TOXsIgN- ApublicrepositoryfortoxicologicalsignaturesattheIRSET
T.A.Darde1,2,P.Gaudriault1,R.Beranger1,N.Costet1,N.Bonvallot1,3,O.Sallou2,O.Collin2,
B.Jégou1,3,C.Chevrier1,E.Becker1,S.Mazaud-Guittot1,A.D.Rolland1andF.Chalmel1
1InsermU1085-Irset;UniversitédeRennes1;F-35042Rennes,France;2Ins<tutdeRechercheenInforma<queetSystèmesAléatoires(IRISA/INRIA)-GenOuestplaNorm,UniversitédeRennes1;F-35042Rennes,France;
Objectives
While generalist repositories allow investigators to submit their raw data (1-2), other specialized databases have paved the way for improving
toxicological data storage, exchange and analysis (3-6). Here we present TOXsIgN a new multi-species public repository for TOXicological sIgNatures. This
database provides a flexible and open environment that facilitates online submission, and retrieval of toxicological signatures deposited by the toxicology
community. One of the unique features of TOXsIgN relies on its ability to archive heterogeneous data from: multiple species; observational and
interventional studies; in vivo, ex vivo or in vitro experiments; physiological, molecular or “omic” studies; transgenerational studies; mixtures studies.
Aproject-centricorganization(Fig.1)
TOXsIgN information is organized in a four-layer architecture (project>study>condition>signature): a project is subdivided into studies which address
specific questions and describe experimental conditions or treatments, the latter being associated with toxicological signatures. All of these layers are
associated with a unique accession number thus facilitating data accessibility. Most of the associated information is described thanks to several
controlled vocabularies (i.e. ontologies).
Experimentalconditions(Fig.2)
1
Each experimental condition or treatment describes the
exposure of a given study model (e.g. cell culture, living
animals, human population) to at least one chemical
(e.g. pesticides, plasticizers, drugs, endocrine
disruptors), physical (e.g. radiations, temperature) or
biological (e.g. pathogens, parasites) factor at a given
dose and at a given time of exposure. This organization
therefore makes TOXsIgN compatible with mixtures
studies. Currently, experimental conditions are
restricted to chemical compounds.
2
DMSO
3
Toxicologicalsignatures(Fig.3)
In TOXsIgN, a toxicological signature is defined as the description of physiological,
cellular, molecular or omics (e.g. epigenomic, transcriptomic, proteomic) effects on
individuals or their descendants, after exposure to single or combined environmental
factors.
Currentstatus
TOXsIgN currently hosts approximatively 700 projects, comprising over 1000 studies
which describe more than 7500 experimental conditions and their corresponding
signatures. These data were extracted from 29 scientific publications among which 26
describe toxicogenomics data, 1 investigate a chemical mixture and 2 report
epidemiological data. Importantly, TOXsIgN integrate data from 2 major toxicogenomics
resources : DrugMatrix (7) and TG-GATEs (8) which describe the altered gene expression
profiles in 5 different tissues in the rat after exposure to 376 and 150 compounds,
respectively.
Perspectives
In the near future, TOXsIgN will allow investigators to submit other types of
environmental factors (i.e physical and biological factors). It also intends to go beyond a
simple public repository and to become a warehouse for toxicogenomics and predictive
toxicology tools. TOXsIgN already includes a powerful search engine that supports
complex queries to retrieve data by accession number and other experimental
parameters such as species, tissues, developmental stages, chemicals, types of
experiment and/or observed toxicological effects. The modular design of TOXsIgN will
facilitate the implementation of other advanced tools (see ChemPSy poster) leaning on
the deposited toxicogenomics signatures that will help investigators analyze, predict
and prioritize the toxicological effects of relevant environmental factors.
Conclusion
TheTOXsIgNrepositoryispublicly available toallacademicusers,
without loginrequirementat:
http://toxsign.genouest.org
Suggestionsfor improvingTOXsIgNandrequestsfor
additionaldatasetsorfunctionalitiesarewelcome!
Contactusat:[email protected]
Figures 1-3 – TOXsIgN interface. Screenshots of the TOXsIgN visualization pages.
1 – The treeview allows an easy and quick navigation between projects, studies
and signatures. 2- Information related to the chemical treatment such as vehicle,
route, dose and exposure time. 3 –Associated toxicogenomic signature
including up and down regulated genes (Entrez Gene IDs), the number of
control and treated samples, the statistical cutoff as well as additional
information.
References
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