# Presentation: 329904

## Development of a Toxicogenomic

- Supportive Database: dbZach

**Lyle D. Burgoon***
**Department of Pharmacology & Toxicology**
**Institute For Environmental Toxicology and **
**The National Food Safety & Toxicology Center**
**Michigan State University**
**tel: (517) 353-1944**
**fax: (517) 353-9334**
**e-mail: burgoonl@msu.edu**
**http://dbzach.fst.msu.edu**

**Research Program Supported by:****	****National Institutes of Health**
**	**** ****P42 ES 04911-12, *T32 ES07255**

## Where Are We Going?

- Brief Introduction to Systems Toxicology
- dbZach Project
- dbZach Components and Architecture
- dbZach Applications
- dbZach Tools
- Availability

## Systems Toxicology

- Marriage of toxicology, bioinformatics, systems engineering
- Estimation of risk from chronic and subchronic exposures
- Understanding of mechanisms of action
- Tissue and organ system interactions
- Ecological factors

## Systems Toxicology

## The dbZach Components

- Platform independent
- Minimum Information About Microarray Experiment (MIAME) Supportive (_[http://www.mged.org](http://www.mged.org/)__)_
- Database
- Oracle 9*i*
- Data Modeling
- Modular Subsystem Architecture
- Data Management
- Tools
- Graphical
- User-friendly
- Java 2
- Data Mining
- Data Visualization

## Modular Architecture of dbZach

## dbZach Components

- Platform independent
- Minimum Information About Microarray Experiment (MIAME) Supportive (_[http://www.mged.org](http://www.mged.org/)__)_
- Database (Oracle 9*i)*
- Data Modeling
- Modular Subsystem Architecture
- Data Management
- Tools
- Graphical
- User-friendly
- Java 2
- Data Mining
- Data Visualization

## dbZach Project Applications

- Microarray Construction
- Clone Tracking
- Clone-Gene Mapping
- Microarray Experiment
- Quality Control
- Genes Represented
- Data Transformation & Normalization
- Rational Data Interpretation
- Toxicology
- Pathology
- Pathways
- Verification

## Core Subsystems

- Clones
- GenBank Accessions
- Physical storage location within lab
- Sequence and vector information
- Genes
- UniGene Cluster
- Names, abbreviations
- Functional annotation
- Automated updates
- Sample Annotation
- Catalogs chemicals, vehicles/solvents
- Comprehensively captures *in vitro* and *in vivo* assay conditions
- Catalogs sample source
- Protocols
- Catalogs laboratory SOPs
- Catalogs analysis algorithms

## Experimental Subsystems

- Microarray
- Clones-to-microarray mapping
- Storage of raw and calculated data
- Toxicology
- Captured measures:
- Clinical chemistry
- Pathology
- Storage of histopathology images
- Enzyme assays
*In vitro *tox assays
- Expandable
- Real-Time PCR
- Microarray verification
- Primers used
- Compatible with TaqMan and SYBR-Green assays

## In Silico Subsystems

- Gene Regulatory
- Tracks gene regulatory information back to genes, microarray and Real-Time PCR subsystems
- Stores 20kb up- and downstream of transcription start site
- Pathways
- Maps pathway information to genes and expression data

## Sources of Data

## Uses and Availability

- Current features
- Clones and Genes Interfaces
- Gene Annotation Tool
- Quality Control
- dbZach Application Programming Interface (API)
- Future applications
- Java Microarray (JM) Suite
- JM-Feature Inspection Tool (JM-FIT)
- JM-Toxicology Correlation Tool (JM-TCT)
- JM-Gene Expression Chromsome Viewer
- Source available

## Microarray Construction

- 1.  Log in

- 2.  Select input

- 3.  Select output

- Select which data fields
- to retrieve for each clone

- Select single file or directory

- Security requires user
- password to access
- selected features within
- dbZach

## Microarray Experimental Data

- Raw Data
- TIFF stored in database
- Facilitates feature-level queries
- Numerical data stored in database
- Data transformations and normalizations
- Higher order analysis
- Protocols
- Quality Control

## Microarray Quality Control

- A. Global Mean
-      Background

- B. Global Mean Feature
- 	Signal Intensity

- Shewhart Plots (SAS/QC)

## Java Microarray-Feature Inspection Tool  (JM-FIT)

- Extends Oracle InterMedia
- InterMedia provides functionality to query microarray images for any number of pixels
- Graphical User Interface (GUI)
- Specify an array, experiment, or user
- Specify clone(s), feature locations, or click on thumbnail view
- Tile y *x* z pixels for inspection
- Currently in development

## JM-FIT

- Brief Intro and
- Directions

- Make Selections

## JM-FITTile Viewer

- Feature Stats

- Feature Image

- Basic Info

- Array Chooser

## Real-Time PCR Interface(in development)

- GUI for entering/viewing Real-Time PCR data
- Catalogs primers used in experiment
- Provide graphical analysis of Real-Time PCR data with microarray data

## Data Visualization and Mining Tools

- Gene Annotation Tool (GAT)
- Toxicogenomic Correlation Tool (TCT)
- Gene Expression Chromosome Viewer
- Pathway Viewer

## Gene Annotation Tool

- Gene Ontology Number
- Frequency Histogram

- output
- formats

- Input Format: Tab-delimited text file (.txt)

- Tab-delimited text file (.txt)

- Excel spreadsheet (.xls)

## Gene Expression Chromosome Viewer(in development)

- Maps microarray data to chromosomal locations
- Identify locus control regions

## Pathway Viewer(in development)

- Java GUI
- Data Entry
- Image file (GIF, JPEG, TIFF)
- Chemical and gene product interactions
- Data View
- View established pathways
- Visualize microarray data on pathway

## Gene Regulation Analysis(in development)

- Storage of 20kb up- and down-stream of transcription start site
- UCSC
- ENSEMBL
- In-house promoter analysis programs query dbZach for promoter sequence
- dbZach stores predicted response elements with the prediction algorithm

## The Source Available dbZach

- Source Available Project
- The source (DLLs, etc...)
- The schemas
- The Perl update scripts (source)
- The dbZach API (Java API)
- The documentation
- You can...
- Customize it to fit your needs
- Take parts and incorporate those into your system
- Initially limited release

## dbZach API

- Facilitates tool development to further leverage dbZach
- Database connectivity
- Standard queries
- GUI tools for uniform “look & feel”

## dbZach Website

- Schemas available
- Updated as schemas are designed or modified
- Basic subsystem-level documentation available
- Table-level documentation available soon
- http://dbzach.fst.msu.edu

## Summary

**	****dbZach is a custom built toxicogenomics supportive**
**	****relational database that indexes large microarray**
**	****datasets and facilitates data analysis**
**Java-based data mining and visualization tools facilitate data mining, quality control monitoring, and correlation analyses**
**Built on Oracle 9*****i***** technology and runs on Windows 2000**
**	****in a Linux-Windows mixed environment**
** **
**dbZach is Minimum Information About Microarray **
**	****Experiment (MIAME) supportive**
**5.   dbZach is a source available project**

## Acknowledgements

**Bioinformatics Group:**
**Post Doc:**
**Yan Sun**
**Coop Students:**
*(alph. order)*
**Raeka Aiyar**
**Paul Boutros**
**Ed Dere**
**Shane Doran**
**Shraddha Pai**
**Jigger Vakharia**