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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-editorGTR Implementation Guide prime editor
HL7 RIMBAA WGPast Co-chair
Haifa Research Lab
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The Mission of HL 7 Clinical Genomics Work Group
� The HL7 Clinical Genomics Work Group (CGWG) supports the HL7 mission to create and promote its standards by enabling the communication between interested parties of clinical and genomic data related to an individual. The focus of the CGWG efforts is the personalization of the genomic data, the so-called ’omics differences in an individual’s genomic – and its association with relevant phenotypic and clinical information. Associations to interpretive/expected phenotypes will be modeled as knowledge that can be utilized to transform an individual's data into meaningful information.
� CGWG will facilitate the development of common standards for clinical research information management across a variety of organizations --including national and international government agencies and regulatory bodies, private research efforts, and sponsored research -- and thus the availability of safe and effective therapies by improving the processes and efficiencies associated with regulated clinical research.
� CGWG will strive to achieve common semantics across the clinical and research environments. Consequently, the group will start each standardization effort in Universal specifications that later on can be refined to specific realms.
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Overview of Activities
v3:
� Family History (Pedigree) Topic
� Genetic Variations Topic
� Gene Expression Topic
� CMETs defined by theDomain
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 (e.g. , gene.exp, c.seq)
� A Domain Information Model (v3) describing the comm on semantics
� Semantic a lignment among the various specs
Three Tracks:
Normative
DSTU
Informative
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The Underlying Paradigm: Encapsulate & Bubble-up
Clinical PracticesGenomic Data Sources
EHR System
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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Current activities
� Family History US Implementation Guide
� GTR (Genetic Testing Report) – CDA Implementation Guide
� v2 genetic testing results message – Laboratory Message Implementation Guide
� Clinical Sequencing Domain Analysis Model
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Family History: PHR-EHR-GEN Convergence
EHR PHR
Genomics
Enable
Decision Support
e.g., risk analysis
algorithms
Population Research
and Public Health
* Detailed description can be found in the Family H istory presentation
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The Family History Model (Payload)
Genomic CMETs
Patient
RelativeHL7 Vocabulary=
“FAMMEMB”
Recursive
Relation
Clinical
Data
Family History
Risk Assessment
Results Estimated age of subject
Estimated age of subject at diagnosis
Relative Mother & Father IDs
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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
sent
ed
in
Bio
info
rmat
ics
mar
kup
HL7
v3
XM
L
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The Pedigree Spec - Updates
� HL7 Normative Standard since 2007 and reaffirmed in May 2012 for 5 more years
� Pilots: � Hughes Risk Applications� Surgeon General’s My Family Health Portrait � Many more…
� HL7 US Realm IG � Under development with expected balloting in Sept 2 012� Transmission supported in CCD� Accommodate MU Stage 2 requirements
� Release 2 in progress� Update representation of genetic data� Accommodating ISO ballot comments
� FHIR Pedigree?!10
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Pedigree Implementation Guide for US Realm
� Specify the exchange format to be compliant with MU� Reusing HITSP CCD exchange; CCD instance references a Pedigree
� Simplify the genetic representation by constraining out the full blown genomic CMETs and use GTR suggested conventions
� Specify clinical data using SNOMED (following HughesRiskApp IG)� Do we need dynamic binding?
� Representing interpretation as in GTR (constrain ou t the interpretation code attribute)
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Pedigree Implementation Guide for US Realm -cont.
� Pedigree R 1 was adopted by MU 2 Final Ruling"The HL7 Pedigree standard was originally released in 2007. Release 1 was recently reaffirmed by the American National Standards Institute (ANSI), which is a process that occurs every five years. We have adopted this reaffirmed version as it is the same version (Release 1) of the standard as the version we proposed. An implementation guide for this standard is scheduled to be published shortly after this final rule. Although EHR technology will not be required to conform to the implementation guide for certification, the implementation guide will provide important guidance for use of the HL7 Pedigree standard with EHR technology."
� Balloted in January 2013:� Passed as follows:HL7 Version 3 Implementation Guide: Family History/Pedigree Interoperability, Release 1 - US RealmLvl. I1; Aff. 36; Neg. 3; Abst. 67; NV 13; TotP. 119; Q. 89.08%; A. 24
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FHIR Pedigree
� Scoping:� Risk assessment results� Genetic models� Branching out to any no. of generation
� Backward compatible ?
