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    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>OLOBO: A new ontology for linking and integrating open biologi- cal and biomedical ontologies</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Edison Ong</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Yongqun He</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Department of Computational Medicine and Bioinformatics, University of Michigan Medical School</institution>
          ,
          <addr-line>Ann Arbor, MI</addr-line>
          ,
          <country country="US">USA</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Unit of Laboratory Animal Medicine, Department of Microbiology and Immunology, and Center of Computational Medicine and Bioinformatics, University of Michigan Medical School</institution>
          ,
          <addr-line>Ann Arbor, MI</addr-line>
          ,
          <country country="US">USA</country>
        </aff>
      </contrib-group>
      <fpage>2</fpage>
      <lpage>3</lpage>
      <abstract>
        <p>To link and integrate different Open Biological and Biomedical Ontologies (OBO) library ontologies, we generated an OLOBO ontology that uses the Basic Formal Ontology (BFO) as the upper level ontology to align, link, and integrate all existing 9 formal OBO Foundry ontologies. Our study identified 524 ontology terms shared by at least two ontologies, which form the core part of OLOBO. Current OLOBO includes 978 ontology classes, 13 object properties, and 90 annotation properties. OLOBO was queried, analyzed, and applied to identify potential deprecated terms and discrepancy among different OBO library ontologies.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>INTRODUCTION</title>
      <p>2.1</p>
    </sec>
    <sec id="sec-2">
      <title>METHODS</title>
      <sec id="sec-2-1">
        <title>Collection of OBO ontologies</title>
        <p>Instead of using all &gt;150 ontologies, we chose the official 9
OBO Foundry ontologies (Table 1). OBO Foundry website
includes their default ontology download websites. We
downloaded the OWL source code of these ontologies.</p>
      </sec>
      <sec id="sec-2-2">
        <title>Development of OLOBO</title>
        <p>
          We developed an in-house Java program that uses OWLAPI
to process ontology OWL files. Many ontologies also reuse
other ontology terms. To integrate all the ontologies, we
first identified and collected all ontology terms shared by at
least two ontologies. This step identified the minimal sets of
ontology terms shared by different ontologies. To notify
from which ontology a term is imported, we generated a
new annotation property called ‘term from ontology’
(OLOBO_0000001). Next, we used Ontofox
          <xref ref-type="bibr" rid="ref4">(Xiang et al.,
2010)</xref>
          to identify terms and axioms related to extracted
ontology terms. To align with BFO, we manually examined
ontologies and ensure appropriate upper level terms added
for the purpose of ontology linkage and integration.
2.3
        </p>
      </sec>
      <sec id="sec-2-3">
        <title>OLOBO source code, deposition, and queries</title>
        <p>
          The OLOBO source code is openly available at GitHub:
https://github.com/biomedontology/olobo. OLOBO is
deposited in Ontobee: http://www.ontobee.org/ontology/OLOBO.
Ontobee SPARQL queries was used to query OLOBO
          <xref ref-type="bibr" rid="ref2">(Ong
et al., 2017)</xref>
          .
2.4
        </p>
      </sec>
      <sec id="sec-2-4">
        <title>OLOBO applications</title>
        <p>OLOBO was used to identify deprecated terms, and we used
the Ontobeep tool (http://www.ontobee.org/ontobeep) to
compare with OLOBO and other OBO ontologies to
identify potential discrepancy among ontologies.</p>
        <p># Prefix</p>
        <p>Ontology full name
# of terms # of shared
terms
1 BFO
2 ChEBI
3 DOID
4 GO
5 OBI
6 PATO
7 PO
8 PRO
9 XAO</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>RESULTS</title>
      <sec id="sec-3-1">
        <title>Alignment of OBO ontologies in OLOBO</title>
        <p>Our study found 524 classes, object properties, and
annotation properties shared by at least two ontologies. In total, our
pipeline removed 178,625 terms from the original 9 OBO
ontologies. The OLOBO statistics is available on Ontobee:
http://www.ontobee.org/ontostat/OLOBO. OLOBO includes
978 classes, and 103 object or annotation properties.</p>
        <p>The overall OLOBO structure (Fig. 1) is aligned with
BFO (http://ifomis.uni-saarland.de/bfo/), the recommended
upper-level ontology in the OBO Foundry, and &gt;100
ontologies are aligned to BFO. The chosen 9 ontologies are
all aligned with BFO as defined by the ontologies themselves
or manually by us.</p>
        <p>UBERON - PO, XAO, ZFA</p>
        <p>GO
ChEBI</p>
        <p>ChEBI (covering PR terms)</p>
        <p>OBI (covering NCBITaxon terms)
covering PATO terms</p>
        <p>DOID</p>
        <p>GO</p>
        <p>GO</p>
        <p>UBERON - PO, XAO, ZFA
3.2</p>
      </sec>
      <sec id="sec-3-2">
        <title>OLOBO applications</title>
        <p>Our study identified three deprecated PATO terms,
PATO_0001237 (quality of a single physical entity),
PATO_0001238 (quality of related physical entities), and
PATO_0001631 (relational spatial quality), which are still
used in OBI. PATO has recommended new PATO terms to
replace these obsolete terms, e.g., ‘physical object quality’
(PATO_0001241) to replace PATO_0001238. We thus
submitted a track issue to OBI
(https://github.com/obiontology/obi/issues/826) to indicate such an issue.</p>
        <p>Another application was to use OLOBO for ontology
comparison and discrepancy detection. Ontobeep is an
Ontobee-based ontology alignment and comparison tool. Our
usage of Ontobeep identified that the UBERON term
‘anatomical entity’, which are included in OLOBO and OBI,
also exists in CLO but under a different parent term. Such
an ontology alignment and surveillance study is expected to
identify achievements as well problematic issues in the
topdown alignment study. These will significantly support
collaborative ontology development and reuse.</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>DISCUSSION</title>
      <p>The basic idea of our project is to generate an integrated
upper level application ontology that links OBO ontologies
in an integrated format. This study only aligned existing 9
official OBO ontologies. We plan to extend OLOBO to
include the other candidate OBO ontologies.</p>
      <p>
        The challenge of ontology integration and orthogonality
is real. Using ontology term labels to analyze OBO ontology
orthogonality
        <xref ref-type="bibr" rid="ref1">(Ghazvinian et al., 2011)</xref>
        , a previous study
found that although progress made, a large amount of
overlap remained among ontologies and achieving orthogonality
would be difficult. Our study proposed and provided a first
solution to address this challenge.
      </p>
      <p>In addition to the demonstrated OLOBO usages,
OLOBO may be used in other cases. For example, to
develop a new OBO-oriented ontology, we may use OLOBO as
the starting point to facilitate the ontology development
process and lead to more efficient alignment. The usage of
OLOBO may also provide an integrated ontology system for
efficient software development for features such as
consistency checking and standard integration. Given the large
number of terms among different ontologies, it is practically
infeasible to develop a single ontology that covers all
ontology terms from all possible ontologies. However, OLOBO
offers an integrative framework to link and integrate
different ontologies in a semantically consistent strategy.</p>
    </sec>
    <sec id="sec-5">
      <title>ACKNOWLEDGEMENTS</title>
      <p>This work was partially supported by a BD2K-LINCS
DCIC external data science research award, which is part of
the grant U54HL127624 (BD2K LINCS Data Coordination
and Integration Center, DCIC) awarded by the National
Heart, Lung, and Blood Institute through funds provided by
the trans-NIH LINCS Program and the trans-NIH Big Data
to Knowledge (BD2K) initiative (http://www.bd2k.nih.gov).
LINCS is an NIH Common Fund projects.</p>
    </sec>
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