Mondo Disease Ontology:

Building a Community-based Disease Resource

Sabrina Toro

University of Colorado Anschutz Medical Campus

ConTech Pharma 2023 - June 8th, 2023

Monarch Initiative integrates disparate data to support disease diagnostic

Unified data model

Tools

Phenotype comparison

Variant prioritization

Disparate Data

Disease Diagnosis

Treatments discovery

Data integration

(use of ontologies)

monarchinitiative.org

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

Ontologies are the optimal controlled vocabularies

• Clearly defined terms and unique permanent identifiers� → Ontologies make data interoperable
• They standardize vocabulary across a domain
• “Everyone speaks the same language, and mean the same thing”
• They enable sharing of information between disparate systems
• Classification, semantics, formal relationship between terms within and across different ontologies� → Ontologies support sophisticated search
• They enable search with synonyms
• They enable both broad or precise search
• Eg searching for treatment for “Alzheimer disease” will include treatment for more general “dementia”
• Connect different domain and question
• Eg connect search for “Alzheimer disease” to other data related to the central nervous system
• Ontologies are the base for Artificial Intelligence

Integration and comparison of disease data support diagnosis and treatment discovery

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

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

We need a resource that allows for disease integration and comparison

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

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

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

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?

xkcd.com/927

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

Mappings are often inconsistent between terminologies

Disease A

Disease a

Disease a

Disease concepts are always not exact: they might be narrower or broader.

Mappings are often inconsistent between terminologies

Disease A

Disease a

Disease a

X

Mappings are often inconsistent between terminologies

Disease A

Disease a

Disease a

Disease B

Mondo supports disease diagnosis and treatments

GENE

VARIANT

TREATMENT

EXPOSURE

Source 1

Source 2

GENE

VARIANT

TREATMENT

EXPOSURE

PHENOTYPE

PHENOTYPE

DISEASE

DISEASE

Mondo integrates disease resources

• Mondo is 1 single ontology for all diseases
• Integrates all diseases standards
• Scope = all diseases from all areas of interest, including human and non-human diseases
• Mondo unifies disease classification
• Mondo offers a set of curated mappings between disease resources
• Mondo was created as a community resource
• Every Mondo product is openly available
• Every code, decision,..., are available
• Everyone is welcome to participate in the ontology review

Mondo was created by evidence-based merging of equivalent classes

1 + 2. OMIM + Phenotypic series

OMIM/OMIMPS

Source

3. Orphanet

Orphanet

Source

4. Genetic and Rare Diseases Information Center

GARD

Source

14. SNOMED

SNOMED

xref/Alignments

5. National Cancer Institute Thesaurus

NCIT

Source

6. Medical Subject Headings

MESH

Source

8. Unified Medical Language System

UMLS

xref/Alignments

9. International Classification of Diseases 9

ICD9

xref/Alignments

7. Disease Ontology

DO

Source

13. Mental Functioning Ontology

MF

xref/Alignments

17. OncoTree

ONCOTREE

xref/Alignments

10. International Classification of Diseases 10

ICD10

xref/Alignments

12. Experimental Factor Ontology

EFO

xref/Alignments

11. MedGen

MEDGEN

xref/Alignments

15. Ontology for General Medical Science

OGMS

xref/Alignments

16. Medical Dictionary for Regulatory Activities

MEDRA

xref/Alignments

ID Space

Role

Disease terminology

Mondo Disease Ontology integrates 17 disease terminologies

https://mondo.monarchinitiative.org/pages/sources/

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

• + 20,000 diseases
• Disease classification is reconciled
• Mappings are reconciled
• Fully mapped with
• OMIM
• OMIMPS
• Orphanet
• GARD
• DO

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

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 (upcoming)

Mondo: an open community driven resource

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

Mondo Community

• disease experts
• clinicians
• veterinarians
• databases
• annotators
• users
• ontologists
• …

• Every Mondo product is openly available
• Every code, discussion, decision,..., are available
• Updates are driven by community submitted issues and requests
• Everyone is welcome to participate in the ontology review

Requesting changes to Mondo

mondo.monarchinitiative.org | github.com/monarch-initiative/mondo

Request new term (or changes) on GitHub

Curators adds term to Mondo, creates a Pull Request (PR)

Pull requests undergo review and are merged; changes are added to mondo-edit.obo file

Term is available in next release (around 1st of each month)

OLS is updated approx 7 days after our release

✔

Community and expert discussions and advice

YOU!

Mondo community involvement and outreach

• Regular weekly meetings: Thursdays, 10am PT / 1pm ET / 6pm GMT (Zoom)
• Workshops (mostly focused subject) https://mondo.monarchinitiative.org/pages/workshop/
• Outreach call: Fridays, every 4 weeks
• gather use cases from users
• share news from the Mondo team
• Github issues!!

​

Sign-up here to join the mailing list:

https://groups.google.com/forum/#!forum/mondo-users

Mondo users and use cases

• Disease annotations
• Databases
• ClinGen : disease - gene variants annotations
• Pombase : disease annotations
• OMIA (Online Mendelian in Animals) use Mondo to refer to their diseases
• Data integration:
• European Bioinformatics Institute (EBI)
• Mondo is used as the primary ontology for disease concepts integrated into the Experimental Factor Ontology (EFO) for integration of data across EBI.
• Gabriella Miller Kids First Data Resource Portal
• use to structure diagnosis information
• Electronic Health Record data
• Data comparison and diagnostic/treatment prediction
• Monarch Initiative (cross-species disease discovery)

Recent updates and upcoming work

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

Mondo is an open community driven resource for diseases

• Mondo is a logic-based ontology that
• integrates key medical and biomedical disease terminologies
• provides a unified classification of diseases
• Mondo provides precise, curated semantic mappings between terminologies
• Mondo is a resource for the community by the community.

GitHub

github.com/monarch-initiative/mondo

>1500 issues reported

Mondo users list

https://groups.google.com/forum/#!forum/mondo-users

Email

sabrina@tislab.org

mondo.monarchinitiative.org

Monarch Initiative integrates disparate data to support disease diagnostic

Unified data model

Tools

Phenotype comparison

Variant prioritization

Disparate Data

Disease Diagnosis

Treatments discovery

Data integration

(use of ontologies)

monarchinitiative.org

Mondo Development Team

mondo.monarchinitiative.org

Mondo Community

Big thanks to the Mondo community and our contributors!

mondo.monarchinitiative.org | github.com/monarch-initiative/mondo

THE END

17 disease terminologies integrated in Mondo

ID Space

Role

Website

17 disease terminologies integrated in Mondo

ID Space

Role

Website

Obsoletion workflow

mondo.monarchinitiative.org

DOS-DP for consistency of similar disease

Infectious diseases

Cancers terms

​

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Not talking this