The landscape of metabolic pathway dependencies in cancer cell lines
Fig 2
Global analysis of metabolic dependency data reveals context-specific pathway essentialities.
A) Metabolic pathway activity was inferred using ssGSEA for 300 adherent cell lines cultured in RPMI and correlated to gene dependency data from The Cancer Dependency Map (DepMap). Correlation coefficients were then ranked and Genetic Pathway Dependency Enrichment Analysis (Genetic PDEA) was run using the KEGG metabolic pathways (see Fig 1). Hierarchical clustering was performed on the Genetic PDEA normalized enrichment scores (NES). Results for pathways with FDR < 0.25 are plotted. Dots are colored according to their NES and sized according to the -log10 of the false discovery rate (FDR). Numerical values for each pathway can be found in S1 Table. Results shown in B and C are highlighted with a black outline. B) Cancer cell dependency on Folate Biosynthesis (hsa00790) was increased when One-Carbon Pool by Folate (hsa00670) pathway activity was high. The scatter plots of pathway activity NES and gene dependency (-CERES) for leading-edge genes QDPR and ALPI are shown. C) Dependency on One-Carbon Pool by Folate metabolism (hsa00670) is increased when TCA cycle (hsa00020) activity is increased. The scatter plots of pathway activity NES and gene dependency (-CERES) for leading-edge genes MTR and MTHFD1 are shown.