=Paper=
{{Paper
|id=Vol-3805/ICBO-2022_paper_3877
|storemode=property
|title=Coordinating Coronavirus Research: The Virus Infectious Disease Ontology
|pdfUrl=https://ceur-ws.org/Vol-3805/ICBO-2022_paper_3877.pdf
|volume=Vol-3805
|authors=John Beverley,Yongqun He,Barry Smith,Shane Babcock,Eric Merrell,Lindsay Cowell,Regina Hurley,Sebastian Deusing
|dblpUrl=https://dblp.org/rec/conf/icbo/BeverleyH0BMCHD22
}}
==Coordinating Coronavirus Research: The Virus Infectious Disease Ontology
==
https://ceur-ws.org/Vol-3805/ICBO-2022_paper_3877.pdf
Coordinating Coronavirus Research: The Virus Infectious Disease Ontology
John Beverley1, Shane Babcock2, Barry Smith3, Yongqun He4, Eric Merrell1,3, Lindsay Cowell5,
Regina Hurley6, Sebastian Deusing7
1
Johns Hopkins University Applied Physics Laboratory, Laurel, MD, USA
2
Department of Philosophy, Niagara University, Lewiston, NY, USA
3
Department of Philosophy, University at Buffalo, Buffalo, NY, USA
4
University of Michigan Medical School, Ann Arbor, MI, USA
5
University of Texas Southwestern Medical School, Dallas TX, USA
6
Department of Philosophy, Northwestern University, Evanston, IL, USA
7
Loyola University, Chicago, Il, USA
Abstract
The COVID-19 pandemic prompted immense work on the investigation of the SARS-CoV-2 virus. Ontologies –
structured, controlled, vocabularies – are designed to support consistency of interpretation, and thereby to prevent
the development of data silos. This paper describes how ontologies are serving this purpose in the virus research
domain, following the principles of the Open Biological and Biomedical Ontology (OBO) Foundry and drawing on
the resources of the Infectious Disease Ontology (IDO) Core. We report the development of the Virus Infectious
Disease Ontology (VIDO), a reference ontology extending IDO Core covering viral infectious diseases. We examine
newly minted terms, showcase ontology term reuse, and illustrate the use of VIDO by annotating selections from
recent life science research on SAR-CoV-2, in the interest of supporting machine learning projects.
Keywords
Virus, SARS-CoV-2, coronavirus, COVID-19, applied ontology, infectious disease ontology, CIDO
1. Introduction entities and relations across disciplines using
consensus terminologies – constitute a well-known
The volume of data collected by life-science solution to the formation of data silos. The need for
researchers, the speed at which it is generated, rapid analysis of evolving datasets representing
range of its sources, quality, accuracy, and need for coronavirus research motivated the development of
assessment of usefulness, results in complex, the Virus Infectious Disease Ontology (VIDO)
multidimensional datasets [1,2], often annotated comprised of textual definitions for terms and
using discipline- or institution-specific relations and logical axioms supporting automated
terminologies and coding systems that lead to data consistency checking, querying over datasets, and
silos. These undermine interoperability, meta-data interoperability with other ontologies. VIDO is an
analysis, pattern identification, and discovery across extension of the widely used Infectious Disease
disciplines [3]. The value of cross-discipline meta- Ontology Core (IDO Core) [7], comprised of
data analysis is evident during the present pandemic terminological content common to all investigations
[4,5]. of infectious disease. VIDO extends IDO with
terms specific to the domain of infectious diseases
Ontologies – interoperable, logically well-defined,
caused by viruses and provides a foundation for
controlled vocabularies representing common
ontologies representing specific viral infectious
ICBO 2022, September 25-28, 2022, Ann Arbor, MI, USA
EMAIL: johnbeverley2021@u.northwestern.edu (A.1);
babcock8@buffalo.edu (A.2); ifomis@gmail.com (A.3);
yongqunh@med.umich.edu (A.4);
Lindsay.Cowell@utsouthwestern.edu (A.5);
ReginaHurley2023@u.northwestern.edu (A.6); sduesing@luc.edu
(A.7)
ORCID: 0000-0002-1118-1738 (A. 1); 0000-0003-0798-114X (A. 2);
0000-0003-1384-116X (A. 3); 0000-0001-9189-9661 (A.4); 0000-
0003-1617-8244 (A.5)
2022 Copyright for this paper by its authors. Use permitted under Creative
Commons License Attribution 4.0 International (CC BY 4.0).
