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<article xmlns:xlink="http://www.w3.org/1999/xlink">
  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>One tagger, many uses</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Lars Juhl Jensen</string-name>
          <email>lars.juhl.jensen@cpr.ku.dk</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Novo Nordisk Foundation Center for Protein Research Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen</institution>
          ,
          <country country="DK">Denmark</country>
        </aff>
      </contrib-group>
      <abstract>
        <p>- Automatic annotation of text is an important complement to manual annotation, because the latter is highly labour intensive. We have developed a fast dictionary-based named entity recognition (NER) system and addressed a wide variety of biomedical problems by applied it to text from many different sources. We have used this tagger both in real-time tools to support curation efforts and in pipelines for populating databases through bulk processing of entire Medline, the openaccess subset of PubMed Central, NIH grant abstracts, FDA drug labels, electronic health records, and the Encyclopedia of Life. Despite the simplicity of the approach, it typically achieves 80-90% precision and 70-80% recall. Many of the underlying dictionaries were built from open biomedical ontologies, which further facilitate integration of the text-mining results with evidence from other sources.</p>
      </abstract>
      <kwd-group>
        <kwd>named entity recognition</kwd>
        <kwd>software</kwd>
        <kwd>dictionaries</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>I. INTRODUCTION</title>
      <p>Named entity recognition (NER) is a fundamental task in
biomedical text mining and can benefit greatly from the use of
ontologies. This is especially true for dictionary-based NER
methods, which with a good ontology at hand can be quickly
adapted to a new task without the need for a manually curated
corpus for training.</p>
    </sec>
    <sec id="sec-2">
      <title>II. SOFTWARE IMPLEMENTATION</title>
      <p>
        The core of our NER system is a highly optimized
dictionary-based tagging engine implemented in C++ [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. The
core tagger makes use of a custom hashing function to process
thousands of PubMed abstracts per second with a single CPU
thread. It is furthermore is inherently thread-safe, allowing for
perfect scalability in multi-threaded use and is both available as
a command-line tool and as a Python module that was
generated in part by the Simplified Wrapper and Interface
Generator (SWIG). For real-time applications, we have
developed a multi-threaded HTTP server that utilizes this
Python module to expose the tagger as a RESTful web service,
which includes support for the Open Annotation model [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ].
      </p>
      <p>
        The ability to perform real-time tagging enabled us to
develop the Reflect [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] and EXTRACT [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ] tools, which helps
curators identify and extract terms from any web page and was
evaluated favourably in the interactive annotation track of
BioCreative V [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ].
      </p>
      <p>This work was in part funded by the Novo Nordisk Foundation
(NNF14CC0001) and the National Institutes of Health (U54 CA189205-01).</p>
    </sec>
    <sec id="sec-3">
      <title>III. DICTIONARIES AND APPLICATION AREAS</title>
      <p>Software is only one half of a NER system; the other half is
the dictionary with all the names that the software matches
against the text. When adapting the NER system to a new
biomedical application area, the main work required is the
construction of a suitable high-quality dictionary and blacklist
names not to be tagged. The latter is created through manual
inspection of the most frequently occurring dictionary names in
a large text corpus.</p>
      <sec id="sec-3-1">
        <title>A. Molecular Entities</title>
        <p>
          NER and normalization of genes and proteins has been the
subject of several BioCreative tasks over the years, most
recently in BioCreative III [
          <xref ref-type="bibr" rid="ref5">5</xref>
          ]. This was also one of the very
first uses of the tagger, which is a key component of the
textmining pipeline in the STRING database [
          <xref ref-type="bibr" rid="ref6">6</xref>
          ]. The underlying
dictionary of gene/protein names is based on Ensembl [
          <xref ref-type="bibr" rid="ref7">7</xref>
          ] and
RefSeq [
          <xref ref-type="bibr" rid="ref8">8</xref>
          ], which were expanded with additional synonyms
from UniProt [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ]. An older version of the system achieved
Fscores of 91% and 66% for recognition and normalization of
yeast and fly genes, respectively [
          <xref ref-type="bibr" rid="ref3">3</xref>
          ]. This NER method is also
heavily used within the Illuminating the Druggable Genome
program to assess how well studied drug targets are based on
both publications and NIH RePORTER funding data.
        </p>
        <p>
          Identification of small-molecule chemical compounds in
text was a task in BioCreative V [
          <xref ref-type="bibr" rid="ref10">10</xref>
          ]. The tagger is also used
for this in the STITCH database [
          <xref ref-type="bibr" rid="ref11">11</xref>
          ], which relies on a
dictionary constructed from a filtered version of PubChem
[
          <xref ref-type="bibr" rid="ref12">12</xref>
          ]. STRING and STITCH both employ a statistical
cooccurrence as well as natural language processing (NLP) for
subsequent extraction of relations between the identified
molecular entities from Medline and the open-access subset of
PubMed Central. These relations are integrated with evidence
from many other sources including experimental data and
manually curated pathway databases.
