Toxicogenomics
Encyclopedia
Toxicogenomics is a field of science
that deals with the collection, interpretation, and storage of information about gene
and protein
activity within particular cell
or tissue
of an organism
in response to toxic substances
. Toxicogenomics combines toxicology
with genomics
or other high throughput molecular profiling technologies such as transcriptomics, proteomics
and metabolomics
. Toxicogenomics endeavors to elucidate 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.
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 markers, and alterations in gene expression that might correlate with drug responses (Lesko and Woodcock 2004, Lesko et al. 2003). Though the term toxicogenomics first appeared in the literature in 1999 (Nuwaysir et al.) it was already in common use within the pharmaceutical industry as its origin was driven by marketing strategies from vendor companies. The term is still not universal accepted, and others have offered alternative terms such as chemogenomics to describe essentially the same area (Fielden et al., 2005).
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
., regularly involving classification approaches.
In pharmaceutical Drug discovery
and development
toxicogenomics is used to study adverse
, i.e. toxic, effects, of pharmaceutical drug
s in defined model systems
in order to draw conclusions on the toxic risk to patients or the environment.
Both the EPA
and the U.S. Food and Drug Administration 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 toxicologic test results.
Courses:
Madurai Kamaraj University, Tamil Nadu offers a Msc (sub-Aqua Marine Ecology and TOXICOGENOMICS).
Science
Science is a systematic enterprise that builds and organizes knowledge in the form of testable explanations and predictions about the universe...
that deals with the collection, interpretation, and storage of information about gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
and protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
activity within particular cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
or tissue
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
of an organism
Organism
In biology, an organism is any contiguous living system . In at least some form, all organisms are capable of response to stimuli, reproduction, growth and development, and maintenance of homoeostasis as a stable whole.An organism may either be unicellular or, as in the case of humans, comprise...
in response to toxic substances
Toxin
A toxin is a poisonous substance produced within living cells or organisms; man-made substances created by artificial processes are thus excluded...
. Toxicogenomics combines toxicology
Toxicology
Toxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
with genomics
Genomics
Genomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
or other high throughput molecular profiling technologies such as transcriptomics, proteomics
Proteomics
Proteomics is the large-scale study of proteins, particularly their structures and functions. Proteins are vital parts of living organisms, as they are the main components of the physiological metabolic pathways of cells. The term "proteomics" was first coined in 1997 to make an analogy with...
and metabolomics
Metabolomics
Metabolomics is the scientific study of chemical processes involving metabolites. Specifically, metabolomics is the "systematic study of the unique chemical fingerprints that specific cellular processes leave behind", the study of their small-molecule metabolite profiles...
. Toxicogenomics endeavors to elucidate 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.
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 markers, and alterations in gene expression that might correlate with drug responses (Lesko and Woodcock 2004, Lesko et al. 2003). Though the term toxicogenomics first appeared in the literature in 1999 (Nuwaysir et al.) it was already in common use within the pharmaceutical industry as its origin was driven by marketing strategies from vendor companies. The term is still not universal accepted, and others have offered alternative terms such as chemogenomics to describe essentially the same area (Fielden et al., 2005).
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
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
and statistics
Statistics
Statistics is the study of the collection, organization, analysis, and interpretation of data. It deals with all aspects of this, including the planning of data collection in terms of the design of surveys and experiments....
., regularly involving classification approaches.
In pharmaceutical Drug discovery
Drug discovery
In the fields of medicine, biotechnology and pharmacology, drug discovery is the process by which drugs are discovered or designed.In the past most drugs have been discovered either by identifying the active ingredient from traditional remedies or by serendipitous discovery...
and development
Drug development
Drug development is a blanket term used to define the process of bringing a new drug to the market once a lead compound has been identified through the process of drug discovery...
toxicogenomics is used to study adverse
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...
, i.e. toxic, effects, of pharmaceutical drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s in defined model systems
Model organism
A model organism is a non-human species that is extensively studied to understand particular biological phenomena, with the expectation that discoveries made in the organism model will provide insight into the workings of other organisms. Model organisms are in vivo models and are widely used to...
in order to draw conclusions on the toxic risk to patients or the environment.
Both the EPA
United States Environmental Protection Agency
The U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
and the U.S. Food and Drug Administration 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 toxicologic test results.
Public Toxicogenomics Projects
- Chemical Effects in Biological Systems (CEBS) - Project hosted by the National Institute of Environmental Health SciencesNational Institute of Environmental Health SciencesThe National Institute of Environmental Health Sciences is a part of the National Institutes of Health , which is in turn a part of the Department of Health and Human Services ....
(NIEHS) building a knowledgebase of toxicology studies including study design, clinical pathology, and histopathology and toxicogenomics data. - InnoMed PredTox assessing the value of combining results from omics technologies together with the results from more conventional toxicology methods in more informed decision making in preclinical safety evaluation.
- Predictive Safety Testing Consortium aiming to identify and clinically qualify safety biomarkers for regulatory use as part of the FDA's Critical Path Initiative
- ToxCast program for Predicting Hazard, Characterizing Toxicity Pathways, and Prioritizing the Toxicity Testing of Environmental Chemicals at the United States Environmental Protection AgencyUnited States Environmental Protection AgencyThe U.S. Environmental Protection Agency is an agency of the federal government of the United States charged with protecting human health and the environment, by writing and enforcing regulations based on laws passed by Congress...
See also
- Comparative Toxicogenomics DatabaseComparative Toxicogenomics DatabaseThe Comparative Toxicogenomics Database is a public website and research tool that curates scientific data describing relationships between chemicals, genes, and human diseases....
- GenomicsGenomicsGenomics is a discipline in genetics concerning the study of the genomes of organisms. The field includes intensive efforts to determine the entire DNA sequence of organisms and fine-scale genetic mapping efforts. The field also includes studies of intragenomic phenomena such as heterosis,...
- ChemogenomicsChemogenomicsChemogenomics is the study of genomic responses to chemical compounds. The goal is the rapid identification of novel drugs and drug targets, embracing multiple early phase drug discovery technologies ranging from target identification and validation, through compound design and chemical synthesis,...
- Structural genomicsStructural genomicsStructural 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 approaches...
- PharmacogeneticsPharmacogeneticsThe terms pharmacogenomics and pharmacogenetics tend to be used interchangeably, and a precise, consensus definition of either remains elusive...
- PharmacogenomicsPharmacogenomicsPharmacogenomics is the branch of pharmacology which deals with the influence of genetic variation on drug response in patients by correlating gene expression or single-nucleotide polymorphisms with a drug's efficacy or toxicity...
- Chemogenomics
- InnoMed PredTox
- ToxicologyToxicologyToxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...
External links
- Comparative Toxicogenomics Database - a public database that integrates toxicogenomic data for chemicals, genes, and diseases from the scientific literature.
- Center for Research on Occupational and Environmental Toxicology definition by the CROET Research Centers: (Neuro)toxicogenomics and Child Health Research Center.
- InnoMed PredTox - official project website
- Netherlands Toxicogenomics Centre - official project website
- ToxCast - official project website
- ToxExpress® Program - Gene Logic's ToxExpress® Program
Courses:
Madurai Kamaraj University, Tamil Nadu offers a Msc (sub-Aqua Marine Ecology and TOXICOGENOMICS).