<!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>Semantic Digitization of Experimental Data in Biological Sciences</article-title>
      </title-group>
      <contrib-group>
        <aff id="aff0">
          <label>0</label>
          <institution>Saurabh Raghuvanshi Department of Plant Molecular Biology University of Delhi South Campus New Delhi</institution>
          ,
          <country country="IN">India</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>- A major bulk of published experimental data, referred to as 'Gold Standard' data, is available in a format that cannot be easily accessed by computers unless effectively curated. Most curation techniques bank on mining the text for information. Here we propose and demonstrate the efficacy of curating the experimental data itself. The data models facilitate digitization of the every aspect of the information associated with the experimental data. The models utilize several universally accepted ontologies as well as in-house developed alphanumeric notations for digitizing different aspect of the data. The data models have sufficient flexibility to address the extensive variability in experimental data. They have a very generic nature and can be used to curate and digitize experimental data from any organism. The digitized data is easily stored in a relational database management system and can thus be rapidly searched and integrated. These models have been successfully used to digitize data from over 20,000 experiments spanning over 500 research articles on rice biology. The entire dataset is available as a database entitled 'Manually Curated Database of Rice Proteins' at www.genomeindia.org/biocuration.</p>
      </abstract>
      <kwd-group>
        <kwd>Digitization</kwd>
        <kwd>Ontologies</kwd>
        <kwd>Rice</kwd>
        <kwd>Gold standard data</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>I. INTRODUCTION</title>
      <p>
        A ‘Systems’ level understanding of any organism requires
integration and analysis of multi-dimensional experimental
data [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Due to its very nature the underlying experimental
data is extremely diverse and complex. Thus, integration of
such data is never straightforward. These are several issues
that impede seamless integration of experimental data. The
foremost is the fact that there is no standard data
representation format, especially for the ‘Gold standard’ or
published experimental data [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Experimental data coming
out of different techniques is presented in very different
formats and thus cannot be easily correlated and integrated.
Moreover, the description of the experimental conditions,
biological material etc. is extremely variable in terms of
details and thus integration of such poorly explained data
might not be very useful. Further, in general, the published
experimental is presented in pictorial format either as an
image of graph and is thus not amenable to computerized
search, let alone seamless integration. Several of the above
mentioned issues could be partially resolved by extensive
manual curation which is very slow and labor intensive and
cannot keep up with the huge amount of experimental data
that gets published every year.
      </p>
      <p>II. DESCRIPTION OF THE DATA PRESENTATION FORMATS
Here we address these issue by proposing formats or
datamodels for digitization and semantic representation of the
experimental data in biological sciences. These formats have a
very generic nature and are flexible enough to be used for
digitization of diverse experimental data. In essence, these
models attempt to represent every aspect of the data in terms
of an alpha-numeric notation which can be an ontology term
or custom notation. As depicted in Fig. 1, every experimental
data is composed of several data units, which are usually
represented by a single ‘bar’ of a bar-chart or a ‘band’ of a gel
profile. Each of these data-points is associated with two types
of information. The first is the actual value of the data-unit
(height of bar) while the other is an array of information such
as Gene id., plant type, tissue, growth condition etc.
Depending on the complexity of the experiment each data-unit
may be associated with upto 10-15 different types of
information. As per the data-models each of these information
types is represented by either a custom alpha-numerical
notation or an ontology term. Thus, every data unit is now
represented as a collection or group of alpha-numeric terms.
This collection can be easily visualized as an array or equation
as depicted in Fig. 1. Every term of this array is actually stored
in a specific relational database table. Consequently, since
experimental data consists of several data-units, there will be
as many groups of alpha-numerical notations, which can be
easily stored in an relational database table.</p>
    </sec>
    <sec id="sec-2">
      <title>III. ALPHANUMERIC NOTATIONS FOR DATA DIGITIZATION</title>
      <p>
        The data models extensively utilize several ontologies such as
plant ontology, environment ontology, trait ontology as well
as gene ontology terms to digitize various aspects of the
information associated with every data-unit [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ][
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]. As is
obvious, plant ontology terms are used to describe plant
part/tissue or development stage whereas environment
ontology term is used to digitize the growth conditions or any
other treatment (chemical or physical) that may have been
administered. Similarly, trait ontology terms define any trait
(molecular, biochemical or phenotypic) that has been studied
in the experiment. Besides these ontologies other notations
have also been used extensively. Some of these include
GenBank accessions or locus identifiers, taxon db ids as well
as several in-house developed notations to represent
information such as promoter type, mutant type, transgenic
line etc. Several of the ontology terms need to be qualified in
order to precisely digitize the information. For example, in
fundamentally it is possible to rapidly retrieve a single
dataunit from a collection of over 80,000 data-units spread over
&gt;500 different research articles. Further, the same information
order to represent plant developmental stage, the age of the
plant (in days) need to be added. Similarly, concentration of
duration of treatment is appended to environment ontology
terms.