� Mapped back to the v3 model !
� Do we have the bandwidth to do it ?
� We’re asked on no. and scope of genomic resources
13
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CDA IG: Genetic Testing Report (GTR)
� Define an implementation guide for a genetic testin g report that is both human readable and machine-processable� Target at all types of GTR producers, e.g., genetic labs, clin. geneticists� Readable content is larger in scope� E.g., detailed description of the tests performed a long with references� Machine-processable should be limited, e.g., exclud e raw data
� Ballot a Universal IG; then derive ���� specific types of GTR:� Healthcare & Research � Realm-specific guides� Omic-specific guides
� Developed using the MDHT open source tool (OHT)
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GTR - Design Principles
� Follow existing report formats commonly used in healthcare & research
� Emphasize interpretations & recommendations
� Provide general background information on tests performed
� Reference HL7 Clinical Genomics instances (e.g., v3 or v2 GeneticVariation and Pedigree) as the place holders of full-blown raw genomic data and fully-structured family histor y data
� Utilize patterns of ‘ genotype-phenotype ’ associations in the HL7 v3 Clinical Genomics Domain� Implement them as ‘ clinical genomic statement ’ entry-level templates
(see next slide), enabling meaningful use of the data
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The Clinical Genomic Statement
� An abstract Clinical Genomic Statement (CGS) templa te that� Has at its core a genomic observation (e.g., a DNA sequence variation)� If it’s a reportable finding, then it should be ass ociated with indications and interpretations,
specimen and genomic source class� The major finding can be associated with associated observation (e.g., amino acid change)� Optionally, performers may be specified (overriding header performers)
� The CGS abstract template is instantiated by specia lized CGS’s, e.g., for genetic variations or cytogenetics
Indications InterpretationsGenomicObservation
Performers
SpecimenGenomic Source
Clin
ical
Ge
nom
ic S
tate
men
t
Associated Observations
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Detailed description can be found in the GTR presentation
17
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CDA GTR Ballot Status
� Balloted in several cycles for comments and DSTU
� Passed as DSTU in Oct. 10 & Sep. 12
� Decided to publish in December 2012
� Motion passed to approve the Publication Request Fo rm
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Collaboration with APWG around CDA IGs
� Development:� How do we share templates with AP (Anatomic Patholo gy)?� MDHT SVN could be an option
� Harmonization:� One consolidated document template or two interrela ted and harmonized docs?� Workflows could dictate the way documents shape up…� Could we share specimen templates?� Could we harmonize summary / diagnosis templates?� Could we agree on a clinical statement approach whe re all pieces are tied
together in one coherent structure?
� Comments on the APSR sample:� Is problem == reason for AP procedure?� Why “Left upper outer quadrant breast palpable mass” is considered illness?� APSR sample has CDA Validation issues
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V2 Implementation Guides
� A v2 laboratory message implementation guide for genetic testing result� A message from the genetic lab to the EHR � An approved informative spec
� It is modeled after the HL7 Version 2.5.1 Implementation Guide: Orders And Observations; Interoperable Laboratory Result Reporting To EHR (U S 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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Clinical Sequencing Analysis Model
� Extends ONC Personalized Healthcare Use Case (2008) for support of clinical sequencing and current understanding of the field
� Serve as� Roadmap for further standards
development/extension� Develop use cases and requirements for related
projects (e.g. Specimen DAM and Specimen CMET Release 2)
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C.Seq. Workflows
Different compatible standards may need to be used at different parts in the workflow (e.g. lab order vs. result reporting). Therefore, starting with workflow definition and key data needs is important (e.g. clinical indication for ordering the test).
