Deriving time-concordant event cascades from gene expression data: A case study for Drug-Induced Liver Injury (DILI)
Fig 4
Enrichment of known events in DILI before adverse histopathology based on gene sets as well as individual gene members.
The enrichment of first activation before or at adverse histopathology is shown for gene sets mapping to known key events in DILI, for which first activation was defined as first timepoint of differential GSVA-derived gene set activity. Furthermore, also enrichment of individual genes within these genesets is shown and was derived based on the first timepoints of differential expression. Aligning with the expected direction, a significant down-regulation of Liver X Receptor (LXR) signalling and bile acid-related pathways is observed, while all other gene sets were found to be more significantly up-regulated. Only for peroxisomal pathways, both directions were significantly enriched indicating that dysregulation in direction might be linked to adverse histopathology.