Extended Data Fig. 6: GNE-7883 suppresses sotorasib resistance in NCI-H23 cells.
(a) Schematic illustrating TraCe-seq setup comparing the response of NCI-H23 cells to sotorasib treatment alone versus in combination with GNE-7883. (b) Number of TraCe-seq barcodes belong to each of the categories. (c) The MAPK pathway (left) and YAP/TAZ target (right) scores for NCI-H23 cells belonging to different barcode categories (n = 28 distinct depleted barcodes, n = 19 distinct unchanged barcodes, n = 9 distinct enriched barcodes) at baseline (Day 0) or under treatment for 3 or 15 days. Boxes represent the distribution of scores per barcode (average of all cells with the same barcode) for all barcodes in a given category. (d) Comparison of the MAPK pathway (left) and YAP/TAZ target (right) scores for each NCI-H23 barcode categories (n = 28 distinct depleted barcodes, n = 19 distinct unchanged barcodes, n = 9 distinct enriched barcodes) treated for 3 days with sotorasib alone or in combined with GNE-7883. For panels (c) and (d), Boxes represent the distribution of scores per barcode for all barcodes in a given category (Counts are aggregated based on the cell barcodes and the box plots comprise the pseudo-bulk values for barcodes in the different categories). Lower and upper hinges correspond to the first and third quartiles (the 25th and 75th percentiles). The lower and upper whiskers extend from the hinge to the smallest or largest value no further than 1.5 × interquantile range (IQR) from the hinge. Data beyond the end of the whiskers are called ‘outlying’ points and are plotted individually. p-values were derived from two-sided Wilcoxon’s rank sum tests between time points, and from Kruskal-Wallis one-way analysis of variance between categories for each time point. NS, not significant (p > 0.05).
