sequence
      fhir:orientation [ code ] ; # 0..1 sense | antisense
      fhir:strand [ code ] ; # 0..1 watson | crick
    ] ;
    fhir:edit ( [ # 0..* Changes in sequence from the starting sequence
      fhir:start [ integer ] ; # 0..1 Start position of the edit on the starting sequence
      fhir:end [ integer ] ; # 0..1 End position of the edit on the starting sequence
      fhir:replacementSequence [ string ] ; # 0..1 Allele that was observed
      fhir:replacedSequence [ string ] ; # 0..1 Allele in the starting sequence
    ] ... ) ;
  ] ... ) ;
]

Changes from both R4 and R4B

MolecularSequence

MolecularSequence.subject

Renamed from patient to subject
Type Reference: Added Target Types Group, Substance, BiologicallyDerivedProduct, NutritionProduct

MolecularSequence.focus

Added Element

MolecularSequence.literal

Added Element

MolecularSequence.formatted

Added Element

MolecularSequence.relative

Added Element

MolecularSequence.relative.coordinateSystem

Added Mandatory Element

MolecularSequence.relative.ordinalPosition

Added Element

MolecularSequence.relative.sequenceRange

Added Element

MolecularSequence.relative.startingSequence

Added Element

MolecularSequence.relative.startingSequence.genomeAssembly

Added Element

MolecularSequence.relative.startingSequence.chromosome

Added Element

MolecularSequence.relative.startingSequence.sequence[x]

Added Element

MolecularSequence.relative.startingSequence.windowStart

Added Element

MolecularSequence.relative.startingSequence.windowEnd

Added Element

MolecularSequence.relative.startingSequence.orientation

Added Element

MolecularSequence.relative.startingSequence.strand

Added Element

MolecularSequence.relative.edit

Added Element

MolecularSequence.relative.edit.start

Added Element

MolecularSequence.relative.edit.end

Added Element

MolecularSequence.relative.edit.replacementSequence

Added Element

MolecularSequence.relative.edit.replacedSequence

Added Element

MolecularSequence.coordinateSystem

Deleted (>relative.coordinateSystem)

MolecularSequence.quantity

Deleted (Removed. Covered by the Variant Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

MolecularSequence.referenceSeq

Deleted (->relative.startingSequence.sequence[x])

MolecularSequence.variant

Deleted (Removed. Covered by the Variant Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

MolecularSequence.observedSeq

Deleted (->relative.startingSequence.sequenceString)

MolecularSequence.quality

Deleted (Removed from the resource.)

MolecularSequence.readCoverage

Deleted (Removed. Covered by the RegionStudied Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

MolecularSequence.repository

Deleted (->formatted)

MolecularSequence.pointer

Deleted (->relative)

MolecularSequence.structureVariant

Deleted (Removed. Covered by the Variant Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

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	Σ C	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	Σ C	0..1	CodeableConcept	The genome assembly used for starting sequence, e.g. GRCh38 Binding: LL1040-6 (Extensible)
chromosome	Σ C	0..1	CodeableConcept	Chromosome Identifier Binding: LL2938-0 (Required)
sequence[x]	Σ C	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  --></coordinateSystem>
  <ordinalPosition value="[integer]"/><!-- 0..1 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 --></sequenceRange>
  <startingSequence>  <!-- 0..1 A sequence used as starting sequence -->
   <genomeAssembly><!-- I 0..1 CodeableConcept The genome assembly used for starting sequence, e.g. GRCh38  --></genomeAssembly>
   <chromosome><!-- I 0..1 CodeableConcept Chromosome Identifier  --></chromosome>
   <sequence[x]><!-- I 0..1 CodeableConcept|string|Reference(MolecularSequence) The reference sequence that represents the starting sequence --></sequence[x]>
   <windowStart value="[integer]"/><!-- 0..1 Start position of the window on the starting sequence -->
   <windowEnd value="[integer]"/><!-- 0..1 End position of the window on the starting sequence -->
   <orientation value="[code]"/><!-- 0..1 sense | antisense -->
   <strand value="[code]"/><!-- 0..1 watson | crick -->
  </startingSequence>
  <edit>  <!-- 0..* Changes in sequence from the starting sequence -->
   <start value="[integer]"/><!-- 0..1 Start position of the edit on the starting sequence -->
   <end value="[integer]"/><!-- 0..1 End position of the edit on the starting sequence -->
   <replacementSequence value="[string]"/><!-- 0..1 Allele that was observed -->
   <replacedSequence value="[string]"/><!-- 0..1 Allele in the starting sequence -->
  </edit>
 </relative>
</MolecularSequence>

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/> .


