Multi-omics HeCaToS dataset of repeated dose toxicity for cardiotoxic & hepatotoxic compounds

• DOI: 10.1038/s41597-022-01825-1
• Publication Date: 2022-11-14T06:04:03Z
• Authors: Marcha Verheijen; Ugis Sarkans; Witold Wolski; Danyel Jennen; Florian Caiment; Jos Kleinjans; ; Irina Agarkova; Francis L. 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 Deeb; Hans Gmuender; Stefano Gotta; Patrick Guye; Anne Hersey; Ralf Herwig; Stephane Heymans; Peter Hunt; Fiona M. I. Hunter; James Hynes; Hector Keun; Eirini Kouloura; Lars Kuepfer; Laura Kunz; Alex Lewalle; Matthias Lienhard; Teresa Martínez-Sena; Jort Merken; Jasmine Minguet; Nhan Nguyen; Steven Niederer; Ramona Nudischer; Juan Ochoteco Ase...; Bernardo Oliveira; Christian Panse; Carla Pluess; Adrian B. Roth; Ralph Schlapbach; Yannick Schrooders; Johannes Schuchhardt; Matthew Segall; Nathalie Selevsek; Pilar Sepulveda; Ines Smit; Christoph Thiel; Bernd Timmermann; Timo Wittenberger; Alexandra Zerck
• Keywords: Bioquímica; Epigenomics; Proteomics; 0301 basic medicine; Biologia; BATCH EFFECT CORRECTION; Data Descriptor; Drug-Related Side Effects and Adverse Reactions; DATABASE; SAMPLES; Science; Q; DNA; Cardiotoxicity; 3. Good health; GENOME; ALIGNMENT; 03 medical and health sciences; SEQ; QUALITY-CONTROL; RNA; Humans; Metabolomics; Transcriptome

AbstractThe data currently described was generated within the EU/FP7 HeCaToS project (Hepatic andCardiacToxicitySystems modeling). The project aimed to develop anin silicoprediction 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 fromin vitroexperiments 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/).