Unravelling the Exposome through integrated exposure biology

The exposome represents the totality of exposures from conception onwards, including the exogenous and endogenous exposures and modifiable risk factors that predispose to and predict disease. Unravelling the exposome implies that environmental exposures and genetic variation are reliably measured and linked through mechanistic analysis of toxicity pathways. To understand the interaction between environmental exposure and disease, we need to capture the biological perturbations initiated by exposure to environmental stressors; and identify which of these perturbations overcome the homeostasis barrier, resulting in observed alterations of the cell/tissue environment and eventually to pathologic phenotypes. Integrated exposure biology provides the methodological elements for the surveillance of changes at different levels of biological organization through the use of the full array of -omics and post-omics technologies including epigenomics. Starting from untargeted transcriptomics and metabolomics we proceed with joint analysis of biological processes induced by exposure to xenobiotics at the molecular level and of metabolic processes induced in parallel. Dynamic flux balance analysis is a key for joint interpretation of gene expression data and metabolite profiles. Thus putative pathways of toxicity are identified; they need to be verified by targeted multi-omics and functional assays. Identification of the functional links among the data derived from different high throughput testing platforms and their proper interpretation are supported by advanced bioinformatics such as support vector machines and clustering algorithms and systems biology models. Examples of the dawn of the exposure biology era are given and the future perspectives discussed in the context of supporting efficiently exposome studies.