The Mondo Disease Ontology (Mondo) represents cross-species diseases, which integrates several source disease terminologies to represent cross-species diseases, and provides precise semantic mappings to the original sources. Mondo spans both rare and 'common' diseases, as well as monogenic, acquired, neoplasms, infectious diseases, and more. Mondo is a community resource and is continuously updated and iteratively curated. Recent efforts sought to improve the representation of viral infectious diseases in Mondo, to properly represent primary infections, diseases caused by reactivation of a latent virus, such as shingles and diseases caused by aftereffects of a primary infection such as long COVID-19. This included the addition of new classes and new relations (object properties), and the creation of new design patterns. The Mondo ontology files are available for download at: https://github.com/monarchinitiative/mondo.
The Mondo Disease Ontology (Mondo) integrates multiple disease terminologies into a coherent
logic-based ontology that provides precise semantic mappings between terms [
Equivalence mapping between these disease resources is provided as database cross-references on
each term using strict semantics, such as MONDO:equivalentTo, or MONDO:relatedTo, which allows
for computational integration of associated data (such as phenotype associated with a disease). Dead
Simple Design Patterns (DOSDPs) [
Mondo currently contains over 20,000 disease terms classified based on anatomical structure affected, genetic etiology (e.g. MONDO:0003847 ‘Mendelian disease’), origin (e.g. MONDO:0005550 ‘infectious disease’), etc., under the MONDO:0000001 ‘disease or disorder’ top-level class. The hierarchical classification allows for multi-inheritance, whereby terms can be classified under more than one parent. For example, the term ‘respiratory tract infectious disease’ (MONDO:0024355) is the child of both ‘respiratory system disease’ (MONDO:0005087, disease by anatomical system), and ‘infectious disease’ (MONDO:0005550).
Mondo is an OBO Foundry community-based ontology available in owl, obo, and JSON formats on GitHub (https://github.com/monarch-initiative/mondo), with new versions released monthly. The ontology is entirely manually curated by our expert curation and semantic development team (https://mondo.monarchinitiative.org/pages/contributors/) based on community feedback and iterative review by our primary development team.
The COVID-19 pandemic prompted the addition of new COVID-19 classes to Mondo, including a COVID-19 disease class and associated diseases. The addition of these new terms revealed the need for reclassification and organization of the ‘viral infectious disease’ hierarchy in Mondo, to more accurately represent the subtypes of viral infections. Here, we report the ongoing work to reorganize the ‘viral infectious disease’ branch of Mondo. We created a new classification of the infectious disease branch of Mondo, including the separation of the “infectious” and “post-infectious” into separate concepts. We created new terms to represent the concepts of ‘primary’ infectious disease versus disease arising from reactivation of a latent virus, and leverage the creation of new design patterns to classify subclass terms. Finally, we added COVID-19 specific terms following the newly created classification and design pattern.
Infectious diseases in Mondo are classified by the infectious agent such as bacterial infectious disease (MONDO:0005113), viral infectious disease (MONDO:0005108), fungal infectious disease (MONDO:0002041), and parasitic infectious disease (MONDO:0005135), by the anatomical structure infected (e.g ear infection (MONDO:0021666), eye infectious disease (MONDO:0043885 )), by the mode of transmission (eg. vector-borne diseases (MONDO:0100120)), and coinfection (MONDO:0100128).
Some infections, such as infections by COVID-19, induce not only an immediate infectious disease but also diseases caused by after-effects or chronic complications resulting from the primary infection. We separated these two different concepts into two classes: ‘infectious disease’ (MONDO:0005550) and ‘post-infectious disorder’ (MONDO:0021669), respectively. A new higher-level classification was introduced to serve as a grouping class, 'infectious disease or post-infectious disorder' (MONDO:0100336), under the top-level term ‘disease or disorder’ (MONDO:0000001) [Figure 1].
We focused on the ‘viral infectious disease’ branch of the ontology, and added the new grouping class, 'viral disease or post-viral disorder' (MONDO:0100321) under ‘infectious disease and postinfectious diseases’ (MONDO:0100336). Children of this class include the existing terms ‘viral infectious disease’ (MONDO:0005108), and 'post-viral disorder' (MONDO:0021674), which groups terms such as ‘long COVID-19’ (MONDO:0100233) [Figure 1].
