Figure 7 from Multistate Gene Cluster Switches Determine the Adaptive Mitochondrial and Metabolic Landscape of Breast Cancer

Pathological and clinical predictions from metabolic gene switches. A, The χ² distribution of discrete histological features across the upper, lower, and non-fork samples of the three biclusters (MB1–MB3). Heatmap shows k-means clustering of χ² test −log₁₀P values, dividing the histological parameters into three groups: high, low, and no association with the bicluster. B, Visualization of histological feature distribution on the MB1 and MB2 switches. Classifiers of histological tumor type (top) and degree of nuclear pleomorphism are overlaid onto two-dimensional distribution plots of TCGA samples. The axes represent the range between the UF and LF of each bicluster. C, Clustering of histological and genetic features of samples belonging to the MB1 and MB2 switches. Fractions of samples for each feature were calculated and clustered with a custom robust to outliers distance measure function and k-means clustering. Genetic features representative of each switch position are highlighted (bold), Pam50 categories (red), and histology types and features (blue and orange, respectively). D, Key genetic and transcriptional architecture of the MB1 and MB2 switches. E–L, Survival analysis of samples in the MB1 switch. Kaplan–Meier survival plots and Cox proportional hazard analysis results from ref. 43 (E–G) and ref. 42 (H–L) are shown, generated by the kmplot.com tool (43). MB1_UF and MB1_LF bicluster (E–J) and OXPHOS (K and L) patterns (Supplementary Table S1) were used to stratify subsets of ER-positive, Her2-negative samples as indicated on the panels.