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  <front>
    <journal-meta>
      <journal-title-group>
        <journal-title>Feb</journal-title>
      </journal-title-group>
    </journal-meta>
    <article-meta>
      <title-group>
        <article-title>The Ontology Viewer: Facilitating Image Annotation with Ontology Terms in the CSIDx Imaging Database</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Yun Bei ybei@liacs.nl</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Amalia Kallergi</institution>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Author Keywords Ontology, life sciences</institution>
          ,
          <addr-line>annotation, graph, images</addr-line>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Fons J. Verbeek</institution>
        </aff>
        <aff id="aff3">
          <label>3</label>
          <institution>section Imaging &amp; BioInformatics - Imagery &amp; Media group Leiden Institute of Advanced Computer Science (LIACS), Leiden University.</institution>
          <addr-line>Niels Bohrweg 1, 2333 CA Leiden</addr-line>
          ,
          <country country="NL">The Netherlands</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2009</year>
      </pub-date>
      <volume>8</volume>
      <issue>2009</issue>
      <abstract>
        <p>In the life sciences data must be described unambiguously. We apply this principle in our multi-modal bio-imaging database in which images are stored together with comprehensive metadata. We use ontology terms to describe the semantic content of images. Ontologies are obtained from dedicated ontology repositories in the life sciences. For our users, the process of image annotation with ontology terms was proven to be a challenging task. Therefore, we have made improvements on both usability and speed of annotation. We developed search facilities across our ontology collection and implemented a new graphical ontology viewer. This tool allows for both querying and visualizing ontology terms by means of a 2Dgraph representation. Our viewer provides a means to collect ontology terms and at the same time familiarizes users with ontologies and their structure. In making these tools available we succeeded in our goals to reduce time and effort for accurate image annotation.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>-</title>
      <p>
        INTRODUCTION
The Cyttron Scientific Image Database for Exchange
(CSIDx) is a multi-modal imaging database for images
produced in the life sciences [
        <xref ref-type="bibr" rid="ref2 ref7">2,7</xref>
        ]. In CSIDx, image
annotation is a fundamental aspect of image submission
and ontology terms, as extracted from life-sciences
ontologies, are used to define the semantic content of an
image. These ontologies with their intrinsic curation and
relations between all terms help to obtain unambiguous
annotations and to assess synonyms. Moreover, CSIDx
aims to explore the added value of the ontological relations
towards integration of images in representing biological
concepts. In this section, we briefly introduce the scope and
aim of the database and provide a short overview of the
image annotation procedure.
      </p>
      <p>
        CSIDx is built to support a wide range of imaging
modalities and techniques and it is the backbone database
of the Cyttron project [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ], a consortium towards an
integrated infrastructure for bio-imaging and modelling
cells down to atomic detail. CSIDx is also a web-based
community in which researchers from various institutes can
share their image resources. The database is accessible via
a web interface and the design is based on rich Internet
application practices that allow for dynamic and responsive
web applications. The system is developed, maintained and
physically hosted by the Imaging and Bio-Informatics
group at Leiden University.
      </p>
      <p>
        In CSIDx, we propose that metadata as the information that
describes an image is essential to support exchange and
linking as well as analysis of images [
        <xref ref-type="bibr" rid="ref1 ref2">1,2</xref>
        ]. A key feature of
CSIDx is linking of imaging modalities via concepts
towards integration of functional concepts and to that end,
an unambiguous annotation is required. Therefore, CSIDx
stores both raw pixel data and user generated annotations.
A major part of the CSIDx development is dedicated to
tools that facilitate the process of an extended annotation
by the image owner. The development process and design
of new features is accomplished in close collaboration with
users; i.e., biologists, structural biologists and others,
whose feedback is registered via observation and informal
interviews.
