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

. 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.

References

External links