8 An Overview of National Toxicology Program’s Toxicogenomic …
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8.6 Example Analysis of dE-71 Gene Expression Data
Using DrugMatrix and ToxFX
To demonstrate the utility of DrugMatrix, we present here an analysis of a toxicogenomic study of a mixture of low molecular weight-brominated flame retardants
(DE-71) that was demonstrated to be carcinogenic in rat liver [3]. Study results have
been published elsewhere, and the reader has referred this manuscript for a more
detailed account of the results [4]. In short, pregnant female Wistar Han rats were
administered 50 mg/kg DE-71 starting at Gestation Day (GD) 6 of the fetus through
Postnatal Day (PND) 12, and then the pups were directly dosed from PND12 to
PND21. The pups were euthanized on PND22, 24 h after the last dose, and livers
were taken at necropsy of the male pups for microarray studies. Of note is that the
dosing paradigm, and the strain and age of sacrifice of rats were different from experiments recorded in the DrugMatrix reference data set. Further, DE-71 treatments are
not part of the DrugMatrix reference data set. The gene expression data was generated using Affymetrix whole-genome 230 2.0 microarrays. A total of 10 microarrays
were run (5 vehicle and 5 chemical treated; all samples were independent biological
replicates).
Table 8.2 List of data analysis tools available in DrugMatrix
Tool
Functionality
List editing tools
Subtract a list (genes, compounds, etc) or group of lists from a
list, combine lists, or generate a list of common items between
lists
Data translation tools
Convert one type of list of items to another type of list (e.g., a
list of genes to a list of associated assays)
Pattern creator
Allows the user to derive a correlation-based signature from
an experiment list and gene set
Data import/export tools
Export or import previously saved lists enabling the user
archive and/or share lists
Hypergeometric analysis
Performs chemical ontology enrichment analysis of a list of
experiments
Expression experiment matrix
Generates a graphical matrix, with a heat-map-type display, to
compare expression ratios for a specified list of genes in a
specified list of experiments
Bio-activity matrix
Creates a graphical matrix, with a heat-map-type display, to
compare the bio-activities from the specified list of assays and
compounds
Pathway impact matrix
Examines the impact of compounds, in a specified expression
experiment list, on gene pathways
Blood chemistry matrix
Creates a heat map display to examine the perturbation of
blood chemistry assays, in a specified expression experiment
list
(continued)
151
8.6 Example Analysis of dE-71 Gene Expression Data
Using DrugMatrix and ToxFX
To demonstrate the utility of DrugMatrix, we present here an analysis of a toxicogenomic study of a mixture of low molecular weight-brominated flame retardants
(DE-71) that was demonstrated to be carcinogenic in rat liver [3]. Study results have
been published elsewhere, and the reader has referred this manuscript for a more
detailed account of the results [4]. In short, pregnant female Wistar Han rats were
administered 50 mg/kg DE-71 starting at Gestation Day (GD) 6 of the fetus through
Postnatal Day (PND) 12, and then the pups were directly dosed from PND12 to
PND21. The pups were euthanized on PND22, 24 h after the last dose, and livers
were taken at necropsy of the male pups for microarray studies. Of note is that the
dosing paradigm, and the strain and age of sacrifice of rats were different from experiments recorded in the DrugMatrix reference data set. Further, DE-71 treatments are
not part of the DrugMatrix reference data set. The gene expression data was generated using Affymetrix whole-genome 230 2.0 microarrays. A total of 10 microarrays
were run (5 vehicle and 5 chemical treated; all samples were independent biological
replicates).
Table 8.2 List of data analysis tools available in DrugMatrix
Tool
Functionality
List editing tools
Subtract a list (genes, compounds, etc) or group of lists from a
list, combine lists, or generate a list of common items between
lists
Data translation tools
Convert one type of list of items to another type of list (e.g., a
list of genes to a list of associated assays)
Pattern creator
Allows the user to derive a correlation-based signature from
an experiment list and gene set
Data import/export tools
Export or import previously saved lists enabling the user
archive and/or share lists
Hypergeometric analysis
Performs chemical ontology enrichment analysis of a list of
experiments
Expression experiment matrix
Generates a graphical matrix, with a heat-map-type display, to
compare expression ratios for a specified list of genes in a
specified list of experiments
Bio-activity matrix
Creates a graphical matrix, with a heat-map-type display, to
compare the bio-activities from the specified list of assays and
compounds
Pathway impact matrix
Examines the impact of compounds, in a specified expression
experiment list, on gene pathways
Blood chemistry matrix
Creates a heat map display to examine the perturbation of
blood chemistry assays, in a specified expression experiment
list
(continued)