      </p>
      <p>
        In order to assure a comprehensive annotation that also
represents the actual image acquisition conditions, CSIDx
maintains metadata about the 'who', the 'what' and the 'how'
of an imaging experiment [
        <xref ref-type="bibr" rid="ref1 ref2 ref7">1,2,7</xref>
        ]. In this paper, we
particularly address the metadata on what an image is about
i.e. information about the biological phenomenon depicted
or the phenomenon the image relates to. This annotation
corresponds to the semantic content of the image and
captures the interpretation of an image as given by the
domain expert or the researcher responsible for the image
acquisition. To assure accurate metadata [
        <xref ref-type="bibr" rid="ref1 ref2">1,2</xref>
        ] and to
explore possible relations between the images, the
'what'part of the annotation is expressed in ontology terms as
extracted from life-science ontologies. In comparison with
free text or user generated keywords, ontology terms
guarantee consistency across the system and prevent
ambiguities and spelling mistakes. Moreover, ontologies
provide well-defined relations across the concepts which
can be further explored in structuring or mining the image
data. The use of domain specific ontologies also
corresponds with the emerging practices in the field of
lifescience data repositories towards well-maintained and
reusable resources by means of a common semantic
representation.
      </p>
      <p>
        In this paper, we describe our efforts and tools to support
and facilitate image annotation with ontology terms. In
particular, we describe our ontology viewer, a graphical
tool developed to assist image annotation based on
ontologies. CSIDx currently incorporates 37 life-science
related ontologies, the majority of which are retrieved from
the Open Biomedical Ontologies (OBO) Foundry [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ]. The
OBO Foundry is a platform to share biological ontologies
in a common syntax and the maintained ontologies are
available in a variety of formats such as OBO [
        <xref ref-type="bibr" rid="ref9">9</xref>
        ], OWL
[10] and RDF [12]. The biological ontologies available are
developed and maintained by researchers in the biomedical
field and provide a fair overview of the domain specific
knowledge and vocabulary in the field of life-sciences. In
this manner, about half a million unique terms are available
for annotation.
      </p>
      <p>
        CHALLENGES OF USING ONTOLOGIES IN IMAGE
ANNOTATION
In an earlier prototype of CSIDx, users could annotate
images by selecting ontology terms from our ontology tree
browser. This application depicts the hierarchical relation
in the ontologies as a tree view; this view only displays the
subClassOf relation. With an interactive tree view (cf.
Figure 1), users can navigate by collapsing and expanding
terms in the hierarchy and can select terms to be assigned
to the image under annotation. The ontology tree browser
parses ontologies in the OWL-format by means of the Jena
framework [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. This tool provides some control and
structure in dealing with the available ontology terms as
well as some means to navigate the ontologies. However,
this approach was found to be insufficient for the extended
annotation and usability requirements of CSIDx.
In fact, the introduction of ontology terms for image
annotation was in itself a significant challenge for our
users. Firstly, the majority of our users were not familiar
with the exact concept of the ontology. Although all the
ontologies used in our system are maintained by the
bioscience community, hardly any of our users had prior
extensive experience with ontologies. In particular, they
had no mental image of the structure of an ontology and
they demonstrated difficulties in comprehending that
relations other than the child-parent relation of a hierarchy
may occur and that terms can be interconnected. During our
sessions with the users, we often found ourselves sketching
out ontology graphs on paper to explain an ontology.
Secondly, most of our users were insufficiently familiar
with the content of the ontologies. Simply, they did not
have sufficient knowledge on what terms are to be found in
each separate ontology. We expected that their biological
knowledge would help them locate the terms of interest in
the hierarchy but the ontology structure as given in the
hierarchy view was not always matching the user's
expectations. Additionally, the vast amount of terms
available was difficult to manage. Even when a term was
known or previously identified, clicking through the several
levels of an ontology hierarchy to locate the term was time
consuming and - from the user's point of view - unpractical
and unacceptable.
