The Monarch Initiative: Unifying, Integrating, and Sharing Genotype ...
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Integrating clinical and model organism genotype-phenotype data for improved disease discovery Melissa Haendel ClinGen/DECIPHER meeting 2015.05.28 @monarchinit www.monarchinitiative.org @ontowonka
Transcript of The Monarch Initiative: Unifying, Integrating, and Sharing Genotype ...
Integrating clinical and model organism genotype-phenotype data
for improved disease discovery
Melissa Haendel ClinGen/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 prioritization
Whole exome
Remove off-target and common variants
Variant score from allele freq and pathogenicity
Phenotype score from phenotypic similarity
PHIVE score to give final candidates https://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
Acknowledgments OHSU Nicole Vasilesky Matt Brush Bryan Laraway Shahim Essaid Kent Shefchek
NIH-UDP
William Bone Murat Sincan David Adams Joie Davis Neal Boerkoel Cyndi Tifft Bill Gahl
UDN Alexa McCray Rachel Ramoni
Garvan Tudor Groza
Lawrence Berkeley Nicole Washington Suzanna Lewis Jeremy Xuan Chris Mungall
UCSD
Jeff Grethe Chris Condit Maryann Martone
U of Pitt
Chuck Borromeo Vincent Agresti Harry Hochheiser
Sanger Anika Oehlrich Jules Jacobson Damian Smedley
Charité
Sebastian Kohler Sandra Doelken Sebastian Bauer Peter Robinson
Toronto
Marta Girdea Sergiu Dumitriu Heather Trang Bailey Gallinger Orion Buske Mike Brudno
JAX
Cynthia Smith
Current Funding: NIH Office of Director: 1R24OD011883 HHSN268201300036C, 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
