HL7 v3 Clinical Genomics – Overview The HL7 Clinical Genomics Work Group Prepared by Amnon Shabo (Shvo), PhD HL7 Clinical Genomics WG Co-chair and Modeling Facilitator HL7 Structured Documents WG CDA Co-editor CCD Implementation Guide Co-editor
Jan 26, 2016
HL7 v3 Clinical Genomics –
Overview
The HL7 Clinical Genomics Work Group
Prepared by Amnon Shabo (Shvo), PhD
HL7 Clinical Genomics WGCo-chair and Modeling Facilitator
HL7 Structured Documents WGCDA Co-editorCCD Implementation Guide Co-editor
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The HL7 Clinical Genomics Work Group
Mission To enable the standard use of patient-related genetic data such as DNA sequence variations and gene expression levels, for healthcare purposes (‘personalized medicine’) as well as for clinical trials & research
Work Products and Contributions to HL7 ProcessesThe Work Group will collect, review, develop and document clinical genomics use cases in order to determine what data needs to be exchanged. The WG will review existing genomics standards formats such as BSML (Bioinformatics Sequence Markup Language), MAGE-ML (Microarray and GeneExpression Markup Language), LSID (Life Science Identifier) and other. This group will recommend enhancements to and/or extensions of HL7's normative standards for exchange of information about clinical genomic orders and observations.
In addition, Clinical Genomics will seek to assure that related or supportive standards produced by other HL7 groups are robust enough to accommodate their use in both research and clinical care use. The group will also monitor information interchange standards developed outside HL7, and attempt harmonization of information content and representation of such standards with the HL7 content and representation.
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Overview of Activities
v3:
Family History (Pedigree) Topic
Genetic Variations Topic
Gene Expression Topic
CMETs defined by the Domain
v2:
v2 Implementation Guides
* The IG “Genetic Test Result Reporting to EHR” is modeled after the HL7 Version 2.5.1 Implementation Guide: Orders And Observations; Interoperable Laboratory Result Reporting To EHR (US Realm), Release 1
CDA:
A CDA Implementation Guide for Genetic Testing Reports
Common:
Domain Analysis Models for the various topics
A Domain Information Model (v3) describing the common semantics
Semantic alignment among the various specs
Three Tracks:
Normative
DSTU
Informative
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HL7 Clinical Genomics: The v3 Track
Family
History
Domain Information Model: Genome
Gene Expression
Phenotype(utilizing the HL7
Clinical Statement)
Utilize
Co
ns
train
Genetic VariationC
on
stra
in
utilize
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To achieve semantic interoperability…
ClinicalTrials
Imaging
EHR
Orders& Observations
Pharmacy
ClinicalGuidelines
Health RIM
ClinicalDocuments
ClinicalGenomics
Central Health RIM (e.g., an extended HL7 V3 Reference Information Model):Bio & medical-informatics standard specs are derived from the same RIM
…we need standard specs derived from a Central Health RIM:
Bioinformatics
Data Models
?
