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To systematically evaluate the pathways driving this sensitivity, we performed continuous gene set enrichment analysis (GSEA) ranking all mapped genes by their Pearson correlation coefficient ( R ) between basal expression (log 2 (TPM + 1)) and the PRISM log 2 (fold de-enrichment) across the 470 matched cell lines (note that 5 cell lines were not listed on HPA and were therefore not included
Additionally, the NNMT substrate nicotinamide 12 is metabolized by the microbiome 56,57 , and thus NNMTi may modulate substrate availability, potentially influencing microbial metabolic capacity to drive the NNMTi-mediated weight loss
It's typically a positive sign, though understandably concerning
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