      </p>
      <p>FORM OF A SOLUTION
To address the challenges of using ontology terms for
annotation, we examined the difficulties faced by our users
and the limitations of the hierarchical visualization of the
ontologies. Testing with our prototype provided useful
knowledge on how users interact with ontologies. Through
participatory evaluations, we learned that users need to
learn the ontology content, to build a mental model of
ontology structure and to extract information from
ontologies. The complexity of the annotation task increases
due to the lack of search facilities, the overwhelming
amount of terms and the lack of experience with and
understanding of ontologies. Hence, we implement a
solution that aims to improve the annotation process both in
terms of usability and in terms of ontology comprehension.
In particular, we provide search facilities on the ontology
terms corpus and implement the ontology viewer, a
graphical tool used for both querying and visualizing
ontology terms. In combination with these facilities and in
order to reduce the annotation effort, the concept of
MyTerms was also introduced in the workflow of the
annotation process.
A⊆B
A⊆∃ P.B
A⊆B∩C
∀x [B(x) → A(x)]
∃x∃y [A(x)∧B(y)∧P(x,y)]
∀x [A(x) → B(x)∧C(x)]
A⊆ B∪C</p>
      <p>
        B⊆A, C⊆A
Querying Ontologies Using a Database Back End
From the user perspective, quick concept (keyword-like)
searches across the ontologies are essential in order to
complete an extensive image annotation with ontology
terms. Keywords and textual descriptions of images as
conceived by the image owner need to be mapped to
existing ontology terms. Such a procedure is not easily
accomplished without any search facilities especially when
the user is not familiar with the content of the ontologies.
Ontology querying mechanisms can involve the use of
dedicated RDF query languages such as SPARQL [13].
More elaborate forms of querying, like reasoning can be
accomplished with reasoners such as Pellet [11] and
KAON2 [
        <xref ref-type="bibr" rid="ref8">8</xref>
        ]. Although powerful, these mechanisms are
heavily challenged when large or complex ontologies are
involved and do not demonstrate fast performance in terms
of speed of a query [4, Bei internal technical report].
CSIDx is focused on the domain of the life science where
ontologies and controlled vocabularies tend to be enormous
in size and/or are constantly updated and expanding. In
addition, the ontology structure tends to include elaborate
relations which result in increased complexity when
querying or reasoning with the ontology. However, the web
based character of CSIDx gives a high priority on speed
and reactivity of the system. Being confronted with such a
practical limitation, we adopted a solution with a Relational
Database Management System (RDBMS) to support fast
ontology queries. Specifically, our ontology resources were
transformed from their original OWL format to a simplified
schema that can be easily stored and queried by means of a
RDBMS. Namely, the indirect relationships in OWL-DL
are transformed into concise, direct relationships and the
complete ontology structure is expressed as a directed
graph of concepts and their relations that can be easily
stored in a database schema. Examples of the
transformations applied are given in Table 1. Such a
representation definitely lacks the completeness,
complexity and expressive power of the OWL- DL
language but allows us to perform queries with high
performance. For the purposes of image annotation, we
believe that such a representation, although incomplete, is
still able to provide a sufficient view on the domain
knowledge.
      </p>
      <p>By designing and populating the ontology database, which
currently consists of 565,600 terms and 825,724 relations,
we are able to support querying facilities across the
ontologies. Users of CSIDx can search for a corresponding
term by keywords using either the ontology viewer (cf.
next section) or a simplified web search form.</p>
      <p>MyTerms: A User Specific Collection of Terms for
Annotation
To reduce the effort required for identifying annotation
terms in the ontology collection, we have introduced the
concept of MyTerms in the workflow of the annotation
process. MyTerms is a collection of user specific ontology
terms that are saved under a user's profile and can be reused
across annotations. Prior to an actual image annotation,
users can browse the ontology collection with the querying
tools available looking for terms that are relevant to their
study or field of research. During an image annotation,
users assign terms to images by selecting terms from their
own relevant subset (MyTerms) instead of the complete
corpus of terms available. This process is an attempt to
minimize the effort of searching for terms (search once, use
in all subsequent annotations) and to reduce the
overwhelming amount of ontology terms to a subset that is
both meaningful to the user and easier to browse and use.