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Utilizations / Implementation
Utilization by other HL7 Domains HL7 RCRIM Work Group (clinical trials specs) utilized the CG models in
their Pharmacogenomics message, which was an extension of the CTLab message (an approved but expired DSTU)
The Lab Work Group might utilize a constrained version of the Genetic Variation model in their Result message
Selected Implementations The Family History spec is used in Mass General Hospital
Expanding to other family history applications including the US Surgeon General Family History tool
The Genetic Variation model is used in Hypergenes (a European project on essential hypertension, http://www.hypergenes.eu/)
The Pedigree and Genetic Variation models are used in Italy, the Rizzoli institute in Bologna
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0..* associatedObservation
typeCode*: <= COMP
component
0..* associatedProperty
typeCode*: <= DRIV
derivedFrom2
0..* polypeptide
typeCode*: <= DRIV
derivedFrom5
SEQUENCES & PROTEOMICS
0..* expression
typeCode*: <= COMPcomponent1
0..* sequenceVariation
typeCode*: <= COMP
component3
IndividualAlleleclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (allele code, drawn from HUGO-HGVS or OMIM)methodCode: SET<CE> CWE [0..*]
GeneticLocusclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CE CWE [0..1] (e.g., ALLELIC, NON_ALLELIC)text: ED [0..1]effectiveTime: IVL<TS> [0..1]confidentialityCode: SET<CE> CWE [0..*] <= ConfidentialityuncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: CD [0..1] (identifying a gene through GenBank GeneID with an optional translation to HUGO name.)methodCode: SET<CE> CWE [0..*]
0..* individualAllele
typeCode*: <= COMP
component1
SequenceclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CD CWE [1..1] (the sequence standard code, e.g. BSML)text: ED [0..1] (sequence's annotations)effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: ED [1..1] (the actual sequence)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*] (the sequencing method)
ExpressionclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CE CWE [1..1] (the standard's code (e.g., MAGE-ML identifier)negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= Uncertaintyvalue: ED [1..1] (the actual gene or protein expression levels)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*]
PolypeptideclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (protein code, drawn from SwissProt, PDB, PIR,HUPO, etc.)methodCode: SET<CE> CWE [0..*]
DeterminantPeptidesclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: CD [0..1] (peptide code, drawn from referencedatabases like those used in the Polypeptide class)methodCode: SET<CE> CWE [0..*]
Constrained to a restrictedMAGE-ML constrained schema,specified separately.
Constraint: GeneExpression.value
Note:A related allele that is ona different locus, and hasinterrelation with thesource allele, e.g.,translocated duplicatesof the gene.
0..* clinicalPhenotype
typeCode*: <= PERTpertinentInformation
ExternalObservedClinicalPhenotypeclassCode*: <= OBSmoodCode*: <= EVNid*: II [1..1] (The unique id of an external observation residing outside of the instance)code: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]
Note:An external observation is preferably a valid observationinstance existing in any other HL7-compliant instance,e.g., a document or a message.Use the id attribute of this class to point to the uniqueinstance identifier of that observation.
Note:A phenotype which has been actuallyobserved in the patient representedinternally in this model.
Note:This is a computed outcome, i.e.,the lab does not test for the actualprotein, but secondary processespopulate this class with thetranslational protein.
SequenceVariationclassCode*: <= OBSmoodCode*: <= EVNid: II [0..1]code: CD CWE [0..1]negationInd: BL [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: ANY [0..1] (The variation itself expressed with recognized notation like 269T>C or markup like BSML or drawn from an external reference like OMIM or dbSNP.)interpretationCode: SET<CE> CWE [0..*] <= ObservationInterpretationmethodCode: SET<CE> CWE [0..*]
KnownClinicalPhenotypeclassCode*: <= OBSmoodCode*: <= DEFcode: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]uncertaintyCode: CE CNE [0..1] <= ActUncertaintyvalue: ANY [0..1]
Note:These phenotypes are not the actual (observed)phenotypes for the patient, rather they are thescientifically known phenotypes of the sourcegenomic observation (e.g., known risks of amutation or know responsiveness to a medication).
Note:Code: COPY_NUMBER, ZYGOSITY, DOMINANCY, GENE_FAMILY,etc. For example, if code = COPY_NUMBER, then the value is oftype INT and is holding the no. of copies of this gene or allele.
0..* clinicalPhenotype
typeCode*: <= PERT
pertinentInformation
EXPRESSION DATA
SEQUENCE VARIATIONS
Polypeptide
Note:The Expression class refers to both gene and proteinexpression levels. It is an encapsulating class that allowsthe encapsulation of raw expression data in its value attribute.
0..* sequence
typeCode*: <= COMPcomponent2
0..* clinicalPhenotypetypeCode*: <= PERT
pertinentInformation
0..* clinicalPhenotype
typeCode*: <= PERT
pertinentInformation
Note:The code attribute indicates inwhat molecule the variation occurs,i.e., DNA, RNA or Protein.
0..* expression
typeCode*: <= COMP
component5
Note:Use the associations to the shadowclasses when the data set type (e.g.,expression) is not at deeper levels(e.g., allelic level) and needs to beassociated directly with the locus(e.g., the expression level is thetranslational result of both alleles).
