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The data currently described was generated within the EU/FP7 HeCaToS project (Hepatic and Cardiac Toxicity Systems modeling). The project aimed to develop an in silico prediction system to contribute to drug safety assessment for humans. For this purpose, multi-omics data of repeated dose toxicity were obtained for 10 hepatotoxic and 10 cardiotoxic compounds. Most data were gained from in vitro experiments in which 3D microtissues (either hepatic or cardiac) were exposed to a therapeutic (physiologically relevant concentrations calculated through PBPK-modeling) or a toxic dosing profile (IC20 after 7 days). Exposures lasted for 14 days and samples were obtained at 7 time points (therapeutic doses: 2-8-24-72-168-240-336 h; toxic doses 0-2-8-24-72-168-240 h). Transcriptomics (RNA sequencing & microRNA sequencing), proteomics (LC-MS), epigenomics (MeDIP sequencing) and metabolomics (LC-MS & NMR) data were obtained from these samples. Furthermore, functional endpoints (ATP content, Caspase3/7 and O2 consumption) were measured in exposed microtissues. Additionally, multi-omics data from human biopsies from patients are available. This data is now being released to the scientific community through the BioStudies data repository (https://www.ebi.ac.uk/biostudies/).

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Transcriptomics is nowadays frequently used as an analytical tool to study the extent of cell expression changes between two phenotypes or between different conditions. However, an important portion of the significant changes observed in transcriptomics at the gene level is usually not consistently detected at the protein level by proteomics. This poor correlation between the measured transcriptome and proteome is probably mainly due to post-transcriptional regulation, among which miRNA and circRNA have been proposed to play an important role. Therefore, since both miRNA and circRNA are also quantified by transcriptomics, we proposed to build a model taking those factors into account to estimate, for each transcript, the fraction of transcripts that would be available for translation. Using a dataset of cells exposed to diverse compounds, we evaluated how our model was able to improve the correlation between the assessed transcriptome and proteome expression level. The results show that the model improved the correlation for a subset of genes, probably due to the regulation of different miRNAs across the genome.