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Transcriptomics as a relevant tool to answer current questions in toxicology

Transcriptomic represents a powerful tool to evaluate the impact of various stimuli on biological systems. By measuring the abundance of thousands of transcripts simultaneously, one can reveal both specific gene expression changes and modulations of entire pathways. Recent developments in transcriptomic data analysis further enable 1) to reveal subtle impacts affecting groups of coregulated genes, even when their individual statistical significance can be doubtful and 2) to integrate transcriptomic data with other levels of observations such as proteomic or metabolomic data. These new possibilities emphasize the advantages transcriptomic offers to study the effects of xenobiotics mixture and low doses and to couple the impacts on the transcriptome to their potential causes or consequences at the phenotypic level.

Development of the TRiX transcriptomic facility at TOXALIM

Since 2000, the Integrative Toxicology & Metabolism group has developed a substantial experience in transcriptomic studies (from foused macroarrays to genome-wide screenings) and high-throughput data analysis (from data pre-processing/filtering to high-level data integration). Based on this experience and on funding by INRA and the Region Midi-Pyrénées (CPER 2007-2013), we propose to develop the TRiX facility (TRanscriptomic impact of Xenobiotics) in order to provide an easy access to expertise and tools to perform transcriptomic studies with Agilent microarrays. TRiX would be fully integrated with the GenoToul biochips platform (biopuce.insa-toulouse.fr) which established an Affymetrix platform and provides several equipments and services for a variety of applications on biochips. TRiX will be open to any project from local, national or international actors of the academic or industrial sectors.

To complete the panel of technologies available to the community, we propose to set up an Agilent platform (including an Agilent scanner) and to develop services which include statistical analysis of the data. Agilent technology is highly complementary to Affymetrix platform, in particular due to its greater flexibility (whole genomes or easy custom chip designs, one- or two-color designs). Based on our experience, the use of an Agilent scanner with Agilent microarrays significantly improves precision and reproducibility.

In addition to Agilent microarray screenings, TRiX will provide an environment suitable for high-throughput or targeted gene expression studies and aims at developing future services for targeted promoter analysis. TiRX will be initially set-up by Pascal Martin (IR2, Integrative Toxicology & Metabolism group), who is specialized in transcriptomics and involved in coordinating the GenoToul biostatistic platform (www.math.univ-toulouse.fr/biostat).

Projects workflow at the TRiX facility

Our short-term project is to provide the workflows presented below for whole-genome or targeted gene expression studies (services provided by TRiX are in blue and products delivered to TRiX client are in red):

In the medium term, TRiX aims at providing effective services for all steps of the gene expression workflows including hands-on manipulations, QC and statistical data analysis reports as well as to develop a reliable quality assurance system (ISO 9001). TRiX will aim at obtaining labels from INRA-CNOC (Commission Nationale des Outils Collectifs) and from the GIS-IBiSA (Infrastructures en Biologie Santé et Agronomie) together with the GenoToul Biochips platform. Additional services for the targeted analysis of promoters would also be developed.

Current TOXALIM Projects using transcriptomics with microarrays: projects PNRPE and Région Midi-Pyrénées on Fipronil and flame retardants (C Viguié), ANR PlastImpact (T Pineau), ANR Metaprofile (JL Sebedio), ANR ExpoMatPest (L Payrastre), ANR HemeCancer (F Pierre), EU 7th FP MycoRed (I Oswald), Priority action of the Nutrition, Chemical Food Safety and Consumer Behaviour division of INRA on Bisphenol-A (E Houdeau), INRA-Formas project on lipid metabolism (H Guillou).