0..* associatedObservationtypeCode*: <= COMP
component2
0..1 associatedObservation
typeCode*: <= COMP
component4 Note:This recursive associationenables the association of anRNA sequence derived froma DNA sequence and apolypeptide sequence derivedfrom the RNA sequence.
0..* clinicalPhenotype
typeCode*: <= PERT
pertinentInformation
Note:
This class is a placeholder for a specific locus on the genome - that is - a position of a particulargiven sequence in the subject’s genome or linkage map.Note that the semantics of the locus (e.g., gene, marker, variation, etc.) is defined by data assignedin the code & value attributes of this class, and also by placing additional data relating to thislocus into the classes associated with this class like Sequence, Expression, etc..
Note:The term 'Individual Allele' doesn't refer necessarily to aknown variant of the gene/locus, rather it refers to theindividual patient data regarding the gene/locus and mightwell contain personal variations w/unknown significance.
AssociatedObservationclassCode*: <= OBSmoodCode*: <= EVNid: SET<II> [0..*]code: CD CWE [0..1]text: ED [0..1]effectiveTime: GTS [0..1]value: ANY [0..1]methodCode: SET<CE> CWE [0..*]
Note:The code attribute could hold codes likeNORMALIZED_INTENSITY, P_VALUE, etc.The value attribute is populated based on theselected code and its data type is then setupaccordingly during instance creation.
Note:The code attribute could hold codes like TYPE,POSITION.GENOME, LENGTH, REFERENCE, REGION, etc..The value attribute is populated based on the selected codeand its data type is then setup accordingly during instancecreation. Here are a few examples:If code = TYPE, then the value is of type CV and holds one of thefollowing: SNP (tagSNP), INSERTION, DELETION,TRANSLOCATION, etc.
if code = POSITION, then value is of type INT and holdsthe actual numeric value representing the variation positionalong the gene.
if code = LENGTH, then value is of type INT and holdsthe actual numeric value representing the variation length.
If code = POSITION.GENE, then value is of type CV and is oneof the following codes:INTRON, EXON, UTR, PROMOTER, etc.
If code = POSITION.GENOME, then value is of type CV and is oneof the following codes:NORMAL_LOCUS, ECTOPIC, TRANSLOCATION, etc.
If the code = REFERENCE, then value istype CD and holds the reference gene identifier drawn from areference database like GenBank.
The full description of the allowed vocabularies for codes and itsrespective values could be found in the specification.
AssociatedObservation
Note:Code: CLASSIFICATION, etc.For example, if code =CLASSIFICATION, then the valueis of type CV and is holding eitherKNOWN or NOVEL.
reference
0..* geneticLocus
typeCode*: <= REFR
Note:A related gene that is on adifferent locus, and stillhas significant interrelationwith the source gene (similarto the recursive associationof an IndividualAllele).
ClinicalPhenotypeclassCode*: <= ORGANIZERmoodCode*: <= EVN
0..* observedClinicalPhenotype
typeCode*: <= COMP
component1
0..* knownClinicalPhenotype
typeCode*: <= COMP
component2
0..* externalObservedClinicalPhenotype
typeCode*: <= COMP
component3
At least one of the target acts ofthe three component act relationshipsshould be populated, since this isjust a wrapper class.
Constraint: ClinicalPhenotype
Note:- code should indicate the type of source, e.g., OMIM- text could contain pieces from research papers- value could contain a phenotype code if known (e.g., if it’s a disease, then the disease code)
ClinicalPhenotype
ClinicalPhenotype
ClinicalPhenotype
ClinicalPhenotype
ClinicalPhenotype
ClinicalPhenotype
0..1 identifiedEntity
typeCode*: <= SBJcontextControlCode: CS CNE [0..1] <= ContextControl "OP"
subject
reference
0..* individualAllele
typeCode*: <= REFR
ObservedClinicalPhenotype
Note:This CMET might be replacedwith the Clinical Statement SharedModel for richer expressivity, whenthe that mode is approved(currently in ballot).
Constrained to a restricted BSMLcontent model, specified in aseparate schema.
