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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>Current Development in the Evidence and Conclusion Ontology (ECO)</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>Rebecca Tauber</string-name>
          <email>rebecca.tauber@som.umaryland.edu</email>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>James B. Munro</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Suvarna Nadendla</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Marcus C. Chibucos</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Michelle Giglio</string-name>
          <xref ref-type="aff" rid="aff0">0</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>Institute for Genome Sciences University of Maryland School of Medicine</institution>
          <addr-line>Baltimore, MD</addr-line>
          ,
          <country country="US">USA</country>
        </aff>
      </contrib-group>
      <pub-date>
        <year>2018</year>
      </pub-date>
      <fpage>7</fpage>
      <lpage>10</lpage>
      <abstract>
        <p>- The Evidence &amp; Conclusion Ontology (ECO) has been developed to provide standardized descriptions for types of evidence within the biological domain. Best practices in biocuration require that when a biological assertion is made (e.g. linking a Gene Ontology (GO) term for a molecular function to a protein), the type of evidence supporting it is captured. In recent development efforts, we have been working with other ontology groups to ensure that ECO classes exist for the types of curation they support. These include the Ontology for Microbial Phenotypes and GO. In addition, we continue to support user-level class requests through our GitHub issue tracker. To facilitate the addition and maintenance of new classes, we utilize ROBOT (a command line tool for working with Open Biomedical Ontologies) as part of our standard workflow. ROBOT templates allow us to define classes in a spreadsheet and convert them to Web Ontology Language (OWL) axioms, which can then be merged into ECO. ROBOT is also part of our automated release process. Additionally, we are engaged in ongoing work to map ECO classes to Ontology for Biomedical Investigation classes using logical definitions. ECO is currently in use by dozens of groups engaged in biological curation and the number of ECO users continues to grow. The ontology, in OWL and Open Biomedical Ontology (OBO) formats, and associated resources can be accessed through our GitHub site (https://github.com/evidenceontology/evidenceontology) as well as the ECO web page (http://evidenceontology.org/).</p>
      </abstract>
      <kwd-group>
        <kwd>evidence</kwd>
        <kwd>gene annotation</kwd>
        <kwd>biocuration</kwd>
        <kwd>ontology mapping</kwd>
        <kwd>ontology development</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>I. INTRODUCTION</title>
      <p>
        The Evidence and Conclusion Ontology systematically
describes scientific evidence types in biological research.
Biocurators, researchers, and data managers use evidence to support
conclusions, such as an assertion that a protein has a particular
function. ECO terms, as ontology classes, contain standard
definitions and are networked with relationships. ECO is in use by
numerous groups including large-scale resources such as
UniProt-Gene Ontology Annotation (UniProt-GOA) which has
&gt;365 million evidence-linked GO annotations [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ].
      </p>
      <p>
        II. USER-DRIVEN DEVELOPMENT AND COLLABORATION
One of the core principles of the OBO Foundry is the
“Commitment to Collaboration” [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. Since our last publication in
No
      </p>
      <p>
        This material (the ontology &amp; related resources) is based upon work
supported by the National Science Foundation (NSF) Division of Biological
Infrastructure (DBI) under Award Number 1458400 to MCC.
vember 2016 [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ] and the end of May 2018, over 1200 new
evidence classes have been added to ECO. Most of our new class
requests arrive directly from individual users via GitHub [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ],
but we work closely with various groups, highlighted below.
      </p>
      <sec id="sec-1-1">
        <title>A. Gene Ontology</title>
        <p>
          Since the origin of ECO, we have collaborated closely with
the Gene Ontology (GO). The original set of ECO classes arose
from the evidence codes used in GO annotations [
          <xref ref-type="bibr" rid="ref1">1</xref>
          ], and each
GO evidence code has a corresponding ECO evidence class.
        </p>
        <p>
          Recently, we added new GO-ECO mapped evidence classes
to describe high throughput experiments, beginning with the
Inferred from High Throughput Experiment (HTP) evidence code
[
          <xref ref-type="bibr" rid="ref5">5</xref>
          ], mapped to ‘high throughput evidence used in manual
assertion’ (ECO:0006056).
        </p>
      </sec>
      <sec id="sec-1-2">
        <title>B. Ontology for Microbial Phenotypes</title>
        <p>The Ontology for Microbial Phenotypes (OMP) has
contributed numerous class requests to support their phenotype
annotations. Currently, we have more than 68 classes traceable to
OMP. Many of these terms fall under ‘experimental phenotypic
evidence’ (ECO:0000059).</p>
      </sec>
      <sec id="sec-1-3">
        <title>C. Ontology for Biomedical Investigations</title>
        <p>We have been working with the Ontology for Biomedical
Investigations (OBI) in a different scope than our other
collaborators. Our goal is to harmonize ECO with OBI by adding
logical definitions to ECO classes to describe how the evidence is
generated during an investigation. While increasing the logic
and consistency of the structure of ECO, this effort also benefits
OBI by increasing their breadth of terminology.</p>
        <p>We have added 41 new classes to OBI with 21 more
pending additions. We have 188 ECO classes mapped to logical
definitions created from OBI and GO classes. Our goal is to map
all descendants of ‘experimental evidence’ (ECO:0000006).</p>
      </sec>
    </sec>
    <sec id="sec-2">
      <title>III. ROBOT WORKFLOW</title>
      <p>
        ROBOT is a command-line tool created to work with open
biomedical ontologies [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ], offering a series of commands to
edit, review, and release ontologies. It is written in Java and the
library is also available for programmatic use
(http://mvnrepository.com/artifact/org.obolibrary.robot).
