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Rolf Sijmons, MD PhD Dept Genetics UMCG UMC Importance of phenotype information genotype phenotype disease Capture info in databases Structured (=coded) rather than free text data “Football” as free text Computer cannot tell the difference Data content should be unambiguous Simply a list of codes is not the best solution…… if ‘the computer’ knows the relationships between the codes your code system in much more powerful Phenotypic abnormality Abnormal skeletal morphology 2‐3 toe syndactly Move up and down the tree’s to ‐ Select more general groups of patients for research / care ‐ Find your syndrome in NGS data ‐ sharp versus broad inclusion criteria etc This type of code system is called an ‘Ontology’ Is a computational representation of a domain of knowledge based upon a controlled, standardized vocabulary for describing entities and the semantic relationships between them Human Phenotype Ontology (HPO) www.human‐phenotype‐ontology.org Köhl et al (Peter Robinson’s Group) Nucl. Acids Res. 2014 The HPO aims to act as a central resource to connect several genomics datasets with the diseasome. Köhler S et al. Nucl. Acids Res. 2014;42:D966-D974 © The Author(s) 2013. Published by Oxford University Press. The Human Phenotype Ontology • Aims to provide a standardized vocabulary of phenotypic abnormalities encountered in human disease. • 10,088 classes (terms) describing human phenotypic abnormalities and • 13,326 subclass relations between the HPO classes. In addition • Logical definitions for 46% of all HPO classes using terms for anatomy, cell types, function, embryology, pathology, etc. Goal: interoperability with several resources, annotat • HPO annotations of 7,278 human hereditary syndromes Different types of phenotypic abnormalities ‘Class’ of phenotype Morphological abnormality HPO example Arachnodactyly (HP:0001166) Abnormal process (organ) Epistaxis (HP:0000421) Abnormal process (cellular) Abnormality of Krebs cycle metabolism (HP:0000816) Abnormal laboratory finding Glycosuria (HP:0003076) Electrophysiological abnormality Hypsarrhythmia (HP:0002521) Abnormality by medical imaging Choroid plexus cyst (HP:0002190) Behavioral abnormality Self‐mutilation (HP:0000742) Phenomizer (HPO browser) SUCCESS! Tools and applications using HPO Differential diagnosis and exome analysis Phenomizer BOQA Exomiser http://www.sanger.ac.uk/ resources/ databases/exomiser/ Clinical data management and analysis Cartagenia http://www.cartagenia.com/ ECARUCA DECIPHER PhenoTips Cross‐species phenotype analysis PhenoDigm MouseFinder Monarch PhenomeNet Uberpheno http://monarchinitiative.org Dutch phenotype coding landscape will change soon (next year?) (Inter)National Genotype‐phenotype Datasharing (LOVD, ECARUCA, etc etc) UMC Other UMC dBases Cartagenia etc UMC EPD EPIC Siemens etc UMC Genetics systems HELIX, Genesis, Miracle, ADLAS ICD, SNOMED CINEAS (sometimes through DHD Diagnostic Thesaurus) HPO Other Other UMC Cartagenia etc UMC EPD UMC Genetics systems ICD, SNOMED (sometimes through DHD Diagnostic Thesaurus) CINEAS HPO Other Other UMC Cartagenia etc UMC EPD UMC Genetics systems International Classification of Diseases (ICD) Is an Ontology The International Classification of Diseases (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems. International Classification of Diseases (ICD) Is an Ontology The International Classification of Diseases (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This includes the analysis of the general health situation of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems. Not suited for detailed recording of diagnosis / phenotypes SNOMED CT = ‘Systematized Nomenclature of Medicine – Clinical