Extended Data Fig. 5: PDAC organoid specific IL-4/IL-13 response module is context specific and unique from other IL-4/IL-13 signatures.
From: Scalable, compressed phenotypic screening using pooled perturbations
a. Left: Heatmap showing the Pearson correlation of the expression of the Moffitt classical and basal transcriptional signatures with the expression of each CS cNMF module over bulk PDAC RNA-seq data from TCGA. Right: Heatmap of the Pearson correlation of the Moffitt classical and basal transcriptional signatures with the expression of each CS cNMF module over malignant PDAC single cells from Raghavan et al. b. Scatterplots showing the correlation between the Moffitt classical score and our PDAC IL-4/IL-13 IL-4/IL-13 response GEP (top) or three IL-4/IL-13 transcriptional signatures from MsigDB as computed over bulk RNA-seq data from PDAC tumors available in TCGA. c. Scatterplots showing the correlation between the Moffitt classical score and our PDAC IL-4/IL-13 response GEP (top) or three IL-4/IL-13 transcriptional signatures from MsigDB as computed across malignant PDAC cells from Raghavan et al. d. Scatterplots showing the correlation between the Moffitt basal score and our PDAC IL-4/IL-13 response GEP (top) or three IL-4/IL-13 transcriptional signatures from MsigDB as computed over bulk RNA-seq data from PDAC tumors available in TCGA. e. Scatterplots showing the correlation between the Moffitt basal score and our PDAC IL-4/IL-13 response GEP (top) or three IL-4/IL-13 transcriptional signatures from MsigDB as computed across malignant PDAC cells from Raghavan et al. f. Venn diagrams for the overlap between single-ligand validation experiment cNMF GEP module genes and genes from existing signatures in the literature. g. Kaplan–Meier survival plots of a pancreatic cancer patient cohort (TCGA PAAD, n = 182, bulk RNA-seq expression data) based on single-ligand IFNγ GEP and TGF-β GEP (left column) compared with their literature counterparts (right column). h. Integrated low-dimensional embedding (UMAP) of the scRNA-seq data from the IL-4 single-ligand perturbation experiment. Color scale indicates the density of the ligand treatment. i. Top 25 differentially expressed genes between IL-4 and DMSO-only treated groups (two-sided Wilcoxon test, BH adjusted p-value < 0.01). j. Overrepresentation Analysis (ORA) of all significant (two-sided Wilcoxon test, BH adjusted p-value < 0.05) differentially expressed genes in IL-4 vs control cells using MsigDB Hallmark dataset. For the ORA, one-sided Fisher’s exact test is computed and FDR correction is applied to the p-value.