      </p>
    </sec>
    <sec id="sec-3">
      <title>IV. IMPLEMENTATION OF THE DATA MODELS</title>
      <p>
        Based on the aforementioned principles, manual data curation
and digitization portals were created. These portals were used
to digitize experimental data from over 500 published research
articles on rice biology. The entire data set has been organized
as a database entitled ‘Manually Curated Database of Rice
Proteins’ (MCDRP) [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. The database contains digitized
experimental data pertaining to over 2300 rice proteins that
has been curated from over 20,000 different experiments.
Altogether, these experiments have over 80,000 data units for
which the information has been digitized by manual curation.
The digitization of the data has been done by utilizing &gt;600
plant ontology, &gt;350 environment ontology, &gt;800 trait
ontology and &gt;350 gene ontology terms. The database is
updated twice a year.
      </p>
      <p>Since every aspect of information associated with data-unit of
an experiment has been digitized as alpha-numeric notations,
can be retrieved from several different aspects. For example,
in the browse page one can easily retrieve all the genes that
have been studied in a particular plant part or developmental
stage. Similarly, all genes that have been associated or studied
for a particular trait can be easily accessed.</p>
    </sec>
    <sec id="sec-4">
      <title>V. ISSUES THAT NEED TO BE ADDRESSED</title>
      <p>The process of digitization is primarily dependent on the depth
of various ontologies. During the process of digitization, it
was realized that there is an extensive amount of untapped
variability in all aspects of data that is not completely
described by the current ontologies. Consequently, a
significant number of terms used in the curation endeavor had
been coined anew (www.genomeindia.org/biocuration).
While several new terms had to be coined since there was no
equivalent term, many were formulated since the existing
terms had a different perspective. Thus, there is a requirement
for consistent efforts to enrich and modify the existing
ontologies by defining more and more terms. Further, several
new ontologies might also be required such as an ontology
describing different methodologies. This is important since the
interpretation of the data can only be done in light of the
precise information about the experimental methodology.
It was also observed, that many times that description of the
experimental data in published literature is not very precise.
This has major consequences in terms of data integration.
Thus, usage of precise ontology terms to describe different
aspect of the experimental data must be encouraged.</p>
      <p>VI. FUTURE
The data digitization formats for the experimental data in
biological sciences enable a very precise digitization of the
data. This makes the experimental data (Gold standard data)
amenable to computerized search and integration. Thus,
consistent curation efforts must be done to digitize the already
published experimental data. Further, while currently, the data
models are being used for digitization of published
experimental data, the main aim is to develop data curation
and exchange formats that can be implemented in every lab
itself even before publication. Thus, at the time of publication
all the experimental data is in a pre-defined digitized format
than can be easily integrated in any database or public
repository.</p>
    </sec>
    <sec id="sec-5">
      <title>VII. DISCUSSION</title>
      <p>Seamless availability and semantic integration of experimental
data is essential to comprehend the complex behavior of
biological systems. The data digitization fundamentals briefly
explained in this article facilitate digitization of almost every
aspect of the experimental data and thus should prove
instrumental in achieving a higher understanding of any
biological system, if implemented universally. The basic
fundamental is very generic in nature and can be applied to
data from any biological system. In essence, the data models
facilitate digitization of every data-unit of the experimental
data in terms of an organized array of alpha-numeric
notations. The structure of the array is important since same
notation can be used in different positions to mean differently.
For example, a plant ontology term can be used to describe the
tissue wherein expression of a particular gene has been
studied. It can also be used to qualify a gene ontology term to
associate a particular ‘molecular activity’ in a specialized
tissue or developmental stage. Thus, same notation can be
used to signify different aspect of the information. This gives
flexibility as well as universality to the concept.</p>
      <p>
        One of the basic aims of this endeavor is to develop data
digitization, archiving and exchange formats that can be used
at a very early stage (pre-publication) to organize the
experimental data. The idea is to implement these data models
as lab data management portals/softwares. This will greatly
facilitate rapid and seamless access of the experimental data
since there would be no or very minimal need for
postpublication data curation [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. Consequently, curators can
address the meta-analysis of such data instead of basic
archiving.
