Extended Data Figure 1: Analysis of screening results by reaction reactants and products.

a, Histogram of shRNA depletion scores. shRNAs (11,370) were scored based on their differential abundance in the in vitro and in vivo screens. shRNAs were further subdivided into those which targeted enzymes that consume O₂ (red, 1,035 shRNAs) and to those targeting other genes (black, 10,335 shRNAs). Bin size = 1 log₂ fold change unit with the upper end of the range indicated on the x axis. The shRNAs in the shaded region are scored, and the percentage of these shRNAs falling in the indicated categories and the median of the entire distribution are reported. b, Enzymes were classified based on whether they catalysed reactions involving specific metabolites, and the most commonly used 25 metabolites are reported. The number of shRNAs differentially depleted in vivo versus in vitro with a log₂ fold change cut-off >2 are reported (scoring shRNAs), as are the total number of shRNAs targeting enzymes in each category. The percentage of scoring shRNAs for each metabolite is reported, and those significantly exceeding the percentage scoring in ‘all enzymes’ or ‘all genes’ classes are indicated. O₂ and water classes were further subdivided (top right) to indicate that shRNAs targeting O₂-consuming enzymes were significantly enriched, whereas shRNAs targeting O₂ producing reactions or reactions that utilize water but do not consume O₂ were not significantly enriched. *P < 0.05, Fisher’s exact test. Raw data are reported in Supplementary Table 2.