# Presentation: 860021

## The Mouse / Human

**The Mouse / Human**
**Anatomy Project**
**caBIG-VCDE-14-02-02**

## Slide 2

## Anatomical Dictionary for Mouse Development

**Anatomical Dictionary for Mouse Development**

**Edinburgh collaborators:**** ****Jonathan Bard, Matthew Kaufman, Duncan Davidson, Richard Baldock**

## Anatomical Dictionary is structured 

**hierarchically**

## Anatomical Dictionary for the Adult Mouse

- multiple hierarchies
-     •  physiological systems
-     •  space / histology
-     •  sampling

- Directed
- Acyclic Graph
-     2405 nodes
-     2922 edges

## Anatomical Dictionary for the Adult Mouse

- multiple hierarchies
-     •  physiological systems
-     •  space / histology
-     •  sampling

## Combine terms from orthogonal vocabularies

**Combine terms from orthogonal vocabularies**
**  ****takes advantage of existing ontologies **
**   ****(terms + relationships)**
**   ****more robust and complete representation**
**   ****normalization and integration**

- See also:
- OBO (Open Biological Ontologies)
- http://obo.sourceforge.net/

## Anatomical Ontologies

- Standardized Representation and Integration of Biomedical Data

## Mouse / Human Anatomy Project

**Mouse / Human Anatomy Project**

**Mapping and harmonization of human and mouse anatomical ontologies**
**       • ****closer integration of human and mouse cancer data**
**       • ****facilitates the use of the mouse as model for cancer research**
**      **
**       • ****accelerates the translation of basic research discoveries **
**         ****into new clinical therapies **

## Mouse / Human Anatomy Project

**Mouse / Human Anatomy Project**

** **

** ****Preliminary mapping using simple lexical and manual methods**
** ****Import and visualize human (NT) and mouse (MA) anatomies into    ****	****various ontology editing tools (Protégé, DAG-Edit, COBrA)**
** ****Evaluate ontology editing tools (utility for comparison and mapping)**
** ****In-depth comparative analysis of both ontologies**
** ****Generate draft mapping of existing ontologies**
** ****Develop roadmap for extension and harmonization of existing ontologies**
** ****Execute roadmap and provide mappings**
** ****Develop procedures for update and maintenance of MA, including mouse ****	****human mappings, in NCI Thesaurus**

##  Preliminary mapping using simple lexical and manual methods

- <date/time>

** ****Preliminary mapping using simple lexical and manual methods**

**Comparison of Adult Mouse Anatomy and NCI Thesaurus anatomy terms to determine the feasibility of the proposed mapping**
**Provide an estimate of the number of concepts in the ontologies that could be mapped directly**
**Utilized several different ‘lexical’ (automated), ‘manual’ and combined approaches to match terms in the two ontologies**

**Notes:**
This phase of the project involved comparison of Adult Mouse Anatomy and NCI Thesaurus anatomy terms in order to determine the feasibility of the proposed mapping between concepts.

The primary goal was to provide an estimate of the number of concepts in the existing ontologies that could be mapped directly.

Several different ‘lexical’ (automated), ‘manual’ and combined approaches were used to match terms in the two anatomy ontologies.

##  Preliminary mapping (continued)

- <date/time>

** ****Preliminary mapping (continued)**

**‘****Lexical’ comparisons by the NCI**
**Independent analysis at the NLM*;   evaluated terms both ‘lexically’ and in terms of structural similarity**
**‘****Manual’ alignment approach involving  side-by-side comparison using web-based ontology browsers**

*** Collaborator: Olivier Bodenreider**

**Notes:**
Independent’ lexical’ comparisons were done 
by the group at the NCI and 
by Olivier Bodenreider and Songmao Zhang from the National Library of Medicine (NLM).

The NLM method evaluated terms both lexically and in terms of structural similarity, comparing shared relations to other equivalent concepts

The ‘manual’ alignment approach involved identification and side-by-side comparison of terms within the two anatomy ontologies using web-based ontology browsers.