24
Clinical Sequencing Workflow – Germline Testing
LaboratoryHealthcare
Provider
Geneticist /
Medical Geneticis t /
Molecular Pathologist
Patient
Clinician/Clinical
Research submits
test order
with clinical/
family history,
indication,
specimen
preference as
appropriate
Specimen
colle ction
Receiving
Accession order and
specimens
Specimen Process ing
Testing
Bioinformatic
Analysis
Interpretation
ReportingReview Re sults/
Report
Care Plan
Development
Receive Structure d
Results
(may include
variome)
into EHR
Consent to Te st
Patient Access to
D ata and Results
(preparation for
future )
Indication for
Genetic Testing
Review Findings
with Patient
Transcoding
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Alternative Workflows
25
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Systems by Stakeholder Group
These serve as potential integration points (e.g. dbSNP ID for links to dbSNP variant record).
26
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Clinical Sequencing – Ballot Results
� Balloted in January 2013 for comments only
� Results:� Didn’t pass, tally follows:
HL7 Version 3 Domain Analysis Model: Clinical Sequencing, Release 1Lvl. O1; Aff. 38; Neg.0; Abst. 75; NV 19; TotP. 132; Q. 85.61%; A 0
27
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For v3 standards – see backup slides
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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 UML and implemen t it in various
ways, e.g., v3 using the existing v3 ITS and v2 bei ng another format (develop an “v2 ITS” for the UML models)
� See proposal made by Amnon in a separate presentati on
� FHIR can be the single source of semantics
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Selected Implementation
� v2� Exchange of genetic testing results between Intermountain and Harvard
� v3� 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
� CDA� GTR has been used in uHealth – a PHR/EHR system in Korea
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Other Domain Analysis Models
Work in progress…
� Clinical Genomics DAM
� Gene Expression DAM
� Harmonize with NCI LS -DAM and CDISC BRIDG
� Specimen (led by OO and AP Work Groups)� Specimen DAM� Specimen Unique ID� Specimen CMET Release 2
31
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Omics in the LS DAM - Molecular Biology (outdated)
class Molecular Biology Core
Chromosome
+ name: ST
NucleicAcidPhysicalLocation
+ endCoordi nate: INT+ startCoordi nate: INT
NucleicAcidSequence
NucleicAcidSequenceFeature
+ orientation: ST+ typeCode: CD
Protein
+ name: DSET<SC>+ symbol: DSET<SC>
Gene
+ name: DSET<SC>+ symbol: DSET<SC>
SingleNucleotidePolymorphism
AminoAcidSequenceFeature
+ typeCode: CD
ExonIntron
MolecularSequence
+ value: SC
AminoAcidSequence
Genome
+ assembl ySource: ST+ assembl yVersi on: ST
CytobandRange
+ endBand: ST+ endChromosomeArm: ST+ startBand: ST+ startChromosomeArm: ST
AminoAcidPhysicalLocation
+ endCoordi nate: INT+ startCoordinate: INT
GeneticVariation
MessengerRNA
DNASequence
RNASequence
MolecularSequenceAnnotation
+ date: TS
Name: Mol ecular Biol ogy CoreAuthor: lschickVersi on: 1.0Created: 6/17/2011 2:49:18 PMUpdated: 1/9/2012 1:43:45 PM
BRIDG-ali gned
LS DAM
Legend0..*