Constraint: Sequence.value
0..* sequence
typeCode*: <= COMP
component4
0..* sequenceVariation
typeCode*: <= COMP
component3
AssociatedPropertyclassCode*: <= OBSmoodCode*: <= EVNcode: CD CWE [0..1]text: ED [0..1]value: ANY [0..1]
0..* associatedProperty
typeCode*: <= DRIVderivedFrom1
AssociatedObservation
0..* associatedObservation
typeCode*: <= COMP
component
AssociatedPropertyAssociatedObservation
0..* associatedProperty
typeCode*: <= DRIV
derivedFrom
AssociatedProperty0..* associatedProperty
typeCode*: <= DRIVderivedFrom1
AssociatedObservation0..* associatedObservation
typeCode*: <= COMPcomponent
0..* sequenceVariationtypeCode*: <= DRIV
derivedFrom3derivedFrom2
0..* sequence
typeCode*: <= DRIV
0..* determinantPeptides
typeCode*: <= DRIV
derivedFrom4
0..* determinantPeptides
typeCode*: <= DRIVderivedFrom
0..* clinicalPhenotype
typeCode*: <= PERT
pertinentInformation 0..* clinicalPhenotype
typeCode*: <= PERT
pertinentInformation
AssociatedProperty
0..* associatedProperty
typeCode*: <= DRIV
derivedFrom
AssociatedProperty
GeneticLociclassCode*: <= OBSmoodCode*: <= EVNid: SET<II> [0..*]code: CD CWE [0..1]effectiveTime: GTS [0..1]value: ANY [0..1]
0..* geneticLocitypeCode*: <= COMPcomponentOf
0..* clinicalPhenotype
typeCode*: <= PERTpertinentInformation
GeneticLoci
0..* geneticLoci
typeCode*: <= COMP
componentOf
GeneticLoci
0..* geneticLoci
typeCode*: <= COMP
componentOf
0..* polypeptide
typeCode*: <= DRIVderivedFrom1
Polypeptide
0..* polypeptide
typeCode*: <= DRIV
derivedFrom2
Note:Use this class to indicate a set of genetic locito which this locus belongs. The loci set couldbe a haplotype, a genetic profile and so forth.Use the id attribute to point to the GeneticLociinstance if available. The other attributesserve as a minimal data set about the loci group.
PHENOTYPES
Note:Any observation related to the variation and is notan inherent part of the variation observation (the lattershould be represented in the AssociatedProperty class).For example, the zygosity of the variation.
Note:Use this class to point to a variationgroup to which this variation belongs.For example, a SNP haplotype.
Note:Any observation related to the sequence and is notan inherent part of the sequence observation (the lattershould be represented in the AssociatedProperty class).For example, splicing alternatives.
Note:Key peptides in the proteinthat determine its function.
Note:There could be zero to manyIndividualAllele objects in aspecific instance. A typicalcase would be an allele pair,one on the paternalchromosome and one on thematernal chromosome.
Note:Use this class toshow an allelehaplotype like in HLA.
Note:Any observationrelated to theexpression assayand is not aninherent part ofthe expressionobservation.
Note:Use this class forinherent dataabout the locus, e.g.chromosome no.
IdentifiedEntityclassCode*: <= IDENTid: SET<II> [0..*]code: CE CWE [0..1] <= RoleCode
Note:Use this role to identify a different subject(e.g., healthy tissue, virus, etc.) than theone propagated from the wrappingmessage or payload (e.g., GeneticLoci).
ScopingEntityclassCode*: <= LIVdeterminerCode*: <= INSTANCEid: SET<II> [0..*]code: CE CWE [0..1] <= EntityCode
0..* assignedEntity
typeCode*: <= PRFcontextControlCode: CS CNE [0..1] <= ContextControl "OP"
performer
0..*
performer
0..*
performer1
0..*
performer2
0..*
performer1
0..*
performer2
Genetic Locus(POCG_RM000010)
The entry point tothe GeneticLocus modelis any locus on the genome.
Constrained to a restricted MAGE-MLcontent model, specified in aseparate schema.
