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. Haifa Research Lab 2 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 HL7 DICOMX12 HL7 Clinical Genomics - A bridge standard… MAGEBSMLPSI GenBankHUGOSwissProtSNOMEDICDLOINC

3. Haifa Research Lab 3 How to Handle Raw and Mass Data Could we learn from the imaging integration effort? existing standards IMAGING DICOM GENOMICS BSML; MAGE-ML;... Mass and noisy data Summary, interpretation, Narrative, etc. Pixels Radiologist- Report Bio-sequences; Pathways; Gene Expression Geneticist- Report

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

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

6. Haifa Research Lab 6 The Underlying Paradigm: Encapsulate & Bubble-up Clinical Practices Genomic Data Sources EHR System HL7 CG Messages with mainly Encapsulating HL7 Objects HL7 CG Messages with encapsulated data associated with HL7 clinical objects (phenotypes) 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.) the challenge… Encapsulation by predefined & constrained bioinformatics schemas Bubbling-up is done continuously by specialized DS applications

7. Haifa Research Lab 7 The GeneticLocus Model Individual Allele Bio Sequenc e Sequence Variation (SNP, Mutation, Polymorphism, etc.) Polypeptide Expression Data Clinical Phenotype Entry Point: GeneticLocus Determinan t Polypeptide Expression Attributes Variation Attributes Encapsulating Obj. Bubbled-up Obj. Related Allele genotype phenotype

8. Haifa Research Lab 8 The GeneticVariation Model Geneti c Loci Geneti c Locus Individual Allele Sequenc e Variation Sequence (observed or reference) Point to CDA Documents participants Associated data (vocab. Controlled)

9. Haifa Research Lab 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. Haifa Research Lab 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 well 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. Haifa Research Lab 11 Cause of allergy Allergen is manifested by… Manifestation of the allergy

12. Haifa Research Lab 12 Referencing a DICOM Object

13. Haifa Research Lab 13 The End Thank you for your attention… Questions?