      </p>
      <p>We regard our study as a step of a much wider area of
research, since experimental data has several dimensions of
interpretations. So far we have only addressed the initial
digitization and archiving of the data. Models for correlating
the digitized data from different studies need to be worked
out. Nevertheless, it was possible to demonstrate an effective
digitization of experimental data in biological sciences.</p>
      <p>ACKNOWLEDGMENT</p>
      <p>The author acknowledgs financial support from Department
of Biotechnology, Government of India.</p>
    </sec>
  </body>
  <back>
    <ref-list>
      <ref id="ref1">
        <mixed-citation>
          [1]
          <string-name>
            <surname>Rhee</surname>
            ,
            <given-names>S.Y.</given-names>
          </string-name>
          and
          <string-name>
            <surname>Mutwil</surname>
          </string-name>
          , M, “
          <article-title>Towards revealing the functions of all genes in plants”</article-title>
          ,
          <source>Trends Plant Sci.</source>
          ,
          <volume>19</volume>
          :
          <fpage>212</fpage>
          -
          <lpage>221</lpage>
          ,
          <year>2014</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref2">
        <mixed-citation>
          [2]
          <string-name>
            <surname>Jaiswal</surname>
            ,
            <given-names>P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ware</surname>
            ,
            <given-names>D.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Ni</surname>
            ,
            <given-names>J.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Chang</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Zhao</surname>
            ,
            <given-names>W.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Schmidt</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Pan</surname>
            ,
            <given-names>X.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Clark</surname>
            ,
            <given-names>K.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Teytelman</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Cartinhour</surname>
            ,
            <given-names>S.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Stein</surname>
            ,
            <given-names>L.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>McCouch</surname>
            ,
            <given-names>S</given-names>
          </string-name>
          , “Gramene:
          <article-title>Development and integration of trait and gene ontologies for rice”</article-title>
          ,
          <source>Comp. Funct. Genomics</source>
          <volume>3</volume>
          :
          <fpage>132</fpage>
          -
          <lpage>136</lpage>
          ,
          <year>2002</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref3">
        <mixed-citation>
          [3]
          <string-name>
            <given-names>Gene</given-names>
            <surname>Ontology</surname>
          </string-name>
          <article-title>Consortium: going forward</article-title>
          .
          <source>Nucleic Acids Res</source>
          .,
          <volume>43</volume>
          :
          <fpage>D1049</fpage>
          -
          <lpage>56</lpage>
          ,
          <year>2014</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref4">
        <mixed-citation>
          [4]
          <string-name>
            <surname>Gour</surname>
            ,
            <given-names>P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Garg</surname>
            ,
            <given-names>P.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Jain</surname>
            ,
            <given-names>R.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Joseph</surname>
            ,
            <given-names>S. V.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Tyagi</surname>
            ,
            <given-names>A.K.</given-names>
          </string-name>
          , and
          <string-name>
            <surname>Raghuvanshi</surname>
            ,
            <given-names>S</given-names>
          </string-name>
          , “
          <article-title>Manually curated database of rice proteins”</article-title>
          .
          <source>Nucleic Acids Res</source>
          .,
          <volume>42</volume>
          ,
          <year>2014</year>
          .
        </mixed-citation>
      </ref>
      <ref id="ref5">
        <mixed-citation>
          [5]
          <string-name>
            <surname>Baumgartner</surname>
            ,
            <given-names>W.A.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Cohen</surname>
            ,
            <given-names>K.B.</given-names>
          </string-name>
          ,
          <string-name>
            <surname>Fox</surname>
            ,
            <given-names>L.M.</given-names>
          </string-name>
          , Acquaah-mensah, G., and
          <string-name>
            <surname>Hunter</surname>
            ,
            <given-names>L</given-names>
          </string-name>
          , “
          <article-title>Manual curation is not sufficient for annotation of genomic databases</article-title>
          ”,
          <volume>23</volume>
          :
          <fpage>41</fpage>
          -
          <lpage>48</lpage>
          ,
          <year>2007</year>
          .
        </mixed-citation>
      </ref>
    </ref-list>
  </back>
</article>