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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>System Description: Reaching Deeper into the Life Science Bibliome with CORAAL</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>V´ıt Nov´aˇcek</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Tudor Groza</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Siegfried Handschuh</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>DERI, National University of Ireland</institution>
          ,
          <addr-line>Galway IDA Business Park, Galway</addr-line>
          ,
          <country country="IE">Ireland</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>Despite being a flourishing field, regarding search, the contemporary online scientific publishing properly exploits mostly raw publication data (bags of words) and shallow meta-data (authors, key words, citations, etc.). The much needed economical mass exploitation of the knowledge implicitly contained in publication texts is still largely an uncharted territory. Within our long-term ambition to quell the lions there, we have made the first step with the CORAAL prototype presented in this report. The tool essentially extracts asserted publication meta-data together with the knowledge implicitly present in the respective text, integrates the emergent content and exposes it via a multiple-perspective search&amp;browse interface.</p>
      </abstract>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>Digital content processing has no doubt introduced a whole lot of new
possibilities of dealing with scientific publications. It makes knowledge much more open
and exploitable than in the old “paper times”. However, one still needs to go
manually through a lot of possibly irrelevant content very often before actually
finding the right answers. If we are to make the next step, it is necessary to
process knowledge (i.e., concepts and their mutual relations), and not just data
or shallow meta-data (i.e., chunks of free text, titles or authors).</p>
      <p>Substantial automation of such meaning-intensive information processing is
hardly possible with the current industry-strength technologies (e.g., full-text
search), since they lack proper support for extraction, representation and
processing of knowledge implicitly present in texts. As an illustration, imagine for
instance finding a support of the claim that acute granulocytic leukemia is
different from T-cell leukemia. With the current solutions, it is easy to find articles
that contain both or either of the terms, however, the number of results may be
quite high (e.g., 593 on PubMed). It is tedious or even impossible to go through
all of them in order to find out which of them actually mention the two leukemias
being different.</p>
      <p>
        Methods for automated knowledge extraction than can dig more than mere
key words from text exist, however, their results are deemed to be to too noisy
and sparse to be exploited by the current state of the art without significant
manual post-processing [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. We have recently researched a novel framework for
effortless exploitation of automatically extracted knowledge that makes use of
similarity-based knowledge representation and respective light-weight inference
services [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. We combined the framework with our repository for semantically
inter-linked publications [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ], delivering a prototype knowledge-based
publication search engine – CORAAL (COntent extended by emeRgent and Asserted
Annotations of Linked publication data). The tool essentially extracts asserted
publication meta-data together with the knowledge implicitly present in the
respective text, integrates the emergent content with existing domain knowledge
and exposes it via a multiple-perspective search&amp;browse interface. This way we
allow for fine-grained publication search combined with convenient and effortless
large scale exploitation of the knowledge that is associated with and hidden in
the publication texts.
1.1
      </p>
      <sec id="sec-1-1">
        <title>Motivating Use Case</title>
        <p>The decision to apply CORAAL to the life sciences domain was motivated by
our cooperation with clinicians and researchers at Masaryk Oncology Institute
in Brno, Czech Republic. When figuring out how to apply our text mining and
light-weight knowledge representation expertise to their needs, we articulated a
particular “translational biomedical knowledge integration” use case. Essentially,
the oncologists were interested in how the information in patient records links
to relevant statements in the biomedical literature, and vice versa. The critical
requirements are, firstly, lack or minimisation of manual efforts necessary for
the knowledge extraction and integration, and, secondly, efficient, exhaustive
and intuitive querying of large amounts of such integrated knowledge. CORAAL
presents a first step towards a practical realisation of the use case, tackling the
extraction, integration and exploitation of the publication knowledge.
1.2</p>
      </sec>
      <sec id="sec-1-2">
        <title>Related Work Overview</title>
        <p>The state-of-the-art applications like ScienceDirect or PubMed Central require
almost no effort in order to expose arbitrary life science publications for search.
However, the benefit they provide is rather limited when compared to
cuttingedge approaches aimed at utilising also the publication knowledge within the
query construction and/or result visualisation. Such innovative solutions may
require much more a priori effort in order to work properly, though.</p>
        <p>
          GoPubMed [
          <xref ref-type="bibr" rid="ref4">4</xref>
          ] is an ontology-based front-end to a traditional publication
full-text search. It allows for effective restriction and intelligent visualisation of
the query results. GoPubMed dynamically extracts parts of the Gene
Ontology (cf. http://www.geneontology.org/) relevant to the query, which are then
used for restriction and a sophisticated visualisation of the classical PubMed
search results. Nevertheless, GoPubMed does not offer querying for or
browsing of arbitrary publication knowledge – terms and relations not present in the
system’s rather static basal ontology simply cannot be reflected in the search.
