Extended Data Fig. 8: Gene modules and CTP analysis in RNAseq of PC9 single-cell derived clones.

(a) gene-gene correlation matrix, showing gene modules unrelated to proliferation gradient defined in Fig.S7d-g, computed based on normalized expression in untreated clones (upper triangle) and in gefitinib treated clones (lower triangle). (b) log normalized clonal expression of gene modules specified in A in untreated (x axis) and drug treated clones (y axis). Dashed light blue line defining the diagonal, indicating changes of absolute expression levels in untreated and treated clones. A higher correlation suggests higher clonal stability of the gene module, amid the transcriptional response to the drug treatment. (c) Showing 50 genes with highest (blue) and lowest (red) fold-change in Mucin-high clones vs Mucin-low clones. Fold-change computed as log ratio of expression geometric mean of each gene in 30% of gefitinib treated clones with highest Mucin expression, to its expression geometric mean in 30% of gefitinib treated clones with lowest Mucin expression. (d) Clonal expression of Mucin gene module is associated with CTP. Showing expression of genes associated with the Mucin and ZNF469 genes modules shown in A for gefitinib treated (upper panel) and DMSO treated clones (lower panel). Each column in both panel defines clone from the same single-cell-derived clonal population, after eliminating one of the n = 195 clones whose CTP-assay failed technically. Expression of each gene is normalized to maximal expression in gefitinib treated clones. Despite the weaker expression in untreated clones, the conserved expression structure which correlated to CTP can be observed also without treatment. (e) Average of the mucin gene module score is presented for clones that were grouped by their CTP gefitinib. P-values were calculated using the chi-square test.