The MyTerm concept can be further elaborated to match
the structure of our system. In CSIDx, users are organized
in groups that correspond to their actual research institute
or group and this organization is often used throughout the
interface as a mechanism for exchanging shared resources,
such as images or microscopes. Therefore, we also provide
the possibility of sharing identified terms among group
members, who are likely to work on a similar topic. In the
case of group shared ontology terms, the time and effort
spent by a group member to locate and identify useful
terms across the ontologies profits all members of the
research group. On the whole, MyTerms assure that the
admiringly time-consuming process of mapping metadata
to existing ontology terms does not need to be
unnecessarily repeated.</p>
      <p>THE ONTOLOGY VIEWER
The ontology viewer provides a graphical interface for
querying ontology terms and a means to visualize the
ontology structure. We believe that a graphical
representation can assist our users in building a mental
model next to building a collection of terms. In practice, it
is a tool to assist building a MyTerms list and an attempt to
demystify ontologies to our users by making the relations
among ontology terms obvious. The application is
developed in Java and deployed as a WebStart application.
It can be accessed via the CSIDx web interface or used as a
standalone application for registered users.</p>
      <p>The ontology viewer (cf. Figure 2) consists of two major
panels: a query form and a 2D viewer. In the query form,
users search for ontology terms within an ontology by
providing one or more keywords and by specifying the
level of detail for the search. Queries can be performed on
the label, synonym or definition of terms and keywords can
be combined in an 'AND' or 'OR' query. Users can choose
from the list of results to either visualize particular terms or
directly add terms to their MyTerms list.</p>
      <p>In the 2D viewer, the ontology structure is represented as a
graph in which terms are graph nodes and relations are
graph edges. Selected ontology terms, as collected from a
query, are used to produce a sub-graph of the ontology
graph. This sub-graph provides the local context for the
selected nodes which are highlighted green to distinguish
from their connected terms.</p>
      <p>
        A short description with information on any given term can
be obtained by mouse over the corresponding graph node.
Regular graphical manipulations are supported on the
ontology graph which can be zoomed, paned, rotated and
sheared. In this manner, user can adjust the view to better
understand the displayed relations. The ontology viewer
also provides different graph layouts to support a more
suitable or preferred arrangement in space, especially in the
case of complex sub-graphs. The supported layouts are
given in Table 2. To improve clarity of the presentation,
both the text labels of either nodes or relations and nodes
other than the selected nodes can be toggled on or off. The
graph drawing and manipulation is implemented by means
of the Java Universal Network/Graph Framework (JUNG)
[
        <xref ref-type="bibr" rid="ref6">6</xref>
        ].
      </p>
      <p>DISCUSSION AND CONCLUSIONS
Overall, the CSIDx ontology viewer provides an
informative graphical interface to the collection of
ontologies in CSIDx. As most ontologies are derived from
the OBO matrix, this viewer is also an alternative graphical
entry point to exploring the most popular and
acknowledged ontologies in the domain of the life sciences.