i ncludes / isi ncluded in
1
1..*
contains / is partof
1
1
is i ncluded i n /incl udes
0..*
1..*i s for /has 0..1
0..*
i s incl uded in /i ncludes
1..*
1
i s l ocated on /has
1..*
1..*
is transl ated to /is transl ated from
0..1
0..*
is representedby / represents
0..*1..*is incl uded i n
/ incl udes 1
0..*is located i n /has
0..*
0..*
is located i n /has
0..*
0..*
is incl uded i n /incl udes
1..*0..*
encodes / i s encodedby
0..*
0..*
i s transcri bed to /i s transcri bed from
0..*
0..*reports / isreported by 0..*
0..*
reports / isreported by 0..*
0..*is representedby / represents 0..*
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Omics in the LS DAM - Experiment (outdated)class Experiment Core
Experiment
+ acti veDa teRange: I VL<TS>+ descr ip tion: ST+ designType : DSET<SC>+ name: ST+ ty peCode : CD
Experi menta lFac tor
+ name: ST+ t ypeCode : SC+ va lue : DS ET<ANY>
Experimenta lPa rame te r
+ descrip ti on : ST+ name: ST+ st at usCode : CD+ typeCode: CD
Experi menta lStudy
+ acti veD ateRange : I VL<TS>+ descr ip tion: ST+ name: ST+ t ypeCode : DSET<CD>
P ointO fContac t
+ ef fectiv eDa teRange : IVL<TS.DATET IME>+ post alA dd ress: AD+ p ri mary Ind ic ato r: BL+ t el ecomAddress: BAG <TEL>+ t ypeCode : CD
cons trai nts{Exc lusi veO r}
Protocol
+ name: ST
Data
+ crea tionDat e: TS. DATETIME
Experi menta lPa rameterVa lue
StringParame te rVa lue
+ v alue : ST
Quanti tat iveParameterVa lue
+ range: IVL<PQ>+ si ng le : PQ
Act ivit y
+ comment : ST+ iden tif ie r: II+ reasonCode : DSET<CD>
Sof tw a re
+ bu ildDat e: TS. DATE+ bu ildNumber: ST+ c on tent : ED+ e ff ect iveDat eRange : IVL<TS>+ i den tifi er : DSET<I I>+ l icenseEffect iveDat eRange : IVL<TS. DATE>+ l icenseKey : ST+ l icenseTypeCode : CD+ name: ST+ t ypeCode : CD+ v ersi on : ST
Product
Equipment
+ manu factu reDa te: TS. DATETIME+ rep rocessedDeviceCode : CD+ va li dat ionDat e: DSE T<TS.DATETIME>
Mate rial
+ descri pt ion: ST+ e ffecti veDa teRange: I VL<TS.DATET IME>+ fo rmCode : CD+ func tionT ypeCode : DSET<CD>+ nameCode : CD+ subTypeCode: CD+ typeCode : C DExperimenta lI tem
+ typeCode : C D
const ra ints{Excl usiveOr }
Def inedAc tiv i ty
+ c at egoryCode : CD+ desc rip tion : ST+ nameCode : CD+ st atusCode : CD+ st atusDat e: TS. DATETIME
PlannedAc tiv it y
+ desc rip tion : ST+ name: ST+ plannedD ura ti on : PQ. TIME+ pu rpose : ST+ targe tAcc rualN umberRange :
URG<INT.NO NNEG >
PerformedActi v ity
+ act ua lDa teRange: I VL<TS.DATETI ME>+ /actual Durati on : PQ. TIME+ /delayDura tion : PQ.TI ME+ missed Ind ic ato r: BL+ missedReason : DSET<SC>+ /repe ti tionNumber : INT.PO S+ st at usCode : CD+ st at usDa te : T S.DATETIME
N ame: Exper imen t CoreA utho r: lsch ickV ersion : 1. 0C rea ted : 11 /16 /2011 9:30 :18 AMU pdat ed : 12 /22 /2011 8:02 :53 AM
Spec imen no att ri butes
BRIDG-al igned
LS D AM
Legend
O rgani zat ion
+ actua lIndi ca tor : BL+ descr ip tion : S T+ name: DSET<ON>+ post al Add ress: AD+ t el ecomAddress:
BAG <TEL>+ t ypeCode : CD
Bio log icEn tity
Person
+ dea th Indi ca tor : BL+ educa tionLeve lCode : CD+ e thni cGroupCode: DSET<CD>+ in it ia ls: ST+ marit al Stat usCode : CD+ name: DSET<PN>+ occupa ti onDat eRange :
IV L<TS.DATE>+ posta lAdd ress: AD+ p rimaryO ccupa ti onCode : CD+ raceCode : DSET<CD >+ te lecomAddress: BAG <T EL>