CEUR Workshop Proceedings (CEUR-WS.org)
©️
CEUR
ceur-ws.org
Workshop ISSN 1613-0073
Proceedings
diseases such as the Coronavirus Infectious Disease Biomedical and Biological Ontologies (OBO)
Ontology (CIDO), which is itself an extension of Foundry was created to provide guidance for
VIDO covering coronavirus infectious diseases ontology developers and promote alignment and
such as COVID-19. The most recent version of interoperability. OBO Foundry design principles
VIDO can be found at the National Center for require ontologies: use a well-specified syntax
Biomedical Ontology Bioportal [8]. unambiguous with a common space of identifiers,
be openly available in the public domain, be
VIDO was developed in collaboration with relevant
modularly developed with a specified scope in a
domain experts and drawing on the expertise of the
collaboration with ontologists covering nearby
IDO developers to ensure alignment with OBO
domains and conform to a common top-level
Foundry principles [9], supporting interoperability
architecture. The OBO library consists of over 250
with Foundry ontologies [10]. Development of
ontologies, including some externally developed
VIDO is transparent, with discussions available on
ontologies such as the NCI Thesaurus [18] and the
GitHub [11]. VIDO term additions are driven by the
NCBI Taxonomy [19], and some constructed ab
needs of researchers investigating viruses and
initio to satisfy OBO principles. At its core is Basic
nearby domains, and so remains sensitive to
Formal Ontology (BFO), a top-level ontology
evolving knowledge.
covering general classes such as material entity,
2. Methods quality, process, and role [20,21,22], which
provides the architecture referred to in the last
VIDO and is formally represented in OWL 2 Web Foundry principle. BFO is, moreover, an ISO/IEC
Ontology Language. VIDO was developed using approved standard 21838-2 [23].
the Protégé-OWL editor and tested against
Where BFO is domain-neutral, OBO Foundry
automated reasoners such as HermiT and Pellet
ontologies represent types of entities in more
[12,13]. Axioms underwriting VIDO were
specific domains, using terms such as disease, cell
translated into a decidable fragment of first-order
division, surgical procedure, and so forth. Each
logic readable by the Mace4 [14] model checker,
domain ontology is constructed using a
which allowed for manual graphical inspection of
methodology for formulating definitions through a
classes of models constrained by the asserted
process of downward population from BFO. The
axioms. An automated proof-checker Prover9
resulting alignment with BFO, and the conformance
bundled with Mace4 was used to validate expected
to OBO Foundry principles, fosters integration
theorems while refining axiom models.
across ontologies. VIDO was designed with
2.1 OBO Foundry Alignment alignment and conformance in mind. Development
followed metadata conventions adopted by many
Ontologies are widely used in bioinformatics, OBO Foundry ontologies. These conventions
supporting data standardization, integration, require that every term introduced into the ontology
sharing, reproducibility, and automated reasoning. has a unique IRI, textual definitions, definition
The Gene Ontology (GO), for example, maintains source, designation of term editor(s), and preferred
species-neutral annotations of gene products and term label. In the interest of coordinating
functions, and – since its inception in 1998 – has development with existing OBO ontologies, VIDO
inspired an explosion of biomedical ontologies developers imported terms where possible from
covering all domains of the life sciences [15,16,17]. OBO library ontologies and constructed logical
These early developments led to worries, however, definitions using imported terms. Development was
that data silos – the very problem ontologies were guided by best practices for definition construction
designed to address – might reemerge as [24]. New terms were introduced when needed,
researchers developed ontologies using concepts after consultation with domain experts, relevant
local to their discipline. By 2007, the Open literature, and examination of the OBO library.
2
2.2 Hub and Spokes Approach disorder =def Material entity that is a clinically
abnormal part of an extended organism.
