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Enhancing the Human Phenotype Ontology for Use by the LaypersonNicole Vasilevsky, Mark Engelstad, Erin Foster, Chris Mungall, Peter
Robinson, Sebastian Köhler, Melissa Haendel
ICBO, August 2016
@n_vasilevsky @MonarchInit @hp_ontology
1.The ProblemDiagnosing rare diseases
10% of the US population has a rare
disease
80% of rare disease cases are
genetic
Citizen scientists can help inform disease diagnosis
• Decreased muscle mass
• Contractures of the chin, arms and feet
• “Popeye” arm deformityEmery-Dreifuss
Jill Viles at age 11
Article: https://www.propublica.org/article/muscular-dystrophy-patient-olympic-medalist-same-genetic-mutation
Podcast: http://www.thisamericanlife.org/radio-archives/episode/577/something-only-i-can-see
Human Phenotype Ontology Standardized vocabulary of
phenotypic abnormalities encountered in human disease
Developed using the medical literature, Orphanet, DECIPHER, and OMIM
Terms are logically defined with terms from other ontologies, ie GO, Uberon and CL
HPO currently contains approximately 12,000 terms (still growing)
sensory perception of smell
eyeball of camera-type eye
CL motor neuron
How do we make HPO accessible so patients can phenotype themselves?
HP:0000252Pref Label: MicrocephalySynonyms: Decreased Head Circumference; Reduced Head Circumference; Small head circumferenceSuggested Synonyms : Small head; Abnormally small head; Small skull; Small cranium…
Small headMicrocephaly
https://commons.wikimedia.org/wiki/File:Microcephaly.png#/media/File:Microcephaly.png
2.HPO Layperson SynonymsPlain language for describing human diseases
Workflow
1 32Check HPO for existing synonyms
Search the web to discover common usage
Wikipedia MedlinePlus Mayo Clinic OMIM Elements of
Morphology
Refer to other ontologies, terminologies, texts
Uberon (for anatomic/ site synonyms)
SNOMED CT browser
Specialty texts
Human Phenotype Ontology, now with 6,200 plain language synonyms
for patients, families, and non-experts
www.human-phenotype-ontology.org
Apert’s Syndrome
Almost half of the 14k synonyms are plain language
4456 terms have layperson synonyms
Layperson synonyms tended to be at the more granular levels
How specific are these layperson synonyms?
18001600140012001000
800
600
400
200
Coun
t (sq
uare
root
scal
e)
0.0 2.5 5.0 7.5 10.0
Information content of HPO class
Challenges
Community contributions welcome!https://github.com/obophenotype/human-
phenotype-ontology
Reconcile with logic and definition
Colorblindness }DyschromatopsiaMonochromacy
Avoid using a definition
VasculitisDef. Inflammation of blood vessel.
Recognize when not to create a synonym Ensure consistency
Flexion contractureDef. A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
HPO developers and clinicians review each other’s work
3.Next stepsValidation
An experiment to determine how much phentoyping is enough?
Create a variety of “derived” diseases– Remove subset(s) (breadth)– More general (depth)– Introduce noise
Assess the change in similarity between the derived disease and the original
Annotation sufficiency metric is available via Monarch services
Original
Original
remove green(orange, red, grey, yellow)
Lift by 1(or 2, 3, 4, 6)
bit.ly/annotationsufficiency http://bit.ly/SufficiencyPaper
Patient self-reported HPO
profileHPO reference
profile
ComparisonDisease 1
Disease 2
Disease 3
Disease 4
Disease 7500
HPO reference profile
HPO reference profile
HPO reference profile
HPO reference profile
Patient self-reported HPO
profilePatient self-
reported HPO profilePatient self-
reported HPO profile
Patient self-reported HPO
profile
Ensure that the HPO layperson profile is maximally diagnostic
Ensure that the HPO layperson profile is maximally diagnostic
Patient
Expert
Phenotypic Profile overlap
Compare phenotypic profiles
For every known disease, fill the survey and ask:Does the profile match the disease best based on the survey
mapping?
Patient self-reported HPO
profile
HPO reference profile
}
Conclusion 44% of the synonyms in the
HPO are layperson Community contributions
welcome HPO can be integrated into
patient registries Promote accessibility of HPO
to patients and interoperability and clinicians and researchers
Enhance rare disease diagnosis
Mark EngelstadOHSU
Erin FosterOHSU
Chris MungallLBNL
Peter RobinsonCharite
Sebastian KohlerCharite
Melissa HaendelOHSU
Acknowledgements
FUNDING: NIH Office of Director: 1R24OD011883; NIH-UDP: HHSN268201300036C, HHSN268201400093P, Phenotype Ontology Research Coordination Network (NSF-DEB-0956049)
Nicole WashingtonLBNL
