Multi-omics HeCaToS dataset of repeated dose toxicity for cardiotoxic & hepatotoxic compounds
Marcha Verheijen, Uğis Sarkans, Witold Wolski, Danyel Jennen, Florian Caiment, Jos Kleinjans, Irina Agarkova, Francis Atkinson, Ivo Bachmann, Vanessa Baier, Gal Barel, Chris Bauer, Twan van den Beucken, Stefan Boerno, Nicolas Bosc, Conn Carey, José V. Castell, Olivia Clayton, Henrik Cordes, Sally J. Deeb, Hans Gmuender, Stefano Gotta, Patrick Guye, Anne Hersey, Ralf Herwig, Stéphane Heymans, Peter Hunt, Fiona Hunter, James T. Hynes, Hector C. Keun, Eirini Kouloura, Lars Kuepfer, Laura Kunz, Alexandre Lewalle, Matthias Lienhard, Teresa Martínez-Sena, Jort J. Merken, Jasmine Minguet, Nhan Nguyen, Steven Niederer, Ramona Nudischer, Juan Ochoteco Asensio, Bernardo Lino de Oliveira, Christian Panse, Carla Pluess, Adrian Roth, Ralph Schlapbach, Yannick Schrooders, Johannes Schuchhardt, Matthew Segall, Nathalie Selevsek, Pilar Sepúlveda, Ines Smit, Christoph Thiel, Bernd Timmermann, Timo Wittenberger, Alexandra Zerck
Abstract
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/ ).