Lynn M. SchrimlUniversity of Maryland, School of Medicine

Institute for Genome Scienceslschriml@som.umaryland.edu

The Disease Ontology: an evolving tool for Disease Curation and Annotation

Warren A. KibbeNU Clinical and Translational Sciences Institute (NUCATS),

Northwestern University

http://www.hormones.gr/17/article/article.html

disequilibrium and disharmony = disease

Hippocrates - the humoral theory for human physiology

Human Genome Project

FISH 2001

Model Organisms

Microbial Genomics – Tree of Life

1995 – first bacteria sequenced H. influenzae

Metagenome Sequencing

Human Microbiome

Genomes

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

SequencedGenomes & Metagenomes

Challenge: curation of disease related data among biomedical databases

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

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

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 Foundry2006

Cell Line Ontology

Susan Tweedie, Nick Brown

Epilepsy SyndromesJohanna Albers, Ingo Helbig

IEDB: Disease Finder

2014

2013 PubChemDO Community DevelopmentOMIM

PROReactome

Building DO

The Disease Ontology provides a unifying structure to map human disease knowledge

between datasets

patient recordsgenome sequencing

microbiome samples drug targets

expression studiesmodel organism disease models

human genesKEGG pathways

37, 988 xref mappings IDs

Mapped to DOIDs ICD9-CM 3,588

3,029 EFO 145KEGG 42MeSH 3,305

3,149NCI Thesaurus 5,307

4,881OMIM 1,693

1,184SNOMED_CT 14,227 5,124 UMLS 7,767 7,767

8,720 termsSubsets: Tick-borne infectious diseaseGram-negative bacterial infectious diseaseZoonotic infectious diseaseSexually transmitted infectious diseaseGram-positive infectious disease

Term definitions: 29 %

Cross link disease terminologiesand concepts

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

HPOHuman 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

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

View PubMed annotated records

Community Relationships and Collaborative Development

FlyBase disease model annotation disease annotations to over 1000 different alleles from around 500 different genesusing nearly 100 distinct disease ontology terms based on phenotypes described inaround 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

Ongoing Collaborative Development of Diseases Terms

Mental Health DiseasesCardiovascular DiseasesSleep disordersDiseases of the Inner EarCancerSyndromespulmonary hypertensionDO to OMIM mappingsDO to SNOMED mappingssequence variants and genetic disordersMultiple Sclerosis disease subtypesDO-EFO mappingsDO-GWAS catalog disease mappings

• 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