HL7 Clinical Genomics and Structured Documents Work Groups

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HL7 Clinical Genomics and Structured Documents Work Groups CDA Implementation Guide: Genetic Testing Report (GTR) 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

HL7 Clinical Genomics Activities Three Tracks: 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 Normative DSTU Informative

The Underlying Paradigm: Encapsulate & Bubble-up Genomic Data Sources the challenge Clinical Practices Human-readable GTR document Knowledge (KBs, Ontologies, registries, reference DBs, Papers, etc.) Encapsulation by predefined & constrained bioinformatics schemas EHR System Bubbling-up is done continuously by specialized CDS 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

CDA IG: Genetic Testing Report (GTR) Define an implementation guide for a genetic testing 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 along with references Machine-processable should be limited, e.g., exclude 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)

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 history 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

Clinical Genomic Statement Haifa Research Lab The Clinical Genomic Statement An abstract Clinical Genomic Statement (CGS) template that Has at its core a genomic observation (e.g., a DNA sequence variation) If it s a reportable finding, then it should be associated 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 specialized CGS s, e.g., for genetic variations or cytogenetics Associated Observations Indications Genomic Observation Interpretations Performers Specimen Genomic Source

Narrative and Structured Data All CGS structured data items shall be part of clinical genomic statement (CGS) instances so that parsing applications can find the full semantics explicitly represented in one coherent structure In the case of the overall interpretation, it is part of CGS that has references to the various testing interpretations Sub-sections such as Indications, Interpretations and Specimen are mainly for presenting narrative, but they may also contain structured data In this way, it is possible to have less redundant documents, e.g., in the case where all tests reported in a GTR document have the same indication, an Indications section in the Summary section consists of a full-blown indication observation which all CGS indication observations reference CGS structured data may point to the respective narrative in subsections (by means of XML ID)

GTR Overall Layout Sections order constraint

GTR Rendered The Header Draft that has not been clinically validated

GTR Rendered Summary Section Draft that has not been clinically validated

GTR Rendered Genetic Variation Sections Draft that has not been clinically validated

GTR Rendered Test Information Section Draft that has not been clinically validated

GTR Main Hierarchies Test Details Section specimen indications interpretations test performed findings test information Abstract section template w/common sub-sections: Extended by specialized sections Genetic Variations Section Genetic variations CGS Cytogenetic Section Genetic variations CGS Gene Expression Section Gene Expression CGS Clinical Genomic Statement (CGS) Abstract CGS template: Extended by specialized CGS s Genetic Variations CGS GV Associated Observations GV Interpretive Phenotypes Cytogenetic CGS Cyt Associated Observations Cyt Interpretive Phenotypes Gene Expression CGS GE Associated Observations GE Interpretive Phenotypes

GTR UML Model - Section Outline

GTR UML Model - Summary Section

GTR Genetic Variation Section

Clinical Genomic Statement Extended by specialized Clinical Genomic Statements

Interpretive Phenotype Observation

GTR XML Snippets Indications Section Summary Section Indication s narrative Indication s structured data

GTR XML Snippets Specimen Section Specimen s narrative Specimen s structured data

GTR XML Snippets Overall Interpretation Section Interpretation s narrative Structured Interpretation

GTR XML Snippets Genetic Variation Section Genetic Variation Genetic Variation associated observations

GTR XML Snippets Genetic Variation Section (cont.) Genetic Variation indication Genetic Variation interpretation

CDA GTR Ballot Status Balloted as DSTU and passed in October 2010 Still under ballot to refine & reconcile ballot comments Main issues: Vocabulary: Universal spec vs. Realm (e.g. mandate the use of LOINC code?) Binding syntax (align with new vocabulary spec and the respective SDWG guidance for CDA IGs) Layout: Semantics compare to recommended layouts in the literature Syntactic works closely with MDHT developers to adhere to SDWG guidelines Sections specific to every type of genetic test (derived from abstract) Section and Entry level template ids registration (when layout agreed) Suggestion to add drug safety template

The End Thank you for your attention Questions?