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

Marcha Verheijen*, Ugis Sarkans, Witold Wolski, Danyel Jennen, Florian Caiment, Jos Kleinjans, HeCaToS Consortium

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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/ ).

Original languageEnglish
Pages (from-to)699
Number of pages11
JournalScientific data
Volume9
Issue number1
DOIs
Publication statusPublished - 14 Nov 2022

Keywords

  • Humans
  • Cardiotoxicity
  • Drug-Related Side Effects and Adverse Reactions
  • Epigenomics
  • Metabolomics
  • Proteomics
  • Transcriptome

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