Mondo Disease Ontology:

Building a Community-based Disease Resource

Sabrina Toro

University of Colorado Anschutz Medical Campus

CEGS 2023

Integration and comparison of disease data support diagnosis and treatment discovery

Disease Diagnosis

Treatment discovery

data comparison

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

data integration

Ontologies are knowledge representations of specific domains

• Terms represent clearly defined concepts
• Terms are arranged in a hierarchy
• Relationship between terms within the same ontology AND across ontologies
• Terms have permanent unique identifiers

central nervous system disorder

neurodegenerative disease

Alzheimer disease 18

tauopathy

Alzheimer disease

dementia

cognitive disorder

ADAM10

Neurofibrillary tangles

central nervous system

nervous system

has material basis in germline mutation in

disease has feature

disease has location

is_a

is_a

is_a

part_of

is_a

is_a

is_a

Mondo

HPO

Uberon

Cerebral degeneration

disease has major feature

Integration and comparison of disease data support diagnosis and treatment discovery

Disease Diagnosis

Treatment discovery

data comparison

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

data integration

Different communities annotate diseases at different levels of granularity and use different vocabularies and terminologies

How do we know that diseases in different resources are the same?

COACH syndrome

Joubert syndrome with hepatic defect

Source #1

Source #2

cerebellar vermis hypoplasia- oligophrenia-congenital ataxia-

coloboma-hepatic fibrosis

Source #3

Gentile syndrome

Source #4

Same disease

GENE

PHENOTYPE

DISEASE

TREATMENT

PHENOTYPE

DISEASE

GENE

PHENOTYPE

DISEASE

TREATMENT

GENE

DISEASE

TREATMENT

How do we know that diseases in different resources are the same?

Peroxisome biogenesis disorder

Zellweger syndrome

Infantile Refsum disease

Neonatal adrenoleukodystrophy

Rare hereditary metabolic disease with peripheral neuropathy

Rare hereditary disease with peripheral neuropathy

Genetic peripheral neuropathy

Leukodystrophy

Peroxisomal disease

Rare non-neoplastic disorder

Non-neoplastic nervous system disorder

Syndrome

Leukodystrophy

adrenoleukodystrophy

Refsum disease

Neonatal adrenoleukodystrophy

Infantile Refsum disease

Peroxisomal biogenesis disorder

Peroxisomal disease

Inherited metabolic disorder

Genetic disease

Disease of metabolism

Zellweger syndrome

Zellweger syndrome

https://github.com/monarch-initiative/mondo/issues/61

Orphanet

NCIt

DO

There are many different disease terminologies…

but none fits the bill or is sufficient

Specialized

• OMIM: Mendelian
• Orphanet: Rare
• NCIt: Neoplasms

Generalized

• MESH
• SNOMED
• UMLS

Some are open source, others are not

Do not include all concepts needed

Lacked sufficient depth/precision in key domains

Mappings can be used as “cross-walk” between terminologies

Disease A

Disease a

Disease a

Disease A

Disease a

Disease A

Disease a

Disease a

Mappings can be used as “cross-walk” between terminologies

… but they are often inconsistent between terminologies

Disease A

Disease a

Disease a

Disease A

Disease a

Disease A

Disease a

Disease a

X

X

Mappings can be used as “cross-walk” between terminologies

… but they are often inconsistent between terminologies

Disease A

Disease a

Disease a

Disease A

Disease a

Disease A

Disease a

Disease a

Standards proliferation: how do you know you need a new one?

For Diseases:

SITUATION:

​

THERE ARE

15*14=210

SETS OF

MAPPINGS.

xkcd.com/927

Mondo supports disease diagnosis and treatments

Disease Diagnosis

Treatment discovery

data comparison

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

data integration

Mondo was created by evidence-based merging of equivalent classes

Mondo covers a broad scope of diseases and reconcile disease classification and mappings between terminologies

• Mondo integrates key medical and biomedical disease terminologies
• Scope:
• all disease types
• human and non-human animals
• Mondo unifies disease classification
• Mondo reconciles mappings between disease resources

disease

human disease

non-human disease

infectious disease

hereditary disease

cancer or benign tumor

nervous system disorder

respiratory system disorder

…

Mondo high-level classification

Example of Mondo term: Alzheimer disease (MONDO:0004975)

https://www.ebi.ac.uk/ols4/ontologies/mondo/terms?iri=http://purl.obolibrary.org/obo/MONDO_0004975

definition

hierarchy

synonyms

+

source

X-ref* / IDs of corresponding concepts in other sources*

unique permanent ID

• exact synonyms
• related synonyms �(used in the literature, but the usage is not strictly correct)

*mappings also available in a separate file

'disease has location' some 'central nervous system' (UBERON:0001017)

‘disease has feature' some 'Neurofibrillary tangles' (HP:0002185)

relations to other ontologies

Mondo: an open community driven resource

• Mondo can be browsed on

- OLS: https://www.ebi.ac.uk/ols/ontologies/mondo

- Ontobee: https://www.ontobee.org/ontology/MONDO

- Bioportal: https://bioportal.bioontology.org/ontologies/MONDO

​

• Mondo can be found on Github: https://github.com/monarch-initiative/mondo

- open source

- monthly releases

- Mondo products:

- ontology (.json, .obo, .owl formats)

- mappings (sssom format)

- rare disease subset

Mondo is a resource for the community by the community.

Work of interest

• Rare diseases subset
• Full mappings between disease resources
• Reviewing branches of the ontology
• Epilepsy
• Infectious diseases
• …
• Veterinary diseases

Mondo supports disease diagnosis and treatments

Disease Diagnosis

Treatment discovery

data comparison

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

data integration

Mondo Development Team

mondo.monarchinitiative.org