Integrating clinical and model
organism genotype-phenotype data
for improved disease discovery
Melissa Haendel
ClinGen/DECIPHER meeting
2015.05.28
@monarchinit
@ontowonka
www.monarchinitiative.org
There are 47,964 variants of
unknown significance in
ClinVar
What are we gonna do about
that?
The Human Phenotype Ontology
Disease or Patient
Each disease is associated with different phenotype nodes in the graph
HPO concepts are not well
represented in other vocabularies
UMLS
SNOMED CT
CHV
MedDRA
MeSH
NCIT
ICD10-C
ICD9-CM
ICD-10
OMIM
MedlinePlus
Winnenburg and Bodenreider, ISMB PhenoDay, 2014
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
Mendelian filters
Phenotype score from phenotypic similarity
PHIVE score to give final candidates
https://www.sanger.ac.uk/resources/databases/exom
iser/query/exomiser2
Cross-species phenotypic profile
comparison for disease discovery
Visualizing phenotypic similarity
http://monarchinitiative.org/page/phenogrid
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
Acknowledgments
Sanger
Anika Oehlrich
Jules Jacobson
Damian Smedley
Lawrence Berkeley
Nicole Washington
Suzanna Lewis
Jeremy Xuan
Chris Mungall
Charité
Sebastian Kohler
Sandra Doelken
Sebastian Bauer
Peter Robinson
UCSD
Jeff Grethe
Chris Condit
Maryann Martone
Toronto
Marta Girdea
Sergiu Dumitriu
Heather Trang
Bailey Gallinger
Orion Buske
Mike Brudno
U of Pitt
Chuck Borromeo
Vincent Agresti
Harry Hochheiser
Current Funding:
JAX
Cynthia Smith
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