Some viruses, such as herpesvirus and varicella zoster, are known to be able to enter a latent phase
after the original infection. The virus, which DNA had been incorporated into the host cell’s genome,
is dormant during this latent phase but can reactivate later after the original infection leading to a new
disease [
These concepts were represented in the ontology: ‘viral infectious disease’ (MONDO:0005108)
was subclassified into ‘primary viral infectious disease’ (MONDO:0100329), referring to the original
infection, and 'disease arising from reactivation of latent virus’ (MONDO:0100330), which refers
to disease that arises from reactivation of a virus from a latent phase to a lytic phase [
To leverage the power of consistent automatic classification and inferencing offered by DOSDPs, we created new design patterns using the newly created relations ‘disease has primary infectious agent’(MONDO:0100332) or ‘disease caused by reactivation of latent infectious agent’ (MONDO:0100333) that use the taxon of the infectious agent from the NCBI Taxonomy in the equivalence axiom to refer to ‘primary’ or ‘arising from reactivation of latent virus’’ infectious diseases, respectively. For example, herpes zoster (synonym: shingles) (MONDO:0005609) has the equivalence axiom: 'infectious disease'
and ('disease caused by reactivation of latent infectious agent' some 'Human alphaherpesvirus 3') boxes - pre-existing terms, solid lines - asserted superclass Of relationship, dotted lines - inferred classes. Oval-shaped boxes indicate terms that overlap in Figure 1 and Figure 2.
After infection with SARS-CoV-2, patients presented not only symptoms of COVID-19 but also associated long term and/or chronic COVID-19 associated disorders, including the newly described disease ‘long COVID-19’. To properly represent these new infectious diseases, terms referring to virus infection or its associated long term diseases in which the virus is SARS-CoV-2 were created: ‘COVID19’ (MONDO:0100096), which is an inferred descendent of ‘primary viral infectious disease’ (MONDO:0100319), and ‘post-COVID-19 disorder' (MONDO:0100320), an inferred child of ‘postviral disorder’ (MONDO:0021674). These 2 terms share the asserted common parent: ‘SARS-CoV-2related disease’ (MONDO:0100318), which is a child of ‘viral disease or post-viral disorder' (MONDO:0100321). The terms 'long COVID-19' (MONDO:0100233), ‘COVID-19-associated MISA’ (MONDO:0100319), and ‘COVID-19-associated MIS-C’ (MONDO:0100163) were created as children of ‘post-COVID-19 disorder (MONDO:0100320), representing the diseases reported in adults and children post-COVID-19 infection [15-20] [Figure 2].
As described in the previous section, infectious disease terms conform to a design pattern that specifies that the disease is an ‘infectious disease’ and ‘has a primary infectious agent’ that is an organism from the NCBI Taxonomy. In this case of these COVID-19 terms, the equivalence axiom for COVID-19 is: 'infectious disease' and ('disease has primary infectious agent' some 'Severe acute respiratory syndrome coronavirus 2') Figure 2: Representation of ‘SARS-CoV-2-related disease’ classification in Mondo Disease Ontology. ‘SARS-CoV-2-related disease’ (MONDO:0100318), child of ‘viral disease of post-viral disorder’ (MONDO:0100321), is a grouping class for ‘COVID-19’ (MONDO:0100096), inferred ‘primary viral infectious disease’ (MONDO: 0100329), and ‘post-COVID-19 disorder’ (MONDO:0100320), inferred ‘post-viral disorder’ (MONDO:0021674). ‘COVID-19’ is defined by an equivalence axiom relating this term to the NCBITaxon ‘Severe acute respiratory syndrome coronavirus 2’ via the ‘disease has primary infectious agent’ relation. ‘post-COVID-19 disorder’ encompasses several subclasses: ‘long COVID-19’ (MONDO:0100233), ‘COVID-19-associated MIS-A’ (MONDO:0100319), and ‘COVID-19-associated MIS-C’ (MONDO:0100163). Yellow filled boxes - newly added terms, blue filled boxes - pre-existing terms, solid lines - asserted superclass Of relationship, dotted lines - inferred classes, bold line and text - object property relationship (‘disease has primary infectious agent’).
Here we reported the enhanced representation of viral infectious diseases in Mondo. We updated the ontology to include the concepts of immediate versus the long-term effect of an infection and primary viral infection versus disease arising from reactivation of latent virus. We created new patterns and introduced new relationships to support these patterns allowing the automatic classification of infectious diseases into these new classes. This work is ongoing and focused exclusively on improving the classification of viral infectious diseases. These improvements will serve as a template to further remodel the infectious disease branch in Mondo, and future efforts will review the bacterial, parasitic and fungal infectious disease terms. This model of infectious disease may be useful as a template for other ontologies that capture this type of disease information. Mondo is an open-source ontology and community input is always welcome. Please submit your feedback or requests for changes in our GitHub issue tracker (https://github.com/monarch-initiative/mondo/issues).
This work is funded by NIH/NHGRI grant #1RM1HG010860-01.
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