Fig. 1

In vivo CRISPR screening identifies novel drug targets. a The experimental outline of in vivo genetic knockout screening in PDX model of PDAC. b The heat map represents log-fold change of the top 2000 enriched and depleted sgRNAs in three separate trametinib-treated tumors relative to the mean of control-treated tumors. c Plot showing the distribution of normalized CRISPR viability scores (treatment vs control) for genes targeted by the sgRNA library. Shown are all targeted genes. Red dots indicate significantly depleted kinetochore genes as assessed by one-sided Kolmogorov–Smirnov test. d The plot showing the significance score (treatment vs control) of all gene depletion (minus log-transformed p values) as determined by Kolmogorov–Smirnov test. Kinetochore genes are labeled with red dots. e Gene ontology (GO) analysis depicts the significantly enriched GO terms for the top enriched and depleted gene sets (n = 100) from in vivo screening. Log-transformed p values are represented by bar plots