Figure 3 from Archetype Analysis of Lung Adenocarcinoma Premalignancy Links Heterogeneity in Premalignant Lesions to Diverging Features of Invasive Disease

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Abstract
Archetype analysis on PMLs demonstrates correlation of archetypes with molecular and clinical phenotypes. A, Scatterplots of first two PCs computed from GSVA scores for PML-derived modules across PML samples from all four cohorts. Each plot is colored by the distance of each sample from an archetype (vertex of polytope). Each sample has four associated distances—one for each archetype vertex. More negative numbers reflect samples further away from the vertex. B, Scatterplot of first two PCs computed from GSVA scores for PML-derived modules for all PML samples. Samples in the top 0.125 proportion of distances from each archetype were assigned archetypes, whereas other samples were labeled as “secondary,” with colors representing samples closest to each respective archetype. Shapes indicate histology of samples. C, Heatmap of t-statistics from linear mixed-effects models of GSVA scores for each PML-derived module (rows) modeled with distance from each archetype (columns) and study as fixed effects and patient as a random effect.*, FDR < 0.05 for the distance term. Rows are hierarchically clustered using ward.d2 similarity of the Euclidean distance. Row annotations represent the median GSVA score for each module in Lung PCA samples of either normal tissue or tumor. D, Visualization of χ2 residuals from χ2 test of association between archetypes and histology. Plot shows contribution of each comparison in the matrix to the test statistic, where circle size is proportional to contribution. Positive (red) values specify a positive association between the corresponding row and column variables (χ2 test, P = 0.18, n = 37 AAH and n = 19 AIS/MIA).