1. Cancer Bioinformatics Infrastructure Objects (caBIO)
Architecting the Future of Genomics
Himanso Sahni & Scott Gustafson
December 7, 2001
Science Applications International Corporation (SAIC)

2. caBIO Team
caBIO was developed as “open source” technology by the National Cancer Institute Center for Bioinformatics (NCICB)
Software developers teamed with scientists from the NCICB Cancer Genome Anatomy Project (CGAP) to define caBIO requirements and use cases, and model the genomics domain

3. Purpose
“To provide an overview of caBIO, its current role in genomics, and future transitions towards intelligent genomics”

4. The Genomic Past Little or no data integration Lack of standards
Little or no software code re-use
Duplication of efforts
Duplication of data
Lack of common vocabulary
Maintenance nightmares

5. caBIO ! The Genomic Challenge INTELLIGENCE! Data Integration Standards
Ease of Maintenance
caBIO !
Normalized Data
Code Re-Use
Common Vocabulary
Increased Productivity
INTELLIGENCE!

6. caBIO Agenda caBIO Overview Development Process Architecture
Data Sources
Usage
Benefits
Future

7. caBIO Overview caBIO is a standards based set of genomic components
caBIO objects simulate the behavior of actual genomic components such as genes, chromosomes, sequences, libraries, clones, ontologies, etc.
caBIO objects provide access to a variety of genomic data sources including GenBank, Unigene, LocusLink, Homologene, Ensemble, GoldenPath, and NCICB’s CGAP (Cancer Genome Anatomy Project) data repositories
caBIO is “open source”

8. Development Process Iterative Approach
An iterative software design and development approach leveraging concepts from RUP and XP was used
Initial Vision and High Level Analysis form the overall goals of the project
Iterative functional design and implementation processes allows for rapid and segmented development of the application

9. Development Process High Level Use Cases
Initial high level Use Cases were developed for gene components
Additional high level Use Cases were added as additional functional areas are mapped (e.g. pathways, therapies, microarray objects, mouse models)
Detailed Use Cases are derived from working with domain experts in requirements gathering.

10. Development Process Detailed Use Cases
Detailed Use Cases were derived from teaming with domain experts during requirements gathering
Detailed Use Cases include
Characteristic Information
Main Success Scenario
Extensions
Related Information

11. Development Process Class Diagrams
Class Diagrams were developed using the Unified Modeling Language (UML)
The class diagram is continually updated as new objects and relationships are defined

12. Development Process Objects
Each object consists of many attributes, operations, and associations
For example a gene object has many attributes such as symbols and keywords. A gene also has operations including getName and getSequnces, and associations which indicate that a gene “has” sequences and “has a ” location

13. Development Process Sequence Diagrams
Additional methods are discovered as the objects are further explored modeling the use cases

14. Development Process Object Development
Java Code is written to implement the Object Model
Documentation (API) is built from the Java Code

15. Development Process Application Development
Applications leveraging caBIO can be developed using multiple programming languages

16. Development Process Example Application
caBIO was used to add intelligence to BioCarta pathways
Gene, pathway, and expression objects were used
Users can select a pathway, and view pathway components that are mutated or expressed
Users can drill down to detailed gene information

17. Architecture Clients Presentation Layer Object Layer Data Sources
Web Server
Servlet Container
JSPs
HTML/HTTP
Databases
Browsers
Servlets
Object Managers
Data Access Objects
SOAP Engine
JDBC
XML/HTTP
External Java Apps
RMI
UI Bean
HTTP
Domain Objects
URLs
Agents
RDF
XML Builder
Genes
Chromosomes
XSLT Engine
FTP
Other Apps
Tissues
Clusters
SOAP
Sequences
Libraries
Flat
Files
DTDs
XML
Docs
XSL
Style Sheet
Diseases
Internal Java Apps
Other

18. Architecture
The core infrastructure exhibits an n-tiered architecture with client interfaces, server components, back-end objects and data sources
Clients (browsers, applications) can receive information (HTML and XML) from back-end objects over HTTP
Client applications can also communicate with back-end objects via Java RMI (Java applications)
Non-Java based applications will communicate via SOAP
Server components communicate with back-end objects via Java RMI
Back-end objects communicate directly with data sources (database, URLs, flat files)
A UDDI registry will be configured to advertise services
RDF is currently used to advertise services to crawlers and agents

19. Architecture Client Technology
Industry Standard Web Browsers - Netscape 4+ and IE 4+
Java Applications – Applications that implement the Java programming language, an object-oriented language which provides portability and many other features
Non-Java Applications - Applications usually written in Perl, C, etc.
Non-Java applications use SOAP clients to interface with caBIO
SOAP::Lite for Perl – A collection of Perl modules which provides a simple and lightweight interface to the Simple Object Access Protocol (SOAP)
Agents - Software programs that perform a function for a user in a trusted fashion, can learn or be taught its function, and can perform actions for the user without permission
RDF – The Resource Description Framework is a foundation that advertises Web services via the Web. RDF is used to describe the content and services available at a particular Web site. (passive)
UDDI – Universal Description, Discovery and Integration is a foundation to enable businesses to discover and transact business with each other using preferred applications (active)

