Fig. 1

Overview of the approach. Two control and two complex I-deficient patient fibroblast cell lines were incubated for three days with vehicle (DMSO) and three compounds that trigger a metabolic response and RNA was harvested in duplicate for RNA sequencing. Expression values of individual genes across the resulting 4 × 4 × 2 = 32 samples were measured, normalized and clustered. This allowed for the analysis of expression profiles per gene. Genes were ranked based on the similarity of their expression profile (co-expression) with the average profile for a bait set of genes, such as the OXPHOS system or complex I. High ranking genes were analyzed for the presence of conserved transcription factor binding sites across 29 mammals. Common, over-represented binding sites are (potential) transcriptional regulators of the system