0. .*
is used by / uses
0 .. *
0. .*
is pe rfo rmed as pe r /descr ibes the stepsto conduct
0.. *
0. .*
inst an tia tes
0 ..1
speci al izesspecia lizes speci al izes
0 ..*suppo rts / issuppo rted by
0 .. *
0. .*
instant iat es
0. .1
0 .. *
suppo rt s / i ssuppo rt ed by
0 ..*
0. .*
i s processed in to /i s processed from1
0 ..*
is p layed by / p lays
0. .1
spec ia lizes
0. .1i s a col lection of /i sconducted as pa rt of
0 .. *
0 .. *suppor ts / issuppor ted by
0 ..*
0 ..*
suppo rts / issuppo rted by
0 .. *
0. .1resu lts i n / is the resu lt of
0. .*
0. .1
resul ts in / is t he resul t o f
0 ..*
0. .*
pa rt icipa tes in /is per fo rmedon
1
1
has va lue /is v alue fo r
0. .*
0 ..*
i s a pa rt of / i s a col lection o f
0 ..*
0 ..*
uses / de fi nes use o f
0. .*
1
has va lue / is va lue f or
0 .. *
0. .*
suppo rts / issuppo rted by
0.. *
0. .*is p layed by / p lays
0. .1
0 ..*
is pl ay ed by / pl ay s
0 ..1
0.. *
suppor ts / issuppor ted by
0 ..*
0. .*
i s pa rt o f / is a co llect ion o f0 ..*
0 .. *uses / de fines use of
0 ..*
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34
Omics in the LS DAM - Specimen (outdated)class Specimen Core
SpecimenCollectionPr otocolSubject
B iologicEntity
+ actual Indic ator: BL+ adm inistrativeGenderCode: CD+ birthCountryCode: CD+ birthDate: TS.DATET IME+ birthO rder: INT.PO S+ deathDate: T S.DATETIM E+ sexG enoty peC ode: CD+ subSpec iesRank: SC
Animal
+ breedC ode: CD+ desc ription: ED+ reproduc tiveOrgansPresentIndic ator: BL+ strain: ST
Person
+ deathIndic ator: BL+ educ ationLevelCode: C D+ ethnicG roupC ode: DSET<CD >+ ini tia ls: ST+ mari talStatus Code: CD+ nam e: DSET<PN>+ oc cupationDateRange: IV L<TS .D ATE>+ postalAddress: AD+ prim aryO cc upationCode: CD+ rac eCode: DSE T<CD>+ telec om Address: BAG <TEL>
Subj ect A ctiv ity
+ com m ent: ST+ identi fier: II+ reasonCode: DSET<CD>
P er for medActiv ity
+ actualDateRange: IVL<TS .DATETIM E>+ /ac tualDuration: PQ.TIM E+ /delay Duration: PQ.TIM E+ mis sedIndic ator: BL+ mis sedReas on: DSET <S C>+ /repeti tionN um ber: IN T.POS+ status Code: CD+ status Date: TS.D ATETIM E
PerformedProcedur e
+ approachAnatomic Si teCode: CD+ approachAnatomic Si teLateral i tyCode: CD+ methodCode: CD+ targetAnatom ic Si teC ode: CD+ targetAnatom ic Si teC ondi tionCode: CD+ targetAnatom ic Si teLateral i ty Code: C D
PerformedSpecimenCollection
+ fastingStatusIndic ator: BL
PerformedObservation
+ bodyP os i tionCode: C D+ /foc alDateRange: IVL<TS.DA TETIM E>+ /foc alDuration: PQ .TIM E+ m ethodC ode: DSET<CD >+ targetAnatom icS iteCode: CD+ targetAnatom icS iteLateral i ty Code: CD
PerformedO bserv ationResult
+ bas elineIndicator: B L+ body Sy stem Code: CD+ com m ent: ST+ confidential i tyCode: CD+ identi fier: II+ reportedDate: TS .D ATETIM E+ resul t: ANY+ resul tC odeM odifiedText: ST+ targetAnatomic Si teCode: CD+ targetAnatomic Si teLateral i tyCode: CD+ typeCode: CD+ unc ertainty Code: CD
PerformedM edicalHistoryResult
+ ageAtDiagnosis : PQ+ endRelativ eToReferenceCode: CD+ oc currenc eDateRange: IVL<TS.DATETIM E>
Per for medClinicalResult
+ asCol lectedIndic ator: BL+ biomarkerIndicator: BL+ /infec tious Agent: ST+ /norm alRangeC om parisonCode: CD+ reportedResul tStatus Code: CD