Constraint: Expression.value
Expression
Sequence
SequenceVariation
SequenceVariation
0..* clinicalPhenotypetypeCode*: <= PERT
pertinentInformation
ClinicalPhenotype
CMET: (ASSIGNED) R_AssignedEntity
[universal](COCT_MT090000)
0..1 scopedRoleName
CMET: (ACT) A_SupportingClinicalInformation
[universal](COCT_MT200000)
The Locus and its Alleles
SequenceVariations
ExpressionData
Sequenceand
Proteomics
ClinicalPhenotypes
The DSTU GeneticLocus Model Focal Areas (DIM forerunner):
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The Underlying Paradigm: Encapsulate & Bubble-up
Clinical PracticesGenomic Data Sources
EHR System
HL7 CG Messages with m
ainly
Encapsulating HL7 Objects HL7 C
G M
essa
ges
with
enca
psul
ated
dat
a as
soci
ated
with
HL7 c
linic
al o
bjec
ts (p
heno
type
s)
Bubble up the most clinically-significant raw
genomic data into specialized HL7 objects and
link them with clinical data from the patient EHR
Decision Support Applications
Knowledge(KBs, Ontologies, registries,
reference DBs, Papers, etc.)
Bridging is the challenge…
Encapsulation by predefined & constrained
bioinformatics schemas
Bubbling-up is done continuously by specialized DS
applications
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Decision Support Applications
Encapsulate & Bubble-up Example
Genetic CounselingDNA Lab
HL7 CG Messages with a Sequence
HL7 Object encapsulating the raw
sequencing results
HL7 C
G M
essa
ges
with
enca
psul
ated
seq
uenc
ing
data
asso
ciat
ed w
ith c
linic
al p
heno
type
s
Bubble up the most clinically-significant SNP data into
HL7 SNP and Mutation objects and
link them with clinical data from the patient EHR
Sequencing Example…
Encapsulation by a constrained BSML schema
Bubbling-up is done dynamically
by specialized applications, e.g.,
sequence analyzing programs
EHR System
Knowledge Sources
on genetic variants
(e.g., OMIM)
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Example: Family History XML Encoding
Point
back…
Bubble
up… To
phenotype
and beyond….
Taken from a patient pedigree, the
portion related to patient’s daughter
(in collaboration with Partners HealthCare
& other HL7 CG SIG members)
Point back to the raw data of this relative providing “personal evidence”
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XML Fusion: Encapsulation of Raw Genomic DataR
aw g
eno
mic
dat
a re
pre
sen
ted
in
Bio
info
rmat
ics
mar
kup
HL
7 v3
XM
L
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The Phenotype Model
Observed Phenotype
Interpretive
Phenotype
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The Genetic Variation CMET (passed normative in Jan. 2010)
Genetic Loci
Genetic
Locus
Individual Allele
Sequence
Variation
Sequence
(observed or reference)
Participants
(including specimen)
Associated data (vocab. Controlled)
Observed or Interpretive phenotypes
Genetic Report (CDA)
Genetic Testing Order
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The HL7 RCRIM CT Laboratory Model- The Pharmacogenomics Extension
Utilizes the Clinical Genomics
CMET
Genetic Lab
Clinical
Trial
Enrolled Subject
Specimen
Consent to Genotype
Pharmacogenomics Test
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Gene Expression Topic
Domain Analysis Model (DAM) Passed informative
ballot Based on several
models for geneexpression dataalong with extensions
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New v3 Models for Future Ballot
Gene Expression CMET Model An Implementation Guide constraining the Genotype models for
gene expression data
Domain Information Model (Genome ) Allows non-locus specific data (e.g., large deletions, cytogenetics,
etc.) to be represented Link to the locus-specific models, i.e., GeneticLoci & GeneticLocus
Query Model Based on the HL7 V3 Query by Parameter Infrastructure Adds selected attributes from the Clinical Genomics models as
parameters of the query message
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The Gene Expression CMET Draft
Genetic Loci
Genetic Locus
Gene Expression
Associated observations
GTR Report
Participants
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The Domain Information Model - Genome
Individual Allele
Bio Sequenc
e
Sequence Variation
(SNP, Mutation,
Polymorphism, etc.)
Polypeptide
Expression Data
Phenotype
Entry Point: Geneome
Expression
Attributes
Variation
Attributes
Encapsulating Obj.