      </p>
      <sec id="sec-2-1">
        <title>A. Template-Generated Modules</title>
        <p>The template command takes a formatted spreadsheet (the
template) and converts each row into one or more ontology
axioms. This command has decreased the time it takes to create
new classes, especially when creating multiple classes at once.
Fig.1 shows a comparison of the standard workflow for creating
classes in Protégé compared to creating classes with ROBOT.</p>
        <p>
          The template command lends itself easily to modular
ontology development, which was first implemented by OBI [
          <xref ref-type="bibr" rid="ref7">7</xref>
          ]. The
first module implemented by ECO is for the ECO-OBI
harmonization project. Previously, the logical axioms were
hardcoded into the eco-edit.owl file, causing inconsistencies due to
human error. We are also adding modules for new class
additions and “evidence used in assertion” classes.
        </p>
      </sec>
      <sec id="sec-2-2">
        <title>B. Import Management</title>
        <p>
          With our commitment to collaboration and ongoing
ECOOBI alignment project, we now import external ontology
classes from OBI and GO into ECO. Both of these, especially GO,
contain many unnecessary classes for our purposes, and
importing the whole ontologies would be counterproductive.
Therefore, we only wish to import a relevant subset of classes for our
mappings using the ROBOT extract command. ROBOT offers
the MIREOT [
          <xref ref-type="bibr" rid="ref8">8</xref>
          ] method of extraction so that our import
modules have the necessary information to use the external classes.
        </p>
        <p>By including extract as part of our release cycle, we
regularly and automatically update the imported classes. Often,
discrepancies are found between ontologies due to out-of-date
imports, so this method of import management may be of use in
other biomedical ontologies.</p>
      </sec>
      <sec id="sec-2-3">
        <title>C. Automating the Release Cycle</title>
        <p>
          In March 2018, we completed our first release using only
ROBOT. Previously, a combination of tools (ROBOT, Protégé,
OWLTools [
          <xref ref-type="bibr" rid="ref9">9</xref>
          ]) were used for different steps of the release. The
release process also involved some manual editing to add
version IRIs and timestamps. Now, the release process is entirely
automated by various ROBOT commands in the Makefile.
        </p>
        <p>Many biomedical ontologies already implement some form
of a release workflow with a Makefile. Often, these workflows
involve some degree of manual editing and review. ROBOT
provides the framework to eliminate most of the need for this,
and because it is a command line tool, it is straightforward to
add to existing Makefiles.</p>
      </sec>
    </sec>
    <sec id="sec-3">
      <title>IV. ONTOLOGY REVIEW</title>
      <sec id="sec-3-1">
        <title>A. Class Annotations</title>
        <p>Annotation axioms are those that describe a class to our
users, such as the label, definition, and so on. These are important
for our users to understand what the class is intended for and
how to appropriately use it.</p>
        <p>As of our last publication (November 2016), all classes had
English labels, but almost 300 were missing definitions. In
November of 2017, definitions were added for 99% of all classes.
Going forward, we require a definition for all new term
requests. We have also begun to annotate classes with their source
using the ‘ontology term requester’ property. Having this level
of provenance allows us to return to the requester if any changes
need to be made, or if other issues arise.</p>
      </sec>
      <sec id="sec-3-2">
        <title>B. Logical Consistency</title>
        <p>
          ECO has been in development for well over 10 years [
          <xref ref-type="bibr" rid="ref4">4</xref>
          ],
but there has not always been a standardized pattern for
categorizing types of evidence. We have been reviewing classes, node
by node, to ensure consistent categorization based on type of
evidence rather than, for example, types of assays.
        </p>
        <p>The goal of this review is to make it easier for users to find
the correct class, and to not be confused by similar and
ambiguous classes. It also sets a standardized pattern for adding new
evidence classes in the future.</p>
      </sec>
    </sec>
    <sec id="sec-4">
      <title>V. FUTURE WORK</title>
      <p>
        We will continue to collaborate closely with GO, OMP,
OBI, and other groups, as well as monitor GitHub requests [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
Finally, we will continue our internal projects to increase logic
between ECO classes by adding logical definitions, complete
the OBI mappings, and review the categorization of evidence.
      </p>
    </sec>
    <sec id="sec-5">
      <title>ACKNOWLEDGMENT</title>
      <p>The ECO working group thanks our collaborators and our
entire user-base for continuing to help us grow.</p>
    </sec>
  </body>
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