Integrating clinical and model organism genotype-phenotype
data for improved disease discovery
Melissa HaendelClinGen/DECIPHER meeting
2015.05.28@monarchinit
www.monarchinitiative.org
@ontowonka
There are 47,964 variants of unknown significance in
ClinVar
What are we gonna do about that?
The Human Phenotype Ontology
Each disease is associated with different phenotype nodes in the graph
Disease or Patient
HPO concepts are not well represented in other
vocabularies
Winnenburg and Bodenreider, ISMB PhenoDay, 2014
UMLS
SNOMED CT
CHV
MedDRA
MeSH
NCIT
ICD10-C
ICD9-CM
ICD-10
OMIM
MedlinePlus
Phenotype “Blast”: Which phenotypic profile is graphically
most similar?Disease X
Patient
Disease Y
Finding the phenotype graph in common
Disease X
Patient
Disease Y
The Human Phenotype Ontology
Why we need all the organisms
Clinicians and researchers speak different languages
Diversity of disease and phenotype vocabularies
Using semantics to bridge vocabularies
Using semantics to bridge vocabularies
Standardizing Cross-species G2P Data + Ontologies
SciGraph: A Neo4j-backed ontology store All species ontologies and G2P data can be
stored in a graph together Advantages: Semantics + Speed + Flexibility Propagate provenance and evidence Using to develop and evaluate GA4GH G2P
schemas
https://github.com/SciGraph/SciGraph
Combining genotype and phenotype data for variant
prioritizationWhole exome
Remove off-target and common variants
Variant score from allele freq and pathogenicity
Phenotype score from phenotypic similarity
PHIVE score to give final candidateshttps://www.sanger.ac.uk/resources/databases/exomiser/query/exomiser2
Mendelian filters
Cross-species phenotypic profile comparison for disease
discovery
Visualizing phenotypic similarity
http://monarchinitiative.org/page/phenogrid
AcknowledgmentsOHSUNicole VasileskyMatt BrushBryan LarawayShahim EssaidKent Shefchek
NIH-UDPWilliam BoneMurat SincanDavid AdamsJoie DavisNeal BoerkoelCyndi TifftBill Gahl
UDNAlexa McCrayRachel Ramoni
GarvanTudor Groza
Lawrence BerkeleyNicole WashingtonSuzanna LewisJeremy XuanChris Mungall
UCSDJeff GretheChris ConditMaryann Martone
U of PittChuck BorromeoVincent AgrestiHarry Hochheiser
SangerAnika OehlrichJules JacobsonDamian Smedley
CharitéSebastian KohlerSandra DoelkenSebastian BauerPeter Robinson
TorontoMarta GirdeaSergiu DumitriuHeather TrangBailey GallingerOrion BuskeMike Brudno
JAXCynthia SmithCurrent Funding:
NIH Office of Director: 1R24OD011883HHSN268201300036C, HHSN268201400093P
If you use Monarch ontologies or tools, please attribute us!
Please send feedback too, don’t let it be a one way street.
Extra
Propagating phenotypes across genotypic levels
We learn different things from different organisms
Monarch in the GA4GH MatchMaker Exchange
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