- <date/time>

** **

**Automated methods**
**Manual comparison**
**using web-based **
**browsers**

**Advantages**

**Disadvantages**

**Fast; low cost; consistent**
**Sensitive at finding matches,**
**especially when used with**
**resources with extensive **
**synonomy**
**Low false-positive rate in**
**identifying matching terms**

**High false-positive rate**
**in identifying matching **
**terms**
**Slow; labor-intensive**
**Many matches “missed”**
**in preliminary analysis **

**=>****	****Combine automated and manual methods**
**	**
**	****Analyze output from automated methods manually**

- e.g. “cerebellum lobule1” [synonym: lingula] in mouse lexically matched to “lingula of the lung” in human

**Notes:**
Independent’ lexical’ comparisons were done 
by the group at the NCI and 
by Olivier Bodenreider and Songmao Zhang from the National Library of Medicine (NLM).

The NLM method evaluated terms both lexically and in terms of structural similarity, comparing shared relations to other equivalent concepts

The ‘manual’ alignment approach involved identification and side-by-side comparison of terms within the two anatomy ontologies using web-based ontology browsers.

##  Results of preliminary mapping

- <date/time>

** **Results of preliminary mapping

**Notes:**
Approximately 830 matches were identified between the existing adult mouse and NCI Thesaurus (human) anatomies.  

Valid potential mappings were identified between ~35% of the current adult mouse anatomy terms and ~35% of the pertinent NCI Thesaurus anatomy subset terms (see below).

A majority of these matches were identified by each of the approaches used.

As part of the ‘manual’ analysis, it was determined that many of the NCI Thesaurus anatomy terms represent concepts that are outside of the scope of the Adult Mouse Anatomy.

Consequently, an NCI Thesaurus anatomy subset was created that excludes cell types, cell parts and other microanatomy terms, as well as embryonic structures.

## Non-matching terms 

- <date/time>

**Non-matching terms**

**  ****high-level conceptual terms**
**  ****low-level terms, representing very detailed anatomical concepts**
**  ****terms for individually named arteries, veins, or muscles**
**  ****terms representing species-specific anatomical concepts**

**Notes:**
Independent’ lexical’ comparisons were done 
by the group at the NCI and 
by Olivier Bodenreider and Songmao Zhang from the National Library of Medicine (NLM).

The NLM method evaluated terms both lexically and in terms of structural similarity, comparing shared relations to other equivalent concepts

The ‘manual’ alignment approach involved identification and side-by-side comparison of terms within the two anatomy ontologies using web-based ontology browsers.

## Equivalent terms but match not supported by Structural Evidence

- <date/time>

**Equivalent terms but match not supported by Structural Evidence**
**	****	****-> Opportunity for Harmonization**

**MA**

**NCI**

**Notes:**
Independent’ lexical’ comparisons were done 
by the group at the NCI and 
by Olivier Bodenreider and Songmao Zhang from the National Library of Medicine (NLM).

The NLM method evaluated terms both lexically and in terms of structural similarity, comparing shared relations to other equivalent concepts

The ‘manual’ alignment approach involved identification and side-by-side comparison of terms within the two anatomy ontologies using web-based ontology browsers.

## MGI browser display

**MGI browser display**

**NCI**
**browser display**

**Notes:**
Results of both the automated matching approaches were also examined ‘manually’, again using web-based ontology browsers and other anatomy reference sources, in order to verify each of the alignments.

A more comprehensive and thorough comparison and mapping of the anatomies will require more sophisticated tools.

## Import and visualize anatomies using various ontology editing tools

**Ontology-editing tools****: DAG-Edit, Protégé-OWL, and COBrA**
**Ontologies have different data structures and were built using different ontology editing tools**
**For comparison and mapping purposes, the two ontologies must be imported into the same tools**

**Notes:**
The ontology editing tools DAG-Edit, Protege-OWL and COBrA will be evaluated for this purpose; each has different input format requirements.

The Adult Mouse Anatomy and NCI Thesaurus have different underlying data structures, and have been built using different ontology editing tools with specific output options.

