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Toxicogenomics

MAY 28, 2003

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Agenda



Introduction




Microarrays




Databases & Software




Conclusions

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Toxicogenomics



Whole genome approach to toxicology



Uses gene expression profiles to infer toxicity



Many more data points in less time than
traditional toxicology

greater accuracy and
higher throughput

Introduction

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Primary Research Goals

Introduction

Other

5%

Basic research

46%

Human drug

development

34%

Environmental

applications

10%

Animal drug

development

4%

Other

consumer

products

1%

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Experimental Design Parameters

Introduction

Academia

Industry

Primary research
objective

Explain underlying
mechanisms of toxicity

Determine expression
profiles for specific
compounds or families

Most frequently used
model system

Mouse

Mouse

Most frequently used
sample type

Liver tissue

Liver tissue

Doses per compound
tested

3

3

Replicates per compound
tested

3

3

Time points per
compound tested

Either 3 or more than 5

2

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DNA Microarrays

Microarrays

Sources

Affymetrix Gene Chips Are Used Most Frequently

Human Genome U133

Rat Genome U34

Human Genome U95

Rat Toxicology U34

CYP450 Assay


Affymetrix

GeneChip

37%

Printed in my

lab/department

20%

Supplied by

collaborator

12%

Clontech

Atlas

11%

Agilent

8%

Other

commercially

available

5%

Amersham

CodeLink

4%

PHASE
-
1

Molecular

Toxicology

Arrays

3%

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Databases Used in Toxicogenomics Research

Databases & Software

In
-
house databases

36%

National Library of

Medicine TOXNET

18%

Clontech AtlasInfo

11%

Gene Logic ToxExpress

9%

Other commercial

or public database

8%

EPA GENE
-
TOX

7%

Iconix

DrugMatrix

1%

PHASE
-
1

TOXbank

4%

CDER

Pharmacology

/Toxicology

6%

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Features and Opinions: Databases

Databases & Software

Commercial database users





Value tissue representation



Want a greater ability to hyperlink to other data sources

Publicly available and in
-
house database users…




Seek greater species representation



Value user interface

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Data Analysis Software Usage

Databases & Software

In
-
house developed software

26%

Agilent Rosetta Resolver Suite

9%

Spotfire DecisionSite Software

7%

Other publicly available software

7%

BioDiscovery ImaGene Software

5%

InforMax Vector Xpression

5%

Gene Logic Genesis Enterprise

System

4%

Molecular Mining GeneLinker

Software

4%

Gene Data Expressionist

3%

CuraGen GeneScape Portal

2%

MolecularWare DigitalGenome

Software

2%

Silicon Genetics GeneSpring

14%

Other commercially available

software

10%

PHASE
-
1 Molecular Toxicology

MatrixExpress Software

2%

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Features and Opinions: Software

Databases & Software



Data normalization



Expression profile comparisons



Script building

Most Important Software Features:

Analytical Capabilities Valued in Commercial Software:



Data integration



Gene annotation



Data clustering

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67% of toxicologists use toxicogenomics in their research.



Microarray users want greater sensitivity and
reproducibility.


Toxicogenomicists most often use in
-
house databases and
have a strong need for integration of gene expression,
proteomic, and metabolic data.


The large number of toxicogenomics software suppliers
reflects a lack of widely adopted standards for archiving
and data analysis.



Conclusions