View source for Toxicogenomics

'''Toxicogenomics''' is a subdiscipline of [[pharmacology]] that deals with the collection, interpretation, and storage of information about [[gene]] and [[protein]] activity within a particular [[Cell (biology)|cell]] or [[Tissue (biology)|tissue]] of an [[organism]] in response to exposure to [[toxin|toxic substances]]. Toxicogenomics combines [[toxicology]] with [[genomics]] or other high-throughput molecular profiling technologies such as [[transcriptomics]], [[proteomics]] and [[metabolomics]].<ref>{{cite book|publisher=The National Academies Press|title= Communicating Toxicogenomics Information to Nonexperts: A Workshop Summary|year=2005|url=http://books.nap.edu/openbook.php?record_id=11179&page=3|doi= 10.17226/11179|pmid= 20669449|isbn= 978-0-309-09538-9|author1= National Research Council (US) Committee on Communicating Toxicogenomics Information to Nonexperts}}</ref><ref>{{cite book|title=Toxicogenomics: Principles and Applications|veditors=Hamadeh HK, Afshari CA|year=2004|publisher=Wiley-Liss|location  =Hoboken, NJ|isbn=0-471-43417-5 }}<br />{{cite journal|vauthors=Omenn GS|title=Book Review: Toxicogenomics: Principles and Applications|journal=Environ. Health Perspect.|volume=112|issue=16|pages=A962|date  =November 2004|doi=10.1289/ehp.112-1247673|pmc=1247673 }}</ref> Toxicogenomics endeavors to elucidate the molecular mechanisms evolved in the expression of toxicity, and to derive molecular expression patterns (i.e., molecular [[biomarker]]s) that predict toxicity or the genetic susceptibility to it.<ref>{{Cite journal |last1=Meier |first1=Matthew J. |last2=Harrill |first2=Joshua |last3=Johnson |first3=Kamin |last4=Thomas |first4=Russell S. |last5=Tong |first5=Weida |last6=Rager |first6=Julia E. |last7=Yauk |first7=Carole L. |date=2024-09-02 |title=Progress in toxicogenomics to protect human health |url=https://www.nature.com/articles/s41576-024-00767-1 |journal=Nature Reviews Genetics |volume=26 |issue=2 |language=en |pages=105–122 |doi=10.1038/s41576-024-00767-1 |pmid=39223311 |issn=1471-0064|url-access=subscription }}</ref>

==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]] markers, and alterations in [[gene expression]] that might correlate with drug responses.<ref name="pmid15340386">{{cite journal|vauthors=Lesko LJ, Woodcock J|title=Translation of pharmacogenomics and pharmacogenetics: a regulatory perspective|journal=Nature Reviews. Drug Discovery|volume=3|issue=9|pages=763–9|year=2004|pmid=15340386|doi=10.1038/nrd1499 |s2cid=33145913|url=https://zenodo.org/record/1233517}}</ref><ref name="pmid12723455">{{cite journal|vauthors=Lesko LJ, Salerno RA, Spear BB, Anderson DC, Anderson T, Brazell C, Collins J, Dorner A, Essayan D, Gomez-Mancilla B, Hackett J, Huang SM, Ide S, Killinger J, Leighton J, Mansfield E, Meyer R, Ryan SG, Schmith V, Shaw P, Sistare F, Watson M, Worobec A|title=Pharmacogenetics and pharmacogenomics in drug development and regulatory decision making: report of the first FDA-PWG-PhRMA-DruSafe Workshop|journal=Journal of Clinical Pharmacology|volume=43|issue=4|pages=342–58|year=2003|pmid=12723455|doi=10.1177/0091270003252244 |s2cid=5902873|url=https://zenodo.org/record/1235536}}</ref> Though the term toxicogenomics first appeared in the literature in 1999,<ref name="pmid10204799">{{cite journal|vauthors=Nuwaysir EF, Bittner M, Trent J, Barrett JC, Afshari CA|title=Microarrays and toxicology: the advent of toxicogenomics|journal=Molecular Carcinogenesis|volume=24|issue=3|pages=153–9|year=1999|pmid=10204799|doi=10.1002/(SICI)1098-2744(199903)24:3<153::AID-MC1>3.0.CO;2-P |url=https://zenodo.org/record/1235508}}</ref> 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.<ref name="pmid15952870">{{cite journal|vauthors=Fielden MR, Pearson C, Brennan R, Kolaja KL|title=Preclinical drug safety analysis by chemogenomic profiling in the liver|journal= American Journal of Pharmacogenomics|volume=5|issue=3|pages=161–71|year=2005|pmid=15952870|doi=10.2165/00129785-200505030-00003 |s2cid=24834075}}</ref>