        </p>
        <p>
          Textpresso [
          <xref ref-type="bibr" rid="ref5">5</xref>
          ] enables searching for relations between concepts in
particular chunks of text (namely for gene-to-gene interactions). The tools described
in [
          <xref ref-type="bibr" rid="ref6 ref7">6, 7</xref>
          ] support complex ontology-based querying for relationships identified in
free texts (related to dengue literature and lipidospehere, respectively).
However, the underlying ontologies have to be provided manually for all the above
systems. Moreover, their scale regarding the number of publications’ full-texts
and concepts covered is quite low.
        </p>
        <p>
          Regarding more recent and/or scalable tools for expressive search in
biomedical literature, EBIMed [
          <xref ref-type="bibr" rid="ref8">8</xref>
          ], novo|seek (http://www.novoseek.com), iHOP [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ]
and u-Compare [
          <xref ref-type="bibr" rid="ref10">10</xref>
          ] are among the most relevant. EBIMed performs classical
full-text search and annotates the results with possible associations between
co-occurring protein, gene, drug or species names. novo|seek provides for
synonymy resolution and disambiguation of the search terms, in effect extending the
coverage and precision of the classical full-text search. iHOP allows for
browsing publications along links induced from occurrence of same gene or protein
names across different resources. Finally, u-Compare allows for drag-and-drop
style building of custom NLP workflows in order to analyse life science
publications. All the tools focus mostly on the extraction and/or annotation of entities
(and possibly also their relationships), however, they do not exploit any
underlying knowledge representation allowing for, e.g., reasoning (which is essential
for sophisticated querying).
        </p>
        <p>From the overview of the state of the art in the field, it is obvious that the
two biggest challenges are: 1. reliable automation of more expressive content
acquisition; 2. representation of the acquired content allowing for exhaustive and
expressive querying. None of the related systems addresses both problems
appropriately. On the other hand, CORAAL, the system we present in this paper,
can easily employ legacy domain resources or even work without any human
intervention. Apart of full-text indexing, the extracted statements are integrated
into a light-weight knowledge base with similarity-based inference capabilities
that allow for refinement, augmentation and querying of the stored facts. In
effect, CORAAL delivers a comprehensive combination of full-text and
knowledgebased search in life science publications that is to large extent complementary
to the related state of the art.
1.3</p>
      </sec>
      <sec id="sec-1-3">
        <title>Structure of the Paper</title>
        <p>The rest of the paper is organised as follows. Section 2 presents the essentials
of the processing pipeline in CORAAL and outlines the relevant technological
aspects of the tool. The deployment and user perspectives of CORAAL are
covered in Section 3. We summarise the delivered work and outline future directions
in Section 4.
2</p>
      </sec>
    </sec>
    <sec id="sec-2">
      <title>CORAAL Essentials</title>
      <p>
        In order to provide comprehensive search capabilities in CORAAL, we decided
to complement a standard (full-text) publication search approach with advanced
services catering for knowledge-based search. By knowledge-based search we
mean querying for and browsing of expressive statements capturing relations
between concepts in the respective source articles. CORAAL is built on the top
of two substantial research outputs of our group at DERI – the KONNEX [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ]
and EUREEKA [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ] frameworks. The former is used for storing and querying
of publication full-text and meta-data. The latter serves for exploitation of the
knowledge (i.e., concepts and their mutual relations) implicitly contained in the
publication texts by means of knowledge-based search.
2.1
      </p>
      <sec id="sec-2-1">
        <title>Data Processing Outline</title>
        <p>
          EUREEKA provides for knowledge extraction from text and other knowledge
resources (e.g., ontologies or machine readable thesauri). It employs two data
structures. Firstly, a lexicon takes care of mapping extracted lexical labels to
unique entity identifiers and vice versa (i.e., dealing with synonymy resolution
and disambiguation). The extraction process continually updates the second
data structure in EUREEKA – a light-weight knowledge base supporting
arbitrary extensions by custom rules, as well as similarity-based reasoning and
querying of the stored data. The knowledge bases are exposed to consumers
via a query answering interface. The interface allows for evaluating conjunctive
argument-relation-argument queries with negation and variables. It returns
extracted and/or inferred statements relevant to the query, sorted according to
their intrinsic relevance degree (derived from all particular relationships in the
knowledge base using a generalised IR ranking algorithm). Theoretical and
technical details of EUREEKA and its deployment in CORAAL are provided in [
          <xref ref-type="bibr" rid="ref2">2</xref>
          ].
        </p>
        <p>
          KONNEX tackles the integration of the extracted publication text and
metadata, represented as RDF graphs in a triple store. Operations related to data
registration (inclusion and integration with the stored content), repository
maintenance, full-text query processing and indices are handled by respective manager
KONNEX modules, possibly composed of sub-modules handling particular data
or query types. Details are given in [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ].