Bubbled-up Obj.
genotypephenotype
Genetic Loci
Genetic Locus
Non-locus specific
data
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The CG V3 Query Model: Query by Parameter
QueryByParameterPayload(QueryByParameter)queryId: II [0..1]statusCode: CS CNE [0..1] <= QueryStatusCoderesponseElementGroupId: SET<II> [0..*]responseModalityCode: CS CNE [0..1] <= ResponseModalityresponsePriorityCode: CS CNE [0..1] <= QueryPriorityinitialQuantity: INT [0..1]initialQuantityCode: CE CWE [0..1] <= QueryRequestLimit
ControlActProcessclassCode*: <= CACTmoodCode*: <= ActMoodCompletionTrack
0..1queryByParameterPayload
GeneticLocus.value(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (GeneticLocus.value)
0..*geneticLocus.value
Query(POCG_RM000090)
Entry point for Clinical Genomics query message
GeneticLocus.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (GeneticLocus.ID)
0..*geneticLocus.id
IndividualAllele.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (IndividualAllele.id)
IndividualAllele.value(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (IndividualAllele.value)
0..1individualAllele.value
0..*individualAllele.id
SequenceVariation.value(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (SequenceVariation.value)
SequenceVariation.id(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (SequenceVariation.id)
0..1sequenceVariation.value
0..1sequenceVariation.id
Expression.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Expression.id)
Sequence.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Sequence.id)
0..*sequence.id
0..*expression.id
Polypeptide.value(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Polypeptide.value)
Polypeptide.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Polypeptide.id)
0..*polypeptide.value
0..*polypeptide.id
DeterminantPeptide.value(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (DeterminantPeptide.value)
DeterminantPeptide.id(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (DeterminantPeptide.value)
0..*determinantPeptide.value
0..*determinantPeptide.id
GeneticLoci.id(ParameterItem)value: II CWE [0..1]semanticsText: ST [0..1] (GeneticLoci.id)
GeneticLoci.value(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (GeneticLoci.value)
0..*geneticLoci.value
0..*geneticLoci.id
GeneticLoci.code(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (GeneticLoci.code)
0..*geneticLoci.code
ClinicalPhenotype.id(ParameterItem)value: II CWE [0..1]semanticsText: ST [0..1] (ClinicalPhenotype.id)
ClinicalPhenotype.code(ParameterItem)value: CD CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (ClinicalPhenotype.code)
ClinicalPhenotype.value(ParameterItem)value: ANY CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (ClinicalPhenotype.value)
0..*clinicalPhenotype.id
0..*clinicalPhenotype.code
0..*clinicalPhenotype.value
RecordTarget.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (RecordTarget.id)
0..*recordTarget.id
Subject.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Subject.id)
0..*subject.id
Performer.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Performer.id)
0..*performer.id
Author.id(ParameterItem)value: II CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Author.id)
0..*author.id
Method.code(ParameterItem)value: CE CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Method.code)
Interpretation.code(ParameterItem)value: CE CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (Interpretation.code)
effectiveTime(ParameterItem)value: GTS CWE [0..1] <= QueryParameterValuesemanticsText: ST [0..1] (effectiveTime)
0..*method.code
0..*interpretation.code
0..*effectiveTime
GeneticLocus parameters
Starting point with query
identifiers and attributes
Miscellaneous parameters
GeneticLoci parameters
participants parameters
Phenotype parameters
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V2 Implementation Guides
The IG “Genetic Test Result Reporting to EHR” passed informative ballot
It is modeled after the HL7 Version 2.5.1 Implementation Guide: Orders And Observations; Interoperable Laboratory Result Reporting To EHR (US Realm), Release 1
Is used in a pilot of information exchange between Partners Healthcare and Intermountain Health Care
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The v2 Message Structure
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V2 Sample Message OBR|1||PM-08-J00094^HPCGG-LMM^2.16.840.1.113883.3.167.1^ISO|