VIDO follows the “hub and spokes” methodology
[25] for ontology development. VIDO is a spoke A part of a material entity is “clinically abnormal”
ontology, extending from the Infectious Disease if it is not expected in the life plan for entities of the
Ontology Core (IDO Core) as its hub. IDO Core is relevant type and is causally linked to elevated risk
an OBO ontology consisting of terms, relations, – that is, risk exceeding some threshold – of illness,
natural language definitions and associated logical death, or disfunction [32]. Organism is imported
axioms representing phenomena common across from OBI:
infectious diseases research [26]. IDO Core has organism =def Object that is an individual living
long provided a base from which more specific system, such as animal, plant, bacteria, or virus,
infectious disease ontologies extend and has been that is capable of replicating or reproducing,
recently updated to keep pace with scientific and growth and maintenance in the right environment.
top-level architecture changes [27]. Extensions of An organism may be unicellular or made up, like
IDO Core covering specific infectious diseases are humans, of many billions of cells divided into
created, first, by importing needed terms from IDO specialized tissues and organs.
Core and other OBO Foundry ontologies, and
second, by constructing the domain-specific terms Here we run into the first of several ontological
where needed to adequately characterize entities in puzzles that emerged while developing VIDO. On
the relevant domain. Examples include the the one hand, this definition aligns with common
Brucellosis Infectious Disease Ontology (IDOBRU) use of the term “organism” among researchers
the Influenza Infectious Disease Ontology insofar as instances are cellular entities [33,34]. On
(IDOFLU), and more recently the Coronavirus the other hand, the textual definition includes
Infectious Disease Ontology (CIDO), each viruses among instances, which are in every case
semantically interoperable with other OBO library acellular. Debates [35] among ontology developers
ontologies [28,29,30]. over organism have resulted in deprecation of the
OBI term in favor of a term from the Common
VIDO was designed to occupy the ontological Anatomy Reference Ontology [36]: organism or
space between such virus-specific ontologies and virus or viroid. This avoids the preceding worries
IDO Core. As a result, more specific virus-related but reveals two more. First, introducing disjunctive
ontologies such as CIDO and IDOFLU are being classes suggests closure over instances. We should,
curated to extend directly from VIDO, rather than however, avoid suggesting that classes – especially
IDO Core. in biological domains – are settled results of
scientific discoveries. Second, this disjunctive class
3. Results leads naturally to debates over whether viruses are
VIDO takes IDO Core as its starting point, but also alive, since it classifies viruses alongside
imports terms relevant to the domain of viruses paradigmatic living entities. Decades of discussion
from other OBO Foundry ontologies, such as GO, have not resolved this question [37,38,39], and it is
the Ontology for General Medical Science (OGMS) not obvious we need an answer for the purposes of
and the Ontology for Biomedical Investigation ontological modelling. Rather than introduce an ad
(OBI) [31]. hoc disjunctive class, IDO Core and VIDO
developers collaborated to add the following
3.1 Virus disjoint sibling class of organism to IDO Core:
Like IDO Core, VIDO imports from OGMS: acellular structure =def Object consisting of an
arrangement of interrelated acellular parts
3
forming an acellular biological unit that is able to exhaustive classes based on genetic structure. For
initiate replication of the structure in a host. example, a subclass of virus:
Imported to VIDO as the parent class of the term positive-sense single-stranded RNA virus =def
virus. The term virus is imported from the Virus with genetic material encoded in single-
NCBITaxon [40], alongside other terms stranded RNA that can be translated directly into
representing entities investigated by virologists, proteins.
such as prion, viroid, and satellite.
Which provides the parent class for:
The NCBITaxon provides an exhaustive list of life
coronavirus =def Positive-sense single-stranded
science terms but has its limitations. First, with
RNA virus with a helically symmetrical
respect to virus terms NCBITaxon appears to align
nucleocapsid, lipid bilayer viral envelope, and
with the International Committee on Taxonomy of
surface spike peplomers.
Viruses (ICTV). The ICTV, however, lacks
systematic classification criteria and consequently Figure 1 illustrates how the Baltimore
leaves several viruses unclassified [41,42]. Second, Classification appears in the Protégé visualization
when NCBITaxon is combined with automated of the class positive-sense single-stranded RNA
importing tools such as Ontofox [43], ontology virus, supplemented by a textbook image of the
developers (for example, the developers of the seven viral replication pathways underwritten by
Schistosomiasis Ontology [27]) sometimes import virus genetic differences.
entire ICTV hierarchies –from kingdom to species –
resulting in large, unwieldy, taxonomies obscuring
classes of interest. Third, NCBITaxon provides few
textual definitions for terms. To align with OBO
Foundry metadata conventions and best practices,
definitions are needed for virus and its subclasses.