2.2
        </p>
      </sec>
      <sec id="sec-2-2">
        <title>Technological Aspects</title>
        <p>There are several conceptually separate modules in CORAAL, moreover,
EUREEKA is written in the Python programming language, while KONNEX in
Java. Therefore we utilise an inter-process communication layer implemented
using the D-BUS framework (cf. http://en.wikipedia.org/wiki/D-Bus). On
the top of the core-level EUREEKA and KONNEX APIs, a set of helper web
services rests. These manage the user requests and forward the data returned by
the core APIs to the web hub, which is a set of Java servlets handling particular
types of search. The servlets produce machine-readable RDF representing
answers to user queries. The RDF has XSL style sheets attached in order to render
the results in a human-readable form via the Exhibit faceted browsing web
frontend (cf. http://www.simile-widgets.org/exhibit/). Such a solution results
in CORAAL being a pure Semantic Web application, as the data-flow between
the core infrastructure and the other modules is strictly based on RDF graphs.
While being presented in a human-readable form in the browser, the produced
data can be directly analyzed by an application or fetched by a crawler.
3
3.1</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>Deploying the System</title>
      <sec id="sec-3-1">
        <title>Processed Data</title>
        <p>We have processed 11,761 Elsevier journal articles from the provided XML
repositories that were related to cancer research and treatment. The access to
the articles was kindly provided within the Elsevier Grand Challenge
competition we participated in (cf. http://www.elseviergrandchallenge.com). The
domain was selected so due to the expertise of our sample users and testers
from Masaryk Oncology Institute in Brno, Czech Republic. We processed
articles evenly distributed across journals dedicated to the following topics:
oncology, genetics, pharmacology, biochemistry, general biology, cell research, and
clinical medicine. From the article repository, we extracted the knowledge and
publication metadata for further processing by CORAAL. Besides the
publications themselves, we employed legacy machine-readable vocabularies for the
refinement and extension of the extracted knowledge (currently, we use the
NCI and EMTREE thesauri – see http://www.cancer.gov/cancertopics/
terminologyresources and http://www.embase.com/emtree/, respectively).</p>
        <p>CORAAL exposes two data-sets as an output of the publication
processing: 1. We used a triple store containing publication meta-data (citations,
their contexts, structural annotations, titles, authors and affiliations)
associated with respective full-text indices. The resulting store contained 7, 608, 532
of RDF subject-predicate-object statements describing the input articles. This
included 247, 392 publication titles and 374, 553 authors (both from full-texts
and references processed). 2. We employed a custom EUREEKA knowledge
base with facts of various certainty extracted and inferred from the article texts
and the seed life science thesauri. Directly from the articles, 215, 645 concepts
were extracted (and analogically extended). Together with the data from the
initial thesauri, the domain lexicon contained 622, 611 terms, referring to 347, 613
unique concepts. The size of the emergent knowledge base was 4, 715, 992 weighed
statements (ca. 99 and 334 extracted and inferred statements per publication in
average, respectively). This number is significantly smaller than in the case of
the semifinal prototype. However, this is due to a full integration of the
knowledge from formerly separate contexts, the data themselves are still the same.
The contextual meta-knowledge related to the statements (like provenance
information) amounts to more than 10, 000, 000 additional statements should it be
expressed in RDF triples.
3.2</p>
      </sec>
      <sec id="sec-3-2">
        <title>Accessing and Using CORAAL</title>
        <p>CORAAL can be accessed at http://coraal.deri.ie:8080/coraal/. The
following browsers have been tested with CORAAL and are known to work on
most desktop configurations and operating systems: (1) Firefox (versions 2.x,
3.x and newer); (2) Internet Explorer (versions 7.x and newer; in most cases
only on Windows Vista, though); (3) Opera (versions 9.6 and newer); (4) Safari
(versions 3.1 and newer); (5) Google Chrome (all versions).</p>
        <p>For the user interface of our system, we employed the MIT’s state-of-the-art
Exhibit framework (cf. http://www.simile-widgets.org/exhibit/). It
supports faceted browsing (cf. http://en.wikipedia.org/wiki/Faceted_browser)
of the knowledge-based search results, letting users to conveniently focus on the
relevant answers. Similarly, we allow for faceted browsing of the classical
fulltext search results that are tightly integrated with the knowledge extracted or
inferred from the respective articles. Both types of search (knowledge-based and
full-text) are illustrated in the rest of the section.</p>
        <p>
          Knowledge-Based Search We expose the content of the CORAAL
knowledge base via a query-answering module. It returns answer statements sorted
according to their relevance scores and similarity to the query (see [
          <xref ref-type="bibr" rid="ref2">2</xref>
          ] for the
details of the process). Answers are provided by an intersection of
publication provenance sets corresponding to the respective statements’ subject and
object terms. The module currently supports queries in the following form:
t | s : (N OT )?p : o( AN D s : (N OT )?p : o)∗, where N OT and AN D stands for
negation and conjunction, respectively. s, o, p may be either variable—anything
starting with the ? character or even the ? character alone—or a lexical
expression. t may be lexical expressions only. The ? and ∗ wildcards mean zero or one
and zero or more occurrences of the preceding symbols, respectively, | stands for
or. Only one variable name is currently allowed to appear within a single query
statement and across a statement conjunction.