20. Architecture Presentation Layer Technology
Jakarta Tomcat - Servlet+JSP Engine which is a subproject of the Jakarta Project
JSPs - Java Server Pages are web pages with Java embedded in the HTML to incorporate dynamic content in the page
Java Servlets – Server-side Java programs that web servers can run to generate content in response to client requests
Java Beans – Reusable software components that work with Java
XML – The Extensible Markup Language is a universal format for structured data on the Web
XSL/XSLT – The Extensible Stylesheet Language is a language for expressing stylesheets. XSL Transformations (XSLT) is a language for transforming XML documents
XLink – The XML Linking Language allows elements to be inserted into XML documents in order to create and describe links between resources
DOM – The Document Object Model is a platform and language independent interface that allows programs to dynamically access content, structure, and document style

21. Architecture Presentation Layer Technology (cont.)
SOAP – The Simple Object Access Protocol is a lightweight XML based protocol for the exchange of information in a decentralized, distributed environment. It consists of an envelope that describes the message and a framework for message transport
Apache SOAP – An implementation of the W3C SOAP specification. The Apache SOAP provides a server-side infrastructure for deploying, managing, and running SOAP enabled services.

22. Architecture Presentation Layer
The Mediator Servlet manages the user session, forwards requests to the JSP, and returns HTML
JSPs forward requests to the UI Bean, and returns XML or HTML to the client
The UI Bean receives the a Domain Object and converts the object to XML or HTML
The DOM Writer performs the Conversion to XML while the Conversion Servlet represents the Domain Object as a Document Object (DOM)
The conversion is performed by calling the Domain Objects toXML() method
HTML/HTTP
Mediator Servlet
Domain Objects
XML/HTTP
JSPs
RMI
RDF
UI Bean
Manager Proxies
SOAP
DOM Writer
ConversionServlet
XML Builder

23. Architecture Object Layer Technology
Java Applications/Objects – Applications/Objects that implement the Java programming language, an object-oriented language which provides portability and many other features
Java RMI – Remote Method Invocation is distributed computing in Java. It is a simple technology for object communication that allows remote objects to act as local Java objects
JDBC – Java Database Connectivity is a Java API for executing SQL statements and connecting to databases
SOAP – Simple Object Access Protocol extends object interoperability to other programming languages (Perl, Python, C++)
DAS – The Distributed Annotation System is an emergent system for retrieving genomic annotations from a variety of data sources (GoldenPath, Ensembl)

24. Remote Interface Manager
Architecture
Object Layer
Object Managers are created to implement complex scientific concepts
The Role Model object verifies user permissions to the data if applicable
The Remote Manager interface abstracts the RMI layer
Allows RMI to be easily replaced by EJB or other communication venues
Domain Objects are serialized and XML enabled
Object Managers
Role Model
GeneManager
Data Access Objects
SequenceManager
RMI
LibraryManager
Remote Interface Manager
Other Managers
Domain Objects

25. Architecture Data Access Objects Data Access Objects Data Sources
Provides the object relational mapping
Database independent persistence
Allows for the introduction of new data sources
Abstracts persistence details from the domain objects
Allows for federated database topology
Data Access Objects
Data Sources
LibraryPersistence
ClonePersistence
Databases
TissuePersistence
JDBC
SequencePersistence
HTTP
GenePersistence
URLs
ProteinPersistence
FTP
Other
Flat
Files

26. Data Sources CGAP (NCI Cancer Genome Anatomy Project) GenBank (NCBI)
Provides gene expression profiles of normal, pre-cancer, and cancer cells
GenBank (NCBI)
Sequence submission software
Unigene (NCBI)
Partitions sequences into unique gene-oriented clusters
LocusLink (NCBI)
Provides an interface to curated sequence and descriptive info about genetic loci

27. Data Sources Homologene (NCBI) GoldenPath (UCSC)
Provides curated orthologs and homologs for UniGene and LocusLink genes
GoldenPath (UCSC)
Contains a working draft of the human genome

28. Usage
Java developers use the caBIO jar file for immediate access to genomic object attributes and methods
caBIO objects can easily be extended to support customized objects
Non-Java and Java developers can use SOAP to access genomic object attributes and methods over HTTP
Developers can obtain detailed descriptions of available services via the RDF site
URIs of desired services can be obtained via RDF
Developers can host a caBIO server or leverage the existing NCICB caBIO server

29. Benefits
Provides an abstraction layer that allows developers to access genomic information using a standardized tool set without concerns for implementation details
Permits access to allow developers to obtain the information they need from a variety of data sources without data management
Manages the display of large volumes of data to assist in load balancing
Provides an effective mechanism for comparing similar objects that rely on diverse data sources
Facilitates information sharing without managing linkages between multiple data sources

30. Future The Semantic Web Natural Language Processing (NLP) Concept
“The Semantic Web is an extension of the current web in which information is given well-defined meaning, better enabling computers and people to work in cooperation." -- Tim Berners-Lee, James Hendler, Ora Lassila (W3C)
Implementation
Agent Based Technology may be used to create programs that implement semantic web concepts
Natural Language Processing (NLP)
NLP involves understanding natural language and extracting information
NLP can be used as a tool to help automate tasks, refine searches and improve genomic algorithms

31. Questions?