Standard definitions of “virus” provide a starting
point, but caution is needed. Viruses are often
described as obligate pathogens [44,45], since virus Figure 1: Baltimore Classification in Protégé Editor
replication requires host machinery for production
By incorporating the Baltimore Classification,
and assembly of viral components. However,
VIDO provides developers of more specific virus
defining a class virus solely in terms of what
classes within a succinct, navigable, ontological
viruses typically do runs the risk of overlooking
structure which refers to viral replication pathways,
what viruses are, materially speaking. Compare:
and so to virus pathogenicity.
Homo sapiens are obligate aerobes, but this is no
definition of the class. Insofar as we are defining VIDO subclasses of virus include those common in
the material entity virus, better to attend to genetic virology research, such as bacteriophage – viruses
and structural components common to all viruses, that infect bacteria – virophage – viruses that infect
and best to define the material entity in a way that viruses – oncovirus – viruses that cause cancer –
captures obligate pathogenicity. VIDO defines: and mycovirus – viruses that infect fungi. One
subclass of virus imported from NCBITaxon is the
virus =def Acellular structure with RNA or DNA
VIDO term:
genetic material which uses host metabolic
resources for RNA or DNA replication. virion =def Virus that is in its assembled state
consisting of genomic material (DNA or RNA)
Subclasses of virus in VIDO are imported from
surrounded by coating molecules.
NCBITaxon in alignment with the Baltimore
Classification [46], which groups viruses into seven
4
Some researchers use “virion” and “virus” The term “pathogen” is indexed to species or to
synonymously [47]. Some define “virion” so that stages in the developmental cycle of a species. A
instances only exist outside host cells [48] or given virus may engage in mutual symbiosis with
distinguish virions outside host cells from those one species, while exhibiting pathogenic behavior
inside host cells, calling the former “mature towards others [55,56]. Mature plants are often
virions.” Some claim “virion” is best understood as susceptible to different pathogens than developing
analogous to a sperm cell [49,50]. Ontologically plants [57,58]. We capture virus pathogenicity in
speaking, one might model the relationship between VIDO in steps. From IDO Core, we import
a virus and its virion in a variety of ways: virion is dispositions borne by pathogens and infectious
to a virus as human infant is to human, or as human agents, as follows:
student is to human, or as human gamete is to
pathogenic disposition =def Disposition borne by a
human. Treating virions as akin to gametes is
material entity to establish localization in or
uncommon among researchers. Between the
produce toxins that can be transmitted to an
remaining options, we adopt the first, treating virion
organism or acellular structure, either of which
as a type of virus, since adopting the alternative
may form disorder in the entity or
would suggest a virion is just a virus in a specific
immunocompetent members of the entity’s
context, with a specific role.
species.
Some viruses do not replicate faithfully, perhaps
infectious disposition =def Pathogenic disposition
resulting in genetically distinct mutants or – in
borne by a pathogen to be transmitted to a host
extreme cases – an inactive aggregate of virion
and then become part of an infection in that host
components. Virus mutations may undermine host
or immunocompetent members of the same
immune system recognition of viral threats, as
species as the host.
evidenced by the difficulty in developing vaccines
for certain influenza strains. Too many mutations, The class infectious agent in IDO Core is a subclass
however, and a virus may lose its ability to of organism, and so cannot include instances of
replicate, an observation used in development of virus. To address this issue, the term infectious
treatments for polio and hepatitis C which structure was developed to parallel the IDO Core
exacerbate respective virus mutations [51,52]. term infectious agent and is a logically defined
VIDO provides the term: subclass of acellular structure. The term infectious
disposition bridges infectious acellular structures
disordered virus =def Acellular structure having
and infectious organisms since instances of each
some clinically abnormal arrangement of viral
bear an infectious disposition. Moreover, the logical
components (e.g. viral capsid, viral DNA/RNA)
definitions of infectious structure and infectious
Viruses falling in this class may be associated with agent are such that, though the former is a defined
diseases much different from those of the clinically subclass of acellular structure and the latter a
normal variety. Terms for viral components are subclass of organism, they are both inferred
imported to VIDO. From GO, VIDO imports viral subclasses of pathogen.
