Toxicogenomics is a subdiscipline of

pharmacology Pharmacology is a branch of medicine, biology and pharmaceutical sciences concerned with drug or medication action, where a drug may be defined as any artificial, natural, or endogenous (from within the body) molecule which exerts a biochemica ...

that deals with the collection, interpretation, and storage of information about gene and protein activity within a particular cell or tissue of an organism 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 with

genomics Genomics is an interdisciplinary field of biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, three-dim ...

or other high-throughput molecular profiling technologies such as transcriptomics,

proteomics Proteomics is the large-scale study of proteins. Proteins are vital parts of living organisms, with many functions such as the formation of structural fibers of muscle tissue, enzymatic digestion of food, or synthesis and replication of DNA. In ...

and metabolomics. Toxicogenomics endeavors to elucidate the molecular mechanisms evolved in the expression of toxicity, and to derive molecular expression patterns (i.e., molecular biomarkers) 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 as it responds to adverse xenobiotic exposure. It is the toxicological subdiscipline of pharmacogenomics, which is broadly defined as the study of inter-individual variations in whole-genome or candidate gene single-nucleotide polymorphism maps,

haplotype A haplotype ( haploid genotype) is a group of alleles in an organism that are inherited together from a single parent. Many organisms contain genetic material ( DNA) which is inherited from two parents. Normally these organisms have their DNA or ...

markers, and alterations in

gene expression Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, protein or non-coding RNA, and ultimately affect a phenotype, as the final effect. The ...

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'' 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 Bioinformatics () is an interdisciplinary field that develops methods and software tools for understanding biological data, in particular when the data sets are large and complex. As an interdisciplinary field of science, bioinformatics combi ...

and

statistics Statistics (from German language, German: ''wikt:Statistik#German, Statistik'', "description of a State (polity), state, a country") is the discipline that concerns the collection, organization, analysis, interpretation, and presentation of ...

, often including statistical classification approaches.

Drug discovery

In pharmaceutical

drug discovery In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which new candidate medications are discovered. Historically, drugs were discovered by identifying the active ingredient from traditional remedies or by ...

and development, toxicogenomics is used to study possible

adverse Adverse or adverse interest, in law, is anything that functions contrary to a party (law), party's interest. This word should not be confused with wikt:averse, averse. Adverse possession In property law, adverse possession refers to an interest i ...

(i.e. toxic) effects of pharmaceutical

drug A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via insuffla ...

s 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 (EPA) and the Food and Drug Administration (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 The National Institute of Environmental Health Sciences (NIEHS) conducts research into the effects of the environment on human disease, as one of the 27 institutes and centers of the National Institutes of Health (NIH). It is located in the Rese ...

building a knowledge base of toxicology studies including study design, clinical pathology, and

histopathology Histopathology (compound of three Greek words: ''histos'' "tissue", πάθος ''pathos'' "suffering", and -λογία '' -logia'' "study of") refers to the microscopic examination of tissue in order to study the manifestations of disease. Spe ...

and toxicogenomics data. InnoMed PredTox assesses the value of combining results from various omics 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'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. Tox21 is a federal collaboration involving the National Institutes of Health (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

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