P er for medDiagnosis
+ diseaseStatusCode: CD+ rec urrenc eIndic ator: BL
PerformedHistopathology
+ c el lTypeCode: D SET<CD>+ di fferentiationGradeCode: DSET <C D>+ inv olvedSurgic alMarginIndic ator: BL
PerformedLesionDescription
+ appearanc eTypeCode: C D+ c ontac tAnatom ic Si teCode: CD+ /dim ensionP roduc t: PQ+ lesionNum ber: INT.NO NNEG+ ly m phatic Inv asion: CD+ m easurableIndicator: BL+ perineural Invas ion: CD+ v enous Inv asion: CD+ x Dim ension: PQ+ y Dim ension: PQ+ z Dim ension: PQ
PerformedS pecimenQ ualityReview
PerformedPathologicalStaging
+ dis tantM etastasisStage: CD+ lym phNodeStage: CD+ metastasisS ite: CD+ num berLym phNodesE xam ined: INT+ num berLym phNodesInv olv ed: IN T+ prim aryT um orStage: CD
PerformedSpecimenReview Result
+ nam eCode: CD
PerformedMaterialProcessS tep
P er for medSpecimenEmbedded
+ embeddingM ediumTy pe: C D
PerformedSpecimenFixed
+ fix ationTy pe: CD
PerformedSpecimenFroz en PerformedSpecimenR eturn
PerformedSpecimenSpun
+ grav i tyForce: PQ
PerformedSpecimenThaw
PerformedSpecimenC heckInCheckO ut
+ storageStatus: CD
M aterial
+ desc ription: ST+ effectiv eDateR ange: IVL<T S.DATETIM E>+ form Code: CD+ func tionTy peC ode: DSET<CD >+ nam eCode: CD+ s ubTy peCode: CD+ ty peCode: CD
Specimen no attributesCellCulture
+ biosafety Level : CD
ExperimentalItem
+ typeCode: C D
constraints{Exc lusiveO r}
Product
+ ex pirationDate: T S.DATE.FULL+ lotNum berT ex t: ST.SIM PLE+ ty peCode: CD
Equipment
+ manufactureDate: TS .DATETIM E+ reproc es sedDevic eC ode: CD+ val idationDate: DSET<TS.DATETIM E>
M aterialR elationship
+ subTy peC ode: CD+ ty peCode: CD
Nam e: Specim en CoreAuthor: lsc hic kVersion: 1.0Created: 2/7/2011 9:02:28 AMUpdated: 1/10/2012 12:56:05 P M
C ontainer
+ c ontainerType: CD+ desc ription: ST+ dim ens ionO neCapaci ty : INT+ dim ens ionO neLabel : ST+ dim ens ionPointOfO rigin: ST+ dim ens ionThreeCapac i ty: INT+ dim ens ionThreeLabel : ST+ dim ens ionTwoCapaci ty : INT+ dim ens ionTwoLabel : ST+ nam e: ST
Place
+ identifier: DSET<II>+ loc atorTy peC ode: CD+ loc atorValue: S T+ phys icalAddres s: AD+ ty peCode: CD
StorageEquipment
+ dim ensionO neCapac i ty: INT+ dim ensionO neLabel : ST+ dim ensionP ointO fOrigin: ST+ dim ensionT hreeCapaci ty : INT+ dim ensionT hreeLabel : ST+ dim ensionT woCapac i ty: INT+ dim ensionT woLabel : ST
PerformedS pecimenP lacement
+ from Posi tionDim ensionO ne: INT+ from Posi tionDim ensionThree: INT+ from Posi tionDim ensionTwo: INT+ toP os i tionDim ensionO ne: INT+ toP os i tionDim ensionT hree: INT+ toP os i tionDim ensionT wo: INT
B iologicEntityIdentifier
+ effectiv eD ateRange: IVL<TS.D ATETIM E>+ identifier: II+ ty peCode: CD
Organization
+ ac tual Indic ator: BL+ des cription: ST+ nam e: DSET<O N>+ pos talAddress: AD+ telec omAddress: BAG <TEL>+ typeCode: CD
SubjectIdentifier
+ effec tiv eDateR ange: IV L<TS.D ATETIM E>
+ identi fier: II+ prim aryIndicator: BL+ ty peCode: CD
Manufacturer
Pr ocessor
R eprocessor
MaterialName
+ nam e: E N.TN+ ty peCode: CD
M aterialIdentifier
+ identi fier: II+ typeCode: CD
SpecimenCollectionG roup
+ nam e: ST
SpecimenCollectionProtocol
