Download Day 3 Sijmons Using HPO fenotyping

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