lm_DCM-pnlB_L^Dilated Cardiomyopathy Panel B (5 genes)^99LMM-ORDER-TEST-ID||20080702000000|20080702100909|||||||||234567891^Pump^Patrick^^^^^^NPI^L||||||20080703000000|||F||||||00000009^Cardiovascular^99HPCGG-GVIE-INDICATION^^^^^^Clinical Diagnosis and Family History of DCM|&Geneticist&Gene&&&&&NPI^^^^^^^HPCGG-LMM&2.16.840.1.113883.3.167.1&ISO|||||||||||||||55233-1^Genetic analysis master panel ^LN
SPM|1|||119273009&Peripheral blood&SNM3&&&&0707Intl&&Blood, Peripheral|||||||||||||20080702000000
OBR|2||PM-08-J00094-1^HPCGG-LMM^2.16.840.1.113883.3.167.1^ISO|55232-3^Genetic analysis summary panel^LN|||20080702000000|||||||||||||||20080703000000|||F||||^PM-08-J00094&HPCGG-LMM&2.16.840.1.113883.3.167.1&ISO
OBX|1|CWE|51967-8^Genetic disease assessed^LN||399020009^DCM-Dilated Cardiomyopathy^SNM3^^^0707Intl||||||F|20080702100909|||||||||||Laboratory for Molecular Medicine^L^22D1005307^^^CLIA&2.16.840.1.113883.4.7&ISO|1000 Laboratory Lane^Ste. 123^Cambridge^MA^99999^USA^B
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Haifa Research Lab
CDA IG for Genetic Testing Reports
Scope The Clinical Genomics Work Group develops a CDA Implementation
Guide (IG) for genetic testing report co-sponsored by the Structured Documents Work Group
Design principles Follow existing report formats commonly used in healthcare &
research Emphasize interpretations & recommendations Provide general background information on tests performed Represent interpretation by utilizing patterns of ‘genotype-
phenotype’ associations in the HL7 v3 Clinical Genomics and implement them as harmonized clinical statement entry-level templates in this IG
Reference HL7 Clinical Genomics instances as the place holders of raw data (personal evidences), similarly to referencing images (technically-wise)
Developed using the MDHT open source tool (OHT)
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Haifa Research Lab
CDA GTR Ballot Status
Balloted as DSTU and passed in October 2010
Major negative comments: Vocabulary binding (need to align to the new principles) Layout issues (needs to get the help of the MDHT developers) Sample XML snippets cannot have sample data OIDs for LOINC panels Sub-template ids registration Document type refinement Alignment with sub-templates in other CDA IGs
(e.g., Findings, Care Plan, etc.) Add drug safety Clarify definitions of LOINC codes
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Haifa Research Lab
CDA GTR Issues
Ballot a Universal IG along with specific types of GTR: Healthcare - US Realm; Research; etc.
Get family history data by linking to an HL7 Pedigree instance
Similarly, link to HL7 Clinical Genomics instances to get the richest expression of genotype-phenotype associations along with encapsulated raw data (e.g., sequences)
Get volenteers to contribute to the editorial group
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Haifa Research Lab
CDA GTR Section Outline
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Haifa Research Lab
GTR Genetic Variation Section
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Haifa Research Lab
Clinical Genomic Statement
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Haifa Research Lab
Interpretive Phenotype Observation
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Haifa Research Lab
Summary Section
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Haifa Research Lab
Alignment Among the Various Specs
v3 specs and CDA are all based the RIM CDA GTR-IG will be based on CDA R3 Depending on the “right side” of R3, if it allows RIM-based domain
models, then alignment is trivial
v3-v2 alignment: Proposal: represent semantics with v3 and implement it in various
ways, one of which is v2; develop an “v2 ITS” for the v3 models See proposal made by Amnon in a separate presentation
(click here to see that presentation)
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Haifa Research Lab
Summary
Small group coping with v3, v2 and CDA Clinical & Research environments
Genetic Variation - Normative CMET Vocabulary harmonization's (facilitator is back to activity) Timing confusing:
collecting specimen, extracting genetic material, identifying genomic observations, interpretation
Entry point into a choice box
CDA GTR through OHT CDA Editor
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Haifa Research Lab
The End
• Thank you for your attention…
• Questions? Contact Amnon at [email protected]
• Comments of general interest should be posted to the CG mailing list at [email protected]