[ a fhir:MolecularSequence;
  fhir:nodeRole fhir:treeRoot; # if this is the parser root

  # from Resource: .id, .meta, .implicitRules, and .language
  # from DomainResource: .text, .contained, .extension, and .modifierExtension
  fhir:identifier  ( [ Identifier ] ... ) ; # 0..* Unique ID for this particular sequence
  fhir:type [ code ] ; # 0..1 aa | dna | rna
  fhir:subject [ Reference(BiologicallyDerivedProduct|Group|NutritionProduct|Patient|Substance) ] ; # 0..1 Subject this sequence is associated too
  fhir:focus  ( [ Reference(Any) ] ... ) ; # 0..* What the molecular sequence is about, when it is not about the subject of record
  fhir:specimen [ Reference(Specimen) ] ; # 0..1 Specimen used for sequencing
  fhir:device [ Reference(Device) ] ; # 0..1 The method for sequencing
  fhir:performer [ Reference(Organization) ] ; # 0..1 Who should be responsible for test result
  fhir:literal [ string ] ; # 0..1 Sequence that was observed
  fhir:formatted  ( [ Attachment ] ... ) ; # 0..* Embedded file or a link (URL) which contains content to represent the sequence
  fhir:relative ( [ # 0..* A sequence defined relative to another sequence
    fhir:coordinateSystem [ CodeableConcept ] ; # 1..1 Ways of identifying nucleotides or amino acids within a sequence
    fhir:ordinalPosition [ integer ] ; # 0..1 Indicates the order in which the sequence should be considered when putting multiple 'relative' elements together
    fhir:sequenceRange [ Range ] ; # 0..1 Indicates the nucleotide range in the composed sequence when multiple 'relative' elements are used together
    fhir:startingSequence [ # 0..1 A sequence used as starting sequence
      fhir:genomeAssembly [ CodeableConcept ] ; # 0..1 I The genome assembly used for starting sequence, e.g. GRCh38
      fhir:chromosome [ CodeableConcept ] ; # 0..1 I Chromosome Identifier
      # sequence[x] : 0..1 I The reference sequence that represents the starting sequence. One of these 3
        fhir:sequence [  a fhir:CodeableConcept ; CodeableConcept ]
        fhir:sequence [  a fhir:string ; string ]
        fhir:sequence [  a fhir:Reference ; Reference(MolecularSequence) ]
      fhir:windowStart [ integer ] ; # 0..1 Start position of the window on the starting sequence
      fhir:windowEnd [ integer ] ; # 0..1 End position of the window on the starting sequence
      fhir:orientation [ code ] ; # 0..1 sense | antisense
      fhir:strand [ code ] ; # 0..1 watson | crick
    ] ;
    fhir:edit ( [ # 0..* Changes in sequence from the starting sequence
      fhir:start [ integer ] ; # 0..1 Start position of the edit on the starting sequence
      fhir:end [ integer ] ; # 0..1 End position of the edit on the starting sequence
      fhir:replacementSequence [ string ] ; # 0..1 Allele that was observed
      fhir:replacedSequence [ string ] ; # 0..1 Allele in the starting sequence
    ] ... ) ;
  ] ... ) ;
]

Changes from both R4 and R4B

MolecularSequence

MolecularSequence.subject

Renamed from patient to subject
Type Reference: Added Target Types Group, Substance, BiologicallyDerivedProduct, NutritionProduct

MolecularSequence.focus

Added Element

MolecularSequence.literal

Added Element

MolecularSequence.formatted

Added Element

MolecularSequence.relative

Added Element

MolecularSequence.relative.coordinateSystem

Added Mandatory Element

MolecularSequence.relative.ordinalPosition

Added Element

MolecularSequence.relative.sequenceRange

Added Element

MolecularSequence.relative.startingSequence

Added Element

MolecularSequence.relative.startingSequence.genomeAssembly

Added Element

MolecularSequence.relative.startingSequence.chromosome

Added Element

MolecularSequence.relative.startingSequence.sequence[x]

Added Element

MolecularSequence.relative.startingSequence.windowStart

Added Element

MolecularSequence.relative.startingSequence.windowEnd

Added Element

MolecularSequence.relative.startingSequence.orientation

Added Element

MolecularSequence.relative.startingSequence.strand

Added Element

MolecularSequence.relative.edit

Added Element

MolecularSequence.relative.edit.start

Added Element

MolecularSequence.relative.edit.end

Added Element

MolecularSequence.relative.edit.replacementSequence

Added Element

MolecularSequence.relative.edit.replacedSequence

Added Element

MolecularSequence.coordinateSystem

Deleted (>relative.coordinateSystem)

MolecularSequence.quantity

Deleted (Removed. Covered by the Variant Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

MolecularSequence.referenceSeq

Deleted (->relative.startingSequence.sequence[x])

MolecularSequence.variant

Deleted (Removed. Covered by the Variant Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

MolecularSequence.observedSeq

Deleted (->relative.startingSequence.sequenceString)

MolecularSequence.quality

Deleted (Removed from the resource.)

MolecularSequence.readCoverage

Deleted (Removed. Covered by the RegionStudied Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

MolecularSequence.repository

Deleted (->formatted)

MolecularSequence.pointer

Deleted (->relative)

MolecularSequence.structureVariant

Deleted (Removed. Covered by the Variant Profile in the CG IG: http://hl7.org/fhir/uv/genomics-reporting/index.html)

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

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.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.

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/ icon

Extensible

MolecularSequence.relative.startingSequence.genomeAssembly

http://loinc.org/LL1040-6/ icon

Extensible

MolecularSequence.relative.startingSequence.chromosome

http://loinc.org/LL2938-0/ icon

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.

10.7.4.2 Constraints

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()

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.

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

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.

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:

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).

In a FGFR2:MET Fusion use case, where the fusion was uncovered through RNA sequencing, a partial representation can be found here.

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:

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.

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 .

Here are two examples:

0-based example: here
1-based example: here

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
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