Presentation at the International Conference on Biological Ontology & BioCreative, August 1-4, 2016, Corvallis, Oregon, USA. Abstract In rare or undiagnosed diseases, physicians rely upon genotype and phenotype information in order to compare abnormalities to other known cases and to inform diagnoses. Patients are often the best sources of information about their symptoms and phenotypes. The Human Phenotype Ontology (HPO) contains over 12,000 terms describing abnormal human phenotypes. However, the labels and synonyms in the HPO primarily use medical terminology, which can be difficult for patients and their families to understand. In order to make the HPO more accessible to non-medical experts, we systematically added new synonyms using non-expert terminology (i.e., layperson terms) to the existing HPO classes or tagged existing synonyms as layperson. As a result, the HPO contains over 6,000 classes with layperson synonyms.

1. Enhancing the
Human Phenotype Ontology for Use
by the Layperson
Nicole Vasilevsky, Mark Engelstad, Erin Foster, Chris Mungall, Peter
Robinson, Sebastian Köhler, Melissa Haendel
ICBO, August 2016
vasilevs@ohsu.edu
@n_vasilevsky @MonarchInit @hp_ontology

2. 1.
The Problem
Diagnosing rare diseases

3. 10% of the US population
has a rare disease

4. 80% of rare disease
cases are genetic

5. Citizen scientists can help inform disease
diagnosis
• Decreased muscle mass
• Contractures of the chin,
arms and feet
• “Popeye” arm deformity
Emery-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

6. 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

7. How do we make HPO accessible so
patients can phenotype themselves?
HP:0000252
Pref Label: Microcephaly
Synonyms: Decreased Head Circumference;
Reduced Head Circumference; Small head
circumference
Suggested Synonyms : Small head;
Abnormally small head; Small skull; Small
cranium…
Small headMicrocephaly
https://commons.wikimedia.org/wiki/File:Microcephaly.png#/media/File:Microcephaly.png

8. 2.
HPO Layperson
Synonyms
Plain language for describing human diseases

9. Workflow
1 32
Check 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

10. Human Phenotype Ontology, now with 6,200
plain language synonyms
for patients, families, and non-experts
www.human-phenotype-ontology.org
Apert’s Syndrome

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Synonyms were either added to existing classes, or exisitng
classes were tagged as layperson. New synonyms were typed
either as exact, broad, related or narrow. The final numbers of
each type are reported in Table I.
Table I: Layperson synonyms in HPO
All synonyms in
HPO
Layperson
synonyms marked
as lay
All synonyms 14253 6240
Exact 12167 5357
Broad 441 298
Related 1236 419
Narrow 409 166
Information content of HPO classes
We aimed to understand the impact of adding lay
synonyms to the HPO if they were to be used for disease
Almost half of the 14k synonyms are plain
language
4456 terms have layperson synonyms

12. Layperson synonyms tended to be at the more granular levels
How specific are these layperson synonyms?
1800
1600
1400
1200
1000
800
600
400
200
Count(squarerootscale)
0.0 2.5 5.0 7.5 10.0
Information content of HPO class

13. Challenges
Community contributions welcome!
https://github.com/obophenotype/human-phenotype-ontology
Reconcile with logic
and definition
Colorblindness}Dyschromatopsia
Monochromacy
Avoid using a
definition
Vasculitis
Def.
Inflammation of blood vessel.
Recognize when not
to create a synonym
Ensure
consistency
Flexion contracture
Def. 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

14. 3.
Next steps
Validation

16. 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

17. Patient self-reported
HPO profile
HPO reference
profile
Comparison
Disease 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 profile
Patient self-reported
HPO profile
Patient self-reported
HPO profile
Patient self-reported
HPO profile
Ensure that the HPO layperson profile is maximally
diagnostic

18. 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
}

19. 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

20. Mark Engelstad
OHSU
Erin Foster
OHSU
Chris Mungall
LBNL
Peter Robinson
Charite
Sebastian Kohler
Charite
Melissa Haendel
OHSU
Acknowledgements
FUNDING: NIH Office of Director: 1R24OD011883; NIH-UDP: HHSN268201300036C,
HHSN268201400093P, Phenotype Ontology Research Coordination Network (NSF-DEB-0956049)
Nicole Washington
LBNL

21. Any questions ?
You can find me at:
@n_vasilevsky
vasilevs@ohsu.edu
Thanks!