Importantly, for most CSIDx users, this interface is their
first impression on biological ontologies and a first step
towards familiarizing themselves with the concept and
content of ontologies. Compared also to the web based
querying facility that lacks the graph display, users have
reported that the connected terms often help clarify
ambiguities: when the label of a term can be explained
differently depending on the context or when the
description of a term is insufficient, the connected terms are
often conclusive on the exact meaning of the term. As a
result, users feel more confident that they have selected the
proper term for precise annotation. The graph
representation also seems to assist users in rethinking the
way they translate their desired annotation to ontology
terms. By exploring the ontology, users often conclude on
more terms than they initially queried for and they often
express the desire to automatically add to their user term
list (MyTerms) the whole graph structure as displayed in
the 2D viewer. Overall, the ontology viewer contributes
towards a more complete and accurate annotation based on
ontology terms.</p>
    </sec>
    <sec id="sec-2">
      <title>Layout</title>
      <sec id="sec-2-1">
        <title>KKLayout</title>
      </sec>
      <sec id="sec-2-2">
        <title>FRLayout</title>
      </sec>
      <sec id="sec-2-3">
        <title>CircleLayout</title>
      </sec>
      <sec id="sec-2-4">
        <title>SpringLayout</title>
      </sec>
      <sec id="sec-2-5">
        <title>SpringLayout2</title>
      </sec>
      <sec id="sec-2-6">
        <title>ISOMLayout</title>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Algorithm</title>
      <sec id="sec-3-1">
        <title>The Kamada-Kawai algorithm</title>
      </sec>
      <sec id="sec-3-2">
        <title>The Fruchterman-Rheingold algorithm</title>
      </sec>
      <sec id="sec-3-3">
        <title>A simple layout which places vertices randomly on a circle</title>
      </sec>
      <sec id="sec-3-4">
        <title>A simple force-directed spring-embedder</title>
      </sec>
      <sec id="sec-3-5">
        <title>Another simple force-directed spring-embedder</title>
      </sec>
      <sec id="sec-3-6">
        <title>Meyer's "Self-Organizing Map" layout</title>
        <p>As they familiarize themselves with the ontology structure,
users demonstrate the wish to further interact with the
ontology. Often, they request to expand the displayed
nodes, a requirement that equals with interactively
traversing the complete ontology. While the ontology
viewer was basically aimed to provide some context for the
queried terms rather than a complete overview of an
ontology, we are interested to explore if the graph
representation can be useful as a querying tool in itself.
While the contributions of a graphical interface for
ontology exploration are encouraging, the overall
performance remains an issue. Querying an ontology is
satisfactory fast but displaying the graph structure has
significant memory requirements and may halt for large
ontologies. Also, while mapping familiar keywords to
ontology terms, many users reported a difficulty in
specifying which ontology to query in. In the current
prototype, querying for a keyword in the whole collection
of ontologies is not supported and needs further attention.
Our results
conclusions:
can
be
represented
by
the
following
1. The Ontology viewer provides an intuitive interface for
(novice) users; the options are self explanatory and the
user is assisted in understanding ontology concepts while
at the same time ontologies are queried and terms
selected. The mapping to the graphs is very helpful to that
respect.
2. The MyTerms list provides a good simplification to the
otherwise “oversized” ontologies. Users can now use
ontology concepts with ease in their image annotations.
3. To assure visibility in the interface of the ontology
viewer a fast response to queries is required which can be
provided through a transformation of the ontology
structure to an RDBMS.</p>
        <p>FUTURE DIRECTIONS
The work presented in this paper is the result of a
participatory design trajectory; in the design phase we
aimed to learn how we could bring the concept of
annotation of images with ontologies across the users of the
CSIDx database. The design process also included
requirement generation by users. We accomplished this
design phase with an artifact that is a fully working
prototype, rather than proposing a final application. Now
that we have gained sufficient information on how novice
users can work with ontologies, we can make next steps
towards observatory evaluations in which different
annotation strategies can be tested. Further user evaluations
by surveys will render sufficient data for statistical analysis
on ontology interaction.</p>
        <p>Annotations are the basic components of the semantic
structure in CSIDx. Furthermore, the relations included in
the ontologies provide additional material to be explored.
Initially, we wish to investigate the direct relations as
maintained in the RDBMS. Still, mechanisms to profit
from the OWL-DL expressiveness can be expanded based
on the existing annotation with ontology concepts.</p>
      </sec>
      <sec id="sec-3-7">
        <title>Framework</title>
        <p>for Java,</p>
      </sec>
    </sec>
  </body>
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</article>