HL7 Clinical Genomics and Structured Documents Work Groups

1. HL7 Clinical Genomics and Structured Documents Work Groups CDA Implementation Guide: Genetic Testing Report DRAFT PROPOSAL Amnon Shabo (Shvo), PhD shabo@il.ibm.com HL7 Clinical Genomics WG Co-chair and Modeling Facilitator HL7 Structured Documents WG CDA R2 Co-editor CCD Implementation Guide Co-editor

2. HL7 Clinical Genomics - A bridge standard… MAGE HL7 DICOM X12 BSML PSI GenBank ICD HUGO SNOMED SwissProt LOINC The HL7 Clinical Genomics SIG • 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 Genomic Data Clinical Data

3. How to Handle Raw and Mass Data • Could we learn from the imaging integration effort?

4. HL7 Clinical Genomics v3 Static Models Family History CDA IG Normative RCRIM LAB Reference DSTU Utilize Utilize Utilize Utilize Reference Comments Genetic Loci Other domains Constrained GeneticVariation Utilize Implementation Topic Genetic Locus Constrained Gene Expression Implementation Topic Utilize Phenotype (utilizing the HL7 Clinical Statement)

5. The GeneticLocus Model - Focal Areas: Expression Data The Locus and its Alleles Sequence and Proteomics Sequence Variations Clinical Phenotypes

6. The Underlying Paradigm:Encapsulate & Bubble-up Genomic Data Sources Clinical Practices the challenge… HL7 CG Messages with encapsulated data associated with HL7 clinical objects (phenotypes) Knowledge (KBs, Ontologies, registries, reference DBs, Papers, etc.) HL7 CG Messages with mainly Encapsulating HL7 Objects Encapsulation by predefined & constrained bioinformatics schemas EHR System Bubbling-up is done continuously by specialized DS applications Decision Support Applications Bubble up the most clinically-significant raw genomic data into specialized HL7 objects and link them with clinical data from the patient EHR

7. Entry Point: GeneticLocus The GeneticLocus Model Encapsulating Obj. Individual Allele Determinant Polypeptide Bubbled-up Obj. Bio Sequence Expression Attributes Expression Data Related Allele Polypeptide genotypephenotype Clinical Phenotype Variation Attributes Sequence Variation (SNP, Mutation, Polymorphism, etc.)

8. Genetic Loci Genetic Locus The GeneticVariation Model Associated data (vocab. Controlled) participants Individual Allele Point to CDA Documents Sequence (observed or reference) Sequence Variation

9. CDA IG for Genetic Testing Report • Design principles: • Follow existing report formats commonly used in healthcare & research • Emphasis on interpretations & recommendations • Provide inline & detailed (generic) information on tests performed • Interpretation: Utilize patterns of ‘genotype-phenotype’ associations in the HL7 v3 Clinical Genomics and implement them as templates in this IG • Reference HL7 Clinical Genomics instances (most likely constrained) • Place holders of raw data (evidences) and for structured family history • Section outline: • Content sections: Genetic Variations, Gene Expression, others • Sub-sections in each content section: • Specimen • Findings • Interpretations • Recommendations • Test Information • Family History Open the draft outline

10. Technical Issues • Design & register genotype-phenotype templates • Similar a bit to the CCD templates for “Allergies, Adverse Reactions, Alerts” where ‘agent’ is the genomic entity/observation and the reaction is the phenotypic information • Note that in CCD the relationship is fixed to “MFST” while in genomics we’ll have a variety of codes representing various ‘genotype-phenotype’ relationships • Enable associating a genotype to phenotypes in several places across the document (reference an observation) • Links to HL7 v3 Clinical Genomics instances • Similar to referencing images in CDA Diagnostic Report IG

11. Cause of allergy Allergen is manifested by… Manifestation of the allergy

12. Referencing a DICOM Object

13. The End • Thank you for your attention…  • Questions?