Fig. 2

Exploratory kinome analysis demonstrates individual kinase activity profiles of CCAOs. A Schematic representation of the experimental setup. Kinase activity profiles were established for three CCAO lines with two matched non-tumorous adjacent tissue-derived organoid lines (CCAO1, CCAO2 with matched HAO2, and CCAO3 matched with HAO3) and three healthy donor-derived intrahepatic cholangiocyte organoid lines (ICO1, ICO2 and ICO3). Comparison of these profiles leads to the identification of potential druggable targets. CCAOs were also subjected to a screening of targeted therapeutics to identify pan-effective and selective compounds. Correlation between drug response and kinase activity leads to the discovery of potential biomarkers for treatment stratification. Schematic created with BioRender.com. B Violin plots with box plots showing that the overall kinase activity data density distribution is similar for all samples. Colors represent sample types (CCAO in yellow, HAO in green, ICO in blue). There was a significant difference in values among samples (p-value = 1.488e−03). C PCA plot of kinase activity of all peptides included in the kinome profiling array based on principle component 1 and 2. Each sample is represented by one dot (CCAO in yellow, HAO in green, ICO in blue). CCAO3 is the most distinct sample in the dataset. CCAOs are positioned far apart. D Heatmap of all kinase target peptides on the array analyzed by unsupervised clustering for samples and for kinase target peptides. Data is shown by log10(AUC target peptide). Three peptide clusters are emphasized: (i) peptides highly phosphorylated in all samples, (ii) peptides with heterogeneous phosphorylation patterns between samples, and (iii) peptides lowly/not phosphorylated in all samples