1. The public EGA metadata for EGAS50000000808 appears to identify only two H3K27ac ChIP samples per condition and one input sample per condition, whereas the Statistical Analysis section states that all data had a minimum of three independent experiments per group. Could the authors clarify the exact biological replicate and donor structure for Figures 2 and 4, explain how the input samples were generated and assigned, and provide a sample-to-donor map?
2. Clarification is also requested regarding the target-specific mechanistic conclusions. The effects of 3PO do not alone establish PFKFB3 dependence, and 6,8-bis(benzylthio)octanoic acid inhibits both PDH and α-ketoglutarate dehydrogenase; moreover, the concentration of the latter compound is not reported in the principal Methods. Please provide the relevant target-engagement, viability, metabolic, and raw expression data or qualify the conclusions as effects of the pharmacological compounds rather than specific evidence for PFKFB3 and PDH. Finally, the raw isotopologue tables and analysis protocol underlying the 13C-glucose experiment in Figure 1A would help resolve how the reported picomole values and biological/technical triplicates were defined.