nucleocapsid, viral capsid, capsomere, from the
Establishment of localization used in pathogenic
Chemical Entities of Biological Interest (ChEBI)
disposition is characterized using the GO term
ontology [53] the terms nucleic acid and ribonucleic
establishment of localization in host representing
acid, and from the Protein Ontology [54] the terms
tethering or adhesion to a host, while “formation of
protein and viral protein are imported.
disorder” abbreviates two imported IDO Core
3.2 Infectious Structure terms: appearance of disorder, which is a process
that results in formation of a disorder. The
definition of pathogenic disposition is meant to
5
reflect a temporal ordering between establishment counts as a human infant pathogen. Nevertheless,
of localization and appearance of disorder. This is because C. botulinum is not itself disposed to
reflected explicitly in the logical axioms associated invade or be transmitted to human infants, we do
with the class. Similarly, in the definition of not say the bacterium is infectious [62]. Being part
infectious disposition there is an intended temporal of an infection is not itself sufficient to be counted
ordering between transmission to a host – as infectious. Pathogens bearing an infectious
represented by pathogen transmission process disposition must be disposed to both transmit and
imported from the Pathogen Transmission Ontology become part of an infection. Many opportunistic
[59] – and becoming part of an infection – pathogens are not infectious.
represented by the IDO Core process of establishing
The immunocompetence and species membership
an infection. A pathogen bearing an infectious
clauses in the respective definitions of infectious
disposition that generates disorder in a host will
disposition and pathogenic disposition are included
have been transmitted to the host prior to
in IDO Core to address instances where mutations
establishing localization in the host and will have
in hosts may block realization of disorder or
established an infection prior to the appearance of
infection. In such cases, an infectious pathogen may
disorder.
nevertheless be transmissible and cause disorder or
The complexity of the definitions of pathogenic infection in others. For example, HIV-1 is a
disposition and infectious disposition reflect the pathogen that may localize in a host with CCR-5
variety of pathogen examples in contemporary mutations [63] that block the virus from attaching to
literature. Consider S. aureus, an opportunistic host cells, and so block pathogenesis to AIDS.
pathogen [60] in humans. We count S. aureus as a Similarly, P. falciparum may be transmitted to a
pathogen, even when it does not realize disorder in host with a sickle-cell trait that blocks manifestation
a host, since it is nevertheless disposed to localize of the disease malaria [64,65]. However, P.
in a human host and generate disorder if given the falciparum and HIV-1 count as pathogens even if
opportunity. This is a disposition of S. aureus in they do not result in the formation of disorders for
BFO terms because it is an “internally-grounded” hosts with a sickle-cell trait or CCR-5 mutation,
property of the entity [61]. That is, it is part of the respectively. Each pathogen may be transmitted to
material basis of S. aureus to generate disorder in immunocompetent members of the same species as
human hosts if given the chance. This is analogous the host, and so counts as bearing instances of
to the way salt has a disposition to dissolve, based infectious disposition and pathogenic disposition.
on its lattice structure, independently of whether it Note, that P. falciparum and HIV-1 do not result in
ever realizes this disposition. Opportunistic the formation of disorders in hosts with sickle-cell
pathogens are not pathogens because of an traits or CCR-5 mutations should not suggest there
opportunity; they are pathogens because they are are no clinical abnormalities associated with these
disposed to localize and cause disorder in a host. traits or mutations. Individuals with, say, CCR-5
mutations may exhibit clinical abnormalities [66],
Consider now, C. botulinum, a pathogen which
and so do exhibit disorders. But these disorders are
produces toxin spores sometimes ingested by
due to the CCR-5 mutation rather than the HIV-1
humans. This bacterium is a pathogen for adult
infection.
