# Presentation: 181779

## Slide 1

## Who is NCI Center for Bioinformatics?
Part of US Government National Institutes of Health (NIH)
The Center for Bioinformatics is the National Cancer Institute’s strategic and tactical arm for research information management 
We collaborate with both intramural and extramural groups
Mission to integrate and harmonize disparate research data
Production, service-oriented data management

- Part of US Government National Institutes of Health (NIH)
- The Center for Bioinformatics is the National Cancer Institute’s strategic and tactical arm for research information management
- We collaborate with both intramural and extramural groups
- Mission to integrate and harmonize disparate research data
- Production, service-oriented data management

## Enable investigators and research teams nationwide, or worldwide, to combine and leverage their findings and expertise in order to meet this goal

**Our advantage: **A homogeneous community of
- interest with a common focus, willing to adopt
- standards and recommended best practices

**NCI Goal: **Relieve pain, suffering and
- death due to cancer by the year 2015

## ability of a system to access and use 
the parts or equipment 
of another system

- ability of a system to access and use
- the parts or equipment
- of another system

- Semanticinteroperability

- Syntacticinteroperability

**Critical Success Factor: Semantic Interoperability**

- Emphasis on Machine Interoperability
- Over a cancer bioinformatics Grid

**Notes:**
Our terms are Interoperability and Innovation.  Lets start with some definitions.

Interoperability is a relatively new concept, centered on the idea that one system can use parts of another.  

If you focus on computer interoperability, the IEEE definition includes two concepts.

Functional interoperability – the ability to exchange information – and semantic interoperability – the ability to use the information that has been exchanged.

As an aside, standards are frequently thought of as focusing primarily on functional interoperability, whereas the critical sine qua non for health care is semantic interoperability -  if you don’t know exactly what the information you received means, having received it is useless, or worse, maybe even dangerous!

## Bruce BargmeyerWe have come to join ...

- Terminology& Metadata
- ..... &
- Information Models

**Notes:**
Dearly Beloved, we are gathered here in the presence of these witnesses, to join TC 37 and WG 2. ... This is an honorable institution and is therefore not to be entered into lightly or inadvisably, but reverently, and discreetly.

## An XMDR approach to Harmonization of Terminolgy, Information Models and Metadata

_**Achieved through**_**: **
** ****3 layers of semantics**
** ****Infrastructure and compatibility guidelines**
** ****Model Driven Architecture**
** ****Open Standards**
** ****Tools**
** ****Community Governance**

**The NCI’s**
**Cancer Data Standards Repository (caDSR)**

## caBIG Compatibility Guidelines

**SYNTACTIC**

**caBIG Compatibility Guidelines**

## MDA Approach

- Analyze the problem space and develop the artifacts for each scenario
- Use Cases
- Use Unified Modeling Language (UML) to standardize model representations and artifacts. Design the system by developing artifacts based on the use cases
- Class Diagram – Information Model
- Sequence Diagram – Temporal Behavior
- Use meta-model tools to generate the code

## Limitations of MDA

- Limited expressivity for semantics
- No facility for runtime semantic metadata management

## caCORE

- MDA plus a whole lot more!
- Open software
- Open development
- ISO/IEC 11179

## caCORE Tools

- _NCI Terminology Browser_ to search and Navigate NCI Thesaurus and other terminologies curated by EVS
- _caDSR _– Repository and administration Tool
- _CDE Browser_ to Search for, View and Download
- _Side-by-Side_ Compare
- _Form Builder_ to Create user specified collections of CDEs
- _- Sentinel Tool_ to Generate end user ‘Alerts’ triggered by metadata changes
- _- caCORE SDK_ is a toolkit to create “semantically integrated” applications -- all exposed API elements have runtime accessible metadata that defines the meaning of the elements using controlled vocabualries.