        </p>
        <p>Statement queries can be asked either directly in the CORAAL Knowledge
tab, or one can use an interface for assisted query construction with
autocompletion capability, as seen in Figure 1. The auto-completion is
contextsensitive – if you settle, e.g., on a subject, only relations (properties) actually
associated with the particular subjects in the knowledge base are offered.
Negative or conjunctive statements are created using the NOT, AND check-box or
button, respectively. This allows for very convenient query construction even for
users who are not sure how exactly should they ask the system.</p>
        <p>The knowledge search results (Figure 2) are displayed as particular
statements provided with several types of meta-information:
– source provenance – articles relevant to the statement
– context provenance – sub-domain of life sciences the statement relates to
(determined according to the main topic of the journal that contained the
articles the statement was extracted from)
– certainty – how certain the system is that the statement holds and is relevant
to the query (values between 0 and 1)
– inferred – whether the statement was inferred or not (i.e., directly extracted)
One can filter the answer statements based on their particular elements (subjects,
properties and objects), associated meta-information and their negativity. The
filtering boxes have a contextual help associated with them – after pressing the
(?) symbol, an inline hint on the usage of the respective box is opened. Using
a particular filtering, one can conveniently focus only on statements of interest.
Article provenance summaries of particular statements can be displayed in-line
as shown in Figure 3.</p>
        <p>After clicking on the concept names, statements related to it are displayed
(similarly to the previously shown answer display). Additionally, we provide
a box with further information on the concept (Figure 4). Currently we
automatically fetch an abstract, image and biomedical classification details from
the respective Wikipedia entries (looking up the synonyms of the concept in
question). However, other online sources, such as the KEGG service (cf. http:
//www.genome.jp/kegg/kegg2.html) can be easily incorporated.
Full-Text Search Besides the knowledge-based search, CORAAL supports
also classical full-text search, which results in article paragraphs containing the
queried terms. Links to the detailed view of the respective publication are
provided, as well as citation contexts for the queried terms (i.e., publications
referenced from the adjacent text). The full-text search results can be filtered, for
instance by authors or citation contexts. One can also filter publications according
to the concepts they contain, but also according to the associated indirect
(inferred) general topics or specific instances. Besides publications, one can search
for titles and authors. The respective results can be filtered, too. Figure 5 shows
list of authors corresponding to the “Lin” name filtered only to those who have
written an article concerned with the “gene amplification abnormality” topic.
This feature of CORAAL can be used when looking for candidate experts on
certain topics of interest.
4</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>Conclusions and Future Work</title>
      <p>With CORAAL, we started to implement the requirements of the use case
outlined in Section 1.1. We have processed non-trivial amount of publication data
purely automatically, extracted and processed the knowledge hidden in the
articles, and exposed it conveniently to the users. The next and rather
straightforward step is to integrate the publication knowledge with knowledge in patient
records. For that, an appropriate parser for the patient records is essentially
enough, as the EUREEKA engine employed in CORAAL is agnostic w.r.t. the
origin of the input data. In the long-term perspective, one major task lies ahead
of us, though. To make CORAAL really useful in practice, we still need to reduce
the noise level in the exposed knowledge. Perhaps the easiest way is to utilise the
wisdom of the crowds by supporting secure, error-prone and unobtrusive user
involvement in the knowledge base updates (namely by (in)validation of existing
statements, introduction of new statements and submission of new rules refining
the domain semantics).</p>
      <p>Acknowledgments This work has been supported by the ‘L´ıon’, ‘L´ıon II’
projects funded by Science Foundation Ireland under Grants No. SFI/02/CE1/
I131, SFI/08/CE/I1380, respectively. We acknowledge much appreciated help
from Ioana Hulpus, who developed the initial user interface for CORAAL. Very
special thanks goes to the people who have actively participated in the
continuous prototype evaluation and testing, namely to (in an alphabetical order):
Doug Foxvog, Peter Gr´ell, MD, Miloˇs Hol´anek, MD, Matthias Samwald, Holger
Stenzhorn and Jiˇr´ı Vyskoˇcil, MD.</p>
    </sec>
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