==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]],<ref>{{cite journal|vauthors=Mattes WB, Pettit SD, Sansone SA, Bushel PR, Waters MD|title=Database development in toxicogenomics: issues and efforts|journal=Environmental Health Perspectives|volume=112|issue=4|pages=495–505|date=March 2004|pmid=15033600|pmc=1241904|doi=10.1289/ehp.6697|bibcode=2004EnvHP.112..495M |url=http://ehp.niehs.nih.gov/txg/members/2004/6697/6697.html|url-status=dead|archive-url=https://web.archive.org/web/20080704171519/http://ehp.niehs.nih.gov/txg/members/2004/6697/6697.html|archive-date=2008-07-04}}</ref> often including [[statistical classification]] approaches.<ref>{{cite journal|vauthors=Ellinger-Ziegelbauer H, Gmuender H, Bandenburg A, Ahr HJ|title=Prediction of a carcinogenic potential of rat hepatocarcinogens using toxicogenomics analysis of short-term in vivo studies|journal=Mutation Research|volume=637|issue=1–2|pages=23–39|date=January 2008|pmid=17689568|doi=10.1016/j.mrfmmm.2007.06.010 |bibcode=2008MRFMM.637...23E }}</ref>

==Drug discovery==
In pharmaceutical [[drug discovery]] and [[drug development|development]], toxicogenomics is used to study possible [[adverse effect (medicine)|adverse]] (i.e. [[toxic]]) effects of pharmaceutical [[drug]]s in defined [[model organism|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 [[U.S. Food and Drug Administration|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.<ref>{{cite journal|vauthors=Corvi R, Ahr HJ, Albertini S, Blakey DH, Clerici L, Coecke S, Douglas GR, Gribaldo L, Groten JP, Haase B, Hamernik K, Hartung T, Inoue T, Indans I, Maurici D, Orphanides G, Rembges D, Sansone SA, Snape JR, Toda E, Tong W, van Delft JH, Weis B, Schechtman LM|title=Meeting report: Validation of toxicogenomics-based test systems: ECVAM-ICCVAM/NICEATM considerations for regulatory use|journal=Environmental Health Perspectives|volume=114|issue=3|pages=420–9|date=March 2006|pmid=16507466|pmc=1392237|doi=10.1289/ehp.8247|bibcode=2006EnvHP.114..420C |url=http://www.ehponline.org/members/2005/8247/8247.html|url-status=dead|archive-url=https://web.archive.org/web/20081017084247/http://www.ehponline.org/members/2005/8247/8247.html|archive-date=2008-10-17}}</ref>

== 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.<ref>{{cite journal|author=Waters MD, Fostel JM|year=2004|title=Toxicogenomics and systems toxicology: aims and prospects|journal=Nature Reviews Genetics|volume=5|issue=12|pages=938–948|doi=10.1038/nrg1493|pmid=15573125 |s2cid=1368324}}</ref><ref>{{cite journal|vauthors=Collins BC, Clarke A, Kitteringham NR, Gallagher WM, Pennington SR|title=Use of proteomics for the discovery of early markers of drug toxicity|journal=Expert Opinion on Drug Metabolism & Toxicology|volume=3|issue=5|pages=689–704|date=October 2007|pmid=17916055|doi=10.1517/17425255.3.5.689 |s2cid=27489795}}</ref>

