A Progenesis QI workflow in Exposomics

Following on from the previous post about our 3 Progenesis QI lunchtime presentations at IMSC 2018, we are proud to present to you the talk given by Emilien Jamin from the Toxalim, Research Centre in Food Toxicology, Toulouse University, available to view here.

Emilien’s work in contaminant discovery and analysis shows how Progenesis QI can be used very effectively for untargeted analysis in the Exposomics field.   This workflow goes beyond suspect screening which requires prior knowledge.  Emilien uses several examples of how Progenesis QI was used to discriminate between different populations and finally touches on a proof of concept on lipids peroxidation.

You can view the talk for yourself and you can read an overview of his presentation below.

Metabolomic profiling of reactive metabolites in toxicology by MSE and Progenesis QI

Metabolomic profiling of reactive metabolites in toxicology by MSE and Progenesis

Emilien Jamin, Robin Costantino, Jean-François Martin, Françoise Guéraud, Laurent Debrauwer

Toxalim (Research Centre in Food Toxicology) Toulouse university, INRA, ENVT, INP-Purpan, UPS, F-31027 Toulouse, France.

Axiom Platform, MetaToul-MetaboHUB, National Infrastructure for Metabolomics and Fluxomics, F-31027 Toulouse, France

In food safety, current exposure assessment approaches are based on food consumption data crossed with food contamination data or biomonitoring data. This allows evaluating exposure only in a targeted way on a few families of compounds. Based on our previous results in exposomics [1], food or environmental toxicology should focus on the exposure to a mixture of compounds (contaminant cocktails), mostly at low doses, and in an untargeted way to detect/identify unknown compounds. And among these numerous known and unknown metabolites, it seems a priority to focus on potentially toxic compounds.

In this context; we developed an untargeted method using high resolution mass spectrometry coupled to liquid chromatography to specifically profile electrophilic metabolites, in parallel with a classic untargeted metabolomic study. This allows the study of the exposure of potentially toxic compounds on one hand, and the study of the effects of this exposure on the endogenous metabolites on the other hand. More precisely, we used the MSE mode of a Synapt G2-Si mass spectrometer to detect all the metabolites displaying a neutral loss specific of metabolites conjugated with mercapturic acid. Data from MSE and from untargeted HRMS analyses were processed with Progenesis QI, to highlight discriminant reactive metabolites, as well as endogenous metabolites.

As a proof of concept, this approach has been applied to the study of different groups of rats fed diets containing various oils. According to our previous results on lipid peroxidation [2] these diets led to the production of different aldehydes conjugated to mercapturic acid. The most well known is DHN-MA which corresponds to the mercapturate conjugate of 4-hydroxynonenal (4-HNE), which is commonly used as a biomarker of lipid peroxidation [2]. Using our methodology, we were able to detect without a priori, dozens of mercapturate conjugates, including DHN-MA and other known conjugated aldehydes. Furthermore, our approach also allowed the detection of conjugates of unexpected aldehydes, and of other chemical classes, for which putative identifications have been proposed based on complementary structural analyses. Interestingly, multivariate statistical analyses of the HRMS signals carried out on the mercapturate conjugates yield a better characterization of the studied animal groups compared to results obtained from a classic untargeted metabolomic approach.

[1] Jamin E.L. et al. Anal Bioanal Chem (2014) 406:1149–1161

[2] Guéraud F. Free Radic Biol Med (2017) 111:196-208

Progenesis QI is a powerful tool for contaminant analysis and has been used in the food, cosmetics, natural products, chemical materials, sports doping, biopharma, metabolomics and proteomics fields.

Why not download the software and see how it can help you in your research? Progenesis QI for Progenesis QIP for proteomics