Extended Data Fig. 5: Gut microbial gene differences discriminate between non-progressors and progressors during anti-PD-1 therapy in the Pittsburgh early sample cohort.

a. t-distributed uniform manifold approximation and projection (t-UMAP) plot depicting genetic differences of gut microbiomes between non-progressors (NPs; blue) and progressors (Ps; red) at time of maximal difference from start of therapy (10 months). Filled circles represent centroids, with connecting lines corresponding to samples from each group. Two-tailed p-value was calculated using PERMANOVA. b. Metagenomic shotgun sequencing of fecal microbiota samples identifies differentially abundant genes in Ps vs. NPs at 10 months from start of therapy. Heatmap shows differentially abundant genes identified by metagenomic shotgun sequencing (FDR < 0.2 and FC > 1.5). Columns denote patients grouped by progression status and clustered within P/NP groups; rows denote bacterial genes significantly upregulated (red) or downregulated (blue) in Ps versus NPs. c and d. Select genes involved in representative microbial processes of lipopolysaccharide (LPS) processing (c) and iron metabolism (d).