The landscape of metabolic pathway dependencies in cancer cell lines
Fig 3
Media composition influences metabolic pathway dependency.
For adherent cancer cell lines cultured in RPMI (Fig 2) and DMEM (S2 Fig), the metabolic pathway dependency NESs from Genetic PDEA analysis were weighted by -log10 FDR. The weighted NESs were then averaged across all 69 KEGG metabolic pathways. Pathways are ranked by the difference between DMEM and RPMI. The relative media composition between RPMI and DMEM are shown on the right on a purple to green heat map with the relevant metabolite(s) indicated. For pathways with multiple metabolites, the average of the metabolites was taken. For example, the concentration of folate in RPMI and DMEM is 1 mg/L and 4 mg/L, respectively. Folate is shown twice because it is both the product of Folate Biosynthesis and the input to One-Carbon Pool by Folate. The dependency on Folate Biosynthesis was much higher in RPMI than in DMEM because these cells must synthesize more folate. Conversely, the dependency on oxidative phosphorylation is much higher in DMEM. This may be due to differences in aspartate levels (RPMI 150 μM, DMEM 0 μM). The indicated pathways are highlighted in bold. Overall, pathways that contained a metabolite which is differentially abundant in cell culture media exhibited a significant difference in pathway essentiality in DMEM and RPMI (p = 3.9x10-4 by paired Mann-Whitney U test). In contrast, pathways that do not contain differentially abundant cell culture media metabolites did not exhibit significantly different pathway dependencies (p = 0.545 by paired Mann-Whitney U test).