Pathways for Ligand Activated Nuclear Receptors to Unravel the Genomic Responses Induced by Hepatotoxicants
J.H.M. van Delft.
The liver is a vital organ in vertebrates that can be subject to disease, among others due to exposure to toxic xenobiotic
compounds. A group of transcription factors named ligand activated nuclear receptors (LANR) influence and regulate important liver
functions, and can be activated by many xenobiotic compounds, which thereby can cause hepatotoxicity. Systematic analysis of the gene
pathways regulated by LANR using modern ‘omics technologies is important for investigating modes-of-action of hepatotoxicants. So
far, these pathways are not publicly available in a format that allows these studies.
We used PathVisio to build liver-specific LANR pathways, both for rats and humans. Since many LANR pathways are linked to each
other, we also merged them into a meta-pathway. The pathways are in a GPML-format that enables pathway statistics and visualisations,
and will be made available to the public through WikiPathways. We demonstrate the performance of these novel pathways in evaluating
transcriptomic studies from the Japanese toxicogenomics project database (Open TG-GATEs).
We show that the new pathways can be used to accurately analyse and visualize the effects of prototypical hepatotoxicants in important
liver processes, and thus to evaluate the possible mode-of-actions of hepatotoxic xenobiotic compounds by assessing which LANRs are
Keywords: Gene expression, hepatotoxicants, human, ligand activated nuclear receptors, pathways, rodent.
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