+ ac tiveDateRange: IVL<TS>+ al iquotInSam eContainer: BL+ c onsentsWaiv ed: BL+ enrol lm ent: INT+ i rbIdentifier: ST+ s hortTi tle: ST
Protocol
+ name: ST
Laboratory
+ identifier: II
CollectingLabor atory
BRIDG-al igned LS DA M
LS DAM
Legend
DefinedActiv ity
DefinedCompositionR elationship
CellLine
+ originC el lNam e: ST+ passageNum ber: INT+ sourc eA ge: PQ+ sourc eA natom icSi teCode: C D+ sourc eD ev elopm entalS tage: SC+ sourc eT is sueType: CD
M icrobiologicalCulture
0..1
plays / is played by
0..*
0..*
is the parent of 1
spec ial iz es
s pec ial iz es
0..*
identi fies
1
1..*
names/ isnamedby
1
0..*
is assigned by
0..1
spec ial iz es
0..1
play s / is play ed by
0..*
0..*
is a function perform ed by
{functions as}0..1
special iz es
0..*
iscontainedin
0..1
0..*
ins tantiates
0..1
s pec ial izes
1
is the produc t of / produc es
1
1
is the subjec t of / is performed on
0..*
spec ial izes0..*
is a func tion performed by
{functions as}1
0..1
is a func tionperform ed by
{func tions as}
1
0..*
is ass igned by{assigns}
1
0..*
identi fies / isidenti fied by
{is identi fied by } 1
0..1
is a function perform ed by{func tions as }
1
0..*
produc es
1..*
0..*
ex ec utes/ is executed at 1..*
0..*is the c om ponent of
1
0..*
is located at/is the location of
1
0..*
is enc losed by / enc los es
1
0..*is c onv erted into
0..1
1
is ass igner of/is as signed to
0..*
0..*
is assessed via / is an as sessm ent of
0..*
0..*
is part of / inc ludes
0..1
0..1is tak enfrom / takes
0..*
1
has / is a part of
0..*
0..*
is assignedby / ass igns
1
0..*
produces / is produc ed by
0..*
0..*
is deriv ed from / is source of
1
0..*
is perform ed on / is the subject of
1..*
0..*partic ipates in / is perform ed on
1
1
func tions as / is afunc tion perform ed by
0..*
0..*
is a resul t of
1
special iz es
special izes
special izes special iz es
s pec ial izes
1
isplac edat/plac es 0..*
0..1
res ul ts in / is the resul t of
0..*
1..*is col lected during / res ul ts in
0..1
0..1
produces / is the product of
0..1
0..* is part of / iscom pos ed of
1
0..*
is an assess ment of / is as sessed via
0..*
0..1
perform s / is perform ed at
1..*
0..*
is partic ipated inby / partic ipatesin
0..1
1
is identi fiedby /identi fies
0..*
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Gene Expression Topic (outdated)
� Domain Analysis Model (DAM)� Passed informative
ballot� Based on several
models for geneexpression dataalong with extensions
Haifa Research Lab
Looking forward….
36
Haifa Research Lab
The rise of the 'narciss-ome‘…
� Transformative paper in the Cell Journal
� Reviewed in Nature (http://www.nature.com/news/the-rise-of-the-narciss-ome-1.10240)
� iPOP – Integrative Personal Omics Profile� Our personal omics change over time!� Longitudinal examinations of genome, proteome, meta bolome,
autoantibodies, etc. of an individual (one of the a uthors)� Monitor healthy and disease states� Predict and act accordingly (the data predicted dia betes and diabetes
was diagnosed; life style changes make it manageabl e!)
37
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iPOP –Integrative Personal
Omics Profile
Should be standardized and be part of
the lifetime EHR !!
Haifa Research Lab
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HL7 WG Health Check – Need to Improve!