        </p>
      </sec>
      <sec id="sec-3-2">
        <title>B. Protein Localization and Expression</title>
        <p>
          The COMPARTMENTS [
          <xref ref-type="bibr" rid="ref13">13</xref>
          ] and TISSUES [
          <xref ref-type="bibr" rid="ref14">14</xref>
          ] databases
take a very similar integrative approach to associate proteins
with their subcellular localizations and tissue expression
patterns. To this end, we constructed dictionaries based on the
cellular component part of Gene Ontology [
          <xref ref-type="bibr" rid="ref15">15</xref>
          ] and the Brenda
Tissue Ontology [
          <xref ref-type="bibr" rid="ref16">16</xref>
          ], respectively. Both ontologies were well
populated with synonyms, which were automatically expanded
to construct plural and adjective forms. The resulting resources
can be used to filter protein networks from STRING to include
only proteins from certain subcellular and/or tissue contexts.
This is useful, for example, in prediction of host–pathogen
interactions.
        </p>
      </sec>
      <sec id="sec-3-3">
        <title>C. Diseases and Adverse Drug Reactions</title>
        <p>
          The DISEASES database [
          <xref ref-type="bibr" rid="ref17">17</xref>
          ] uses the very same approach
to extract disease–gene associations from Medline abstracts. In
this case, we run the tagger with a dictionary based on Disease
Ontology [
          <xref ref-type="bibr" rid="ref18">18</xref>
          ]; this NER approach has been shown to compare
favourably with other methods [
          <xref ref-type="bibr" rid="ref19">19</xref>
          ].
        </p>
        <p>
          When treating diseases with drugs, patents may experience
adverse drug reactions (ADRs). The SIDER database [
          <xref ref-type="bibr" rid="ref20">20</xref>
          ]
extracts information on known ADRs from FDA drug labels
using an NLP system, which uses the tagger Python module to
recognize names from the Unified Medical Language System
(UMLS) Metathesaurus for all terms of the Medical Dictionary
for Regulatory Activities (MedDRA). In a separate study, we
showed that it is also possible to identify ADRs in the clinical
narrative text of electronic health records, which required the
construction of a separate ADR dictionary in Danish [
          <xref ref-type="bibr" rid="ref21">21</xref>
          ]. The
latter achieved 89% precision and 75% recall.
        </p>
      </sec>
      <sec id="sec-3-4">
        <title>D. Organisms and Environments/Habitats</title>
        <p>
          The applications described so far all fall within molecular
biomedicine; however, the tagger has proven equally useful
within biodiversity and ecology. Specifically, we have created
dictionaries of taxa [
          <xref ref-type="bibr" rid="ref1">1</xref>
          ] and environmental descriptors [
          <xref ref-type="bibr" rid="ref22">22</xref>
          ]
from the NCBI Taxonomy [
          <xref ref-type="bibr" rid="ref23">23</xref>
          ] and the Environment Ontology
[
          <xref ref-type="bibr" rid="ref24">24</xref>
          ], respectively. This achieved 83.9% precision and 72.6%
recall for species [
          <xref ref-type="bibr" rid="ref1">1</xref>
          ] and 87.8% precision and 77.0% recall for
environments [
          <xref ref-type="bibr" rid="ref22">22</xref>
          ]. We use these dictionaries with the tagger to
extract structured information on habitats of organisms based
on their textual descriptions in the Encyclopedia of Life [
          <xref ref-type="bibr" rid="ref22">22</xref>
          ].
        </p>
        <p>
          Most recently we participated in the related 2016 BioNLP
shared task on bacterial biotopes, specifically NER of bacteria
and biotopes. To this end we implemented rules to refine the
match boundaries and normalization of bacterial names and
compiled a biotope dictionary by extending the OntoBiotope
habitat ontology with additional synonyms from other relevant
ontologies [
          <xref ref-type="bibr" rid="ref25">25</xref>
          ].
        </p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>IV. CONCLUSIONS</title>
      <p>Despite its simplicity, dictionary-based NER is a powerful
approach that in many cases can give comparable performance
to more advanced methods, if care is taken when constructing
the dictionaries. The dictionary-based approach is particularly
attractive in the biomedical domain due to the many ontologies
that provide excellent starting points constructing dictionaries.</p>
    </sec>
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