**Access, Develop, Manage, Consume**

**Notes:**
Guest Form Builder
Create form from existing content and download it
Form Builder Only User (Adopter)
Create form from existing content and download it
Revising Browser Classification Schemes to support Forms 

Ways to track usage of data elements (you didn’t create)
Designating - “Used by”
Ascribe additional attributes 
Alternate Names
Reference Document
Easier to track or search DEs that you are using
Classifying - “Classification Schemes”
Using on a Form - “Used on a Forms”

## caCORE ToolkitSDK Components

**UML Modeling Tool **(any with XMI export)
**Semantic Connector **(concept binding utility)
**UML Loader **(model registration in caDSR)
**Codegen **(middleware code generator)
**Security Adaptor **(Common Security Module)

- caCORE SDK Generates a
- caBIG Silver-Compliant System

## caCORE Semantic Components

- 3 Layers of Semantics

## Application Objects

**Application Objects**
**(UML)**

## What do all those data classes and attributes actually mean, anyway?
Data descriptors or “semantic metadata” required
Computable, commonly structured, reusable units of metadata are “Common Data Elements” or CDEs. 
NCI uses the ISO/IEC 11179 standard for metadata structure and registration
Semantics drawn from Enterprise Vocabulary Service resources

- Data descriptors or “semantic metadata” required
- Computable, commonly structured, reusable units of metadata are “Common Data Elements” or CDEs.
- NCI uses the ISO/IEC 11179 standard for metadata structure and registration
- Semantics drawn from Enterprise Vocabulary Service resources

- Common Data Elements (11179)

## Description Logic

- Preferred Name

- Synonyms

- Definition

- Relationships

- Concept Code

**Enterprise Vocabulary**

- _Description Logic_

## Description Logic

- Relationships

**Enterprise Vocabulary**

- _Description Logic_

** *****“*****Carcinoma*****”****** ******Disease_Associated_with_Disease****** “*****Lytic Bone Lesions*****” ***
***“*****TP53*****”****** ******Gene_associated_with_Disease****** ******“*****Breast Carcinoma***”*
***Semantic Types******: ***
***Gene_associated_with_Disease****** *****C43780** Molecular abnormalities in the gene may be associated with the manifestation of disease. The role is used to assert a link between gene and disease and is considered to have clinical relevance. The domain and range kind for this role are **Gene_Kind** and **Findings_and_Disorders_Kind**, respectively.

## How? Cancer Ontologic Research Environment (caCORE) 

-  MDA - UML domain models  (Blue)
- Model Driven Architecture (MDA)
- Simplify application development
- Embed semantic integration – annotate model with cancer Concepts

-  caDSR IEC/ISO 11179 Metadata Registry** (Gold)**
- 	- Common Data Elements
- 	- provides the semantics for data elements
- - NCI expanded 11179 register models: UML, forms, protocols, analytic services, analytic tools, data services

-  EVS Shared Terminology **(Red)**
- 	- Enterprise Vocabulary Services (EVS)
- 	- Standard terms and definitions
- 	- Cancer specific ontology

## Created a UML  caDSR Mapping

- ValueDoman:Enumeration

## caCORE SDK - Common Methodology Workflow

## caCORE

**XMDR**

## Computable Interoperability

**Agent**

- name

- nSCNumber

- FDAIndID

- CTEPName

- IUPACName

**Drug**

- id

- NDCCode

- approver

- approvalDate

- fdaCode

**My model**

**Your model**

## Tying it all together: The caCORE semantic management framework

**	****	****Desc. Logic**
_**CDEs**__**	**_**	**_**Concept Codes**_
**2223333****	****C1708**
**2223866****	****C1708:C41243**
**2223869****	****C1708:C25393**
**2223870****	****C1708:C25683**
**2223871****	****C1708:C42614**

- Enterprise Vocabulary

- Common Data Elements

- Application Objects

## caCORE Infrastructure

- user
- application

**Notes:**
Starting on the left side of the slide, this represents the genesis of data elements arising from clinical trials and scientific research, and their transformation into descriptive metadata represented in the caDSR.  APIs between the caDSR and EVS provide access to standard vocabularies and ontologies curated by external standards development groups such as the National Library of Medicine, LOINC and MGED.  These vocabularies are used in naming and defining the metadata for the data elements.   

caBIO data objects provide a roadmap of the biology of cancer, represented in UML.  The UML is transformed into ISO 11179 metadata, including data elements.  caBIO Model Driven Architecture (MDA), allows users to easily generate public APIs to access the data model. 

Today we will delve into the caDSR in more detail.

