Workshop: Carrying out a Meta-Analysis

Carrying out a Meta-Analysis across Multiple Heterogenous Sources of Evidence
OpenTox Euro 2014 Workshop: Carrying out a Meta-Analysis

Barry Hardy


Douglas Connect, Switzerland


Barry Hardy and Markus Hegi

Mon, 22. Sep. 2014


1) Hardy, B. et al, Collaborative Development of Predictive Toxicology Applications, Journal of Cheminformatics 2010, 2:7, 31 August 2010.
2) Kohonen, P., et al, “The ToxBank Data Warehouse: Supporting the Replacement of In Vivo Repeated Dose Systemic Toxicity Testing”, Molecular Informatics, Special Issue: Advances in Computational Toxicology, (2013), Volume 32, Issue 1, 47–63.

In this workshop we will examine the meta analysis of evidence based upon data on SEURAT-1 Gold Compounds (SGCs) used as mechanistic reference compounds. We will examine data which were obtained from the literature and organised and made available through the ToxBank wiki and data warehouse.

The data analysis will include transcriptomics data from TG-Gates, assay data from PubChem and ToxCast, toxicokinetics data and parameters from the literature, and in vivo data resources. Analysis methods for Read Across, enriched meta analysis of multiple omics and functional data, background knowledge from GO ontologies and Kegg pathways, and pathway visualisation will be applied to the SGCs. We will examine the variation of pathway interactions as a function of dose and time.

SGCs within ToxBank available for study will include reactive compounds (e.g., acetaminophen, CCl4), mitochondrial disruptors (e.g., Rotenone), promiscuous binders (e.g., valproic acid, amiadarone), nuclear hormone receptor ligands (e.g., tamoxifen, WY14643), selective binders (e.g. fluoxetine) and cardiotoxins (e.g., Doxorubicin, Nifedipine). Adverse events of interest that are represented include cytotoxicity, fibrosis, steatosis, cholestasis and phospholipidosis.