humans since the toxins often result in disorder
when ingested. Furthermore, C. botulinum may 3.3 Host
cause infection in human infants if, say honey
colonized by C. botulinum is ingested. The sugar IDO Core and VIDO prioritize neither host nor
content of honey inhibits C. botulinum growth, but pathogen in representation of pathogens and
in the low-oxygen, low-acid intestines of human associated diseases, adopting the Damage Response
infants, spores can localize, grow, and produce Framework (DRF) for guidance in development of
toxins resulting in disorder. Thus, C. botulinum relevant terms [67,68]. According to the DRF,
6
pathogenesis results from interactions between both circle to the term disorder introduced above, since
host and pathogen interacting primarily through clinical abnormality is associated with disorder.
host damage, which is a function of the intensity When that disorder stems from infection it counts as
and degree of host response and pathogen factors. an:
Host and pathogen interactions thus influence
infectious disorder =def Disorder that is part of an
manifestations of signs, symptoms, and disease.
extended organism which has an infectious
IDO Core defines terms reflecting the DRF:
pathogen part, that exists as a result of a process
host role=def Role borne by an acellular structure of formation of disorder initiated by the infectious
containing a distinct material entity, or organism pathogen.
whose extended organism contains a distinct
And when the adverted pathogen is a virus, it falls
material entity, realized in use of that structure or
in the VIDO class:
organism as a site of reproduction or replication.
virus disorder =def Infectious disorder that exists
pathogen host role =def Host role borne by an
as a result of a process of formation of disorder
organism having a pathogen as part of its
initiated by a virus.
extended organism.
Medical researchers draw a distinction between
Symptomatic cases of virus infection can be
symptoms and signs, which OBO Foundry
represented by importing terms from the Symptom
ontologies respect (from OGMS):
Ontology, such as dry cough, fever, taste alteration,
smell alteration, among others [69]. Given the symptom =def Process experienced by the patient
importance of asymptomatic carriers in viral which can only be experienced by the patient, that
infection spread, moreover, attention is also given is hypothesized to be clinically relevant.
to:
qualitative sign =def Abnormal observable quality
symptomatic carrier role =def Pathogen host role of a part of a patient that is hypothesized to be
borne by an organism whose extended organism clinically relevant.
contains a pathogen bearing an infectious
disposition towards the host, and the host has processual sign =def Abnormal processual entity
manifested symptoms of the infectious disease occurring in a patient that is hypothesized to be
caused by the pathogen. clinically relevant.
asymptomatic carrier role =def Pathogen host role An asymptomatic carrier infected with SARS-CoV-
borne by an organism whose extended organism 2 likely exhibits signs indicating that the infection is
contains a pathogen bearing an infectious clinically abnormal, such as ground-glass opacities
disposition towards the host, and the host has no or positive PCR test results. Such asymptomatic
symptoms of the infectious disease caused by the carriers exhibit an instance of the VIDO class virus
pathogen. disorder which is the material basis of a viral
disease:
subclinical infection =def Infection that is part of
an asymptomatic carrier. infectious disease =def Disease whose physical
basis is an infectious disorder.
The term subclinical infection reflects standard – if
somewhat obscure – use of the terms “subclinical” viral disease =def Infectious disease inhering in a
and “asymptomatic” while allowing for cases of virus disorder that is a disorder due to the
clinically abnormal infections without symptoms. presence of the virus.
VIDO defines subclinical virus infection as an This result aligns with the CDC’s case criteria
infection caused by some virus part of an adopted on April 5, 2020 which indicate that the
asymptomatic carrier. These remarks bring us full
7
presence of the SARS-CoV-2 genome or relevant needed to characterize transporters are imported
antigens in an individual is sufficient to count as a from IDO Core:
case of COVID-19, asymptomatic or not [70,71].
pathogen transporter role =def Role borne by a
3.4 Viral Pathogenesis material entity in or on which a pathogen is
located, from which the pathogen may be
Accurately representing viral pathogenesis is of transmitted to a new host.
great importance, in particular, as researchers are
still working to understand how SARS-CoV-2 A subclass – fomite role, roughly, a pathogen
infections cause such a wide range of signs and transporter role borne by non-living entities – plays
symptoms across demographics. Representing an important function in virus transmission.
disease pathogenesis is aided by importing terms Viral pathogenesis involves replication in a host.
from relevant OBO Foundry ontologies, to define: The term virus replication is defined in VIDO as a
viral pathogenesis =def Pathogenesis process subclass of the IDO Core term replication,
realization of an infectious disposition inhering in a specifically:
virus or virus population, having at least the proper virus replication =def Replication process in which
process parts: a virus containing some portion of genetic
(1) pathogen transmission, material inherited from a parent virus is
(2) establishment of localization in host, replicated.