## Kevin KeckXMDR 11179 Edition 3Concepts and Relationships

- Kevin KeckXMDR 11179 Edition 3Concepts and Relationships

## *Concept Use and Integrationwith 11179 Part 3, Edition 2

_**Object Class**_
- Chemopreventive
**Agent**

_**Property**_
**NSCNumber**

_**Conceptual Domain**_
**Agent**

_**Data Element Concept**_
**Chemopreventive Agent **
**NSC Number**

_**Data Element**_
**Chemopreventive Agent Name**

_**Value Domain**_
**NSC Code**

_**Context**_
**caCORE**

_**Representation**_
**Code**

_**Classification Schemes**_
**caDSRTraining**

_**Valid Values**_
**Cyclooxygenase Inhibitor**
**Doxercalciferol**
**Eflornithine**
**...**
**Ursodiol**

- *Concept Use and Integrationwith 11179 Part 3, Edition 2

**Notes:**
We talked about a Data Element being formed by a concept taking on a specific representation.  In ISO 11179 terms this translates to the combination of a specific Data Element Concept and a specific Value Domain, you see this denoted in the middle of this chart by the yellow box outlined in red.  caDSR administered items are backed by the use of externally defined terminologies and controlled vocabularies.  With UMLS as a framework NCI has developed vocabulary services that are accessed via API – application to application interfaces – to provide touch points during creation of content, resulting in administered components that are bound to immutable concept codes.  These touchpoints, denoted by the EVS logos, are currently implemented at the Object Class, Property, Representation Term, Value Domain and Valid Value levels of the metadata model.   

## Concept Use and Integration

_**Data Element Concept**_
**Chemopreventive Agent Namet**

- Concept Use and Integration

*** based on  ISO/IEC 11179 Part 3 Metamodel**

**UML attribute**

**UML datatype**
**or Enumeration**

_**Valid Values**_
**Anethole Trithione C246**
**Cyclooxygenase Inhibitor C1323**
**Ginger C2691  **
**Green Tea C2694 **
**Iloprost C48397**
**...**
**Ursodiol C1818**

_**Object Class**_
**Chemopreventive Agent**
**C1892**

_**Property**_
**Name**
**C42614**

_**Conceptual Domain**_
**Drugs and Chemicals**
**C1913**

_**Value Domain**_
**Drug Name Text**

_**Representation**_
**Name**
**C42614**

-         Data Element**: **Chemopreventive Agent Drug Name
-    caDSR 11179 ID: 2008765v1.0

- Semantic Signature: C1913.C1892.C42614.C42614.C246.C1323....
-                                         (ConceptualDomain.ObjectClass.Property.Repsentation.Values)

_**Classification Schemes**_
**caDSR Training**

**UML Model/Package**

**UML Class**

**Everything in Red in the caDSR is directly **
**Associated with a CONCEPT**

**Notes:**
The “EVS” icon is meant to illustrate where NCI has linked concepts from controlled vocabularies to NCI Metadata

## Where have we been? Where are we now?...& where are we planning to go?

**Where have we been? Where are we now?...& where are we planning to go?**

- System manuals

- Data dictionaries

- 11179 E1

- 11179 E3

**Terminologies, ontologies, etc.**

- XML & related standards

**Semantic grids**** **

- 11179 E2

- Semantics management for data

**Semantics services (SSOA)**

- Complex semantics management

- Data engineering/XML Data

- Data Standards/Data Administration

**XMDR Project**

- caGrid

- EVS/caDSR

- caDSR

- caCORE

- EVS

## Acknowledgements

**NCICB**
- Peter Covitz
- Denise Warzel
- George Komatsoulis
- Frank Hartel
- Sherri De Coronado
- Gilberto Fragoso
**Oracle**
- Steve Alred
- Prerna Aggarwal
- Christophe Ludet
- Shaji Kakkodi
- Jane Jiang
- Anwar Anhad
- Jennifer Dong
**NCICB URL ****http://ncicb.nci.nih.gov/infrastructure/cacore_overview**

**ScenPro**
- Bill McCurry
- Tom Phillips
- Robert Harding
- Jennifer Brush
- Larry Hebel
- Smita Hastak
**ISO**
- ISO/IEC 11179 Information Technology - Metadata Registries (MDR) Parts 1-6
- 2002(E) +

**  ****Semantic Bits**
-      - Ram Chilukuri
-  **MSD**
-       - Nicole Thomas
**XMDR**
- Bruce Bargmeyer (LBNL)
- Kevin Keck (LBNL)
- Frank Olken (LBNL)
- John McCarthy (LBNL)
- Karlo Berket (LBNL)
- Harold Solbrig (Mayo)
- Gayle Hodge (USGS)
- Denise Warzel (NCI)
- Larry Fitzwater (EPA)
- Nancy Lawler (DOD)
- Sam Chance  (DOD**)**
**     **