Chapter 8
An Overview of National Toxicology
Program’s Toxicogenomic Applications:
DrugMatrix and ToxFX
Daniel L. Svoboda, Trey Saddler and Scott S. Auerbach
Abstract DrugMatrix and its automated toxicogenomics reporting system, ToxFX
are the scientific communities’ largest molecular toxicology reference database and
informatics systems. DrugMatrix consists of the comprehensive results of thousands
of highly controlled and standardized toxicological experiments where rats or primary rat hepatocytes were systematically treated with more than 600 therapeutic,
industrial, or environmental chemicals at both non-toxic and toxic doses. Following administration in vivo, comprehensive studies of the effects of these compounds
were carried out after multiple durations of exposure, and in multiple target organs.
Study types included pharmacology, clinical chemistry, hematology, histology, body
and organ weights, and clinical observations. Additionally, a curation team extracted
all relevant information on the compounds from the literature, the Physicians’ Desk
Reference, package inserts, and other relevant sources. At the heart of the DrugMatrix database are thousands of gene expression data sets generated by extracting RNA
from the toxicologically relevant organs and tissues and analyzing these RNAs using
the GE Codelink rat array, and the Affymetrix whole-genome 230 2.0 rat GeneChip
array systems. Additionally, the database contains 148 scorable genomic signatures,
covering 96 distinct phenotypes derive from mining the DrugMatrix gene expression data. The signatures are informative of organ-specific pathology (e.g., hepatic
steatosis), and mode of toxicological action (e.g., PXR activation in the liver). The
phenotypes cover several common target tissues in toxicity testing (liver, kidney,
heart, bone marrow, spleen, and skeletal muscle). Taken as a whole, DrugMatrix
D. L. Svoboda
Sciome LLC, Durham, NC, USA
e-mail: daniel.svoboda@sciome.com
T. Saddler
Kelly Government Solutions, Durham, NC, USA
e-mail: trey.saddler@nih.gov
S. S. Auerbach (B)
Division of the National Toxicology Program, National Institute of Environmental Health
Sciences, National Institutes of Health, Durham, NC, USA
e-mail: auerbachs@niehs.nih.gov
© Springer Nature Switzerland AG 2019
H. Hong (ed.), Advances in Computational Toxicology, Challenges and Advances
in Computational Chemistry and Physics 30,
https://doi.org/10.1007/978-3-030-16443-0_8
141
An Overview of National Toxicology
Program’s Toxicogenomic Applications:
DrugMatrix and ToxFX
Daniel L. Svoboda, Trey Saddler and Scott S. Auerbach
Abstract DrugMatrix and its automated toxicogenomics reporting system, ToxFX
are the scientific communities’ largest molecular toxicology reference database and
informatics systems. DrugMatrix consists of the comprehensive results of thousands
of highly controlled and standardized toxicological experiments where rats or primary rat hepatocytes were systematically treated with more than 600 therapeutic,
industrial, or environmental chemicals at both non-toxic and toxic doses. Following administration in vivo, comprehensive studies of the effects of these compounds
were carried out after multiple durations of exposure, and in multiple target organs.
Study types included pharmacology, clinical chemistry, hematology, histology, body
and organ weights, and clinical observations. Additionally, a curation team extracted
all relevant information on the compounds from the literature, the Physicians’ Desk
Reference, package inserts, and other relevant sources. At the heart of the DrugMatrix database are thousands of gene expression data sets generated by extracting RNA
from the toxicologically relevant organs and tissues and analyzing these RNAs using
the GE Codelink rat array, and the Affymetrix whole-genome 230 2.0 rat GeneChip
array systems. Additionally, the database contains 148 scorable genomic signatures,
covering 96 distinct phenotypes derive from mining the DrugMatrix gene expression data. The signatures are informative of organ-specific pathology (e.g., hepatic
steatosis), and mode of toxicological action (e.g., PXR activation in the liver). The
phenotypes cover several common target tissues in toxicity testing (liver, kidney,
heart, bone marrow, spleen, and skeletal muscle). Taken as a whole, DrugMatrix
D. L. Svoboda
Sciome LLC, Durham, NC, USA
e-mail: daniel.svoboda@sciome.com
T. Saddler
Kelly Government Solutions, Durham, NC, USA
e-mail: trey.saddler@nih.gov
S. S. Auerbach (B)
Division of the National Toxicology Program, National Institute of Environmental Health
Sciences, National Institutes of Health, Durham, NC, USA
e-mail: auerbachs@niehs.nih.gov
© Springer Nature Switzerland AG 2019
H. Hong (ed.), Advances in Computational Toxicology, Challenges and Advances
in Computational Chemistry and Physics 30,
https://doi.org/10.1007/978-3-030-16443-0_8
141