=Paper=
{{Paper
|id=Vol-2285/ICBO_2018_paper_8
|storemode=property
|title=Using Equivalence Axioms from the Mammalian Phenotype Ontology to Facilitate Phenotype and Expression Comparisons
|pdfUrl=https://ceur-ws.org/Vol-2285/ICBO_2018_paper_8.pdf
|volume=Vol-2285
|authors=Susan M. Bello,Terry F. Hayamizu,Cynthia L. Smith,Martin Ringwald,The MGI Software Group
|dblpUrl=https://dblp.org/rec/conf/icbo/BelloHSR18
}}
==Using Equivalence Axioms from the Mammalian Phenotype Ontology to Facilitate Phenotype and Expression Comparisons==
https://ceur-ws.org/Vol-2285/ICBO_2018_paper_8.pdf
Proceedings of the 9th International Conference on Biological Ontology (ICBO 2018), Corvallis, Oregon, USA 1
Using Equivalence Axioms from the Mammalian
Phenotype Ontology to Facilitate Phenotype and
Expression Comparisons
Susan M Bello, Terry F. Hayamizu, Cynthia L Smith, Martin Ringwald and The MGI Software Team
Mouse Genome Informatics
The Jackson Laboratory
Bar Harbor, USA
Abstract—Comparisons of expression and phenotypes EMAPA terms. For example the MP term ‘abnormal heart
associated with a gene can enhance the understanding of gene morphology’ has an equivalence axiom containing the
function. These comparisons can be difficult to make due to UBERON term ‘heart’ (UBERON:0000948) which is mapped
differences in the ontologies used to annotate the data. Using to EMAPA:16105. While this is a relatively simple example,
equivalence axioms in the Mammalian Phenotype (MP) ontology
these mappings also allow for MP terms to be associated with
and mappings between Uber-anatomy (UBERON) and mouse
developmental anatomy (EMAPA) terms MGI has implemented more than one anatomy term. For example the MP term
gene expression + phenotype comparison matrices for genes in ‘tracheoesophageal fistula’ (MP:0003321) maps to both
MGI. These matrices used the shared anatomical concepts esophagus (EMAPA:16833) and trachea (EMAPA:16853) as
between expression and phenotype ontologies to facilitate the equivalence axiom includes the UBERON terms for both
comparisons between annotations in these two domains. anatomical structures. This approach also takes advantage of
the hierarchical structures of the ontologies. Thus annotations
Keywords—phenotype; expression; mouse; to the MP term ‘abnormal semilunar valve morphology’ are
linked to the anatomical term heart via the relation of the
I. INTRODUCTION EMAPA term ‘semilunar valve’ (EMAPA:35760) to the
Visualizing the correlation between gene expression patterns EMAPA term ‘heart’ (EMAPA:16105).
and phenotypes associated with mutations in the same gene
enhances the ability of researchers to investigate gene function
and identify potential candidate genes for disease. At MGI
phenotype annotations use the Mammalian Phenotype
ontology (MP) [1] and expression annotations use the
developmental mouse anatomy ontology (EMAPA) [2] that
incorporates both anatomical structures and the developmental
stages when these structures are present. To facilitate
comparisons between phenotype and expression, MGI
(www.informatics.jax.org) has implemented comparison
matrices (Fig. 1) displaying developmental and adult gene
expression and genotype specific phenotype annotations.
Using the equivalence axioms in the MP to determine the
relationship between MP and EMAPA terms, these matrices
display the expression and phenotype data for a given gene in
the common anatomical framework of the hierarchically
structured EMAPA ontology.
II. USE OF EQUIVALENCE AXIOMS Fig. 1. Gene expression + phenotype comparison matrix for Fgf9
Over the years, the MP and EMAPA curators at MGI have There are currently 6149 MP terms containing UBERON
worked with UBERON in establishing anatomical cross- terms in the equivalence axiom, out of a total of 9086 MP
references to enable the comparative analysis of expression terms with equivalence axioms (Table 1). Using this approach,
and phenotype data across species. The MP to EMAPA annotations to 5067 MP terms can be mapped to the 1369
mappings described here rely on the usage of the Uber- relevant mouse anatomical structure. There are two primary
Anatomy ontology (UBERON) [3] terms in the equivalence reasons why an MP term with a logical definition may not
axioms of MP terms and the mapping of UBERON terms to
MGD is supported by program project grant HG000330 from the
National Human Genome Research Institute (NHGRI). GXD is supported by
grant HD062499 from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development (NICHD).
