Extended Data Fig. 10: Targeting MTHFD2 across co-occurring genetic mutations and heterogenous stromal microenvironment in tumors.
(a) Multidimensional scaling-based 2D projection of complete transcriptional profiles of the four HGSOC clusters with 19p13.3 deletion. (b) Venn diagram representing the overlap of reactions in reconstruction of metabolic models illustrating the average expression of four ovarian tumor clusters with 19p13.3 deletion and the overall original ovarian cancer model with 19p13.3 deletion used in Fig. 2. (c) Unsupervised PHATE analysis on scRNASeq data from ascites of ovarian cancer patients to assign cell-types. (d) UQCR11 and MTHFD2 mRNA expression across cell types projected on 2D PHATE embedding of scRNASeq data. (e-g) Average expression (pathway score) of genes in the one carbon metabolic signature #1 (e, Supplementary Information S5), serine glycine threonine metabolism signature #1 (f, Supplementary Information S5), and the NAD+ synthesis metabolism (g, Supplementary Information S5) in ovarian tumors from TCGA with 19p13.3 intact or 19p13.3 deletion. Data are represented as mean ± s.d, analyzed using Student’s two-tailed t-test with Welch’s correction (e-g). (h) Average expression (pathway score) of genes remaining signatures related to the serine-glycine one carbon metabolism (Supplementary Information S5) and mitochondrial metabolism (Supplementary Information S5) across the quadrants of the stromal 2D PHATE embedding. (i) UQCR11 mRNA expression and one carbon metabolism (signature #1) pathway score in microdissected malignant and stromal ovarian tumor compartments (GSE115635). Pairs that have reduced UQCR11 expression in malignant compartments compared to stromal compartments (lower than median of expression difference) are colored red, while those with higher UQCR11 expression in malignant compartments are marked in grey. Data analyzed using paired two-tailed Student’s t-test (n=17 red pairs, n=17 grey pairs).
