<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD v1.0 20120330//EN" "JATS-archivearticle1.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>miRNAO: An Ontology for microRNAs</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Vicky Dritsou</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Pantelis Topalis</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Emmanuel Dialynas</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Elvira Mitraka</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Christos Louis</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Department of Biology, University of Crete</institution>
          ,
          <country country="GR">Greece</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology - Hellas</institution>
          ,
          <country country="GR">Greece</country>
        </aff>
      </contrib-group>
      <abstract>
        <p />
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        MicroRNAs (miRNAs) are short RNA molecules ( 22 nt long)
that act as gene regulators in many eukaryotes. By binding to
complementary strands of messenger RNAs (mRNAs), they induce
translational repression or target degradation. Since their discovery
in 1993
        <xref ref-type="bibr" rid="ref7">(Lee et al., 1993)</xref>
        , they have received a lot of attention
in the research area and some thousands of miRNAs have been
reported in the literature; version 18.0 of miRBase
        <xref ref-type="bibr" rid="ref6">(Kozomara and
Griffiths-Jones, 2011)</xref>
        contains 18.226 entries representing
precursor miRNAs in 168 species, which express 21.643 mature miRNA
products.
      </p>
      <p>
        Each of these small RNA structures regulates many target
mRNAs
        <xref ref-type="bibr" rid="ref2">(Baek et al., 2008)</xref>
        , while the detection of the targets
is a great challenge for researchers. Besides the number of
identified miRNAs that grows very fast, the experiments performed
aiming at detecting targets have also increased. Large data sets
of miRNAs and their experimentally detected targets are
stored in various databases. Examples of popular miRNA databases
are microRNA.org
        <xref ref-type="bibr" rid="ref3">(Betel et al., 2008)</xref>
        , miRBase
        <xref ref-type="bibr" rid="ref6">(Kozomara and
Griffiths-Jones, 2011)</xref>
        and TarBase 6.0
        <xref ref-type="bibr" rid="ref11">(Vergoulis et al., 2011)</xref>
        .
      </p>
      <p>
        Sharing knowledge among different knowledge bases is beneficial
and can be achieved with the use of ontologies. The classification of
the aforementioned huge data sets under an ontology that expresses
the features of miRNAs and their functions can facilitate
information discovery and extraction, while it can also be used to inter-relate
the databases and/or their schemata. Yet, there is no ontology
representing the necessary information regarding miRNAs. The only
ontology related to miRNAs is the Ontology for MicroRNA
Target Prediction
        <xref ref-type="bibr" rid="ref10">(Townsend et al., 2010)</xref>
        , which only captures the
information required to express the prediction of targets and does
not fully cover all the aspects considered in the area. On the other
hand, RNA Ontology (RNAO)
        <xref ref-type="bibr" rid="ref5">(Hoehndorf et al., 2011)</xref>
        serves as an
upper ontology, while miRNAO has been instead developed as an
application ontology.
      </p>
      <p>
        In an attempt to capture and represent the existing knowledge
regarding miRNAs and their functions, we have developed
miRNAO. miRNAO has been designed according to the OBO Foundry
Principles
        <xref ref-type="bibr" rid="ref8">(OBO-Foundry, 2006)</xref>
        , as these are described in the
current release. Moreover, the Basic Formal Ontology (BFO)
        <xref ref-type="bibr" rid="ref9">(Simon
et al., 2006)</xref>
        has been used for the classification of the upper classes.
Since many ontologies of the domain adhere to the
conceptualization of BFO, interoperability among them is thus achieved.
      </p>
      <p>
        The set of concepts captured and described in miRNAO
includes among others molecular entities and parts, their structures, the
processes they take place in, the functions and their roles within.
Some information related to miRNAs has already been expressed
To whom correspondence should be addressed: louis[at]imbb.forth.gr
in other popular ontologies. A decision we had to take while
developing miRNAO was to either borrow the existing terms and their
definitions from other ontologies or to create our own concepts and
define them regardless of the existing sources. Even though creating
our own terms would allow us to define them according only to our
scope, we chose not to re-create those. Instead, we prefer to re-use
the existing knowledge by importing them from other ontologies, in
an attempt to facilitate knowledge sharing and reuse.
