Toxicogenomics is a subdiscipline of
pharmacology that deals with the collection, interpretation, and storage of information about
gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...
and
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
activity within a particular
cell
Cell most often refers to:
* Cell (biology), the functional basic unit of life
Cell may also refer to:
Locations
* Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...
or
tissue of an
organism
In biology, an organism () is any living system that functions as an individual entity. All organisms are composed of cells (cell theory). Organisms are classified by taxonomy into groups such as multicellular animals, plants, and ...
in response to exposure to
toxic substances
Poison is a chemical substance that has a detrimental effect to life. The term is used in a wide range of scientific fields and industries, where it is often specifically defined. It may also be applied colloquially or figuratively, with a broa ...
. Toxicogenomics combines
toxicology
Toxicology is a scientific discipline, overlapping with biology, chemistry, pharmacology, and medicine, that involves the study of the adverse effects of chemical substances on living organisms and the practice of diagnosing and treating e ...
with
genomics or other high-throughput molecular profiling technologies such as
transcriptomics
Transcriptomics technologies are the techniques used to study an organism's transcriptome, the sum of all of its RNA transcripts. The information content of an organism is recorded in the DNA of its genome and expressed through transcription. H ...
,
proteomics and
metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites, the small molecule substrates, intermediates, and products of cell metabolism. Specifically, metabolomics is the "systematic study of the unique chemical fingerprin ...
. Toxicogenomics endeavors to elucidate the molecular mechanisms evolved in the expression of toxicity, and to derive molecular expression patterns (i.e., molecular
biomarker
In biomedical contexts, a biomarker, or biological marker, is a measurable indicator of some biological state or condition. Biomarkers are often measured and evaluated using blood, urine, or soft tissues to examine normal biological processes, p ...
s) that predict toxicity or the genetic susceptibility to it.
Pharmaceutical research
In pharmaceutical research, toxicogenomics is defined as the study of the structure and function of the
genome
In the fields of molecular biology and genetics, a genome is all the genetic information of an organism. It consists of nucleotide sequences of DNA (or RNA in RNA viruses). The nuclear genome includes protein-coding genes and non-coding g ...
as it responds to adverse xenobiotic exposure. It is the toxicological subdiscipline of
pharmacogenomics
Pharmacogenomics is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup of an individual affects the ...
, which is broadly defined as the study of inter-individual variations in whole-genome or candidate gene
single-nucleotide polymorphism
In genetics, a single-nucleotide polymorphism (SNP ; plural SNPs ) is a germline substitution of a single nucleotide at a specific position in the genome. Although certain definitions require the substitution to be present in a sufficiently lar ...
maps,
haplotype markers, and alterations in
gene expression that might correlate with drug responses.
Though the term toxicogenomics first appeared in the literature in 1999,
it was by that time already in common use within the pharmaceutical industry as its origin was driven by marketing strategies from vendor companies. The term is still not universally accepted, and others have offered alternative terms such as ''
chemogenomics
Chemogenomics, or chemical genomics, is the systematic screening of targeted chemical libraries of small molecules against individual drug target families (e.g., GPCRs, nuclear receptors, kinases, proteases, etc.) with the ultimate goal of id ...
'' to describe essentially the same field of study.
Bioinformatics
The nature and complexity of the data (in volume and variability) demands highly developed processes of automated handling and storage. The analysis usually involves a wide array of
bioinformatics and
statistics, often including
statistical classification
In statistics, classification is the problem of identifying which of a set of categories (sub-populations) an observation (or observations) belongs to. Examples are assigning a given email to the "spam" or "non-spam" class, and assigning a diagn ...
approaches.
Drug discovery
In pharmaceutical
drug discovery and
development
Development or developing may refer to:
Arts
*Development hell, when a project is stuck in development
*Filmmaking, development phase, including finance and budgeting
*Development (music), the process thematic material is reshaped
* Photograph ...
, toxicogenomics is used to study possible
adverse (i.e.
toxic
Toxicity is the degree to which a chemical substance or a particular mixture of substances can damage an organism. Toxicity can refer to the effect on a whole organism, such as an animal, bacterium, or plant, as well as the effect on a subs ...
) effects of pharmaceutical
drugs in defined
model systems in order to draw conclusions on the toxic risk to patients or the environment. Both the
United States Environmental Protection Agency
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it ...
(EPA) and the
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) currently preclude basing regulatory decision-making on genomics data alone. However, they do encourage the voluntary submission of well-documented, quality genomics data. Both agencies are considering the use of submitted data on a case-by-case basis for assessment purposes (e.g., to help elucidate mechanism of action or contribute to a weight-of-evidence approach) or for populating relevant comparative databases by encouraging parallel submissions of genomics data and traditional toxicological test results.
Public projects
Chemical Effects in Biological Systems is a project hosted by the
National Institute of Environmental Health Sciences building a knowledge base of toxicology studies including study design, clinical pathology, and
histopathology and toxicogenomics data.
InnoMed PredTox assesses the value of combining results from various
omics
The branches of science known informally as omics are various disciplines in biology whose names end in the suffix '' -omics'', such as genomics, proteomics, metabolomics, metagenomics, phenomics and transcriptomics. Omics aims at the collect ...
technologies together with the results from more conventional toxicology methods in more informed decision-making in preclinical safety evaluation.
Open TG-GATEs (Toxicogenomics Project-Genomics Assisted Toxicity Evaluation System) is a Japanese public-private effort which has published gene expression and pathology information for more than 170 compounds (mostly drugs).
The Predictive Safety Testing Consortium aims to identify and clinically qualify safety biomarkers for regulatory use as part of the
FDA
The United States Food and Drug Administration (FDA or US FDA) is a federal agency of the Department of Health and Human Services. The FDA is responsible for protecting and promoting public health through the control and supervision of food ...
's "Critical Path Initiative".
ToxCast is a program for Predicting Hazard, Characterizing Toxicity Pathways, and Prioritizing the Toxicity Testing of Environmental Chemicals at the
United States Environmental Protection Agency
The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it ...
.
Tox21 is a federal collaboration involving the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH), Environmental Protection Agency (EPA), and Food and Drug Administration (FDA), is aimed at developing better toxicity assessment methods.
Within this project the toxic effects of chemical compounds on cell lines derived from the
1000 Genomes Project
The 1000 Genomes Project (abbreviated as 1KGP), launched in January 2008, was an international research effort to establish by far the most detailed catalogue of human genetic variation. Scientists planned to sequence the genomes of at least one th ...
individuals were assessed and associations with genetic markers were determined.
Parts of this data were used in the NIEHS-NCATS-UNC DREAM Toxicogenetics Challenge in order to determine methods for cytotoxicity predictions for individuals.
See also
*
Comparative Toxicogenomics Database
The Comparative Toxicogenomics Database (CTD) is a public website and research tool launched in November 2004 that curates scientific data describing relationships between chemicals/drugs, genes/proteins, diseases, taxa, phenotypes, GO annotations ...
*
Pharmacogenetics
Pharmacogenomics is the study of the role of the genome in drug response. Its name ('' pharmaco-'' + ''genomics'') reflects its combining of pharmacology and genomics. Pharmacogenomics analyzes how the genetic makeup of an individual affects the ...
*
Structural genomics
Structural genomics seeks to describe the 3-dimensional structure of every protein encoded by a given genome. This genome-based approach allows for a high-throughput method of structure determination by a combination of experimental and modeling ...
References
External links
Center for Research on Occupational and Environmental Toxicologydefinition by the CROET Research Centers: (Neuro)toxicogenomics and Child Health Research Center.
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