Transcriptomic Biomarkers in Food Safety: RNA Biomarkers against the abuse of growth promoters

Abstract
The use of growth promoting agents in animal husbandry is strictly forbidden the European Union. This ban is controlled within a strict control plan where residues of known growth promoting agents are identified using chromatographical methods in combination with mass spectrometry or may be screened by immuno assays. New designed xenobiotic agents or new modes of application, e.g. the administration of substance cocktails are not detectable with those methods. To ensure an efficient tracing of misused anabolic agents, new detection methods have to be developed. One promising way is to monitor the physiological effects of the given substances on the molecular level. The analysis of the transcriptome has already been shown to be a promising approach to detect the pharmacological action of a substance in different organs and matrices.
In a pilot study, RNA-Sequencing technology was used to screen for changes in the transcriptome of bovine liver caused by treatment with steroid hormones. Thereby a first biomarker pattern could be identified that enabled the separation of treated animals versus untreated animals using biostatistical clustering methods.
In order to test the drug dependence of such biomarkers, the identified biomarker candidates were validated in livers of veal calves treated with the b-agonist clenbuterol or another steroid hormone implant, respectively. Using the dynamic principal components analysis (PCA) algorithm, a biomarker signature could be detected that allowed the discrimination of treated and untreated individuals.
High throughput sequencing was also used to screen for additional biomarker candidates on mRNA and small RNA level in other target tissues. Those results indicate a high potential of transcriptomic biomarkers for the development of a new screening method that is independent of the given drug.