Interoperability among different databases is then easier achieved. The majority
of shared terms come from the Gene Ontology (GO)
        <xref ref-type="bibr" rid="ref1">(Ashburner
et al., 2000)</xref>
        and the Sequence Ontology (SO)
        <xref ref-type="bibr" rid="ref4">(Eilbeck et al., 2005)</xref>
        .
      </p>
      <p>miRNAO is the first ontology designed to express all the
information related to miRNAs. Exploiting this ontology in different
knowledge bases can be very beneficial, both by extracting
information from each source and also by interchanging and deriving
information from different sources.</p>
      <p>ACKNOWLEDGEMENTS
The work was supported by the Hellenic General Secretariat for
Research and Technology (MicroRNA project, 09SYN-13-1055)
and, in part, by the VectorBase project (NIAID).</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          <string-name>
            <surname>Ashburner</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ball</surname>
            ,
            <given-names>C. A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Blake</surname>
            ,
            <given-names>J. A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Botstein</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Butler</surname>
            ,
            <given-names>H.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Cherry</surname>
            ,
            <given-names>J. M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Davis</surname>
            ,
            <given-names>A. P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dolinski</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dwight</surname>
            ,
            <given-names>S. S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Eppig</surname>
            ,
            <given-names>J. T.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Harris</surname>
            ,
            <given-names>M. A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Hill</surname>
            ,
            <given-names>D. P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>IsselTarver</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Kasarskis</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Lewis</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Matese</surname>
            ,
            <given-names>J. C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Richardson</surname>
            ,
            <given-names>J. E.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ringwald</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Rubin</surname>
            ,
            <given-names>G. M.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Sherlock</surname>
            ,
            <given-names>G.</given-names>
          </string-name>
          (
          <year>2000</year>
          ).
          <article-title>Gene Ontology: tool for the unification of biology</article-title>
          .
          <source>Nat Genet</source>
          ,
          <volume>25</volume>
          (
          <issue>1</issue>
          ),
          <fpage>25</fpage>
          -
          <lpage>29</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          <string-name>
            <surname>Baek</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          , Ville´n, J.,
          <string-name>
            <surname>Shin</surname>
            ,
            <given-names>C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Camargo</surname>
            ,
            <given-names>F. D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Gygi</surname>
            ,
            <given-names>S. P.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Bartel</surname>
            ,
            <given-names>D. P.</given-names>
          </string-name>
          (
          <year>2008</year>
          ).
          <article-title>The impact of microRNAs on protein output</article-title>
          .
          <source>Nature</source>
          ,
          <volume>455</volume>
          (
          <issue>7209</issue>
          ),
          <fpage>64</fpage>
          -
          <lpage>71</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          <string-name>
            <surname>Betel</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          , Wilson,
          <string-name>
            <given-names>M.</given-names>
            ,
            <surname>Gabow</surname>
          </string-name>
          ,
          <string-name>
            <given-names>A.</given-names>
            ,
            <surname>Marks</surname>
          </string-name>
          ,
          <string-name>
            <given-names>D. S.</given-names>
            , and
            <surname>Sander</surname>
          </string-name>
          ,
          <string-name>
            <surname>C.</surname>
          </string-name>
          (
          <year>2008</year>
          ).
          <article-title>The microrna.org resource: targets and expression</article-title>
          .
          <source>Nucleic Acids Research</source>
          ,
          <volume>36</volume>
          ,
          <fpage>D149</fpage>
          -
          <lpage>D153</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          <string-name>
            <surname>Eilbeck</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Lewis</surname>
            ,
            <given-names>S. E.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Mungall</surname>
            ,
            <given-names>C. J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Yandell</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Stein</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Durbin</surname>
            ,
            <given-names>R.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Ashburner</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          (
          <year>2005</year>
          ).
          <article-title>The Sequence Ontology: a tool for the unification of genome annotations</article-title>
          .
          <source>Genome Biology</source>
          ,
          <volume>6</volume>
          (
          <issue>5</issue>
          ),
          <fpage>R44</fpage>
          +.
