Extended Data Fig. 1: Correlation of nutrient utilization with gene expression identifies uridine and UPP1.

a. Schematic overview of the parameters measured by the Biolog Phenotype Microarray. b. Heatmap showing the high confidence metabolites (HCMs), namely, the metabolites that were utilized above or below the median of negative controls as determined by one-tailed Wilcoxon rank sum test. Legend denotes fold change relative to median negative control signal, where red shows high utilization and blue shows low utilization. c. Spearman correlation plot, indicating the genes that showed positive or negative correlation with metabolites’ RMA in the Biolog screen. d. Spearman correlations, r, between UPP1 expression in cell lines (ref. ¹⁷) and RMA of nucleosides that were included in the Biolog screen. n = 16 PDA cell lines. e. Heatmap showing the expression of glycolysis genes in human PDA tumours ranked based on UPP1 expression (dataset: GSE71729, UPP1 low, n = 72; high, n = 73). On the right: GSEA plot indicating the enrichment of glycolysis hallmark in the UPP1 high relative to the low tumours. NES, normalized enrichment score. f. Downregulated pathways in PDA cell lines that metabolize uridine at a high level, as revealed by gene ontology (GO) analysis of the differentially expressed genes (P < 0.05). GO analysis was performed with DAVID (https://david.ncifcrf.gov/tools.jsp). Analysis was based on the differential genes derived from CCLE data and part of the data shown in Fig. 1g. g. GSEA plots of significantly enriched KEGG pathways in UPP1-high PDA tumours relative to UPP1 low tumours. Plots are part of the data (e) from the analysis of GSE71729 human PDA dataset. Statistics and reproducibility: a, The kinetic measurement evaluated several parameters, including the time taken for cells to adapt to and catabolize a nutrient (lambda), the rate of uptake and catabolism (mu or slope), the total metabolic activity (area under the curve; AUC), and the maximum metabolic activity. The values from the maximum catabolic efficiency (maximum height, A) of the respective metabolites were used to determine relative metabolic activity (RMA).