� Active projects� SWOT current� 3 year plan current� Mission and charter current� Co-chair post-WGM survey participation� Ballot presence� Minutes posted since last WGM� Last listserv activity� Wiki presence � WG conference calls schedules� Steering division conference call participation� Steering division co-chair (TSC representation) election participatio n� WG rep at steering division WGM� WG meetings at WGM scheduled� WG has an approved DMP based on review of the updat ed template
Haifa Research Lab
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Planning ahead
� May 2013 WGM (Atlanta)� Schedule (from Tuesday Q4 to Thursday Q1)� Joint meetings with:
� Wed. Q1: OO+AP+II� Wed. Q3: AP
� Weekly conf. calls� Continue Tuesday’s 11EST
� Three year plan update
Haifa Research Lab
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Summary
� Small group coping with � Various HL7 formats: v3, v2 and CDA� Clinical & Research environments
� Developing a DAM and component models (CMETs) to be used in other HL7 domains� Genetic Variation� Gene Expression
� CDA Genetic Testing Report (GTR)� Bridge from raw data to human readable reports and bubbled-up data� Model-driven development of standards (use of MDHT CDA Editor)
Haifa Research Lab
A new member? Here is how to participate:
� Through our mailing list (open to nonmembers as wel l)
� Provide comments to specs� Formally through the balloting process� Informally through the list or by corresponding wit h spec editors
� Weekly conference calls
� Project specific conf. calls:� Clinical sequencing� CG & GE DAMs� Specimen
42
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43
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]
•See backup slides for more info on v3 standards
Haifa Research Lab
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HL7 Clinical Genomics v3 Static Models
Family
History
Utilize
Genetic
Locus(DSTU Expired)
Constrained GeneticVariation
Phenotype(utilizing the HL7
Clinical Statement)
Utilize
Implementation Topic
Normative
DSTU
Constrained Gene Expression
Implementation Topic
Comments
RCRIM LAB
Other domains
Utilize
Utilize
CDA IG
Re
fere
nce
Reference
Domain Information
Model: Genome
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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 Refere nce Information Model):Bio & medical-informatics standard specs are derive d from the same RIM
…we need standard specs derived from a Central Health RIM:
Bioinformatics
Data Models
Haifa Research Lab
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The Locus
and its Alleles
Sequence
Variations
Expression
Data
Sequence
and
Proteomics
(Clinical)
Phenotypes
The DSTU GeneticLocus Model (deprecated) Focal Area s:
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The Underlying Paradigm: Encapsulate & Bubble-up
Clinical PracticesGenomic Data Sources
EHR System
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
Bubble up the most clinically-significant SNP data intoHL7 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
sent
ed
in
Bio
info
rmat
ics
mar
kup
HL7
v3
XM
L
Haifa Research Lab
Other v3 Models / Efforts
� The Genome � An HL7 Domain Information Model (DIM)� Evolved as generalization of the Genotype DSTU model s� Was not balloted� Will be updated based on the DAM efforts� In the future, DAM balloting will require the mappi ng to DIM
� The RCRIM use of our DSTU CMETs
� Query model
51
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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.
genotype ��������phenotype
Genetic Loci
Genetic Locus
Non-locus specific
data
Haifa Research Lab
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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
Haifa Research Lab
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The CG V3 Query Model: Query by Parameter
GeneticLocus parameters
Starting point with query
identifiers and attributes
Miscellaneous parameters
GeneticLoci parameters
participants parameters
Phenotype parameters
Haifa Research Lab
HL7 Clinical Genomics CMETs
� CMET – a shared v3 model used by domain models
� Current CMET efforts:� Phenotype � Genetic Variation � Gene Expression� Pedigree
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Haifa Research Lab
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The Phenotype CMET Model
Observed Phenotype
Interpretive Phenotype
Haifa Research Lab
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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
Timing issues: collecting specimen, extracting genetic material, identifying genomic observations, interpretation
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The Gene Expression CMET Draft
Genetic Loci
Genetic Locus
Gene Expression
Associated observations
GTR Report
Participants
Haifa Research Lab
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Utilizations in HL7
� Clinical Trials:HL7 RCRIM Work Group (clinical trials specs) utilized the CG DSTU model (Genetic Locus) in their Pharmacogenomics message, which was an extension of the CTLab message(an approved but expired DSTU)
� Laboratory:The Lab Work Group might utilize a constrained version of the Genetic Variation model in their next release if the Lab Result message