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          <string-name>
            <surname>Hoehndorf</surname>
            ,
            <given-names>R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Batchelor</surname>
            ,
            <given-names>C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Bittner</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dumontier</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Eilbeck</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Knight</surname>
            ,
            <given-names>R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Mungall</surname>
            ,
            <given-names>C. J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Richardson</surname>
            ,
            <given-names>J. S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Stombaugh</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Westhof</surname>
            ,
            <given-names>E.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Zirbel</surname>
            ,
            <given-names>C. L.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Leontis</surname>
            ,
            <given-names>N. B.</given-names>
          </string-name>
          (
          <year>2011</year>
          ).
          <article-title>The RNA Ontology (RNAO): An ontology for integrating RNA sequence and structure data</article-title>
          .
          <source>Appl</source>
          . Ontol.,
          <volume>6</volume>
          (
          <issue>1</issue>
          ),
          <fpage>53</fpage>
          -
          <lpage>89</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref6">
        <mixed-citation>
          <string-name>
            <surname>Kozomara</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          and
          <string-name>
            <surname>Griffiths-Jones</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          (
          <year>2011</year>
          ).
          <article-title>miRBase: integrating microRNA annotation and deep-sequencing data</article-title>
          .
          <source>Nucleic Acids Research</source>
          ,
          <volume>39</volume>
          (
          <issue>suppl 1</issue>
          ),
          <fpage>D152</fpage>
          -
          <lpage>D157</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref7">
        <mixed-citation>
          <string-name>
            <surname>Lee</surname>
            ,
            <given-names>R. C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Feinbaum</surname>
            ,
            <given-names>R. L.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Ambros</surname>
            ,
            <given-names>V.</given-names>
          </string-name>
          (
          <year>1993</year>
          ).
          <article-title>The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14</article-title>
          . Cell,
          <volume>75</volume>
          (
          <issue>5</issue>
          ),
          <fpage>843</fpage>
          -
          <lpage>854</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref8">
        <mixed-citation>
          <string-name>
            <surname>OBO-Foundry</surname>
          </string-name>
          (
          <year>2006</year>
          ). Available at http://obofoundry.org/crit.shtml.
        </mixed-citation>
      </ref>
      <ref id="ref9">
        <mixed-citation>
          <string-name>
            <surname>Simon</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Santos</surname>
            ,
            <given-names>M. D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Fielding</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Smith</surname>
            ,
            <given-names>B.</given-names>
          </string-name>
          (
          <year>2006</year>
          ).
          <article-title>Formal ontology for natural language processing and the integration of biomedical databases</article-title>
          .
          <source>Int J Med Inform</source>
          ,
          <volume>75</volume>
          (
          <issue>3-4</issue>
          ),
          <fpage>224</fpage>
          -
          <lpage>231</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref10">
        <mixed-citation>
          <string-name>
            <surname>Townsend</surname>
            ,
            <given-names>C.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Huang</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dou</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dalvi</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Hayes</surname>
            ,
            <given-names>P. J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>He</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>chang Lin</surname>
            ,
            <given-names>W.</given-names>
          </string-name>
          , Liu,
          <string-name>
            <given-names>H.</given-names>
            ,
            <surname>Rudnick</surname>
          </string-name>
          ,
          <string-name>
            <given-names>R.</given-names>
            , and
            <surname>Shah</surname>
          </string-name>
          ,
          <string-name>
            <surname>H.</surname>
          </string-name>
          (
          <year>2010</year>
          ).
          <article-title>OMIT: Domain Ontology and Knowledge Acquisition in MicroRNA Target Prediction</article-title>
          .
          <source>In OTM Conferences (2)</source>
          , pages
          <fpage>1160</fpage>
          -
          <lpage>1167</lpage>
          .
        </mixed-citation>
      </ref>
      <ref id="ref11">
        <mixed-citation>
          <string-name>
            <surname>Vergoulis</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Vlachos</surname>
            ,
            <given-names>I.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Alexiou</surname>
            ,
            <given-names>P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Georgakilas</surname>
            ,
            <given-names>G.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Maragkakis</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Reczko</surname>
            ,
            <given-names>M.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Gerangelos</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Koziris</surname>
            ,
            <given-names>N.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Dalamagas</surname>
            ,
            <given-names>T.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Hatzigeorgiou</surname>
            ,
            <given-names>A.</given-names>
          </string-name>
          (
          <year>2011</year>
          ).
          <article-title>TarBase 6.0: Capturing the exponential growth of miRNA targets with experimental support</article-title>
          .
          <source>Nucleic Acids Res</source>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>