The Human Disease Ontology (DO), organized as a directed acyclic graph, represents a knowledge base of inherited, environmental, infectious diseases (http://www.disease-ontology.org). DO's textual definition model incorporates a semi-structured format describing the disease etiology built to capture the complex nature of human disease etiology within a is_a hierarchy. DO includes disease concepts for cancer, metabolic disease, infectious disease, mental disorders, genetic disease and syndromes. DO contains disease definitions, external references to resources including ICD, NCI-metathesaurus, SNOMED, MeSH and OMIM and extended relationships that conform to OBO guidelines. DO provides a central ‘switchboard’ for connecting resources, datasets, and computational tools that include disease terms or relationships.

1. Lynn M. Schriml
University of Maryland, School of Medicine
Institute for Genome Sciences
lschriml@som.umaryland.edu
The Disease Ontology: an evolving tool for Disease
Curation and Annotation
Warren A. Kibbe
NU Clinical and Translational
Sciences Institute
(NUCATS), Northwestern University

2. http://www.hormones.gr/17/article/article.html
disequilibrium and disharmony = disease
Hippocrates - the humoral theory for human physiology

3. Human Genome Project
FISH
2001
Model Organisms
Microbial Genomics – Tree of Life
1995 – first bacteria sequenced
H. influenzae
Metagenome Sequencing
Human Microbiome
Genomes

4. 10,000 monogenic human disease
3,076,748
http://www.ncbi.nlm.nih.gov/pubmed/?term=disease
3,043,175
http://www.ncbi.nlm.nih.gov/nuccore/?term=disease
6,800 rare diseases
Sequenced
Genomes & Metagenomes

5. Challenge: curation of disease related data among biomedical databases

6. genetic disease
disease of mental health
disease of infectious agent
disease of cellular proliferation
cancer
benign neoplasm
disease of anatomical entity
NCI
DSM
- IV
[C04] neoplasms
[F03] mental disorders
[C01] bacterial infections and
mycoses
[C02] virus diseases
[C03] parasitic diseases
[C19] endocrine system diseases
[C20] immune system diseases
disease of metabolism
inherited metabolic disorder
MeSH
[C] Diseases OMIM
phenotypes
phenotypes
ICD9
neoplasms
mental
disorders
infectious
and parasitic
diseases
disease of …
system
congenital anomalies
Challenge: Cross-mapping disease concepts,
disparate representation of disease across
vocabularies
Orphanet: Rare Diseases

7. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245088/

8. DO v3: reorganization by UMLS disease concepts
mappings to SNOMED CT and ICD-9
DO http://www.disease-ontology.org
2011
2004
Rex Chisholm & Kibbe (Northwestern): founded DO
DO v1: ICD-9 as foundational vocabulary
DO v2: DO reorganized by process, system
affected, and cause (genetic
disorders, infectious diseases, metabolic
disorders)
MeSH added
2008
DO R01 (ARRA, NIH/NCRR, R01RR025342)
DO Advisory Board
(Michael Ashburner, Suzi Lewis, Barry Smith, Alan
Ruttenberg, Chris Mungall, Judy Blake, Rex Chisholm)
DO submitted to OBO Foundry
2006
Cell Line Ontology
Susan Tweedie, Nick Brown
Epilepsy Syndromes
Johanna Albers, Ingo
Helbig
IEDB: Disease Finder
2014
2013 PubChemDO Community Development
OMIM
PRO
Reactome
Building DO

9. The Disease Ontology provides a
unifying structure to map
human disease knowledge
between datasets
patient records
genome sequencing
microbiome samples
drug targets
expression studies
model organism disease models
human genes
KEGG pathways

10. 37, 988 xref mappings
IDs Mapped to DOIDs
ICD9-CM 3,588 3,029
EFO 145
KEGG 42
MeSH 3,305 3,149
NCI Thesaurus 5,307 4,881
OMIM 1,693 1,184
SNOMED_CT 14,227 5,124
UMLS 7,767 7,767
8,720 terms
Subsets:
Tick-borne infectious disease
Gram-negative bacterial infectious disease
Zoonotic infectious disease
Sexually transmitted infectious disease
Gram-positive infectious disease
Term definitions: 29 %
Cross link disease terminologies
and concepts

11. Domain Ontology Application Ontologies
IDO: Influenza
Ontology
ADO: Alzheimer’s disease ontology
Pathogenic disease ontology version 0.1
ProteomeXchange
Sample annotation:
- Cell type. Use the “Cell Type” ontology (CL);
- Disease. Use the “Human Disease” ontology (DOID).
Metadata Standard and Data Exchange Specifications to
Describe, Model, and Integrate Complex and Diverse High-Throughput
Screening Data from the Library of Integrated Network-based Cellular
Signatures (LINCS)
GSC MIxS metadata standard: diseases status, for humans the terms
should be chosen from DO (Disease Ontology)
- a concept mapping tool
- a data annotation tool

12. HPO
Human Phenotype
Ontology
Gene Wiki
DO Community
Samples, Phenotypes, Ontology Team
Sifem Inner
Ear disease
Improving the quality and content of DO
Serving Our Community
• Term requests & review
• Integrating rare diseases
• Coordinating development
with clinicians
Providing support for disease
curation & annotation

13. http://testpubchem.ncbi.nlm.nih.gov/classification/#hid=1

14. View PubMed annotated records

15. Community Relationships and Collaborative Development
FlyBase disease model annotation
disease annotations to over 1000 different alleles from around 500 different genes
using nearly 100 distinct disease ontology terms based on phenotypes described in
around 300 papers. http://flybase.org
WormBase: Human disease model data
Curated and orthology-based human disease related data for genes
Currently, over 250 genes have been manually curated, for their relevance to human
disease and several hundred genes are flagged as potential models, based on
orthology to human disease genes.http://www.wormbase.org
OMIM: DOs 947 OMIM xref annotations utilized for OMIM API
Reactome: To identify disease-associated entities and events, a new
‘disease’ attribute is added, taking its value terms from a disease ontology.
Protein Ontology (PRO): Disease references are curated DO mappings.
http://pir.georgetown.edu/pro/pro.shtml

16. Ongoing Collaborative Development of Diseases Terms
Mental Health Diseases
Cardiovascular Diseases
Sleep disorders
Diseases of the Inner Ear
Cancer
Syndromes
pulmonary hypertension
DO to OMIM mappings
DO to SNOMED mappings
sequence variants and genetic disorders
Multiple Sclerosis disease subtypes
DO-EFO mappings
DO-GWAS catalog disease mappings

17. • Follow DO on twitter
• Send us your disease terms DO Term Tracker - Submit new terms, definitions or
suggestions for the Disease Ontology to the DO Term Tracker.
http://sourceforge.net/p/diseaseontology/feature-requests/
• Download DO:
http://sourceforge.net/p/diseaseontology/code/HEAD/tree/trunk/HumanDO.obo