(3) process of establishing an infection, and
(4) appearance of a virus disorder. Instances of virus pathogenesis have virus
replication parts. Viral replication typically occurs
Where pathogenesis is imported from GO: within an:
pathogenesis =def Process that generates the ability incubation process =def Process beginning with the
of a pathogen to induce disorder in an organism. establishing of an infection in a host and ending
As defined, pathogenesis is a success term, in that it with the onset of symptoms by the host during
encompasses formation of disorder in an entity. which pathogens are multiplying in the host.
This is reflected in (1)-(4) of the viral pathogenesis Which occupies an incubation interval and may
definition and motivated by the GO Consortium precede a communicability interval. The
focus on canonical biological processes [72]. This is corresponding process during which viral hosts bear
not to say all virus infections result in successful a contagiousness disposition has proper part some
pathogenesis. An individual may be infected by a latency process which itself has an eclipse process
virus without a relevant disorder. Absent the part:
disorder, there is no material basis for the
associated disease. Consequently, this would not communicability interval =def One-dimensional
count as an instance of viral pathogenesis. temporal region during which a pathogen host
bears a contagiousness disposition.
Viral pathogenesis involves transmission of virions.
From PTRANS [59] is imported: latency process =def Process beginning with the
establishing of an infection in a host and ending
pathogen transmission process =def Process during when the host becomes contagious, during which
which a pathogen is transmitted directly or pathogens are multiplying in the host.
indirectly to a new host.
eclipse process =def Process beginning with the
Role terms – reflecting “externally-grounded” establishment of a virus in a host and ending with
realizable entities acquired based on circumstance, the first appearance of a virion following viral
such as the role a student takes on in university –
8
release, during which an infecting virus is vaccines. Several members of both the IDO Core
uncoating to begin genome replication. and the VIDO development teams are members of
the CIDO development team working to ensure
The last being specific to viruses, so specific to
alignment among these ontologies. Terms reflecting
VIDO. The remaining terms are found in IDO Core.
common features of coronaviruses can be imported
Viral dormancy is a virus-specific term from VIDO
from OBO ontologies to characterize features of
occurring over a:
coronaviruses, such as the viral genome including a
viral dormancy interval =def One-dimensional five-prime nucleotide cap, or the common
temporal region on which a virus is no longer glycoprotein spikes found in the viral envelope
replicating but remains within a host cell and [76,77]. Some terms are specializations of terms
which may be reactivated to begin replication from the Protein Ontology [54], including
again. membrane protein (SARS-CoV-2) and spike
glycoprotein (SARS-CoV-2). Worth noting is that
With participants found from familiar viruses such while CIDO is not the only ontology developed to
as varicella zoster and herpes simplex. support curation of COVID-19 data [78,79,80,81],
Generative stage is imported from IDO Core, most alternatives are stand-alone initiatives, and so
defined as a temporal subdivision of a subject to the silo problems typically found in
developmental process, as well as: ontologies developed outside the scope of the OBO
Foundry and with no attention to its principles.
virus generative stage =def Infectious structure
generative stage that is a temporal subdivision of 3.6 Annotations
a virus developmental process.
The extent of coverage in VIDO and related
Subclasses of which include the stages through ontologies can be illustrated by annotation of
which viruses may proceed during replication: coronavirus research articles.
virus attachment stage =def Virus generative stage
during which a virion protein binds to molecules
on the host surface or host cell surface projection.
virus penetration stage =def Virus generative stage
during which a virion or viral nucleic acid
breaches the barriers of a host.