Terms’ Is an Ontology Is a comprehensive clinical terminology, originally created by the College of American Pathologists (CAP) and, as of April 2007, owned, maintained, and distributed by the International Health Terminology Standards Development Organisation (IHTSDO), a not‐for‐profit association in Denmark. SNOMED CT = ‘Systematized Nomenclature of Medicine – Clinical Terms’ Is an Ontology Is a comprehensive clinical terminology, originally created by the College of American Pathologists (CAP) and, as of April 2007, owned, maintained, and distributed by the International Health Terminology Standards Development Organisation (IHTSDO), a not‐for‐profit association in Denmark. Is suited for detailed recording of diagnosis / phenotypes Unfortunately still sizable gaps in SNOMED and ICD codes for genetics Sollie et al Human Mutation 2013 ICD, SNOMED CINEAS (Al dan niet via DHD Diagnostische Thesaurus) Overig (HPO,…) Go for 1 system? Overig UMC Cartagenia etc UMC EPD UMC Genetica systeem Go for 1 ontology in UMCs/Health care? Genetics department uses / needs to use general hospital EHR Want to avoid double coding Costs of maintaining CINEAS is a burden CINEAS is NOT an ontology More universal/international is better ‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐‐ + a more universal/international broad Ontology in NL Genetics (with external financial support and guarantee of continuity) National solution: Diagnostic Thesaurus Order from VWS: as of Januari 2015 Put ICD‐10 code On every hospital bill Thesaurus pushed by Government Have Contacted Professional Societies (domains) Incl Genetics To help modify/expand Diagnostic Thesaurus Proposal to Koepel • Enrich Diagnostic Thesaurus (SNOMED) with cleaned codes from CINEAS, HPO (+ Orphanet) in 2015 • Discontinue CINEAS after 2015 (keep legacy codes for future research in old cohorts) • and Switch for phenotype coding to Thesaurus • Develop local IT solutions for the switch • Develop logistics for cleaning/updating codes (engage society members) SSAGA, symptom‐ and sign‐assisted genome analysis • matches 227 clinical terms to • 591 recessive genetic diseases with pediatric presentations • helps interpret WGS results Langley et al (Kingsmore group) Sci. Transl. Med. 2012 Mapping codes between code systems through tables supports data exchange DHD Thesaurus CINEAS SNOMED‐ CT ICD‐10 HPO 1234 44 F53‐8 753.1 1011 1235 891 A23344‐88 008.2 2 etc …….. timeline Aanleveren lijst van termen (selectie) bij DHD: (ID, +(tijdelijk) SNOMED ID RIVM checkt ICD‐10 codes Release 1‐9‐14 nu 1‐1‐2015 Lokale ziekenhuis IT systemen (incl Genetica) : maken van de aanpassingen om e.e.a. mogelijk te maken (3) Toekomst CINEAS ‐ In de lucht houden zolang er geen goede (Internationale) opvolger/alternatief is ‐ Als die er wel is ‐ Kosten (goedkoper?) ‐ Beheer ? ‐ “ koppelbaarheid” , “ universeel karakter” ? ‐ Beschikbaar houden van alle CINEAS codes voor wetenschap, kliniek etc om te kunnen blijven zoeken in oude data (Goedkoop) (3) Toekomst CINEAS ‐ VOORSTEL tussen nu en eind 2015 ‐ Stap in bij Diagnostische Thesaurus en daarmee SNOMED (& ICD‐10) ‐ Stel zorgvuldig je domein termen vast voor DHD ‐ CINEAS ‐ NL / NFU werkgroep Rare Diseases ‐ Internationale lijst van 2300 termen om fenotypen binnen de genetica te beschrijven (www.ichpt.org) [OMIM, Orphanet, HPO, …..) ‐ ‐ ‐ ‐ ‐ ‐ VKGN werkgroep Theasaurus die dat coordineert Overleg DHD (RIVM) Implementatie via beheerders ZH en Genetica IT systemen Archiveren / toegankelijk houden oude CINEAS codes Opzeggen contracten CINEAS support Communicatieplan!!! ‐ Borrel timeline Aanleveren lijst van termen (selectie) bij DHD: (ID, +(tijdelijk) SNOMED ID RIVM checkt ICD‐10 codes Release 1‐9‐14 nu 1‐1‐2015