A Tiered Approach for Screening and Assessment of Environmental Mixtures by Omics and In Vitro Assays

New methodology approaches with a broad coverage of the biological effects are urgently needed to evaluate the safety of the universe of environmentally relevant chemicals. Here, we propose a tiered approach incorporating transcriptomics and in vitro bioassays to assess environmental mixtures. The mixture samples and the perturbated biological pathways are prioritized by concentration-dependent transcriptome (CDT), and then be used to guide the selection of in vitro bioassays for toxicant identification. To evaluate omics' screening capability, we first applied a CDT technique to test mixture samples by HepG2 and MCF7 cells. Effect recoveries of large-volume solid-phase extraction on overall bioactivity of mixture were 48.9% in HepG2 and 58.3% in MCF7. The overall bioactivity potencies obtained by transcriptomics were positively correlated with the panel of 8 bioassays among 14 mixture samples combining with the previous data. Transcriptomics could predict their activation status (AUC=0.783) and relative potency (p