{{anchor|InnoMed PredTox}}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.<ref name=Mattes>{{Cite book|last1=Mattes|first1=William B.|name-list-style=vanc|chapter=Public Consortium Efforts in Toxicogenomics|doi=10.1007/978-1-60327-048-9_11|title=Essential Concepts in Toxicogenomics|editor1-last=Mendrick|editor1-first=Donna L.|editor2-last=Mattes|editor2-first=William B.|series=[[Methods in Molecular Biology]]|volume=460|pages=221–238|year=2008|isbn=978-1-58829-638-2|pmid=18449490}}</ref>

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).<ref>{{cite journal|vauthors=Igarashi Y, Nakatsu N, Yamashita T, Ono A, Ohno Y, Urushidani T, Yamada H|title=Open TG-GATEs: a large-scale toxicogenomics database|journal=Nucleic Acids Research|volume=43|issue=Database issue|pages=D921–7|date=January 2015|pmid=25313160|pmc=4384023|doi=10.1093/nar/gku955 }}</ref>

The Predictive Safety Testing Consortium aims to identify and clinically qualify safety biomarkers for regulatory use as part of the [[U.S. Food and Drug Administration|FDA]]'s "Critical Path Initiative".<ref name=Mattes />

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]].<ref>{{cite journal|vauthors=Dix DJ, Houck KA, Martin MT, Richard AM, Setzer RW, Kavlock RJ|title=The ToxCast program for prioritizing toxicity testing of environmental chemicals|journal=Toxicological Sciences|volume=95|issue=1|pages=5–12|date=January 2007|pmid=16963515|doi=10.1093/toxsci/kfl103 |doi-access=free}}</ref>

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.<ref name="TOX21project">{{cite web|url=http://www.ncats.nih.gov/research/reengineering/tox21/tox21.html|title=Toxicology in the 21st century project|website=www.ncats.nih.gov}}</ref> Within this project the toxic effects of chemical compounds on cell lines derived from the [[1000 Genomes Project]] individuals were assessed and associations with genetic markers were determined.<ref name="Abdo2015">{{cite journal|vauthors=Abdo N, Xia M, Brown CC, Kosyk O, Huang R, Sakamuru S, Zhou YH, Jack JR, Gallins P, Xia K, Li Y, Chiu WA, Motsinger-Reif AA, Austin CP, Tice RR, Rusyn I, Wright FA|title=Population-based in vitro hazard and concentration-response assessment of chemicals: the 1000 genomes high-throughput screening study|journal=Environmental Health Perspectives|volume=123|issue=5|pages=458–66|date=May 2015|pmid=25622337|pmc=4421772|doi=10.1289/ehp.1408775 |bibcode=2015EnvHP.123..458A }}</ref> Parts of this data were used in the NIEHS-NCATS-UNC DREAM Toxicogenetics Challenge in order to determine methods for cytotoxicity predictions for individuals.<ref name="TOXGenChal">{{cite web|title=NIEHS-NCATS-UNC-DREAM Toxicogenetics Challenge|url=https://www.synapse.org/#!Synapse:syn1761567|publisher= Sage Bionetworks }}</ref><ref name="DeepTox">{{cite web|title=DeepTox: Deep Learning for Toxicity Prediction|url=http://www.bioinf.jku.at/research/DeepTox/|publisher=Institute of Bioinformatics, Johannes Kepler University Linz }}</ref>

== See also ==
* [[Comparative Toxicogenomics Database]]
* [[Pharmacogenetics]]
* [[Structural genomics]]

== References ==
{{Reflist|2}}

== External links ==
* [https://wayback.archive-it.org/all/20071029174920/http://www.ohsu.edu/croet/research/centers/toxicogenomics/whatis.html Center for Research on Occupational and Environmental Toxicology] definition by the CROET Research Centers: (Neuro)toxicogenomics and Child Health Research Center.

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[[Category:Genomics]]
[[Category:Toxicology]]
[[Category:Medical genetics]]