3.5 Bridge to CIDO
Figure 2: Relationships in the VIDO ecosystem
VIDO serves as a bridge between IDO Core and the
IDO extension ontologies representing specific viral Consider the following overview of SARS-CoV-2
diseases. An extension of importance during the pathogenesis (color coded as in Figure 5):
pandemic is the recently developed Coronavirus
Following replication, cell lysis of SARS-
Infectious Disease Ontology (CIDO). CIDO
CoV-2 coronavirus virions causes host cells
provides semantic resources needed for
to release molecules which function to warn
representing coronavirus genome, surveillance, nearby cells. When recognized by epithelial
vaccine, and host data. The ontology has been used cells, endothelial, and alveolar macrophages,
to annotate data pertaining to 136 known anti- proteins such as IL-6, IP-10, and MCPI, are
coronavirus drugs [73], to identify 110 candidate released which attract T cells, macrophages,
drugs for potential COVID-19 drug repurposing and monocytes to the site of infection,
[74,75], and to provide input to machine learning promoting inflammation. In disordered
efforts [4] in identifying potential COVID-19 immune systems, immune cells accumulate
9
in the lungs, then propagate to and damage challenges, however. Often, terms were developed
other organs. In normal immune systems, then presented to domain specialists for vetting,
inflammation attracts T cells which after which they were refined through discussion.
neutralize the virus at the site of infection. As in the case of all scientific ontologies,
Antibodies circulate, preventing SARS-CoV- refinement will continue as research advances, and
2 infection, and alveolar macrophages further collaborators are welcome and necessary.
recognize SARS-CoV-2 and eliminate virions
via phagocytosis [82]. The existence of IDO Core extensions covering
infectious disease-causing entities other than
In more a more ontologically oriented language, we viruses suggests a need for the creation of reference
speak of the relevant part of a host’s immune ontology extensions of IDO covering bacteria,
response as being disposed to manifest a response fungi, and parasites. The methodology illustrated in
that eliminates SARS-CoV-2 infection, while the development of VIDO provides a recipe for
SARS-CoV-2 has a disposition to block such reference ontology creation. Additionally, the
manifestation of this immune system response. methodology illustrated in the development of
Consider next a color-coded selection from the coronavirus-specific terms outlined above provides
Lancet [83] concerning SARS-CoV-2: a recipe for the creation of novel virus-specific
“The viral loads in throat swabs and sputum ontologies, namely, by extending them from
samples peaked at around 5-6 days after existing virus ontologies such as CIDO where
symptom onset, ranging from around 10^4 to possible. Adoption of these methodologies by
10^7 copies per mL during this time.” developers during ontology construction will
significantly reduce the labor involved in ontology
SARS-CoV-2 infected hosts contain the highest creation.
concentration of SARS-CoV-2 virions – the viral
load – during the incubation interval [84]. Viral VIDO represents a substantial effort to characterize
load is a common measurement of the proportion of viruses in a collaborative, computationally tractable
virions to fluid, and for SARS-CoV-2 is frequently manner. Ontologies like these are crucial in the
measured from host sputum. VIDO also provides contemporary Big Data era and will provide
resources for annotating virus quantification: researchers needed resources for gathering and
coordinating increasingly important life science
viral load =def Quality inhering in a portion of data.
fluid that is the proportion of virions to volume of
that portion of fluid. 5. Acknowledgments
Our color-coding of this passage models term reuse JB, SB supported by NIH/NLM T15LM012495-01
across existing ontologies. For example, developers Buffalo Research Innovation in Genomic and
can use VIDO terms alongside terms from the Healthcare Technology (BRIGHT) Education
Common Core Ontology [85] such as is measured Training Programs, 2020-2021. BS’s contributions
by, measurement information content entity, has were supported by the NIH under NCATS
integer value, uses measurement unit, and milliliter 1UL1TR001412 (Buffalo Clinical and Translational
measurement unit. Other virus quantification metric Research Center). VIDO is available under the
terms, such as multiplicity of viral infection - the Creative Commons Attribution 4.0 license and an
ratio of virions to susceptible cells in a target area – up-to-date version of the ontology.
can be found in VIDO as well.
Many thanks to Asiyah Yu Lin for assistance in
4. Discussion VIDO development; to Darren Natale for helpful
critical feedback on an earlier draft. Figures were
VIDO enables extensive representation of virus- designed by or in consultation with Rain Yuan.
related research. The very scope of VIDO provides
10
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