This document discusses efforts to enhance accessibility of rare disease literature for researchers and patients. It describes adding layperson synonyms to the Human Phenotype Ontology to help patients understand disease descriptions. Over 44% of existing synonyms were marked as layperson terms. The document also discusses a pilot project to annotate rare disease case reports with associated genes and phenotypes to identify the rarest cases and facilitate information sharing and community building. Next steps include further literature annotation and incorporating the data into databases. The overall goal is to improve dissemination of information on rare diseases.

1. Enhancing accessibility of
rare disease literature for
researchers and patients
Erin D. Foster, MSLS
MLA Annual Conference
29 May 2017

2. Some backstory & co-authors
2
Mark Engelstad
OHSU
Nicole Vasilevsky
OHSU
Melissa Haendel
OHSU
Peter Robinson
The Jackson Laboratory
Sebastian Köhler
Charite
Chris Mungall
The Berkeley Lab

3. What’s the problem?I
3

4. 4
10% of the US population
has a rare disease

5. 5
80% of rare disease
cases are genetic

6. A biology-ism
Genes
Phenotypes
Observable traits
e.g., eye color
Environment
+ =
6

7. Linking phenotypes across organisms to
diagnosis rare disease
7
???
Obesity,
Diabetes mellitus,
Insulin resistance
Kcnj11c14/c14; insrt143/+(AB)
Increased weight,
Adipose tissue volume,
Glucose homeostasis altered
B6.Cg-Alms1foz/foz/J
Increased food intake,
Hyperglycemia,
Insulin resistance

8. Ontology-isms
1. Domain specific
2. Structured hierarchies
3. Describe relationships
8

9. Human Phenotype Ontology (HPO)
<human-phenotype-ontology.github.io/>
Abnormality of vision
Abnormality of color vision
Abnormality of
binocular vision
Monochromacy
Dyschromatopsia
Achromatopsia
Red-green
dyschromatopsia
Dichromacy
9

10. The Monarch Initiative
10
<monarchinitiative.org
/>

11. How can patients be more
involved?
II
11Image credit to Aaron Kuehn

12. Adding layperson synonyms to the
Human Phenotype Ontology
12
Abnormality of vision
Abnormality of color vision
Abnormality of
binocular vision
Monochromacy
Dyschromatopsia
Achromatopsia
Red-green
dyschromatopsia
Dichromacy

13. Adding layperson synonyms to the
Human Phenotype Ontology
13
Abnormality of vision
Abnormality of color vision
Abnormality of
binocular vision
Monochromacy
Dyschromatopsia
Achromatopsia
Red-green
dyschromatopsia
Dichromacy
Synonym: Color
blindness
Synonym: Red-green
color blindness

14. Team laypersonese
14Image credit to Aaron Kuehn
Erin & Nicole
Mark
Systematically reviewed all of
HPO (i.e. 12,000 classes)
Searched for synonyms
• Medline Plus
• Mayo Clinic
• Wikipedia
Assigned synonyms or marked
existing as layperson
Quality Assurance
• Reviewed by 3 curators
• Checked for duplicated synonyms, valid
character-encoding, title case formatting, and
annotation consistency
• SNOMED CT
• Elements of
Morphology

15. Example of layperson terms applied to a
disease
15Image credit to Julie McMurry

16. Primary outcomes
44% of synonyms in HPO are
identified as layperson
16
14253 6240
All synonyms
in HPO
Layperson synonyms
marked as lay

17. How to identify the rarest
of the rare cases?
III
17

18. Identifie
d
Screene
d
Include
d ‘case reports’[pubtype]
identified in PubMed
(n =1,778,204)
Records <=10 years
(n =532,130)
European Journal of Human
Genetics (EJHG)
(n =143)
Focused on journals
to narrow sample
size
18
Excluded PMIDs
listed in OMIM
(n=22,756)
Reported
EJHG sub-sample
(n =20)
Sub sample of
EJHG articles to
figure out workflow

19. Annotate disease, associated genes and
phenotypes for each paper
Gene: CHRNA7
Disease: 15q13.3 homozygous microdeletion syndrome
Phenotypes: severe cerebral visual impairment,
congenital hypotonia, refractory epilepsy
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20. Preliminary results
20
20 articles
352
phenotypes
identified
12%
not in HPO
Need term
and/or
synonym
created

21. Challenges (in brief)
1. Maintaining consistency in HPO
term definitions and use
2. Establishing a curation
workflow
3. Ensuring annotation reliability
21

22. How does this all come
together?
IV
22

23. (some) Next steps
23
• Review of patient forums,
medical message boards
• Track and analyze user
comments
• Complete annotation of
literature sample
• Incorporate annotations
into databases (like
Monarch)

24. What’s possible?
24
Facilitate information
dissemination
• Patient registries
• Community based
organizations
Build communities
• Compare patient profiles
• Patient discovery

25. Acknowledgements
The OHSU Library
Melissa Haendel, PhD*
Nicole Vasilevsky, PhD*
Mark Engelstad, MD*
Sebastian Köhler, PhD*
Peter Robinson, PhD*
Chris Mungall, PhD*
Kathel Dunn, PhD
NLM Associate Fellowship Program
25
*involved in project work
discussed

26. Thank you!
ANY QUESTIONS?
edfoster10@gmail.com
@erdifo
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