ICBO 2018 August 7-10, 2018 1
Proceedings of the 9th International Conference on Biological Ontology (ICBO 2018), Corvallis, Oregon, USA 2
map to a relevant anatomical term. Either (1) the UBERON This reflects the range and variability of phenotypes that many
file lacks the EMAPA mapping or (2) the MP equivalence be displayed in a single tissue including both morphological
axiom uses a term from a different ontology, typically the and physiological phenotypes.
Gene Ontology (GO) or Cell Ontology (CL). Many of the GO
terms used incorporate anatomy into the GO term. MP terms III. CONCLUSION
using GO terms are primarily anatomy specific development
or physiology MP terms, such as ‘delayed caudal neuropore Overall the use of UBERON terms in equivalence axioms may
closure’ (MP:0012709) or ‘arrest of tooth development’ be used to significantly enhance the ability of users to
(MP:0000118). There are currently 1893 MP terms that use at transverse between disparate types of data that share a
least one GO term in their equivalence axiom and 1295 MP common anatomical reference point. The new MGI gene
terms that use at least on CL term. Explicit incorporation of expression + phenotype comparison matrices and tissue and
the anatomy terms related to these MP terms, when phenotype cross-links in browsers represent a practical
appropriate, would enhance the mapping. Not all MP terms application of equivalence axioms in the MP and mappings
refer to specific anatomical structures so there may always be from EMAPA to UBERON. These tools increase the ability of
some MP terms that do not map to EMAPA terms. For MP MGI’s users fully utilize the data in MGI.
terms using GO in the axioms, this will require incorporating
the GO equivalence axioms into the MGI mapping process to
incorporate the GO axiom that already include a reference to a ACKNOWLEDGMENT
relevant anatomical term, or the addition of anatomy axioms We thank the MGI team and UBERON developers for all their
to the appropriate MP terms when these don’t exist in the GO. hard work. The MGI Software Group includes; Richard M.
The mapping of MP terms to EMAPA terms also supports Baldarelli, Jonathan S. Beal, Olin Blodgett, Jeffrey W.
links directly from MP terms in the Mammalian Phenotype Campbell, Lori E. Corbani, Sharon C. Giannatto, Peter Frost,
Browser to the relevant EMAPA term in the MGI Anatomy David B. Miers, James A. Kadin, Joel E. Richardson.
Browser. This allows a user to easily traverse from a
phenotype term to genes expressed in the relevant tissues and
from an anatomy term to mice with phenotypes in those REFERENCES
tissues. As mentioned above, most MP terms link to a single [1] C. L. Smith and J. T. Eppig, “The mammalian phenotype ontology:
EMAPA term, with a few mapping to 2 or at most 3 enabling robust annotation and comparative analysis,” Wiley
Interdiscip. Rev. Syst. Biol. Med., vol. 1, no. 3, pp. 390–399, Nov.
UBERON terms. However, for EMAPA terms with at least 2009.
one mapped MP term, the EMAPA term may map to multiple [2] T. F. Hayamizu, R. A. Baldock, and M. Ringwald, “Mouse anatomy
MP terms. The 6149 MP terms with UBERON in the logical ontologies: enhancements and tools for exploring and integrating
definition use a total of just 1866 UBERON terms. Of these biomedical data,” Mamm. Genome, vol. 26, no. 9–10, pp. 422–430,
Oct. 2015.
about half are used in in a single equivalence axiom, with a [3] C. J. Mungall, C. Torniai, G. V Gkoutos, S. E. Lewis, and M. A.
further 500+ used in 2 or 3 axioms. However, almost 400 Haendel, “Uberon, an integrative multi-species anatomy ontology,”
UBERON terms are used in 4 or more MP term axiom with Genome Biol., vol. 13, no. 1, p. R5, 2012.
almost half of these being used in 6 or more axioms. For
example the EMAPA term parathyroid gland
TABLE I. SUMMARY OF MAPPING OUTCOMES
(EMAPA:32812) is associated with 12 MP terms (Fig. 2).
Count of terms
MP terms with axioms 9086
MP terms with UBERON in
axioms 6149
Total number of UBERON terms
used in the MP 1866
Total number of MP terms that
map to EMAPA 5067
MP terms with GO in axioms 1893
MP terms with CL in axioms 1295
Total number of EMAPA terms
that map to MP terms 1369
Fig. 2. Display of MP terms mapped to the EMAPA term parathyroid gland
in the MP browser.
ICBO 2018 August 7-10, 2018 2