Following is a short summary of the steps taken to convert the two ontologies to the same formats in order to import them into DAG-Edit, Protege-OWL and COBrA.

## Adult Mouse Anatomy

- (DAG-Edit)

- GO, OBO

- GO

- OWL

- DAG-Edit

- COBrA

- Protégé-OWL

- OBO

- NCI

**Notes:**
The Adult Mouse Anatomy was built using DAG-Edit.  Consequently the MA can be read and saved by DAG-Edit, and exported in GO flat file and OBO formats.

The MA has also been loaded into COBrA which accepts ontologies as GO flat files.  

The Protege-OWL application requires files in specific formats, none of which could be generated by either DAG-Edit or COBrA.  

In order to address this, we provided an MA file in OBO format to the NCI group, which converted the MA to an appropriate OWL format.  This file has been successfully imported into Protege-OWL

## NCI Thesaurus

- anatomy subset

- OWL

- Protégé-OWL

- OBO

- DAG-Edit

- GO

- COBrA

**Notes:**
The NCI Thesaurus was created using Terminology Development Environment from Apelon, which exports data in Ontylog XML and OWL format, neither of which could be read by DAG-Edit or COBrA.

NCI provided an NCI Thesaurus anatomy subset file in OBO format, which could be imported by DAG-Edit.  

DAG-Edit was used to convert the data to a GO flat file, which was then read by COBrA.

NCI also created files with the NCI Thesaurus anatomy domain subset in OWL format, which could be used by Protege-OWL

In both OBO and OWL files, NCI Thesaurus ‘has_location’ relationships were converted to ‘part-of’ relationships.

## Adult Mouse 

- Adult Mouse
- Anatomy

- NCI Thesaurus
- anatomy subset

- Protégé-
- OWL

**Notes:**
The MA and NCI Thesaurus files can also be loaded simultaneously into Protege-OWL.

Since Protege-OWL display only subclass relationships in a hierarchical view; ‘part-of’ relationships are displayed as properties.  To deal with this, in the OWL formatted files, ‘part-of’ relationship information has been preserved as properties, but converted to subclass relations.

The NCI group also created an object annotation property “maps_to”nci” defined in the MA OWL file, as an example of how manual mapping could be done using Protege-OWL.

## Adult Mouse 

- Adult Mouse
- Anatomy

- NCI Thesaurus
- anatomy subset

- COBrA

**Notes:**
It is also possible to load the MA and NCI Thesaurus files simultaneously using COBrA, and to create an independent ‘mapping’ file which can be exported in GO flat file format.

This tool has been previously used by the Standards and Ontologies for Functional Genomics (SOFG) anatomy working group to create mappings between a short list of anatomical terms (SAEL) and terms in other anatomy ontologies, including the MA.

## Slide 23

## Mouse / Human Anatomy Project

**Mouse / Human Anatomy Project**

** **

** ****Preliminary mapping using simple lexical and manual methods**
** ****Import and visualize human (NT) and mouse (MA) anatomies into    ****	****various ontology editing tools (Protégé, DAG-Edit, COBrA)**
** ****Evaluate ontology editing tools (utility for comparison and mapping)**
** ****In-depth comparative analysis of both ontologies**
** ****Generate draft mapping of existing ontologies**
** ****Develop roadmap for extension and harmonization of existing ontologies**
** ****Execute roadmap and provide mappings**
** ****Develop procedures for update and maintenance of MA, including mouse ****	****human mappings, in NCI Thesaurus**

## Mouse/Human Anatomy Project

**Mouse/Human Anatomy Project**
**caBIG-VCDE-14-02-02**

** **

**   **
**       **

**MGI project team **
**Terry Hayamizu**
**Jim Kadin**
**Martin Ringwald**

**NCI project team**
**Sherri De Coronado**
**Gilberto Fragoso**
**Nick Sioutos**
**Wen-Ling Shaiu**
**Frank Hartel**

**Booz Allen Hamilton**
**Michael Keller**
**Brian Davis**
**NCI VCDE-WS Lead**
**George Komatsoulis**